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ω-Azido fatty acids as probes to detect fatty acid biosynthesis, degradation, and modification
(2014)
FAs play a central role in the metabolism of almost all known cellular life forms. Although GC-MS is regarded as a standard method for FA analysis, other methods, such as HPLC/MS, are nowadays widespread but are rarely applied to FA analysis. Here we present azido-FAs as probes that can be used to study FA biosynthesis (elongation, desaturation) or degradation (β-oxidation) upon their uptake, activation, and metabolic conversion. These azido-FAs are readily accessible by chemical synthesis and their matization with high sensitivity by HPLC/MS, contributing a powerful tool to FA analysis, and hence, lipid analysis in general.
Four species of mole crickets (Orthoptera: Gryllotalpidae) are known from the West Indies: Neocurtilla hexadactyla (Perty), Scapteriscus abbreviatus Scudder, S. didactylus (Latreille), and S. imitatus Nickle and Castner. All are adventive (not native). We document their distributions in West Indian islands/countries by use of records from the literature and examination of specimens. Scapteriscus abbreviatus has been suggested to have arrived in, and been transported about the West Indies in ship ballast (immigration). Based on records of arrival in various parts of the West Indies and the species’ inability to fly, this suggestion seems reasonable. Scapteriscus imitatus pparently was released in Puerto Rico as a result of mistaken identification (introduction – arriving with assistance from humans – although inadvertent), and has not expanded its range in the West Indies. Although the principal mode of dispersal for the other two species also has been suggested to be ship ballast, we present an alternative based on flight which would seem at least equally as plausible. We suggest that S. didactylus could have dispersed by flight from South America through the Lesser Antilles; likewise N. hexadactyla probably from the Yucatan Peninsula to Cuba, and from South America northward through the Lesser Antilles, in at least some localities assisted by wind. Our zoogeographical alternative, if correct, means that the natural range expansions of these latter two species began very long ago and without human assistance – they were not introduced recently to the West Indies.
Salzer, Ralf ; Herzberg, Martin ; Nies, Dietrich H. ; Joos, Friederike ; Rathmann, Barbara ; Thielmann, Yvonne ; Averhoff, Beate
The traffic AAA-ATPase PilF is essential for pilus biogenesis and natural transformation of Thermus thermophilus HB27. Recently, we showed that PilF forms hexameric complexes containing six zinc atoms coordinated by conserved tetracysteine motifs. Here we report that zinc binding is essential for complex stability. However, zinc binding is neither required for pilus biogenesis nor natural transformation. A number of the mutants did not exhibit any pili during growth at 64 °C but still were transformable. This leads to the conclusion that type 4 pili and the DNA translocator are distinct systems. At lower growth temperatures (55 °C) the zinc-depleted multiple cysteine mutants were hyperpiliated but defective in pilus-mediated twitching motility. This provides evidence that zinc binding is essential for the role of PilF in pilus dynamics. Moreover, we found that zinc binding is essential for complex stability but dispensable for ATPase activity. In contrast to many polymerization ATPases from mesophilic bacteria, ATP binding is not required for PilF complex formation; however, it significantly increases complex stability. These data suggest that zinc and ATP binding increase complex stability that is important for functionality of PilF under extreme environmental conditions.
Three years after the advent of Zimbabwe's Inclusive Government in February 2009, the country still awaits the elections that people hope will lead to a more enduring political settlement. Zimbabwe: Mired in Transition reviews the experience of recent years assesses the progress that has been made. What is the public mood, and how has it changed? What steps have been taken to reform the media? How important is a new constitution. Although the economy has stabilised to some extent with the adoption of a multi-currency regime, industrial and agricultural production are depressed, and investment inflows are limited; what spaces exist for fiscal reform? Are local authority structures and the state bureaucracy equipped to handle the tasks that will ne asked of them? In terms of two important areas, the book extends its analysis further back than 2009. First, is the issue of emigration. Estimates of the number of Zimbabweans in the diaspora range from three to four million; what impact us this having on national development, and to what extent might the trend of migration be reversed? The second concerns young people, the chapter on which concludes: 'We already have a 'lost generation' - those who were once called the 'born frees'. Unless positive changes are made, we will still have another'. This collection of eleven essays examines in detail some of the pressing questions which Zimbabweans must ask as they chart a way forward.
