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The number of invasive alien species is increasing and so are the impacts these species cause to the environment and economies. Nevertheless, resources for management are limited, which makes prioritization unavoidable. We present a prioritization framework which can be useful for decision makers as it includes both a scientific impact assessment and the evaluation of impact importance by affected stakeholders. The framework is divided into five steps, namely 1) stakeholder selection and weighting of stakeholder importance by the decision maker, 2) factual description and scoring of changes by scientists, 3) evaluation of the importance of impact categories by stakeholders, 4) calculation of weighted impact categories and 5) calculation of final impact score and decision making. The framework could be used at different scales and by different authorities. Furthermore, it would make the decision making process transparent and retraceable for all stakeholders and the general public.
Several major hypotheses have been proposed to explain and predict biological invasions, but the general applicability of these hypotheses is largely unknown, as most of them have not been evaluated using a standard approach across taxonomic groups and habitats. We offer such an evaluation for six selected leading hypotheses. Our global literature review reveals that those hypotheses that consider interactions of exotic invaders with their new environment (invasional meltdown, novel weapons, enemy release) are better supported by empirical evidence than other hypotheses (biotic resistance, island susceptibility, tens rule). We also show that empirical support for the six hypotheses has declined over time, and that support differs among taxonomic groups and habitats. Our results have implications for basic and applied research, policy making, and invasive species management, as their effectiveness depends on sound hypotheses.
One of the most robust emerging generalisations in invasion biology is that the probability of invasion increases with the time since introduction (residence time). We analysed the spatial distribution of alien vascular plant species in a region of north-eastern Italy to understand the influence of residence time on patterns of alien species richness. Neophytes were grouped according to three periods of arrival in the study region (1500–1800, 1800–1900, and > 1900). We applied multiple regression (spatial and nonspatial) with hierarchical partitioning to determine the influence of climate and human pressure on species richness within the groups. We also applied variation partitioning to evaluate the relative importance of environmental and spatial processes. Temperature mainly influenced groups with species having a longer residence time, while human pressure influenced the more recently introduced species, although its influence remained significant in all groups. Partial regression analyses showed that most of the variation explained by the models is attributable to spatially structured environmental variation, while environment and space had small independent effects. However, effects independent of environment decreased, and spatially independent effects increased, from older to the more recent neophytes. Our data illustrate that the distribution of alien species richness for species that arrived recently is related to propagule pressure, availability of novel niches created by human activity, and neutral-based (dispersal limitation) processes, while climate filtering plays a key role in the distribution of species that arrived earlier. This study highlights the importance of residence time, spatial structure, and environmental conditions in the patterns of alien species richness and for a better understanding of its geographical variation.
Plant-fungal interactions are essential for understanding the distribution and abundance of plants species. Recently, arbuscular mycorrhizal fungal (AMF) partners of non-indigenous invasive plants have been hypothesized to be a critical factor influencing the invasion processes. AMF are known to improve nutrient and moisture uptake, as well as disrupt parasitic and pathogenic microbes in the host plant. Such benefits may enable invaders to establish significant and persistent populations in environments previously dominated by natives. Coupling these findings with studies on invader pathogen-disrupting root exudates is not well documented in the literature describing plant invasion strategies. The interaction effects of altered AMF associations and the impact of invader root exudates would be more relevant than understanding the AMF dynamics or the phytochemistry of successful invaders in isolation, particularly given that AMF and root exudates can have a similar role in pathogen control but function quite differently. One means to achieve this goal is to assess these strategies concurrently by characterizing both the general (mostly pathogens or commensals) and AM-specific fungal colonization patterns found in field collected root samples of successful invaders, native plants growing within dense patches of invaders, and native plants growing separately from invaders. In this review I examine the emerging evidence of the ways in which AMF-plant interactions and the production of defensive root exudates provide pathways to invasive plant establishment and expansion, and conclude that interaction studies must be pursued to achieve a more comprehensive understanding of successful plant invasion.
Recently, Müller and Nentwig (2011) reviewed the plant pathogens that have been considered for biological control of the weed Cirsium arvense (L.) Scop. (Canada thistle, Californian thistle, creeping thistle), and concluded that the prospects have been largely overestimated. The premise of their conclusion is that no bioherbicide products have achieved marketability, which they surmise is due to lack of host specificity, effectiveness, and issues with application. While it is true that no microbial products have achieved marketability for this weed, we believe their reasoning for this is erroneous, and likely due to lack of distinction between two biocontrol approaches, specifically classical biocontrol, and innundative biocontrol (often referred to as the biopesticide approach). These two different types of biocontrol have different goals, and are applied in different ways.
Invasive knotweeds, native to Eastern Asia, are among the most dominant plant invaders of European and North American temperate ecosystems. Recent studies indicate that one cause of this dominance might be allelopathy, but the possible sources and modes of action of this allelopathy are insufficiently understood. Here, we asked whether the invasive knotweed Fallopia × bohemica can exert allelopathic effects on native plants also through its leaf litter, or through persistent soil contaminants, and whether these affect the germination or growth of native plants. In a germination experiment with nine native species neither litter leachate, an aqueous extract of knotweed leaves added to the soil, nor trained soil with a history of Fallopia pre-cultivation suppressed the germination or early growth of natives. A mesocosm study with experimental native communities showed that the presence of F. × bohemica, although not a dominant in these communities, caused significant shifts of life-history strategy in two dominant natives, and that similar effects could be elicited through litter leachates or trained soil alone. However, there were hardly any effects on the biomass of natives. Our study indicates that knotweed allelopathy acts on the growth rather than germination of natives, and that soil contamination through persistent allelochemicals may not be a significant problem in habitat restoration. It also shows that allelopathic effects can sometimes be subtle changes in life-history and allocation patterns of the affected species.
Many successful invasions involve long initial periods in which the invader exists at low densities followed by sudden population increases. The reasons for such time-lags remain poorly understood. Here we document a sudden increase in density of the introduced Japanese white-eye (Zosterops japonicus) in a restoration area contiguous with old-growth forest at Hakalau Forest National Wildlife Refuge on the Island of Hawaii. The refuge, with very high density of native birds, existed in a pocket of low whiteeye density that persisted for at least 20 years since the late 1970s. The refuge began an extensive native trees restoration project in 1989 within a 1314 ha abandoned pasture above old-growth forest. This area was soon colonized by white-eyes and their population grew exponentially once the trees had grown tall enough to develop a canopy. This increase was in turn followed by significantly more white-eyes in the open and closed forests adjacent to the restoration area. Competition between white-eyes and native species was documented on study sites within these forests. Density data indicate that competition was more widespread, with loss of tens of thousands of native birds in the 5371 ha area surveyed. Our results are consistent with the view that ecological barriers may delay the population increase of invaders and that human-derived activities may help invaders cross these barriers by creating new ecological opportunities. Control of white-eye numbers may be essential for recovery of native species.
We examined temporal introduction patterns of 132 invasive alien plant species (IAPS) to Australia since European colonisation in 1770. Introductions of IAPS were high during 1810–1820 (10 species), 1840– 1880 (51 species, 38 of these between 1840 and 1860) and 1930–1940 (9 species). Conspicuously few introductions occurred during 10-year periods directly preceding each introduction peak. Peaks during early European settlement (1810–1820) and human range expansion across the continent (1840-1860) both coincided with considerable growth in Australia’s human population. We suggest that population growth during these times increased the likelihood of introduced plant species becoming invasive as a result of increased colonization and propagule pressure. Deliberate introductions of IAPS (104 species) far outnumbered accidental introductions (28 species) and were particularly prominent during early settlement. Cosmopolitan IAPS (25 species) and those native solely to South America (53 species), Africa (27 species) and Asia (19 species) have been introduced deliberately and accidentally to Australia across a broad period of time. A small number of IAPS, native solely to Europe (5 species) and North America (2 species), were all introduced to Australia prior to 1880. These contrasting findings for native range suggest some role for habitat matching, with similar environmental conditions in Australia potentially driving the proliferation of IAPS native to southern-hemisphere regions. Shrub, tree and vine species dominated IAPS introduced prior to 1840, with no grasses or forbs introduced during early colonisation. Since 1840, all five growth forms have been introduced deliberately and accidentally in relatively large numbers across a broad period of time. In particular, a large number of grass and forb IAPS were deliberately introduced between 1840 and 1860, most likely a direct result of the introduction of legislation promoting intensive agriculture across large areas of the continent. Since the 1980s, only three IAPS have been introduced (all deliberately introduced forbs). The decline in IAPS introductions is most likely a reflection of both increased surveillance and biosecurity efforts and the likelihood that many potential IAPS are still within a pre-expansion lag period.
Previous studies on alien species establishment in the United States and around the world have drastically improved our understanding of the patterns of species naturalization, biological invasions, and underlying mechanisms. Meanwhile, relevant new data have been added and the data quality has significantly increased along with the consistency of related concepts and terminology that are being developed. Here using new and/or improved data on the native and exotic plant richness and many socioeconomic and physical variables at the state level in the United States, we attempt to test whether previously discovered patterns still hold, particularly how native and exotic species are related and what are the dominant factors controlling the plant naturalization. We found that, while the number of native species is largely controlled by natural factors such as area and temperature, exotic species and exotic fraction are predominantly influenced by social factors such as human population. When domestically introduced species were included, several aspects in earlier findings were somewhat altered and additional insights regarding the mechanisms of naturalization could be achieved. With increased data availability, however, a greater challenge ahead appears to be how many and which variables to include in analyses.
Seed disperser preferences may mediate the impact of invasive, non-native plant species on their new ecological communities. Significant seed disperser preference for invasives over native species could facilitate the spread of the invasives while impeding native plant dispersal. Such competition for dispersers could negatively impact the fitness of some native plants. Here, we review published literature to identify circumstances under which preference for non-native fruits occurs. The importance of fruit attraction is underscored by several studies demonstrating that invasive, fleshy-fruited plant species are particularly attractive to regional frugivores. A small set of studies directly compare frugivore preference for native vs. invasive species, and we find that different designs and goals within such studies frequently yield contrasting results. When similar native and non-native plant species have been compared, frugivores have tended to show preference for the non-natives. This preference appears to stem from enhanced feeding efficiency or accessibility associated with the non-native fruits. On the other hand, studies examining preference within existing suites of co-occurring species, with no attempt to maximize fruit similarity, show mixed results, with frugivores in most cases acting opportunistically or preferring native species. A simple, exploratory meta-analysis finds significant preference for native species when these studies are examined as a group. We illustrate the contrasting findings typical of these two approaches with results from two smallscale aviary experiments we conducted to determine preference by frugivorous bird species in northern California. In these case studies, native birds preferred the native fruit species as long as it was dissimilar from non-native fruits, while non-native European starlings preferred non-native fruit. However, native birds showed slight, non-significant preference for non-native fruit species when such fruits were selected for their physical resemblance to the native fruit species. Based on our review and case studies, we propose that fruit characteristics of native plant communities could dictate how well a non-native, fleshy-fruited plant species competes for dispersers with natives. Native bird preferences may be largely influenced by regional native fruits, such that birds are attracted to the colors, morphology, and infructescence structures characteristic of preferred native fruits. Non-native fruits exhibiting similar traits are likely to encounter bird communities predisposed to consume them. If those non-natives offer greater fruit abundance, energy content, or accessibility, they may outcompete native plants for dispersers.
Success of invasive species has been frequently estimated as the present distribution range size in the introduced region. However, the present distribution range is only a picture of the invasion for a given time step and do not inform on the potential distribution range of the species. Based on niche-based models we used climatic, geographic and landscape information on the present distribution range for 78 major plant invaders in Spain to estimate and map their potential distribution range. We found a positive relationship between present and potential distribution of species. Most of the species have not yet occupied half of their potential distribution range. Sorghum halepense and Amaranthus retroflexus have the widest potential distribution range. Sorghum halepense and Robinia pseudoacacia have the highest relative occupancy (i.e. proportion of potential distribution range currently occupied). Species with a larger minimum residence time have, on average, higher relative occupancy. Our study warns managers that it might be only a matter of time that currently localized invasive species reach their potential area of distribution.
The aim of our study is to provide an integrated framework for the management of alien plant invasions, combining insights and experiences from the fields of invasion and restoration ecology to enable more effective management of invasive species. To determine linkages between the scientific outputs of the two disciplines we used an existing data base on restoration studies between 2000 and 2008 and did a bibliometric analysis. We identified the type of restoration applied, determined by the aim of the study, and conducted a content analysis on 208 selected studies with a link to biological invasions (invasion-restoration studies). We found a total of 1075 articles on ecosystem restoration, with only eight percent of the studies having the main objective to control alien invasions. The content analysis of 208 invasion-restoration studies showed that the majority of the studies focused on causes of degradation other than alien invasions. If invaders were referred to as the main driver of degradation, the prevalent cause for degradation was invaders outcompeting and replacing native species. Mechanical control of alien plant invasions was by far the most common control method used. Measures that went beyond the removal of alien plants were implemented in sixty-five percent of the studies. Although invasion control was not as common as other types of restoration, a closer look at the sub-group of invasion-restoration studies shows a clear link between restoration and invasion ecology. Concerns, as identified in the literature review, are firstly that restoration activities mostly focus on controlling the invader while other underlying causes for degradation are neglected, and secondly that the current approach of dealing with alien invasions lacks a combination of theoretical and practical aspects. We suggest that closer collaboration between invasion and restoration ecologists can help to improve the management of alien plant invasions. We conclude with a framework and a case study from Perth Western Australia integrating the two disciplines, with the aim of informing restoration practice.
Background: The t(9;22) translocation leads to the formation of the chimeric breakpoint cluster region/c-abl oncogene 1 (BCR/ABL) fusion gene on der22, the Philadelphia chromosome. The p185(BCR/ABL) or the p210(BCR/ABL) fusion proteins are encoded as a result of the translocation, depending on whether a "minor" or "major" breakpoint occurs, respectively. Both p185(BCR/ABL) and p210(BCR/ABL) exhibit constitutively activated ABL kinase activity. Through fusion to BCR the ABL kinase in p185(BCR/ABL) and p210(BCR/ABL) "escapes" the auto-inhibition mechanisms of c-ABL, such as allosteric inhibition. A novel class of compounds including GNF-2 restores allosteric inhibition of the kinase activity and the transformation potential of BCR/ABL. Here we investigated whether there are differences between p185(BCR/ABL) and p210(BCR/ABL) regarding their sensitivity towards allosteric inhibition by GNF-2 in models of Philadelphia chromosome-positive acute lymphatic leukemia.
Design and methods: We investigated the anti-proliferative activity of GNF-2 in different Philadelphia chromosome-positive acute lymphatic leukemia models, such as cell lines, patient-derived long-term cultures and factor-dependent lymphatic Ba/F3 cells expressing either p185(BCR/ABL) or p210(BCR/ABL) and their resistance mutants.
Results: The inhibitory effects of GNF-2 differed constantly between p185(BCR/ABL) and p210(BCR/ABL) expressing cells. In all three Philadelphia chromosome-positive acute lymphatic leukemia models, p210(BCR/ABL)-transformed cells were more sensitive to GNF-2 than were p185BCR/ABL-positive cells. Similar results were obtained for p185(BCR/ABL) and the p210(BCR/ABL) harboring resistance mutations.
Conclusions: Our data provide the first evidence of a differential response of p185(BCR/ABL)- and p210(BCR/ABL)- transformed cells to allosteric inhibition by GNF-2, which is of importance for the treatment of patients with Philadelphia chromosome-positive acute lymphatic leukemia.
TO THE EDITOR: We read an interesting paper by Palta et al. in a recent issue of the Korean Journal of Hematology titled, "ZBTB16-RARA variant of acute promyelocytic leukemia with tuberculosis: a case report and review of literature" [1]. We would like to add some comments to their article and suggest additional molecular methods to confirm variant translocations in acute promyelocytic leukemia (APL)....
Hereditary Angioedema (HAE) is a rare disease and for this reason proper diagnosis and appropriate therapy are often unknown or not available for physicians and other health care providers. For this reason we convened a group of specialists that focus upon HAE from around the world to develop not only a consensus on diagnosis and management of HAE, but to also provide evidence based grades, strength of evidence and classification for the consensus. Since both consensus and evidence grading were adhered to the document meets criteria as a guideline. The outcome of the guideline is to improve diagnosis and management of patients with HAE throughout the world and to help initiate uniform care and availability of therapies to all with the diagnosis no matter where the residence of the individual with HAE exists.
Hereditary angioedema (HAE) in children and adolescents : a consensus on therapeutic strategies
(2012)
Hereditary angioedema due to C1 inhibitor (C1 esterase inhibitor) deficiency (types I and II HAE-C1-INH) is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible is important to avoid ineffective therapies and to properly treat swelling attacks. At a consensus meeting in June 2011, pediatricians and dermatologists from Germany, Austria, and Switzerland reviewed the currently available literature, including published international consensus recommendations for HAE therapy across all age groups. Published recommendations cannot be unconditionally adopted for pediatric patients in German-speaking countries given the current approval status of HAE drugs. This article provides an overview and discusses drugs available for HAE therapy, their approval status, and study results obtained in adult and pediatric patients. Recommendations for developing appropriate treatment strategies in the management of HAE in pediatric patients in German-speaking countries are provided.Conclusion Currently, plasma-derived C1 inhibitor concentrate is considered the best available option for the treatment of acute HAE-C1-INH attacks in pediatric patients in German-speaking countries, as well as for short-term and long-term prophylaxis.
Research over the past few years has provided fascinating results indicating that biglycan, besides being a ubiquitous structural component of the extracellular matrix (ECM), may act as a signaling molecule. Proteolytically released from the ECM, biglycan acts as a danger signal signifying tissue stress or injury. As a ligand of innate immunity receptors and activator of the inflammasome, biglycan stimulates multifunctional proinflammatory signaling linking the innate to the adaptive immune response. By clustering several types of receptors on the cell surface and orchestrating their downstream signaling events, biglycan is capable to autonomously trigger sterile inflammation and to potentiate the inflammatory response to microbial invasion. Besides operating in a broad biological context, biglycan also displays tissue-specific affinities to certain receptors and structural components, thereby playing a crucial role in bone formation, muscle integrity, and synapse stability at the neuromuscular junction. This review attempts to provide a concise summary of recent data regarding the involvement of biglycan in the regulation of inflammation and the musculoskeletal system, pointing out both a signaling and a structural role for this proteoglycan. The potential of biglycan as a novel therapeutic target or agent for the treatment of inflammatory diseases and skeletal muscular dystrophies is also addressed.
Pattern recognition approaches to the analysis of neuroimaging data have brought new applications such as the classification of patients and healthy controls within reach. In our view, the reliance on expensive neuroimaging techniques which are not well tolerated by many patient groups and the inability of most current biomarker algorithms to accommodate information about prior class frequencies (such as a disorder's prevalence in the general population) are key factors limiting practical application. To overcome both limitations, we propose a probabilistic pattern recognition approach based on cheap and easy-to-use multi-channel near-infrared spectroscopy (fNIRS) measurements. We show the validity of our method by applying it to data from healthy controls (n = 14) enabling differentiation between the conditions of a visual checkerboard task. Second, we show that high-accuracy single subject classification of patients with schizophrenia (n = 40) and healthy controls (n = 40) is possible based on temporal patterns of fNIRS data measured during a working memory task. For classification, we integrate spatial and temporal information at each channel to estimate overall classification accuracy. This yields an overall accuracy of 76% which is comparable to the highest ever achieved in biomarker-based classification of patients with schizophrenia. In summary, the proposed algorithm in combination with fNIRS measurements enables the analysis of sub-second, multivariate temporal patterns of BOLD responses and high-accuracy predictions based on low-cost, easy-to-use fNIRS patterns. In addition, our approach can easily compensate for variable class priors, which is highly advantageous in making predictions in a wide range of clinical neuroimaging applications. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.
We introduce tree-width for first order formulae φ, fotw(φ). We show that computing fotw is fixed-parameter tractable with parameter fotw. Moreover, we show that on classes of formulae of bounded fotw, model checking is fixed parameter tractable, with parameter the length of the formula. This is done by translating a formula φ with fotw(φ)<k into a formula of the k-variable fragment Lk of first order logic. For fixed k, the question whether a given first order formula is equivalent to an Lk formula is undecidable. In contrast, the classes of first order formulae with bounded fotw are fragments of first order logic for which the equivalence is decidable. Our notion of tree-width generalises tree-width of conjunctive queries to arbitrary formulae of first order logic by taking into account the quantifier interaction in a formula. Moreover, it is more powerful than the notion of elimination-width of quantified constraint formulae, defined by Chen and Dalmau (CSL 2005): for quantified constraint formulae, both bounded elimination-width and bounded fotw allow for model checking in polynomial time. We prove that fotw of a quantified constraint formula φ is bounded by the elimination-width of φ, and we exhibit a class of quantified constraint formulae with bounded fotw, that has unbounded elimination-width. A similar comparison holds for strict tree-width of non-recursive stratified datalog as defined by Flum, Frick, and Grohe (JACM 49, 2002). Finally, we show that fotw has a characterization in terms of a cops and robbers game without monotonicity cost.
Background: The recommendation of artemisinin combination therapy (ACT) as first-line treatment for uncomplicated falciparum malaria is supported by a plethora of high quality clinical trials. However, their recommendation for the treatment of mixed-species malaria and the large-scale use for the treatment of non-falciparum malaria in endemic regions is based on anecdotal rather than systematic clinical evidence.
Methods: This study prospectively observed the efficacy of artemether-lumefantrine for the treatment of uncomplicated non-falciparum or mixed-species malaria in two routine district hospitals in the Central African country of Gabon.
Results: Forty patients suffering from uncomplicated Plasmodium malariae, Plasmodium ovale or mixed-species malaria (including Plasmodium falciparum) presenting at the hospital received artemether-lumefantrine treatment and were followed up. All evaluable patients (n = 38) showed an adequate clinical and parasitological response on Day 28 after oral treatment with artemether-lumefantrine (95% confidence interval: 0.91,1). All adverse events were of mild to moderate intensity and completely resolved by the end of study.
Conclusions: This first systematic assessment of artemether-lumefantrine treatment for P. malariae, P. ovale and mixed-species malaria demonstrated a high cure rate of 100% and a favourable tolerability profile, and thus lends support to the practice of treating non-falciparum or mixed-species malaria, or all cases of malaria without definite species differentiation, with artemether-lumefantrine in Gabon.
Trial Registration: ClinicalTrials.gov Identifier: NCT00725777
Recent research suggests that the brain routinely binds together information from gesture and speech. However, most of this research focused on the integration of representational gestures with the semantic content of speech. Much less is known about how other aspects of gesture, such as emphasis, influence the interpretation of the syntactic relations in a spoken message. Here, we investigated whether beat gestures alter which syntactic structure is assigned to ambiguous spoken German sentences. The P600 component of the Event Related Brain Potential indicated that the more complex syntactic structure is easier to process when the speaker emphasizes the subject of a sentence with a beat. Thus, a simple flick of the hand can change our interpretation of who has been doing what to whom in a spoken sentence. We conclude that gestures and speech are integrated systems. Unlike previous studies, which have shown that the brain effortlessly integrates semantic information from gesture and speech, our study is the first to demonstrate that this integration also occurs for syntactic information. Moreover, the effect appears to be gesture-specific and was not found for other stimuli that draw attention to certain parts of speech, including prosodic emphasis, or a moving visual stimulus with the same trajectory as the gesture. This suggests that only visual emphasis produced with a communicative intention in mind (that is, beat gestures) influences language comprehension, but not a simple visual movement lacking such an intention.
This study demonstrates that alkaline earth elements in enamel of hippopotamids, in particular Ba and Sr, are tracers for water provenance and hydrochemistry in terrestrial settings. The studied specimens are permanent premolar and molar teeth found in modern and fossil lacustrine sediments of the Western Branch of the East African Rift system (Lake Kikorongo, Lake Albert, and Lake Malawi) and from modern fluvial environments of the Nile River.
Concentrations in enamel vary by two orders of magnitude for Ba (120–9336 μg g−1) as well as for Sr (9–2150 μg g−1). The variations are partially induced during post-mortem alteration and during amelogenesis, but the major contribution originates ultimately from the variable water chemistry in the habitats of the hippopotamids which is controlled by the lithologies and weathering processes in the watershed areas. Amelogenesis causes a distinct distribution of MgO, Ba and Sr in modern and fossil enamel, in that element concentrations increase along profiles from the outer rim towards the enamel–dentin junction by a factor of 1.3–1.9. These elements are well correlated in single specimens, thus suggesting that their distribution is determined by a common, single process, which can be described by closed system Rayleigh crystallization of bioapatite in vivo.