You reap what you sow! differences in knowledge exchange effectiveness between communication types
(2014)
FOR KNOWLEDGE-INTENSIVE ORGANIZATIONS IN THE FINANCE INDUSTRY, AN EFFECTIVE KNOWLEDGE EXCHANGE AMONG EMPLOYEES IS CRUCIAL FOR THE COMPETITIVE PERFORMANCE. THEREFORE, COMPANIES INCREASINGLY RELY ON SOCIAL MEDIA PLATFORMS TO FACILITATE COMMUNICATION AND COLLABORATION. TO ENHANCE OUR UNDERSTANDING OF SUCCESSFUL COMMUNICATION IN ENTERPRISE SOCIAL MEDIA, WE APPLY HUMAN CODING AND QUANTITATIVE ANALYSIS TO THE CONTENT AND TONE OF 15,505 ENTERPRISE MICROBLOGGING MESSAGES CREATED BY 1,166 EMPLOYEES OF AN INTERNATIONAL FINANCIAL SERVICE PROVIDER. OUR RESULTS SUGGEST THAT A MORE FACTUAL-ORIENTED COMMUNICATION TYPE BENEFITS FROM A HIGHER KNOWLEDGE EXCHANGE EFFECTIVENESS COMPARED TO A PRIMARILY SELF-DISCLOSING COMMUNICATION TYPE.
Wrack burial reduces germination and establishment of the invasive cordgrass Spartina densiflora
(2014)
Abbas, Ahmed M. ; Rubio-Casal, Alfredo E. ; Cires, Alfonso de ; Figueroa, Enrique ; Nieva, Javier J. ; Castillo, Jesús M.
Germination and emergence of halophytes may decrease significantly by seed burial in dead plant material, or wrack, which is common and abundant in tidal marshes. The effects of plant debris (wrack) burial on seed germination and seedling establishment of Spartina densiflora, an invasive cordgrass, were studied under greenhouse conditions and compared with field observations. Five wrack burial depths were applied: control without wrack, 1 cm (1235 ± 92 g DW wrack m-2), 2 cm (3266 ± 13 g DW m-2), 4 cm (4213 ± 277 g DW m-2), and 8 cm (6138 ± 227 g DW m-2). Sediment pH, electrical conductivity, redox potential and temperature were recorded. Quiescence increased with wrack load up to ~20% at 8 cm deep. Germination decreased with wrack load from 96% to 14%, which could be related with anoxic conditions under the debris since sediment redox potential was as low as -83 ± 7 mV at 8 cm. Germination percentage increased and quiescent and dormant percentages decreased at higher daily sediment temperatures and with higher daily temperature fluctuations, conditions that were recorded without or under low loads of wrack. Spartina densiflora did not show primary dormancy, but its seeds entered into a non-deep physiological dormancy below 1 cm deep in plant debris. The establishment of S. densiflora seedlings was also greatly reduced by wrack burial since only 6 seedlings (11 ± 5 % of germinated seeds) emerged above plant debris from 1 cm and all seedlings died from deeper than 1 cm. S. densiflora seedling development was also reduced by wrack burial. The inverse relationship between germination and emergence of S. densiflora with wrack burial recorded in our study is useful to predict its invasion dynamics and to plan the management of invaded marshes.
This book addresses itself to mobilisation and involvement of rural people in development projects. It describes an imperfect but, nonetheless, exciting and thought-provoking exercise that drew social science researchers and students from four public universities in Kenya into an experiment in participatory research, community education and development in two locations. The experiment was grounded on the assumptions that the people of Kenya are a primary resource and that given proper roles and contribution of planners, researchers and programme implementers, self-sustainable development can become a reality. The contributors of this book have focused on the potential of the university to facilitate participation of the people in development. They have given specific suggestions on how this might be accomplished.