Enamel from most hippopotamid specimens has Sr/Ca and Ba/Ca which are typical for herbivores. However, Ba/Sr ranges from 0.1 to 3 and varies on spatial and temporal scales. Thus, Sr concentrations and Ba/Sr in enamel differentiate between habitats having basaltic mantle rocks or Archean crustal rocks as the ultimate sources of Sr and Ba. This provenance signal is modulated by climate change. In Miocene to Pleistocene enamel from the Lake Albert region, Ba/Sr decreases systematically with time from 2 to 0.5. This trend can be correlated with changes in climate from humid to arid, in vegetation from C3 to C4 biomass as well as with increasing evaporation of the lake water. The most plausible explanation is that Ba mobility decreased with increasing aridification due to preferential deposition with clay and Fe-oxide-hydroxide or barite on the watershed of Lake Albert.
has been demonstrated in climate models that both the Indian and East Asian summer monsoons (ISM and EASM) are strengthened by the uplift of the entire Asian orography or Tibetan Plateau (TP) (i.e. bulk mountain uplift). Such an effect is widely perceived as the major mechanism contributing to the evolution of Asian summer monsoons in the Neogene. However, geological evidence suggests more diachronous growth of the Asian orography (i.e. regional mountain uplift) than bulk mountain uplift. This demands a re-evaluation of the relation between mountain uplift and the Asian monsoon in the geological periods. In this study, sensitivity experiments considering the diachronous growth of different parts of the Asian orography are performed using the regional climate model COSMO-CLM to investigate their effects on the Asian summer monsoons. The results show that, different from the bulk mountain uplift, the regional mountain uplift can lead to an asynchronous development of the ISM and EASM. While the ISM is primarily intensified by the thermal insulation (mechanical blocking) effect of the southern TP (Zagros Mountains), the EASM is mainly enhanced by the surface sensible heating of the central, northern and eastern TP. Such elevated surface heating can induce a low-level cyclonic anomaly around the TP that reduces the ISM by suppressing the lower tropospheric monsoon vorticity, but promotes the EASM by strengthening the warm advection from the south of the TP that sustains the monsoon convection. Our findings provide new insights to the evolution of the Asian summer monsoons and their interaction with the tectonic changes in the Neogene.
AIM: To investigate morphological changes of intestinal smooth muscle contractile fibres in small bowel atresia patients. METHODS: Resected small bowel specimens from small bowel atresia patients (n = 12) were divided into three sections (proximal, atretic and distal). Standard histology hematoxylin-eosin staining and enzyme immunohistochemistry was performed to visualize smooth muscle contractile markers α-smooth muscle actin (SMA) and desmin using conventional paraffin sections of the proximal and distal bowel. Small bowel from age-matched patients (n = 2) undergoing Meckel's diverticulum resection served as controls.
RESULTS: The smooth muscle coat in the proximal bowel of small bowel atresia patients was thickened compared with control tissue, but the distal bowel was unchanged. Expression of smooth muscle contractile fibres SMA and desmin within the proximal bowel was slightly reduced compared with the distal bowel and control tissue. There were no major differences in the architecture of the smooth muscle within the proximal bowel and the distal bowel. The proximal and distal bowel in small bowel atresia patients revealed only minimal differences regarding smooth muscle morphology and the presence of smooth muscle contractile filament markers.
CONCLUSION: Changes in smooth muscle contractile filaments do not appear to play a major role in postoperative motility disorders in small bowel atresia.
Musil uses the word 'Dichter', 'poet', as a dignified title reserved for artists of great achievement (different from 'Schriftsteller', 'writer'). His use of the word emphasizes the importance of the specifically poetic qualities of literature (and of the poetic sensibility of criticism,) not as an idle objection to the contemporary merging of literary works with either pure sensation and feeling, or with other forms of discourse. Focusing on "Törless", as well as on Musil's notebooks and essays, this article shows how Musil understands the relationship between rational thinking and the latent ideas and thoughts that emerge within the poetic dimension (the 'other state of mind' or 'other condition.') This approach illuminates Musil's conception of "precision and soul" - the interlocking of sensitive perceptiveness and intellectual rigor - as a necessary pre-condition for valuable literature and valuable life.
The study of acupuncture-related sensations, like deqi and propagated sensations along channels (PSCs), has a long tradition in acupuncture basic research. The phenomenon itself, however, remains poorly understood. To study the connection between PSC and classical meridians, we applied a geographic information system (GIS) to analyze sketches of acupuncture sensations from healthy volunteers after laser acupuncture. As PSC can be subtle, we aimed at reducing the confounding impact of external stimuli by carrying out the experiment in a floatation tank under restricted environmental stimulation. 82.4% of the subjects experienced PSC, that is, they had line-like or 2-dimensional sensations, although there were some doubts that these were related to the laser stimulation. Line-like sensations on the same limb were averaged to calculate sensation mean courses, which were then compared to classical meridians by measuring the mean distance between the two. Distances ranged from 0.83 cm in the case of the heart (HT) and spleen (SP) meridian to 6.27 cm in the case of the kidney (KI) meridian. Furthermore, PSC was observed to “jump” between adjacent meridians. In summary, GIS has proven to be a valuable tool to study PSC, and our results suggest a close connection between PSC and classical meridians.
Which are the factors underlying human information production on a global level? In order to gain an insight into this question we study a corpus of 252–633 mil. publicly available data files on the Internet corresponding to an overall storage volume of 284–675 Terabytes. Analyzing the file size distribution for several distinct data types we find indications that the neuropsychological capacity of the human brain to process and record information may constitute the dominant limiting factor for the overall growth of globally stored information, with real-world economic constraints having only a negligible influence. This supposition draws support from the observation that the files size distributions follow a power law for data without a time component, like images, and a log-normal distribution for multimedia files, for which time is a defining qualia.
Author summary: The generation of new information is limited by two key factors, by the incurring economic costs and by the capacity of the human brain to process and store data and information; the controlling agent needs to retain an overall understanding even when data is generated by semiautomatic processes. These processes are reflected in the statistical properties of the data files publicly available on the Internet. Collecting a corpus of 252–633 mil. files we find that the statistics of the file size distribution are consistent with the supposition that data production on a global level is shaped and limited by the neuropsychological information processing capacity of the brain, with economic and hardware constraints having a negligible influence.
The cellular and molecular mechanisms of tumor angiogenesis and its prospects for anti-angiogenic cancer therapy are major issues in almost all current concepts of both cancer biology and targeted cancer therapy. Currently, (1) sprouting angiogenesis, (2) vascular co-option, (3) vascular intussusception, (4) vasculogenic mimicry, (5) bone marrow-derived vasculogenesis, (6) cancer stem-like cell-derived vasculogenesis and (7) myeloid cell-driven angiogenesis are all considered to contribute to tumor angiogenesis. Many of these processes have been described in developmental angiogenesis; however, the relative contribution and relevance of these in human brain cancer remain unclear. Preclinical tumor models support a role for sprouting angiogenesis, vascular co-option and myeloid cell-derived angiogenesis in glioma vascularization, whereas a role for the other four mechanisms remains controversial and rather enigmatic. The anti-angiogenesis drug Avastin (Bevacizumab), which targets VEGF, has become one of the most popular cancer drugs in the world. Anti-angiogenic therapy may lead to vascular normalization and as such facilitate conventional cytotoxic chemotherapy. However, preclinical and clinical studies suggest that anti-VEGF therapy using bevacizumab may also lead to a pro-migratory phenotype in therapy resistant glioblastomas and thus actively promote tumor invasion and recurrent tumor growth. This review focusses on (1) mechanisms of tumor angiogenesis in human malignant glioma that are of particular relevance for targeted therapy and (2) controversial issues in tumor angiogenesis such as cancer stem-like cell-derived vasculogenesis and bone-marrow-derived vasculogenesis.
Ecological systems contain a huge amount of quantitative variation between and within species and locations, which makes it difficult to obtain unambiguous verification of theoretical predictions. Ordinary experiments consider just a few explanatory factors and are prone to providing oversimplified answers because they ignore the complexity of the factors that underlie variation. We used multi-objective optimization (MO) for a mechanistic analysis of the potential ecological and evolutionary causes and consequences of variation in the life-history traits of a species of moth. Optimal life-history solutions were sought for environmental conditions where different life stages of the moth were subject to predation and other known fitness-reducing factors in a manner that was dependent on the duration of these life stages and on variable mortality rates. We found that multi-objective optimal solutions to these conditions that the moths regularly experience explained most of the life-history variation within this species. Our results demonstrate that variation can have a causal interpretation even for organisms under steady conditions. The results suggest that weather and species interactions can act as underlying causes of variation, and MO acts as a corresponding adaptive mechanism that maintains variation in the traits of organisms.
The aromatic rings in the title compound, C13H8ClNO4, enclose a dihedral angle of 39.53 (3)°. The nitro group is almost coplanar with the ring to which it is attached [dihedral angle = 4.31 (1)°]. In the crystal, molecules are connected by C-H...O hydrogen bonds into chains running along [001]. Key indicators: single-crystal X-ray study; T = 173 K; mean σ(C–C) = 0.002 A°; R factor = 0.044; wR factor = 0.105; data-to-parameter ratio = 18.9.
Early otic development depends on autophagy for apoptotic cell clearance and neural differentiation
(2012)
Autophagy is a highly regulated program of self-degradation of the cytosolic constituents that has key roles during early development and in adult cell growth and homeostasis. To investigate the role of autophagy in otic neurogenesis, we studied the expression of autophagy genes in early stages of chicken (Gallus gallus) inner ear development and the consequences of inhibiting the autophagic pathway in organotypic cultures of explanted chicken otic vesicles (OVs). Here we show the expression of autophagy-related genes (Atg) Beclin-1 (Atg6), Atg5 and LC3B (Atg8) in the otocyst and the presence of autophagic vesicles by using transmission electron microscopy in the otic neurogenic zone. The inhibition of the transcription of LC3B by using antisense morpholinos and of class III phosphatidylinositol 3-kinase with 3-methyladenine causes an aberrant morphology of the OV with accumulation of apoptotic cells. Moreover, inhibition of autophagy provokes the misregulation of the cell cycle in the otic epithelium, impaired neurogenesis and poor axonal outgrowth. Finally, our results indicate that autophagy provides the energy required for the clearing of neuroepithelial dying cells and suggest that it is required for the migration of otic neuronal precursors. Taken together, our results show for the first time that autophagy is an active and essential process during early inner ear development.
Background: Otic neurons and sensory cells derive from common progenitors whose transition into mature cells requires the coordination of cell survival, proliferation and differentiation programmes. Neurotrophic support and survival of post-mitotic otic neurons have been intensively studied, but the bases underlying the regulation of programmed cell death in immature proliferative otic neuroblasts remains poorly understood. The protein kinase AKT acts as a node, playing a critical role in controlling cell survival and cell cycle progression. AKT is activated by trophic factors, including insulin-like growth factor I (IGF-I), through the generation of the lipidic second messenger phosphatidylinositol 3-phosphate by phosphatidylinositol 3-kinase (PI3K). Here we have investigated the role of IGF-dependent activation of the PI3K-AKT pathway in maintenance of otic neuroblasts.
Methodology/Principal Findings: By using a combination of organotypic cultures of chicken (Gallus gallus) otic vesicles and acoustic-vestibular ganglia, Western blotting, immunohistochemistry and in situ hybridization, we show that IGF-I-activation of AKT protects neural progenitors from programmed cell death. IGF-I maintains otic neuroblasts in an undifferentiated and proliferative state, which is characterised by the upregulation of the forkhead box M1 (FoxM1) transcription factor. By contrast, our results indicate that post-mitotic p27Kip-positive neurons become IGF-I independent as they extend their neuronal processes. Neurons gradually reduce their expression of the Igf1r, while they increase that of the neurotrophin receptor, TrkC.
Conclusions/Significance: Proliferative otic neuroblasts are dependent on the activation of the PI3K-AKT pathway by IGF-I for survival during the otic neuronal progenitor phase of early inner ear development.
Autophagy is an evolutionarily conserved catabolic process by which cells degrade their own components through the lysosomal machinery. In physiological conditions, the mechanism is tightly regulated and contributes to maintain a balance between synthesis and degradation in cells undergoing intense metabolic activities. Autophagy is associated with major tissue remodeling processes occurring through the embryonic, fetal and early postnatal periods of vertebrates. Here we survey current information implicating autophagy in cellular death, proliferation or differentiation in developing vertebrates. In developing systems, activation of the autophagic machinery could promote different outcomes depending on the cellular context. Autophagy is thus an extraordinary tool for the developing organs and tissues.
We among others have recently demonstrated that normal cells produce “fusion mRNAs”. These fusion mRNAs do not derive from rearranged genomic loci, but rather they are derived from “early-terminated transcripts” (ETTs). Premature transcriptional termination takes place in intronic sequences that belong to “breakpoint cluster regions”. One important property of ETTs is that they exhibit an unsaturated splice donor site. This results in: (1) splicing to “cryptic exons” present in the final intron; (2) Splicing to another transcript of the same gene (intragenic trans-splicing), resulting in “exon repetitions”; (3) splicing to a transcript of another gene (intergenic trans-splicing), leading to “non-genomically encoded fusion transcripts” (NGEFTs). These NGEFTs bear the potential risk to influence DNA repair processes, since they share identical nucleotides with their DNA of origin, and thus, could be used as “guidance RNA” for DNA repair processes. Here, we present experimental data about four other genes. Three of them are associated with hemato-malignancies (ETV6, NUP98 and RUNX1), while one is associated with solid tumors (EWSR1). Our results demonstrate that all genes investigated so far (MLL, AF4, AF9, ENL, ELL, ETV6, NUP98, RUNX1 and EWSR1) display ETTs and produce transpliced mRNA species, indicating that this is a genuine property of translocating genes.
This article presents an environmental remote sensing application using a UAV that is specifically aimed at reducing the data gap between field scale and satellite scale in soil erosion monitoring in Morocco. A fixed-wing aircraft type Sirius I (MAVinci, Germany) equipped with a digital system camera (Panasonic) is employed. UAV surveys are conducted over different study sites with varying extents and flying heights in order to provide both very high resolution site-specific data and lower-resolution overviews, thus fully exploiting the large potential of the chosen UAV for multi-scale mapping purposes. Depending on the scale and area coverage, two different approaches for georeferencing are used, based on high-precision GCPs or the UAV’s log file with exterior orientation values respectively. The photogrammetric image processing enables the creation of Digital Terrain Models (DTMs) and ortho-image mosaics with very high resolution on a sub-decimetre level. The created data products were used for quantifying gully and badland erosion in 2D and 3D as well as for the analysis of the surrounding areas and landscape development for larger extents.
In the aftermath of an increasing integration of property and financial markets, the real estate industry is subject to soaring internationalization processes. Since international institutional investors appeared, transnational real estate investments have increased tremendously. In recent years, Central and Eastern European countries have been becoming more attractive to institutional investors and are therefore being integrated into international market structures. Within these countries, Warsaw emerged as the most dynamic and important real estate market. But what are the mechanisms and practices through which the real estate market of Warsaw becomes international? Which networks, intermediaries and frames are necessary to constitute a mature real estate market? The article argues that international real estate consultants are playing a crucial role in the underlying internationalization process. They are acting at the interface between investors, developers, construction companies and tenants and are therefore becoming a crucial hinge between real estate actors. With the example of the Warsaw real estate market we argue that international real estate consultancies are key drivers of the transformation process from a local to a global market. They transfer global knowledge, competence and practices and implement transparent and professional structures in the emerging Warsaw real estate market.
Iron-rich structures have been described in the beak of homing pigeons, chickens and several species of migratory birds and interpreted as magnetoreceptors. Here, we will briefly review findings associated with these receptors that throw light on their nature, their function and their role in avian navigation. Electrophysiological recordings from the ophthalmic nerve, behavioral studies and a ZENK-study indicate that the trigeminal system, the nerves innervating the beak, mediate information on magnetic changes, with the electrophysiological study suggesting that these are changes in intensity. Behavioral studies support the involvement of magnetite and the trigeminal system in magnetoreception, but clearly show that the inclination compass normally used by birds represents a separate system. However, if this compass is disrupted by certain light conditions, migrating birds show 'fixed direction' responses to the magnetic field, which originate in the receptors in the beak. Together, these findings point out that there are magnetite-based magnetoreceptors located in the upper beak close to the skin. Their natural function appears to be recording magnetic intensity and thus providing one component of the multi-factorial 'navigational map' of birds.
One challenge of squamous cell carcinoma of the head and neck (SCCHN) chemotherapy is a small percentage of tumor cells that arrest in the G0 phase of the cell cycle and are thus not affected by chemotherapy. This could be one reason for tumor recurrence at a later date. The recruitment of these G0-arresting cells into the active cell cycle and thus, proliferation, may increase the efficacy of chemotherapeutic agents. The aim of this study was to investigate whether stimulation with recombinant epidermal growth factor (EGF) or serotonin leads to an increased tumor cell proliferation in xenografts. Detroit 562 cells were injected into NMRI-Foxn1nu mice. Treatment was performed with 15 µg murine or human EGF, or 200 µg serotonin. The control mice were treated with Lactated Ringer's solution (5 mice/group). Tumor size was measured on days 4, 8 and 12 after tumor cell injection. The EGF stimulated mice showed a significantly higher tumor growth compared to the serotonin-stimulated mice and the untreated controls. In the present study, we show that it is possible to stimulate tumor cells in xenografts by EGF and thus, enhance cell proliferation, resulting in a higher tumor growth compared to the untreated control group. In our future investigations, we plan to include a higher number of mice, an adjustment of the EGF dosage and cell subanalysis, considering the heterogeneity of SCCHN tumors.
The objective of this pilot clinical study was to assess the safety, technical feasibility, pharmacokinetic (PK) profile and tumour response of DC Bead™ with irinotecan (DEBIRI™) delivered by intra-arterial embolisation for the treatment of metastatic colorectal cancer. Eleven patients with unresectable liver metastases from CRC, tumour burden <30% of liver volume, adequate haematological, liver and renal function, performance status of <2 were included in this study. Patients received up to 4 sessions of TACE with DEBIRI at 3-week intervals. Feasibility of the procedure, safety and tumour response were assessed after each cycle. PK was measured after the first cycle. Patients were followed up to 24 weeks. Only mild to moderate adverse events were observed. DEBIRI is a technically feasibile procedure; no technical complications were observed. Average Cmax for irinotecan and SN-38 was 194 ng/ml and 16.7 ng/ml, respectively, with average t½ of 4.6 h and 12.4 h following administration of DEBIRI. Best overall response during the study showed disease control in 9 patients (2 patients with partial response and 7 with stable disease, overall response rate of 18%). Our study shows that transarterial chemoembolisation with irinotecan-loaded DC beads (DEBIRI) is safe, technically feasible and effective with a good PK profile.
Purpose: Hamstring injuries are common among football players. There is still disagreement regarding prevention. The aim of this review is to determine whether static stretching reduces hamstring injuries in football codes.
Methods: A systematic literature search was conducted on the online databases PubMed, PEDro, Cochrane, Web of Science, Bisp and Clinical Trial register. Study results were presented descriptively and the quality of the studies assessed were based on Cochrane’s ‘risk of bias’ tool.
Results: The review identified 35 studies, including four analysis studies. These studies show deficiencies in the quality of study designs.
Conclusion: The study protocols are varied in terms of the length of intervention and follow-up. No RCT studies are available, however, RCT studies should be conducted in the near future.
Purpose: Student circus artists train as both artists and athletes with their bodies holding the key to professional success. The daily training load of student circus artists is often associated with maximum physical and psychological stress with injuries posing a threat to a potential professional career. The purpose of this study is the differentiated analysis and evaluation of work accidents in order to initiate the development of injury preventive programs.
Methods: The 17 years of data were obtained from standardized anonymous work accident records of the Berlin State Accident Insurance (UKB) as well as a State Artist Educational School (n = 169, Male: 70; Female: 99) from student artists. Evaluation and descriptive statistics were conducted with Excel 2007 and PASW Statistics 18.
Results: The injury risk seems to be relatively low (0.3 injuries/1000h). There are gender specific differences as to the location of injuries. Only 7% of the accidents demand a break of more than 3 days. Injury patterns vary depending on the activity and the employment of props/equipment. 75.2% of work accidents have multifactorial and 24.8% exogenous causes.
Conclusions: Because physical fitness is all important in the circus arts there are numerous options for injury prevention programs that should be realized subject to gender-specific differences. Follow-ups on chronic complaints and a more individual approach are indispensable due to the very specific activities in the circus arts.
Forests are important components of the greenhouse gas balance of Europe. There is considerable uncertainty about how predicted changes to climate and nitrogen deposition will perturb the carbon and nitrogen cycles of European forests and thereby alter forest growth, carbon sequestration and N2O emission. The present study aimed to quantify the carbon and nitrogen balance, including the exchange of greenhouse gases, of European forests over the period 2010–2030, with a particular emphasis on the spatial variability of change. The analysis was carried out for two tree species: European beech and Scots pine. For this purpose, four different dynamic models were used: BASFOR, DailyDayCent, INTEGRATOR and Landscape-DNDC. These models span a range from semi-empirical to complex mechanistic. Comparison of these models allowed assessment of the extent to which model predictions depended on differences in model inputs and structure. We found a European average carbon sink of 0.160 ± 0.020 kgC m−2 yr−1 (pine) and 0.138 ± 0.062 kgC m−2 yr−1 (beech) and N2O source of 0.285 ± 0.125 kgN ha−1 yr−1 (pine) and 0.575 ± 0.105 kgN ha−1 yr−1 (beech). The European average greenhouse gas potential of the carbon source was 18 (pine) and 8 (beech) times that of the N2O source. Carbon sequestration was larger in the trees than in the soil. Carbon sequestration and forest growth were largest in central Europe and lowest in northern Sweden and Finland, N. Poland and S. Spain. No single driver was found to dominate change across Europe. Forests were found to be most sensitive to change in environmental drivers where the drivers were limiting growth, where changes were particularly large or where changes acted in concert. The models disagreed as to which environmental changes were most significant for the geographical variation in forest growth and as to which tree species showed the largest rate of carbon sequestration. Pine and beech forests were found to have differing sensitivities to environmental change, in particular the response to changes in nitrogen and precipitation, with beech forest more vulnerable to drought. There was considerable uncertainty about the geographical location of N2O emissions. Two of the models BASFOR and LandscapeDNDC had largest emissions in central Europe where nitrogen deposition and soil nitrogen were largest whereas the two other models identified different regions with large N2O emission. N2O emissions were found to be larger from beech than pine forests and were found to be particularly sensitive to forest growth.
In the original manuscript, Figs. 7–16 included fonts which were not correctly embedded in the file. As such, unless certain propriety software (ArcGIS) is installed on the viewing platform, the figures will appear corrupted. In this Corrigendum, Figs. 7–16 and their captions are reproduced with the fonts correctly embedded. Please find the correct figures below.
The late Miocene palaeorecord provides evidence for a warmer and wetter climate than that of today, and there is uncertainty in the palaeo-CO2 record of at least 200 ppm. We present results from fully coupled atmosphere-ocean-vegetation simulations for the late Miocene that examine the relative roles of palaeogeography (topography and ice sheet geometry) and CO2 concentration in the determination of late Miocene climate through comprehensive terrestrial model-data comparisons. Assuming that these data accurately reflect the late Miocene climate, and that the late Miocene palaeogeographic reconstruction used in the model is robust, then results indicate that:
1. Both palaeogeography and atmospheric CO2 contribute to the proxy-derived precipitation differences between the late Miocene and modern reference climates. However these contributions exibit synergy and so do not add linearly.
2. The vast majority of the proxy-derived temperature differences between the late Miocene and modern reference climates can only be accounted for if we assume a palaeo-CO2 concentration towards the higher end of the range of estimates.
The Late Miocene (∼11.6–5.3 Ma) palaeorecord provides evidence for a warmer and wetter climate than that of today and there is uncertainty in the palaeo-CO2 record of at least 150 ppmv. We present results from fully coupled atmosphere-ocean-vegetation simulations for the Late Miocene that examine the relative roles of palaeogeography (topography and ice sheet geometry) and CO2 concentration in the determination of Late Miocene climate through comprehensive terrestrial model-data comparisons. Assuming that the data accurately reflects the Late Miocene climate, and that the Late Miocene palaeogeographic reconstruction used in the model is robust, then results indicate that the proxy-derived precipitation differences between the Late Miocene and modern can be largely accounted for by the palaeogeographic changes alone. However, the proxy-derived temperatures differences between the Late Miocene and modern can only begin to be accounted for if we assume a palaeo-CO2 concentration towards the higher end of the range of estimates.