This paper investigates the determinants of value and growth investing in a large administrative panel of Swedish residents over the 1999-2007 period. We document strong relationships between a household’s portfolio tilt and the household’s financial and demographic characteristics. Value investors have higher financial and real estate wealth, lower leverage, lower income risk, lower human capital, and are more likely to be female than the average growth investor. Households actively migrate to value stocks over the life-cycle and, at higher frequencies, dynamically offset the passive variations in the value tilt induced by market movements. We verify that these results are not driven by cohort effects, financial sophistication, biases toward popular or professionally close stocks, or unobserved heterogeneity in preferences. We relate these household-level results to some of the leading explanations of the value premium.
Abstract Trial-to-trial variability and spontaneous activity of cortical recordings have been suggested to reflect intrinsic noise. This view is currently challenged by mounting evidence for structure in these phenomena: Trial-to-trial variability decreases following stimulus onset and can be predicted by previous spontaneous activity. This spontaneous activity is similar in magnitude and structure to evoked activity and can predict decisions. Allof the observed neuronal properties described above can be accounted for, at an abstract computational level, by the sampling-hypothesis, according to which response variability reflects stimulus uncertainty. However, a mechanistic explanation at the level of neural circuit dynamics is still missing.
In this study, we demonstrate that all of these phenomena can be accounted for by a noise-free self-organizing recurrent neural network model (SORN). It combines spike-timing dependent plasticity (STDP) and homeostatic mechanisms in a deterministic network of excitatory and inhibitory McCulloch-Pitts neurons. The network self-organizes to spatio-temporally varying input sequences.
We find that the key properties of neural variability mentioned above develop in this model as the network learns to perform sampling-like inference. Importantly, the model shows high trial-to-trial variability although it is fully deterministic. This suggests that the trial-to-trial variability in neural recordings may not reflect intrinsic noise. Rather, it may reflect a deterministic approximation of sampling-like learning and inference. The simplicity of the model suggests that these correlates of the sampling theory are canonical properties of recurrent networks that learn with a combination of STDP and homeostatic plasticity mechanisms.
Author Summary Neural recordings seem very noisy. If the exact same stimulus is shown to an animal multiple times, the neural response will vary. In fact, the activity of a single neuron shows many features of a stochastic process. Furthermore, in the absence of a sensory stimulus, cortical spontaneous activity has a magnitude comparable to the activity observed during stimulus presentation. These findings have led to a widespread belief that neural activity is indeed very noisy. However, recent evidence indicates that individual neurons can operate very reliably and that the spontaneous activity in the brain is highly structured, suggesting that much of the noise may in fact be signal. One hypothesis regarding this putative signal is that it reflects a form of probabilistic inference through sampling. Here we show that the key features of neural variability can be accounted for in a completely deterministic network model through self-organization. As the network learns a model of its sensory inputs, the deterministic dynamics give rise to sampling-like inference. Our findings show that the notorious variability in neural recordings does not need to be seen as evidence for a noisy brain. Instead it may reflect sampling-like inference emerging from a self-organized learning process.
The administration of intravenous fluid to critically ill patients is one of the most common but also one of the most fiercely debated interventions in intensive care medicine. During the past decade, a number of important studies have been published which provide clinicians with improved knowledge regarding the timing, the type and the amount of fluid they should give to their critically ill patients. However, despite the fact that many thousands of patients have been enrolled in these trials of alternative fluid strategies, consensus remains elusive and practice is widely variable. Early adequate resuscitation of patients in shock followed by a restrictive strategy may be associated with better outcomes. Colloids such as modern hydroxyethyl starch are more effective than crystalloids in early resuscitation of patients in shock, and are safe when administered during surgery. However, these colloids may not be beneficial later in the course of intensive care treatment and should best be avoided in intensive care patients who have a high risk of developing acute kidney injury. Albumin has no clear benefit over saline and is associated with increased mortality in neurotrauma patients. Balanced fluids reduce the risk of hyperchloraemic acidosis and possibly kidney injury. The use of hypertonic fluids in patients with sepsis and acute lung injury warrants further investigation and should be considered experimental at this stage. Fluid therapy impacts relevant patient-related outcomes. Clinicians should adopt an individualized strategy based on the clinical scenario and best available evidence. One size does not fit all.
The primary objective of What on Earth is a Ruling Party in a Multiparty Democracy? is to provoke thought and thereby stimulate debate. To this end, provocatively, this collection of topical issues ranges from 'The place of the miniskirt in sociocultural development' to 'Which citizen in Zambia should not take part in (partisan) politics?' The Author, Mubanga E Kashoki, is a Professor of African Languages at the institute of Economic and Social Research in the University of Zambia.
What happened in Cyprus? The economic consequences of the last communist government in Europe
(2014)
This paper reviews developments in the Cypriot economy following the introduction of the euro on 1 January 2008 and leading to the economic collapse of the island five years later. The main cause of the collapse is identified with the election of a communist government in February 2008, within two months of the introduction of the euro, and its subsequent choices for action and inaction on economic policy matters. The government allowed a rapid deterioration of public finances, and despite repeated warnings, damaged the country's creditworthiness and lost market access in May 2011. The destruction of the island's largest power station in July 2011 subsequently threw the economy into recession. Together with the intensification of the euro area crisis in the summer and fall of 2011, these events weakened the banking system which was vulnerable due to its exposure in Greece. Rather than deal with its fiscal crisis, the government secured a loan from the Russian government that allowed it to postpone action until after the February 2013 election. Rather than protect the banking system, losses were imposed on banks and a campaign against them was coordinated and used as a platform by the communist party for the February 2013 election. The strategy succeeded in delaying resolution of the crisis and avoiding short-term political cost for the communist party before the election, but also in precipitating a catastrophe right after the election.
On 23 July 2014, the U.S. Securities and Exchange Commission (SEC) passed the “Money Market Reform: Amendments to Form PF ,” designed to prevent investor runs on money market mutual funds such as those experienced in institutional prime funds following the bankruptcy of Lehman Brothers. The present article evaluates the reform choices in the U.S. and draws conclusions for the proposed EU regulation of money market funds.
Research results confirm the existence of various forms of international tax planning by multinational firms. Prominent examples for firms employing tax avoidance strategies are Amazon, Google and Starbucks. Increasing availability of administrative data for Europe has enabled researchers to study behavioural responses of European multinationals to taxation. The present paper summarizes what we can learn from these recent studies in general and about German multinationals in particular.
BACKGROUND: Micro-RNAs (miRNA) are attributed to the systems biological role of a regulatory mechanism of the expression of protein coding genes. Research has identified miRNAs dysregulations in several but distinct pathophysiological processes, which hints at distinct systems-biology functions of miRNAs. The present analysis approached the role of miRNAs from a genomics perspective and assessed the biological roles of 2954 genes and 788 human miRNAs, which can be considered to interact, based on empirical evidence and computational predictions of miRNA versus gene interactions.
RESULTS: From a genomics perspective, the biological processes in which the genes that are influenced by miRNAs are involved comprise of six major topics comprising biological regulation, cellular metabolism, information processing, development, gene expression and tissue homeostasis. The usage of this knowledge as a guidance for further research is sketched for two genetically defined functional areas: cell death and gene expression. Results suggest that the latter points to a fundamental role of miRNAs consisting of hyper-regulation of gene expression, i.e., the control of the expression of such genes which control specifically the expression of genes.
CONCLUSIONS: Laboratory research identified contributions of miRNA regulation to several distinct biological processes. The present analysis transferred this knowledge to a systems-biology level. A comprehensible and precise description of the biological processes in which the genes that are influenced by miRNAs are notably involved could be made. This knowledge can be employed to guide future research concerning the biological role of miRNA (dys-) regulations. The analysis also suggests that miRNAs especially control the expression of genes that control the expression of genes.
We use data from the 2009 Internet Survey of the Health and Retirement Study to examine the consumption impact of wealth shocks and unemployment during the Great Recession in the US. We find that many households experienced large capital losses in housing and in their financial portfolios, and that a non-trivial fraction of respondents have lost their job. As a consequence of these shocks, many households reduced substantially their expenditures. We estimate that the marginal propensities to consume with respect to housing and financial wealth are 1 and 3.3 percentage points, respectively. In addition, those who became unemployed reduced spending by 10 percent. We also distinguish the effect of perceived transitory and permanent wealth shocks, splitting the sample between households who think that the stock market is likely to recover in a year’s time, and those who do not. In line with the predictions of standard models of intertemporal choice, we find that the latter group adjusted much more than the former its spending in response to financial wealth shocks.