Estimates of the recovery time of stratospheric ozone heavily rely on the exact knowledge of the processes that lead to the decomposition of the relevant halogenated source gases. Crucial parameters in this context are Fractional Release Factors (FRFs) as well as stratospheric lifetimes and Ozone Depletion Potentials (ODPs). We here present data from the analysis of air samples collected between 2009 and 2011 on board research aircraft flying in the mid- and high latitudinal stratosphere and infer the above-mentioned parameters for ten major source gases:CFCl3 (CFC-11), CF2Cl2 (CFC-12), CF2ClCFCl2(CFC-113), CCl4 (carbon tetrachloride),CH3CCl3 (methyl chloroform), CHF2Cl (HCFC-22), CH3CFCl2 (HCFC-141b), CH3CF2Cl (HCFC-142b), CF2ClBr (H-1211), and CF3Br (H-1301). The inferred correlations of their FRFs with mean ages of air reveal less decomposition as compared to previous studies for most compounds. When using the calculated set of FRFs to infer equivalent stratospheric chlorine we find a reduction of more than 20% as compared to the values inferred in the most recent Scientific Assessment of Ozone Depletion by the World Meteorological Organisation (WMO, 2011). We also note that FRFs and their correlations with mean age are not generally time-independent as often assumed. The stratospheric lifetimes were calculated relative to that of CFC-11. Within our uncertainties the inferred ratios between lifetimes agree with those between stratospheric lifetimes from recent WMO reports except for CFC-11, CFC-12 and CH3CCl3. Finally we calculate lower ODPs than WMO for six out of ten compounds with changes most pronounced for the three HCFCs. Collectively these newly calculated values may have important implications for the severity and recovery time of stratospheric ozone loss.
“Far, far away from our areas, somewhere beyond the Mountains of Darkness, on the other side of the Sambatyon River…there lives a nation known as the Red Jews.” The Red Jews are best known from classic Yiddish writing, most notably from Mendele's Kitser masoes Binyomin hashlishi (The Brief Travels of Benjamin the Third). This novel, first published in 1878, represents the initial appearance of the Red Jews in modern Yiddish literature. This comical travelogue describes the adventures of Benjamin, who sets off in search of the legendary Red Jews. But who are these Red Jews or, in Yiddish, di royte yidelekh? The term denotes the Ten Lost Tribes of Israel, the ten tribes that in biblical times had composed the Northern Kingdom of Israel until they were exiled by the Assyrians in the eighth century BCE. Over time, the myth of their return emerged, and they were said to live in an uncharted location beyond the mysterious Sambatyon River, where they would remain until the Messiah's arrival at the end of time, when they would rejoin the rest of the Jewish people.
This article is part of a broader study of the Red Jews in Jewish popular culture from the Middle Ages through modernity. It is partially based on a chapter from my book, Umstrittene Erlöser: Politik, Ideologie und jüdisch-christlicher Messianismus in Deutschland, 1500–1600 (Göttingen: Vandenhoeck & Ruprecht, 2011). Several postdoctoral fellowships have generously supported my research on the Red Jews: a Dr. Meyer-Struckmann-Fellowship of the German Academic Foundation, a Harry Starr Fellowship in Judaica/Alan M. Stroock Fellowship for Advanced Research in Judaica at Harvard University, a research fellowship from the Heinrich Hertz-Foundation, and a YIVO Dina Abramowicz Emerging Scholar Fellowship. I thank the organizers of and participants in the colloquia and conferences where I have presented this material in various forms as well as the editors and anonymous reviewers of AJS Review for their valuable comments and suggestions. I am especially grateful to Jeremy Dauber and Elisheva Carlebach of the Institute for Israel and Jewish Studies at Columbia University, where I was a Visiting Scholar in the fall of 2009, for their generous encouragement to write this article. Sue Oren considerably improved my English. The style employed for Romanization of Yiddish follows YIVO's transliteration standards. Unless otherwise noted, translations from the Yiddish, Hebrew, German, and Latin are my own. Quotations from the Bible follow the JPS translation, and those from the Babylonian Talmud are according to the Hebrew-English edition of the Soncino Talmud by Isidore Epstein.
Taking as starting point some collective volumes since the year 2000 which aspire to provide new views on narratology, this essay discusses the problem of how to conceive the history of narratology in a way that is more enlightening than the linear narrative used so far to tell this story. It lists some aspects which are neglected by the usual narrative and favors a decentered conception of narratology’s development.
European settlement in Australia has always been concentrated along or close to the coast. As a consequence, saltmarshes, mangroves and other coastal marshes have experienced a long history of modification and destruction. Depletion statistics are available for many coastal marshes in the Northern Hemisphere and, in Australia, for parts of New South Wales and Queensland. There are no equivalent State-wide data for Victoria. Using a suite of historical information, including extensive use of early surveyors’ maps, we aimed to provide a consistent view of the change in the extent of coastal marshes since European colonization in Victoria (i.e. the mid-19th century). Notwithstanding the difficulties of interpretation, we estimate that prior to European colonization Victoria supported approximately 346– 421 km2 of coastal marsh, of which approximately 80–95% remains. Although a simplistic interpretation suggests a net loss of 5–20% in wetland area over this time period, it is clear that some parts of the coast have experienced relatively little change since the mid 19th century whereas others have been severely depleted and, in a few sectors, there may have been an expansion of coastal marsh. The situation with the Gippsland Lakes is complex, and according to the method used to interpret the original data sources there has either been a substantial increase or a loss of up to 35% in wetland area around Lake Wellington. The largest absolute losses have probably been of EVC 140 Mangrove Shrubland and of coastal saltmarsh dominated by Tecticornia spp. Parts of the coast where significant losses have occurred include the Lonsdale Lakes, western shore of Port Phillip Bay, Anderson Inlet, Shallow Inlet, Powlett- Kilcunda, Corner Inlet and Nooramunga, and possibly Lake Wellington. With the exception of the Lonsdale Lakes, all these areas are situated along the Gippsland coast. Changes to coastal marshes have not stopped and are unlikely to cease in the near future. The destruction of coastal marshes for industrial development remains an ongoing threat in many regions (e.g. in Western Port) and is likely to be compounded by climate change and, in particular, sea-level rise.
Multivariate analysis and non-metric multidimensional scaling have been used to compare the floristic composition of vegetation dominated by Spotted Gum, Corymbia maculata, and Grey Ironbark, Eucalyptus paniculata, from the Pittwater and Gosford local government areas, and elsewhere on the Central Coast of New South Wales. When placed within a regional context, vegetation from both local government areas is strongly related, and is sufficiently distinct (at 30% similarity) from other areas of Spotted Gum-Ironbark vegetation within the region to warrant their collective consideration as Pittwater Spotted Gum Forest (PSGF), an Endangered Ecological Community in New South Wales. Within Pittwater local government area, two forms of PSGF are present: a dryer, more widespread form present on ridges and slopes, and a moister form with strong littoral rainforest affinities confined to gullies. Gosford local government area supports only the dryer form. Extant and pre-1750 mapping of PSGF from both local government areas (excluding Ku-ring-gai Chase National Park) shows a total extant distribution of 227 ha, and since 1750 an estimated loss of 727 ha (76%) from the original 954 ha. PSGF is present in two secure conservation reserves: Ku-ring-gai Chase National Park (~40 ha, Thomas & Benson 1985) and Bouddi National Park (~30 ha, Bell 2009), totaling ~ 70 ha. Despite this, much of the extant distribution lies at the reserve-urban interface, and is subject to ongoing threats of regular low-intensity fire, unmitigated clearing and weed invasion.
Species may become vulnerable because of a reduction of habitat, leading to reduction of population sizes and an increase in geographic isolation between populations, leading to genetic drift that may result in reduced reproductive fitness. The restricted sedge Gahnia insignis S.T. Blake (family Cyperaceae), occurring in isolated pockets in north-east New South Wales and Queensland, was compared to a closely related, sympatric, common and widespread Gahnia clarkei Benl for flowering phenology and reproductive success. Flowering patterns, examination of pollen, fertilisation and embryo development and seed-ovule ratios show Gahnia clarkei has every indication of successful sexual reproduction, but that Gahnia insignis appears to reproduce mostly by vegetative means, with an occasional sexual event. This was due to the rarity of pollination opportunities, and to poor pollen viability and pollen quantity, resulting in a much lower seed-ovule ratio than Gahnia clarkei. The additional high level of vegetative reproduction in Gahnia insignis suggests it may be largely clonal in Nightcap National Park. A genetic study of the whole distribution would add knowledge of the species genetic diversity and differentiation between populations.
The vegetation of the Mount Murchison and Wilga areas, Paroo Darling National Park (latitude 31o00’-32o 40’S and longitude 142o10’-144o25’E) in north western New South Wales was assessed using intensive quadrat sampling and mapped using extensive ground truthing and interpretation of aerial photograph and Landsat Thematic Mapper satellite images. In the survey 237 vascular plant species including 37 (15.6%) exotic species, from 46 families were recorded. Seventeen vegetation communities were identified and mapped, 15 for Mount Murchison area and 13 for the Wilga area. The most widespread for Mount Murchison being Maireana pyramidata low open shrubland, Flindersia maculosa low open woodland, Muehlenbeckia florulenta open shrubland and Eucalyptus coolabah / Eucalyptus largiflorens open woodland. The most widespread for Wilga being Muehlenbeckia florulenta open shrubland and Eucalyptus coolabah / Eucalyptus largiflorens open woodland. Many of these communities have been impacted by a history of 150 years of pastoral use.
Pentzia is a predominantly southern African genus of low shrubs, many of which are important fodder plants for sheep in semi-arid and arid areas. Attempts since 1869 to introduce Pentzia incana to south-eastern Australia for sheep fodder are described. One of these, near Koonamore in north-eastern South Australia, was temporarily successful there and may have led to the only extant stands in Australia – two well-established populations at Mount Serle in the northern Flinders Ranges. These events are related to the biology of the species and to similar events concerning the deliberate introduction of the species to Arizona. These data are discussed in terms of current ideas about plant introduction, dispersal, invasion and the concept of sleeper weeds. Pentzia globosa is currently known from a single stand in Australia, at Bundaleer Forest in the Mid North of South Australia. The history of this occurrence is briefly discussed. For both species, it is concluded that regular monitoring is needed in case of rapid spread and that further data are needed on the extent to which they exhibit weedy behaviour in southern Africa.
The listed threatened plant taxa within the South Coast Region of New South Wales (Helensburgh to Batemans Bay, as designated by the NSW National Parks and Wildlife Service) are documented. Of the 100 NSW listed taxa, 69 are also listed by the Commonwealth, while two additional taxa are only listed by the Commonwealth. An analysis of the individual taxa and the 62 conservation reserves in the region, found that 30 taxa can with confidence be said to be adequately reserved, while 50 are assessed as inadequately reserved; for the remaining 22 taxa, reservation status is unknown. Examples of challenges for the conservation of threatened plants in the region are examined; these challenges have relevance well beyond the South Coast Region. Managing for individual plant species may be hampered by a lack of basic ecological information; this is particularly so for the rarer species such as orchids. One of the main areas where information is lacking is the response of most species to bushfire. Conservation on private land is becoming an increasingly important and challenging area for plant species conservation as the last large areas of public land are dedicated for one purpose or another. A more co-ordinated approach to conservation on private land may produce improved outcomes for many inadequately reserved taxa.
Vegetation structure and floristics of granite landforms in the South-west Slopes of New South Wales
(2012)
We describe the natural vegetation structure and floristics of 44 small-sized granite outcrops (inselbergs) in agricultural landscapes in the South-west Slopes (SWS) bioregion of New South Wales (35º 26’ S, 147º 23’ E to 35º 58’ S, 146º 59’E) and their relationships with geomorphology. We provide a list of 196 species (117 natives and 79 exotics). We found that structurally complex outcrops supported a greater diversity of native ground cover species and fewer exotic species than structurally simple outcrops. Tor landforms lacked vegetation structural complexity and were deficient in native shrubs, mid-storey and over-storey species but typically supported exotic grasses and broadleaved exotic weeds. Floristic composition differed among landforms and cluster analysis revealed highly dissimilar native plant communities among outcrops. Our study highlights the need to rehabilitate tor landforms and manage a broad spectrum of outcrops to conserve floristic diversity in agricultural landscapes. Selecting genetically diverse species for replanting, considering the density and spatial arrangement of plantings, and controlling invasive plants and feral herbivorous animals are fundamental issues in restoring granite outcrop vegetation in the SWS bioregion.
Spring wetlands on the Strathbogie plateau were mapped using recent aerial photography to estimate their current and former extent. The floristic composition and relationships of the vegetation with topographic, environmental and land use variables were interpreted from an analysis of quadrat data. Wetland condition, threats to their persistence and future management requirements were also identified. More than half of the original wetland vegetation in the study area appears to have been lost, probably as a result of clearing for agriculture. Nine floristic assemblages, identified using agglomerative hierarchical clustering, were identified on acidic to mildly alkaline peat in five different hydrogeomorphic settings. One of these assemblages (Low Open Sedgeland) was uniquely confined to spring-fed mounds, not previously described in Victoria. A key to identification of these groups was developed. Floristic composition was correlated with climate and site disturbance but charcoal throughout sediment cores suggested that historical disturbance regimes included fire. Forested sites at higher elevations where grazing pressure appears to have been less intense were the least disturbed sites. Approximately 60% of the wetlands surveyed were assessed as showing signs of soil moisture loss but there was no evidence that water extraction via dams and known bores was a significant driver of current vegetation composition. Threats requiring management were related to habitat destruction and degradation, dysfunction of physical and biological processes, and changes to disturbance regimes. Establishment of native vegetation buffers and biomass management are likely to be of benefit for future management of spring wetland vegetation.
Newnes Plateau Shrub Swamps are a series of low nutrient temperate montane peat swamps around 1100 m elevation in the upper Blue Mountains, west of Sydney (lat 33° 23’ S; long 150° 13’E). Transect-based vegetation studies show a closely related group of swamps with expanses of permanently moist, gently sloping peatlands. Vegetation patterns are related to surface hydrology and subsurface topography, which determine local peat depth. While there is evidence that a group of the highest elevation swamps on the western side of the Plateau are more dependent on rainwater, the majority of swamps, particularly those in the Carne Creek catchment, and east and south of it, may beconsidered primarily groundwater dependent with a permanently high watertable maintained by groundwater aquifers. An integral part of the swamps are a number of threatened groundwater dependent biota (plants–Boronia deanei subsp. deanei, Dillwynia stipulifera, dragonfly– Petalura gigantea, lizard– Eulamprus leuraensis), which are obligate swamp dwellers. This association of dependence leaves the entire swamp ecosystem highly susceptible to threats from any loss of groundwater, the current major one being the impact of damage to the confining aquicludes, aquitards, aquifers and peat substrates as a result of subsidence associated with longwall mining. Impacts on the swamps may also result from changes to hydrology through damming of creeks, mine waste water discharge, increased moisture competition from pine plantations, recreational motorbike and off-road vehicle tracks and climate change. If these groundwater dependent ecosystems do not receive protection from activities such as longwall mining subsidence, significant ecological damage is unlikely to be avoided or able to be mitigated even where provisions of the Commonwealth Environment Protection and Biodiversity Conservation and NSW Threatened Species Conservation Acts apply to groundwater dependent swamps and biota. The importance of the highest elevation part of the Plateau for a number of restricted (some endemic) plant species is also discussed.
The pre-colonial distribution of grasslands, woodlands and forests on the Werribee plains, Victoria
(2012)
We use historic plans and recent field observations to reconstruct and describe the former (pre-1750) character and distribution of vegetation on the Werribee Plains, near Melbourne. The primary outcome of this research is a detailed vegetation map. The ecological factors controlling the distribution of trees and open-plains are also discussed. The results show that most of the area was treeless grassland at the time of European settlement (1835). This grassland was broken up by clearly-defined areas of Eucalypt forest, some of which remain. There is, in contrast, little remaining trace of the woodlands of Allocasuarina and Banksia, which we show were once widespread on the plains and stony rises beyond the Eucalypt forest. This work is timely, given the proposal for the creation of two large new reserves in the area, which contain many areas that may be subject to restoration.
Little is known about groundwater-dependent ecosystems in south-eastern Australia and few studies have examined the impact of landclearing upslope of such ecosystems. The eastern edge of Porters Creek wetland, near Warnervale on the Central Coast of New South Wales, supports a Eucalyptus parramattensis subsp. Parramattensis (Parramatta Red Gum) population. The population has been listed as an Endangered Population (EP) and was showing signs of dieback during the 2002 to mid-2007 drought. Water table depth, soil moisture tension, soil temperature and groundwater salinity beneath this woodland were measured to investigate whether the woodland is associated with a shallow aquifer and/or high soil moisture conditions, and whether an upslope construction development would impact on the ecosystem. The composition, structure and health of the Eucalyptus parramattensis Woodland was also examined. Monitoring over 5 years demonstrated that Eucalyptus parramattensis is associated with a shallow, slightly saline to saline (8–12 ppt) water table, 1.4–3.1 m beneath the surface of a drainage depression wetland. During the drought water table drawdown rates were quite rapid, and rainfall events took up to a month to replenish water table levels. Landclearing for an upslope development significantly decreased the average water table level by 0.3–0.5 m during the construction phase, while peaks that occurred at the base of the slope after large rainfall events reversed the normal direction of the water table gradient. The water table re-stabilised to pre-construction levels after construction was completed and the area was landscaped and revegetated with grass. The short-term alteration of groundwater conditions did not appear to impact on tree health; the poor tree health observed prior to construction was most likely due to the lowering of the water table (and/or an increase in groundwater/soil salinity) during the drought years. Our results suggest that developments that revegetate slopes above wetlands as quickly as possible after clearing, orundertake clearing in stages, will minimise effects on water table levels. Pervious detention basins designed to capture runoff and allow infiltration into the soil help replenish aquifers, but also require weed maintenance. This study highlights the significance of maintaining shallow aquifer and catchment processes for the conservation and rehabilitation of coastal wetlands, many of which are listed as Endangered Populations or Endangered Ecological Communities.
Using Australian Virtual Herbarium data to find all the woody rain forest plants in Australia
(2012)
Data bases that provide continental and global scale information about species distributions provide a valuable resource for environmental, ecological and evolutionary research. However to bring a large dataset to a standard that is suitable for quantitative analysis, data quality needed to be checked. Here we provide a worked example using a large dataset (c. 320,000 records) from Australia’s Virtual Herbarium (AVH) database, based on an initial data request for full distribution data for c. 2600 woody rain forest species known to occur in Australia. To reconcile inconsistencies around taxonomic identity prior to merging with our trait data-base, and resolve issues around spatial resolution and accuracy, we implemented extensive data filtering using a ‘cloud-based’ solution (Google Refine). This systematic process resulted in 1) the removal of close to 45% of the records originally downloaded, and 2) a clean and powerful data set based on herbarium backed distribution records for Australia’s woody rain forest species. Such resources can contribute significantly to improving research outcomes related to understanding Australia’s vegetation.
The floristic composition and vegetation partitioning of the ephemeral wetlands of the Pilliga Outwash within the Pilliga National Park and Pilliga State Conservation Area (30˚30’S, 149˚22’E) on the North Western Plains of New South Wales are described. SPOT5 imagery was used to map 340 wetlands across the Pilliga Outwash. A total of 240 plots within 31 wetlands explored composition and species richness in relation to water depth and wetland size. The predominant community described is the species-rich herbfield of shallow basin wetlands, along with the structurally distinct but the less common sedgeland/herbfield of the deeper ‘tank’ wetlands and a single wetland with a floristically depauperate Diplachne fusca wet grassland. A total of 131 taxa were recorded including three species listed under the NSW Threatened Species Conservation Act (1995): Eriocaulon australasicum, Lepidium monoplocoides and Myriophyllum implicatum. New records for an additional six taxa were recorded for the North Western Plains. 11% of taxa were exotic in origin.
Particular botanical sites have always been attractive to botanists, and the recording of such sites even in an ad hoc way, adds to our long-term documentation of ecological change. Here we look at records from an unusual dry rainforest site in western Sydney, first recognised in 1910, and re-recorded on several occasions more recently. Though the site has little formal conservation protection, the records indicate that many of the original species still survive at the site, while the periodic recording draws attention to the scientific value of the site, particularly at a local level, and has increased its value as an ecological reference site. Much of the vegetation of the Cumberland Plain has been subject to major clearing and disturbance over the past 200 years, and almost all vegetation is recovering in some way. Repeated visits are valuable for getting a complete picture of the flora; repeated visits by the same botanist over the shorter term (e.g. within a few years) may also be valuable, especially as the revisiting botanist may be more likely to notice changes. By documenting sites now, and continuing this over future years; we can enhance the value of many existing sites.
Aerial photo interpretation of high resolution airborne imagery (ADS40) was used in a three-dimensional (3-D) digital Geographic Information System (GIS) environment to map native plant communities defined in the NSW Vegetation Classification and Assessment (NSW VCA) in central-southern New South Wales. NSW VCA plant community types form part of the NSW BioMetric vegetation type dataset underpinning NSW natural resource management (NRM) planning frameworks. This region was previously devoid of detailed vegetation mapping. In addition to developing a novel method for mapping plant communities, the use of ADS40 imagery allowed for capture of multiple attributes in each map polygon including attributes pertaining to dominant species and vegetation condition. Such data informs multi-attribute models used in conservation planning, providing utility beyond that of a singular plant community map.
A total of 546,150 hectares of native vegetation in 100 native plant communities was mapped across the study area (Coolamon, Cootamundra, Junee, Lockhart, Narrandera, Tarcutta, Urana, Wagga Wagga and Yanco 1:100,000 mapsheets and Ariah Park, Wallaroobie Range and Yoogali 1:50,000 mapsheets). Exotic pine plantations and native species plantings were also mapped. Remnants of greater than one hectare were captured through on-screen GIS digitising at scales of approximately 1:4,000. The plant community type mapping was independently assessed using random blind validation points as having a user accuracy of 87%. This level of accuracy demonstrates the applicability of the methodology for mapping open forests, woodlands and open woodlands of south-eastern Australia and probably other vegetation elsewhere. Such accurate mapping provides end users with confidence when using vegetation maps in environmental assessment and land use planning.
Significant reductions in stratospheric ozone occur inside the polar vortices each spring when chlorine radicals produced by heterogeneous reactions on cold particle surfaces in winter destroy ozone mainly in two catalytic cycles, the ClO dimer cycle and the ClO/BrO cycle. Chlorofluorocarbons (CFCs), which are responsible for most of the chlorine currently present in the stratosphere, have been banned by the Montreal Protocol and its amendments, and the ozone layer is predicted to recover to 1980 levels within the next few decades. During the same period, however, climate change is expected to alter the temperature, circulation patterns and chemical composition in the stratosphere, and possible geo-engineering ventures to mitigate climate change may lead to additional changes. To realistically predict the response of the ozone layer to such influences requires the correct representation of all relevant processes. The European project RECONCILE has comprehensively addressed remaining questions in the context of polar ozone depletion, with the objective to quantify the rates of some of the most relevant, yet still uncertain physical and chemical processes. To this end RECONCILE used a broad approach of laboratory experiments, two field missions in the Arctic winter 2009/10 employing the high altitude research aircraft M55-Geophysica and an extensive match ozone sonde campaign, as well as microphysical and chemical transport modelling and data assimilation. Some of the main outcomes of RECONCILE are as follows: (1) vortex meteorology: the 2009/10 Arctic winter was unusually cold at stratospheric levels during the six-week period from mid-December 2009 until the end of January 2010, with reduced transport and mixing across the polar vortex edge; polar vortex stability and how it is influenced by dynamic processes in the troposphere has led to unprecedented, synoptic-scale stratospheric regions with temperatures below the frost point; in these regions stratospheric ice clouds have been observed, extending over >106km2 during more than 3 weeks. (2) Particle microphysics: heterogeneous nucleation of nitric acid trihydrate (NAT) particles in the absence of ice has been unambiguously demonstrated; conversely, the synoptic scale ice clouds also appear to nucleate heterogeneously; a variety of possible heterogeneous nuclei has been characterised by chemical analysis of the non-volatile fraction of the background aerosol; substantial formation of solid particles and denitrification via their sedimentation has been observed and model parameterizations have been improved. (3) Chemistry: strong evidence has been found for significant chlorine activation not only on polar stratospheric clouds (PSCs) but also on cold binary aerosol; laboratory experiments and field data on the ClOOCl photolysis rate and other kinetic parameters have been shown to be consistent with an adequate degree of certainty; no evidence has been found that would support the existence of yet unknown chemical mechanisms making a significant contribution to polar ozone loss. (4) Global modelling: results from process studies have been implemented in a prognostic chemistry climate model (CCM); simulations with improved parameterisations of processes relevant for polar ozone depletion are evaluated against satellite data and other long term records using data assimilation and detrended fluctuation analysis. Finally, measurements and process studies within RECONCILE were also applied to the winter 2010/11, when special meteorological conditions led to the highest chemical ozone loss ever observed in the Arctic. In addition to quantifying the 2010/11 ozone loss and to understand its causes including possible connections to climate change, its impacts were addressed, such as changes in surface ultraviolet (UV) radiation in the densely populated northern mid-latitudes.