Part IV of our series "Cyberpeace: Dimensionen eines Gegenentwurfs" on cyberpeace. Matthias Schulze argues that what some perceive as cyberwar is not actually war but rather cyber conflict. The question therefore arises if this conflict will ever be solved. Ben Kamis on the other hand identifies motives in the use of language. He argues that talking about cyberpeace reinforces the impression that we are right in the middle of a cyberwar. I would not agree with that. As Johan Galtung puts it: “The use of the term ‘peace’ may in itself be peace-productive” (Galtung 1969: 167). But how do we define cyberpeace? Who should define it and how do we pursue it?...
Water footprints have been proposed as sustainability indicators, relating the consumption of goods like food to the amount of water necessary for their production and the impacts of that water use in the source regions. We further developed the existing water footprint methodology, by globally resolving virtual water flows from production to consumption regions for major food crops at 5 arcmin spatial resolution. We distinguished domestic and international flows, and assessed local impacts of export production. Applying this method to three exemplary cities, Berlin, Delhi and Lagos, we find major differences in amounts, composition, and origin of green and blue virtual water imports, due to differences in diets, trade integration and crop water productivities in the source regions. While almost all of Delhi's and Lagos' virtual water imports are of domestic origin, Berlin on average imports from more than 4000 km distance, in particular soy (livestock feed), coffee and cocoa. While 42% of Delhi's virtual water imports are blue water based, the fractions for Berlin and Lagos are 2 and 0.5%, respectively, roughly equal to the water volumes abstracted in these two cities for domestic water use. Some of the external source regions of Berlin's virtual water imports appear to be critically water scarce and/or food insecure. However, for deriving recommendations on sustainable consumption and trade, further analysis of context-specific costs and benefits associated with export production will be required.
Was Nyakeera my Father
(2014)
Eavesdropping on his parents, James Kirika, a fifteen-year-old teenager, hears a conversation that suggests that he is not the biological son of the man he calls 'Father'. This realisation sends him into a tortured search for the man who brought him into this world. Things get complicated when the chief source of information, his old and hallucinating grandmother, gives him a fuzzy lead. Does he ever find out the truth?
The colour-singlet axial-vector vertex plays a pivotal role in understanding dynamical chiral symmetry breaking and numerous hadronic weak interactions, yet scant model-independent information is available. We therefore use longitudinal and transverse Ward–Green–Takahashi (WGT) identities, together with kinematic constraints, in order to ameliorate this situation and expose novel features of the axial vertex: amongst them, Ward-like identities for elements in the transverse piece of the vertex, which complement and shed new light on identities determined previously for components in its longitudinal part. Such algebraic results are verified via solutions of the Bethe–Salpeter equation for the axial vertex obtained using two materially different kernels for the relevant Dyson–Schwinger equations. The solutions also provide insights that suggest a practical Ansatz for the axial-vector vertex.
Questions about how human-environment-relations can be conceptualized in a non-dualistic way have been intensively discussed throughout the last decades. The majority of the established realist and constructivist perspectives aim at explaining a given situation by analytically dissecting it. Unfortunately, such an interactionist perspective systematically reproduces the dualistic division between humans, environment and nature.
In contrast, this paper offers a transactive perspective origin in classical pragmatism and discusses its meta-theoretical consequences for human-environment-research. A transactionist perspective interprets the world as a flow of unique and entangled events. Instead of ontologically separating humans and environment, it advocates to look at their relations as being part of a "connatural world". Such a point of view raises new ethical and political questions for geographical human-environment research, argues for a renaissance of ideographic methodologies and hints to a fruitful unity of geographical inquiry.
How to write (international) legal histories that would be true to their protagonists while simultaneously relevant to present audiences? Most of us would also want to write "critically" – that is to say, at least by aiming to avoid Eurocentrism, hagiography and commitment to an altogether old-fashioned view of international law as an instrument of progress. Hence we write today our histories "in context". But this cannot be all. Framing the relevant "context" is only possible by drawing upon more or less conscious jurisprudential and political preferences. Should attention be focused on academic debates, military power, class structures or assumptions about the longue durée? Such choices determine for us what we think of as relevant "contexts", and engage us as participants in large conversations about law and power that are not only about what once "was" but also what there will be in the future.