Sulphuric acid, ammonia, amines, and oxidised organics play a crucial role in nanoparticle formation in the atmosphere. In this study, we investigate the composition of nucleated nanoparticles formed from these compounds in the CLOUD chamber experiments at CERN. The investigation is carried out via analysis of the particle hygroscopicity, ethanol affinity, oxidation state, and ion composition. Hygroscopicity was studied by a hygroscopic tandem differential mobility analyser and a cloud condensation nuclei counter, ethanol affinity by an organic differential mobility analyser and particle oxidation level by a high-resolution time-of-flight aerosol mass spectrometer. The ion composition was studied by an atmospheric pressure interface time-of-flight mass spectrometer. The volume fraction of the organics in the particles during their growth from sizes of a few nanometers to tens of nanometers was derived from measured hygroscopicity assuming the Zdanovski-Stokes-Robinson relationship, and compared to values gained from the spectrometers. The ZSR-relationship was also applied to obtain the measured ethanol affinities during the particle growth, which were used to derive the volume fractions of sulphuric acid and the other inorganics (e.g. ammonium salts). In the presence of sulphuric acid and ammonia, particles with a mobility diameter of 150 nm were chemically neutralised to ammonium sulphate. In the presence of oxidation products of pinanediol, the organic volume fraction of freshly nucleated particles increased from 0.4 to ∼0.9, with an increase in diameter from 2 to 63 nm. Conversely, the sulphuric acid volume fraction decreased from 0.6 to 0.1 when the particle diameter increased from 2 to 50 nm. The results provide information on the composition of nucleated aerosol particles during their growth in the presence of various combinations of sulphuric acid, ammonia, dimethylamine and organic oxidation products.
The manuscript name Chelifer longimanus Kollar, 1848, most often cited as Obisium longimanum Kollar, was first introduced in a note by Kollar (1848) that has been overlooked in the taxonomic literature on pseudoscorpions. No description or indication has been associated with this name, which is therefore a nomen nudum. It corresponds to the valid pseudoscorpion species Neobisium spelaeum (Schiödte, 1847), having been found at one of the type localities of the latter (Postojna Cave, Slovenia). Two specimens originally identified as O. longimanum (probably by V. Kollar) are present in the collections of the Naturhistorisches Museum Wien.
Spiders from the Tirana district of Albania were investigated. Currently, 78 species from 24 families and a collection of 400 specimens from January to August 2010 were recorded for Tirana. A total of 32 new records for the Albanian fauna are included in the present paper. Agraecina lineata (Simon, 1878) is the first record for the Balkan Peninsula. Saitis graecus Kulczyński, 1905 was known before only from Greece and Bulgaria. Presently, 373 spider species are known for Albania.
Background: Elucidating the genomic basis of adaptation and speciation is a major challenge in natural systems with large quantities of environmental and phenotypic data, mostly because of the scarcity of genomic resources for non-model organisms. The Atlantic molly (Poecilia mexicana, Poeciliidae) is a small livebearing fish that has been extensively studied for evolutionary ecology research, particularly because this species has repeatedly colonized extreme environments in the form of caves and toxic hydrogen sulfide containing springs. In such extreme environments, populations show strong patterns of adaptive trait divergence and the emergence of reproductive isolation. Here, we used RNA-sequencing to assemble and annotate the first transcriptome of P. mexicana to facilitate ecological genomics studies in the future and aid the identification of genes underlying adaptation and speciation in the system.
Description: We provide the first annotated reference transcriptome of P. mexicana. Our transcriptome shows high congruence with other published fish transcriptomes, including that of the guppy, medaka, zebrafish, and stickleback. Transcriptome annotation uncovered the presence of candidate genes relevant in the study of adaptation to extreme environments. We describe general and oxidative stress response genes as well as genes involved in pathways induced by hypoxia or involved in sulfide metabolism. To facilitate future comparative analyses, we also conducted quantitative comparisons between P. mexicana from different river drainages. 106,524 single nucleotide polymorphisms were detected in our dataset, including potential markers that are putatively fixed across drainages. Furthermore, specimens from different drainages exhibited some consistent differences in gene regulation.
Conclusions: Our study provides a valuable genomic resource to study the molecular underpinnings of adaptation to extreme environments in replicated sulfide spring and cave environments. In addition, this study adds to the increasing number of genomic resources in the family Poeciliidae, which are widely used in comparative analyses of behavior, ecology, evolution, and medical genetics.
C. elegans is used extensively as a model system in the neurosciences due to its well defined nervous system. However, the seeming simplicity of this nervous system in anatomical structure and neuronal connectivity, at least compared to higher animals, underlies a rich diversity of behaviors. The usefulness of the worm in genome-wide mutagenesis or RNAi screens, where thousands of strains are assessed for phenotype, emphasizes the need for computational methods for automated parameterization of generated behaviors. In addition, behaviors can be modulated upon external cues like temperature, O2 and CO2 concentrations, mechanosensory and chemosensory inputs. Different machine vision tools have been developed to aid researchers in their efforts to inventory and characterize defined behavioral “outputs”. Here we aim at providing an overview of different worm-tracking packages or video analysis tools designed to quantify different aspects of locomotion such as the occurrence of directional changes (turns, omega bends), curvature of the sinusoidal shape (amplitude, body bend angles) and velocity (speed, backward or forward movement).
Background: Gastrulation is a key transition in embryogenesis; it requires self-organized cellular coordination, which has to be both robust to allow efficient development and plastic to provide adaptability. Despite the conservation of gastrulation as a key event in Metazoan embryogenesis, the morphogenetic mechanisms of self-organization (how global order or coordination can arise from local interactions) are poorly understood.
Results: We report a modular structure of cell internalization in Caenorhabditis elegans gastrulation that reveals mechanisms of self-organization. Cells that internalize during gastrulation show apical contractile flows, which are correlated with centripetal extensions from surrounding cells. These extensions converge to seal over the internalizing cells in the form of rosettes. This process represents a distinct mode of monolayer remodeling, with gradual extrusion of the internalizing cells and simultaneous tissue closure without an actin purse-string. We further report that this self-organizing module can adapt to severe topological alterations, providing evidence of scalability and plasticity of actomyosin-based patterning. Finally, we show that globally, the surface cell layer undergoes coplanar division to thin out and spread over the internalizing mass, which resembles epiboly.
Conclusions: The combination of coplanar division-based spreading and recurrent local modules for piecemeal internalization constitutes a system-level solution of gradual volume rearrangement under spatial constraint. Our results suggest that the mode of C. elegans gastrulation can be unified with the general notions of monolayer remodeling and with distinct cellular mechanisms of actomyosin-based morphogenesis.
Uncalibrated semi-invasive continous monitoring of cardiac index (CI) has recently gained increasing interest. The aim of the present study was to compare the accuracy of CI determination based on arterial waveform analysis with transpulmonary thermodilution. Fifty patients scheduled for elective coronary surgery were studied after induction of anaesthesia and before and after cardiopulmonary bypass (CPB), respectively. Each patient was monitored with a central venous line, the PiCCO system, and the FloTrac/Vigileo-system. Measurements included CI derived by transpulmonary thermodilution and uncalibrated semi-invasive pulse contour analysis. Percentage changes of CI were calculated. There was a moderate, but significant correlation between pulse contour CI and thermodilution CI both before (r(2) = 0.72, P < 0.0001) and after (r(2) = 0.62, P < 0.0001) CPB, with a percentage error of 31% and 25%, respectively. Changes in pulse contour CI showed a significant correlation with changes in thermodilution CI both before (r(2) = 0.52, P < 0.0001) and after (r(2) = 0.67, P < 0.0001) CPB. Our findings demonstrated that uncalibrated semi-invasive monitoring system was able to reliably measure CI compared with transpulmonary thermodilution in patients undergoing elective coronary surgery. Furthermore, the semi-invasive monitoring device was able to track haemodynamic changes and trends.
Malignant melanoma of the urethra is a rare tumour that is difficult to diagnose and treat, resulting in a poor prognosis. In this paper, we present the case of a 65-year-old woman who was referred to a gynaecologist because of a urethral mass that mimicked a caruncle. The tumour was removed by local excision, and a pathological analysis revealed a malignant melanoma. Distal urethrectomy was performed after three months with no evidence of residual tumour. There was no evidence of disease at a six-year followup. In this paper, we compare the epidemiology, treatment, staging, and prognosis of vulvar cancer in general to malignant melanoma of the vulva in particular.
Cellular models of aging
(2012)
Low-level laser irradiation of visible light had been introduced as a medical treatment already more than 40 years ago, but its medical application still remains controversial. Laser stimulation of acupuncture points has also been introduced, and mast-cells degranulation has been suggested. Activation of TRPV ion channels may be involved in the degranulation. Here, we investigated whether TRPV1 could serve as candidate for laser-induced mast cell activation. Activation of TRPV1 by capsaicin resulted in degranulation. To investigate the effect of laser irradiation on TRPV1, we used the Xenopus oocyte as expression and model system. We show that TRPV1 can functionally be expressed in the oocyte by (a) activation by capsaicin (K 1/2 = 1.1 μM), (b) activation by temperatures exceeding 42°C, (c) activation by reduced pH (from 7.4 to 6.2), and (d) inhibition by ruthenium red. Red (637 nm) as well as blue (406 nm) light neither affected membrane currents in oocytes nor did it modulate capsaicin-induced current. In contrast, green laser light (532 nm) produced power-dependent activation of TRPV1. In conclusion, we could show that green light is effective at the cellular level to activate TRPV1. To which extend green light is of medical relevance needs further investigation.
Analgesia is a well-documented effect of acupuncture. A critical role in pain sensation plays the nervous system, including the GABAergic system and opioid receptor (OR) activation. Here we investigated regulation of GABA transporter GAT1 by δOR in rats and in Xenopus oocytes. Synaptosomes of brain from rats chronically exposed to opiates exhibited reduced GABA uptake, indicating that GABA transport might be regulated by opioid receptors. For further investigation we have expressed GAT1 of mouse brain together with mouse δOR and μOR in Xenopus oocytes. The function of GAT1 was analyzed in terms of Na(+)-dependent [(3)H]GABA uptake as well as GAT1-mediated currents. Coexpression of δOR led to reduced number of fully functional GAT1 transporters, reduced substrate translocation, and GAT1-mediated current. Activation of δOR further reduced the rate of GABA uptake as well as GAT1-mediated current. Coexpression of μOR, as well as μOR activation, affected neither the number of transporters, nor rate of GABA uptake, nor GAT1-mediated current. Inhibition of GAT1-mediated current by activation of δOR was confirmed in whole-cell patch-clamp experiments on rat brain slices of periaqueductal gray. We conclude that inhibition of GAT1 function will strengthen the inhibitory action of the GABAergic system and hence may contribute to acupuncture-induced analgesia.
We introduce a computational model of the negative priming (NP) effect that includes perception, memory, attention, decision making, and action. The model is designed to provide a coherent picture across competing theories of NP. The model is formulated in terms of abstract dynamics for the activations of features, their binding into object entities, their semantic categorization as well as related memories and appropriate reactions. The dynamic variables interact in a connectionist network which is shown to be adaptable to a variety of experimental paradigms. We find that selective attention can be modeled by means of inhibitory processes and by a threshold dynamics. From the necessity of quantifying the experimental paradigms, we conclude that the specificity of the experimental paradigm must be taken into account when predicting the nature of the NP effect.
Faunistic spider collections in the Museum für Naturkunde Berlin: The collection of Erich Hesse
(2012)
The ‘Hesse collection’ of spiders (Araneae) and harvestmen (Opiliones) in the Museum für Naturkunde Berlin is documented. Biographical notes on Erich Hesse – a former arachnid curator at the museum (1921–1940) – are provided. The ‘Hesse collection’ was actually put together by other workers, and can be broadly divided into two parts. One comes from Bielinek (= Bellinchen) on the Polish side of the Oder Valley (West Pommerania); now part of the ‘Unteres Odertal’ National Park. This Bielinek material includes notable records of Heriaeus oblongus Simon, 1918 and Gibbaranea ullrichi (Hahn, 1835). The other part of the collection comes from Colbitz-Letzlinger Heide in Saxony-Anhalt, Germany. Notable here are Pistius truncatus (Pallas, 1772) and Philodromus buchari Kubcová, 2004; the latter representing the first record of this species for Saxony-Anhalt.
Inhibitors of Apoptosis Proteins (IAPs) are well-studied E3 ubiquitin ligases predominantly known for regulation of apoptosis. We uncovered that IAPs can function as a direct E3 ubiquitin ligase of RhoGTPase Rac1. cIAP1 and XIAP directly conjugate polyubiquitin chains to Lysine 147 of activated Rac1 and target it for proteasomal degradation. Consistently, loss of these IAPs by various strategies led to stabilization of Rac1 and mesenchymal mode of migration in tumor cells. IAPs also regulate Rac1 degradation upon RhoGDI1 depletion and CNF1 toxin treatment. Our observations revealed an evolutionarily conserved role of IAPs in regulating Rac1 stability shedding light on to the mechanisms behind ubiquitination–dependent inactivation of Rac1 signaling.
While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
Folding of RNA molecules into their functional three-dimensional structures is often supported by RNA chaperones, some of which can catalyse the two elementary reactions helix disruption and helix formation. Hfq is one such RNA chaperone, but its strand displacement activity is controversial. Whereas some groups found Hfq to destabilize secondary structures, others did not observe such an activity with their RNA substrates. We studied Hfq’s activities using a set of short RNAs of different thermodynamic stabilities (GC-contents from 4.8% to 61.9%), but constant length. We show that Hfq’s strand displacement as well as its annealing activity are strongly dependent on the substrate’s GC-content. However, this is due to Hfq’s preferred binding of AU-rich sequences and not to the substrate’s thermodynamic stability. Importantly, Hfq catalyses both annealing and strand displacement with comparable rates for different substrates, hinting at RNA strand diffusion and annealing nucleation being rate-limiting for both reactions. Hfq’s strand displacement activity is a result of the thermodynamic destabilization of the RNA through preferred single-strand binding whereas annealing acceleration is independent from Hfq’s thermodynamic influence. Therefore, the two apparently disparate activities annealing acceleration and duplex destabilization are not in energetic conflict with each other.
The crystal packing of the title compound, C13H19NO·0.33C7H8, shows a channel at [001], which contains grossly disordered toluene solvent molecules. The angle between the benzene ring and the mean plane of the formamide group is 71.1 (1)°. The amide groups of neighbouring molecules are connected by N—H(...)O hydrogen bonds, forming 21 helical chains propagating along [001]. Molecules are also connected by weak intermolecular C—H(...)O hydrogen bonds, forming 61 helices.
The present study unites data from several excursions in typical Mediterranean lowland ecosystems in Albania during the years 2006 to 2009. Spiders from several different habitat types along the coast were analysed in six districts: Saranda, Fieri, Kavaja, Durrësi, Tirana and Lezha. In total 299 adult specimens were collected. They belong to 82 species, 60 genera and 22 families. Six species are new to the Albanian fauna: Aculepeira armida (Audouin, 1826), Zygiella x-notata (Clerck, 1757), Histopona torpida (C. L. Koch, 1837), Malthonica campestris (C. L. Koch, 1834), Pellenes tripunctatus (Walckenaer, 1802) and Pseudeuophrys erratica (Walckenaer, 1826). With respect to zoogeography, the spider fauna is mainly characterized by the presence of many Palaearctic species.
We recorded the tent-web spider Cyrtophora citricola (Forsskål, 1775) (Araneidae: Cyrtophorinae) from Turkey for the first time at two sites. Body measurements and a brief description of the female are presented, as well as information on the sites (olive and orange orchards, shrubs) and the accompanying spider fauna.
An illustrated description of Withius hispanus (L. Koch, 1873) is provided based on its morphological and morphometric characters. This finding of W. hispanus is the first record of the family Withiidae in Slovakia. The present re-description of this species allows an assessment of the variability of its morphological and morphometric characters.
Among animal constructions, spider’s orb webs represent regular geometrical architecture models. Their construction is the result of successive, simple and reproducible behavioural patterns, often considered as stereotyped. It has recently been shown that spider’s building behaviours vary, which can alter web regularity. The final capture spiral results from the laying of successive threads between two radii, here termed ‘spiral units’. We defined a theoretical normal web, as a web in which each turn of the final spiral should be parallel to the preceding one. Weaving of the spiral units sometimes leads to anomalies in the orb web. Anomalies were identified and analysed in the orb-weaving spider Zygiella x-notata (Clerck, 1757). From video recordings of web construction, we noted the displacements of the legs and of the abdomen of the spider. We compared the frequency of displacements, and their duration, between the construction of spiral units that produce a normal turn and ones that produce an anomalous turn. The position of the legs on the web’s threads was also analysed. Results showed that anomalies were not the consequences of a modification in activity but more likely the result of the position on the radii of the fourth leg. These results suggest that spiders use local information to build the final capture spiral.
A total of 107 spider species from 15 families were recorded in the herbaceous vegetation of the steppe ecosystems of Ukraine and the Central Chernozem region of Russia. Araneidae, Thomisidae, Salticidae and Theridiidae were the most species-rich. The species composition depended on the steppe type; adjacent forest habitats influenced steppe fauna in the forest-steppe and northern part of the steppe natural zone. The number of generalist, forest and wetland dwelling species in the steppe vegetation showed a tendency to decrease towards the south. Dominance of herb-dwelling spiders was specific to each steppe type; no single species was found to predominate in all the steppe habitats.
Maintenance of polymorphism in the orb weaving spider species Agalenatea redii (Araneae, Araneidae)
(2012)
The maintenance of polymorphism within populations may be the consequence of several elements of species life history such as use of space, activity rhythms, predation, parasitism and reproduction. The present study focuses on the latter aspect using an orb weaving spider, Agalenatea redii, which presents five different morphs of the opisthosoma pattern in the adult stage. Over the course of four years, from 2008 to 2011, adult spiders (males, females and pairs) were observed at different sites. In 2011, we also conducted a six-week survey of a single population, observing the number of spiders of each morph and the morph of paired spiders. We collected field data on the spatial and temporal distribution of spiders based on their sex and morph. Using a distance analysis, we compared the field distribution with a simulated one in which pairs were associated at random. The results showed that although there were changes over time and space in the proportions of females of the different morphs, as well as in the proportion of the pair associations, pairing according to morphs probably occurs at random.
The spider fauna of buildings and other urban habitats (city parks, green areas of industrial enterprises, and housing estates) of Chernivtsi city was surveyed. In the period 2002-2011, 212 species belonging to 26 families were recorded. Previous studies found a total of 173 species of spiders belonging to 26 families from the territories which are now included in the city limits of Chernivtsi. Currently, the total spider species list for Chernivtsi includes 260 species of 30 families, of which 125 species (21 families) were recorded both by earlier researchers and by ourselves. The most important reasons for changes in urban spider assemblages are as follows: species habitat change, introduction of alien species, and description of new species unknown in the late 19th – early 20th centuries.
Examination of the L. Koch collection of the Zoological Museum in Berlin allows us to propose the following new synonyms and combinations: Erigone marina L. Koch, 1882 = Oedothorax fuscus (Blackwall, 1834) n. syn.; Theridion elimatum L. Koch, 1882 = Enoplognatha diversa (Blackwall, 1859) n. syn.; Liocranum variabilis Wunderlich, 2008 = Zora inornata L. Koch, 1882 n. syn. = Liocranum inornatum n. comb.; Lycosa perspicax L. Koch, 1882 = Arctosa fulvolineata (Lucas,1846) n. syn.; Alopecosella Roewer, 1960 = Arctosa C. L. Koch, 1847 n. syn.; Lycosa subhirsuta L. Koch, 1882 = Arctosa lacustris (Simon, 1876) n. syn.; Philodromus vegetus L. Koch, 1882 = Thanatus vulgaris Simon, 1870 n. syn.; Ozyptila bicuspis Simon, 1932 = Ozyptila furcula L. Koch, 1882 n. syn.; Haplodrassus maroccanus Denis, 1956 = Drassus parvulus L. Koch, 1882 n. syn. = Haplodrassus parvicorpus (Roewer, 1951) n. comb. (replacement name); Zelotes ruscinensis Simon, 1914 = Zelotes semirufa (L. Koch, 1882) n. syn.; Phlegra simoni L. Koch, 1882 = Phlegra bresnieri Lucas, 1846 n. syn.; Trochosula conspersa (L. Koch, 1882), Lycorma fraisnei (L. Koch, 1882), Lycorma insulana (L. Koch, 1882), Arctosa misella (L. Koch, 1992) and Pirata simplex (L. Koch, 1882) are all retransferred to their original genus Lycosa stat. rev. Cheiracanthium occidentale L. Koch, 1882, Ozyptila furcula L. Koch, 1882 and Zelotes callidus (Simon, 1878) are redescribed.
The E-pathway of transmembrane proton transfer has been demonstrated previously to be essential for catalysis by the diheme-containing quinol:fumarate reductase (QFR) of Wolinella succinogenes. Two constituents of this pathway, Glu-C180 and heme b(D) ring C (b(D)-C-) propionate, have been validated experimentally. Here, we identify further constituents of the E-pathway by analysis of molecular dynamics simulations. The redox state of heme groups has a crucial effect on the connectivity patterns of mobile internal water molecules that can transiently support proton transfer from the b(D)-C-propionate to Glu-C180. The short H-bonding paths formed in the reduced states can lead to high proton conduction rates and thus provide a plausible explanation for the required opening of the E-pathway in reduced QFR. We found evidence that the b(D)-C-propionate group is the previously postulated branching point connecting proton transfer to the E-pathway from the quinol-oxidation site via interactions with the heme b(D) ligand His-C44. An essential functional role of His-C44 is supported experimentally by site-directed mutagenesis resulting in its replacement with Glu. Although the H44E variant enzyme retains both heme groups, it is unable to catalyze quinol oxidation. All results obtained are relevant to the QFR enzymes from the human pathogens Campylobacter jejuni and Helicobacter pylori.
Recent psychophysical research supports the notion that horizontal information of a face is primarily important for facial identity processes. Even though this has been demonstrated to be valid for young adults, the concept of horizontal information as primary informative source has not yet been applied to older adults’ ability to correctly identify faces. In the current paper, the role different filtering methods might play in an identity processing task is examined for young and old adults, both taken from student populations. Contrary to most findings in the field of developmental face perception, only a near-significant age effect is apparent in upright and un-manipulated presentation of stimuli, whereas a bigger difference between age groups can be observed for a condition which removes all but horizontal information of a face. It is concluded that a critical feature of human face perception, the preferential processing of horizontal information, is less efficient past the age of 60 and is involved in recognition processes that undergo age-related decline usually found in the literature.
Two new and five known oxazoles were identified from two different Pseudomonas strains in addition to the known pyrones pseudopyronine A and B. Labeling experiments confirmed their structures and gave initial evidence for a novel biosynthesis pathway of these natural oxazoles. In order to confirm their structure, they were synthesized, which also allowed tests of their bioactivity. Additionally, the bioactivities of the synthesis intermediates were also investigated revealing interesting biological activities for several compounds despite their overall simple structures.
During polychemotherapy, cytotoxic drugs are given in combinations to enhance their anti-tumor effectiveness. For most drug combinations, underlying signaling mechanisms responsible for positive drug-drug interactions remain elusive. Here, we prove a decisive role for the Bcl-2 family member NOXA to mediate cell death by certain drug combinations, even if drugs were combined which acted independently from NOXA, when given alone. In proof-of-principle studies, betulinic acid, doxorubicin and vincristine induced cell death in a p53- and NOXA-independent pathway involving mitochondrial pore formation, release of cytochrome c and caspase activation. In contrast, when betulinic acid was combined with either doxorubicine or vincristine, cell death signaling changed considerably; the drug combinations clearly depended on both p53 and NOXA. Similarly and of high clinical relevance, in patient-derived childhood acute leukemia samples the drug combinations, but not the single drugs depended on p53 and NOXA, as shown by RNA interference studies in patient-derived cells. Our data emphasize that NOXA represents an important target molecule for combinations of drugs that alone do not target NOXA. NOXA might have a special role in regulating apoptosis sensitivity in the complex interplay of polychemotherapy. Deciphering the differences in signaling of single drugs and drug combinations might enable designing highly effective novel polychemotherapy regimens.
The loading of antigenic peptides onto major histocompatibility complex class I (MHC I) molecules is an essential step in the adaptive immune response against virally or malignantly transformed cells. The ER-resident peptide-loading complex (PLC) consists of the transporter associated with antigen processing (TAP1 and TAP2), assembled with the auxiliary factors tapasin and MHC I. Here, we demonstrated that the N-terminal extension of each TAP subunit represents an autonomous domain, named TMD0, which is correctly targeted to and inserted into the ER membrane. In the absence of coreTAP, each TMD0 recruits tapasin in a 1:1 stoichiometry. Although the TMD0s lack known ER retention/retrieval signals, they are localized to the ER membrane even in tapasin-deficient cells. We conclude that the TMD0s of TAP form autonomous interaction hubs linking antigen translocation into the ER with peptide loading onto MHC I, hence ensuring a major function in the integrity of the antigen-processing machinery.