Grammatikos, Georgios ; Lange, Christian ; Susser, Simone ; Schwendy, Susanne ; Dikopoulos, Nektarios ; Buggisch, Peter ; Encke, Jens ; Teuber, Gerlinde ; Goeser, Tobias ; Thimme, Robert ; Klinker, Hartwig ; Boecher, Wulf O. ; Schulte-Frohlinde, Ewert ; Penna Martinez, Marissa ; Badenhoop, Klaus ; Zeuzem, Stefan ; Berg, Thomas ; Sarrazin, Christoph
Background: Different parameters have been determined for prediction of treatment outcome in hepatitis c virus genotype 1 infected patients undergoing pegylated interferon, ribavirin combination therapy. Results on the importance of vitamin D levels are conflicting. In the present study, a comprehensive analysis of vitamin D levels before and during therapy together with single nucleotide polymorphisms involved in vitamin D metabolism in the context of other known treatment predictors has been performed.
Methods: In a well characterized prospective cohort of 398 genotype 1 infected patients treated with pegylated interferon-α and ribavirin for 24–72 weeks (INDIV-2 study) 25-OH-vitamin D levels and different single nucleotide polymorphisms were analyzed together with known biochemical parameters for a correlation with virologic treatment outcome.
Results: Fluctuations of more than 5 (10) ng/ml in 25-OH-vitamin D-levels have been observed in 66 (39) % of patients during the course of antiviral therapy and neither pretreatment nor under treatment 25-OH-vitamin D-levels were associated with treatment outcome. The DHCR7-TT-polymorphism within the 7-dehydrocholesterol-reductase showed a significant association (P = 0.031) to sustained viral response in univariate analysis. Among numerous further parameters analyzed we found that age (OR = 1.028, CI = 1.002–1.056, P = 0.035), cholesterol (OR = 0.983, CI = 0.975–0.991, P<0.001), ferritin (OR = 1.002, CI = 1.000–1.004, P = 0.033), gGT (OR = 1.467, CI = 1.073–2.006, P = 0.016) and IL28B-genotype (OR = 2.442, CI = 1.271–4.695, P = 0.007) constituted the strongest predictors of treatment response.
Conclusions: While 25-OH-vitamin D-levels levels show considerable variations during the long-lasting course of antiviral therapy they do not show any significant association to treatment outcome in genotype 1 infected patients.
Changes in vitamin D serum levels have been associated with inflammatory diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis (MS), atherosclerosis, or asthma. Genome- and transcriptome-wide studies indicate that vitamin D signaling modulates many inflammatory responses on several levels. This includes (i) the regulation of the expression of genes which generate pro-inflammatory mediators, such as cyclooxygenases or 5-lipoxygenase, (ii) the interference with transcription factors, such as NF-κB, which regulate the expression of inflammatory genes and (iii) the activation of signaling cascades, such as MAP kinases which mediate inflammatory responses. Vitamin D targets various tissues and cell types, a number of which belong to the immune system, such as monocytes/macrophages, dendritic cells (DCs) as well as B- and T cells, leading to individual responses of each cell type. One hallmark of these specific vitamin D effects is the cell-type specific regulation of genes involved in the regulation of inflammatory processes and the interplay between vitamin D signaling and other signaling cascades involved in inflammation. An important task in the near future will be the elucidation of the regulatory mechanisms that are involved in the regulation of inflammatory responses by vitamin D on the molecular level by the use of techniques such as chromatin immunoprecipitation (ChIP), ChIP-seq, and FAIRE-seq.
Kröger, Anne ; Hof, Katharina ; Krick, Christoph ; Siniatchkin, Michael ; Jarczok, Tomasz Antoni ; Freitag, Christine M. ; Bender, Stephan
Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by problems in social behaviour, which are sometimes similar to some symptoms of autism-spectrum disorders (ASD). However, neuronal mechanisms of ASD-like deficits in ADHD have rarely been studied. The processing of biological motion–recently discussed as a marker of social cognition–was found to be disrupted in ASD in several studies. Thus in the present study we tested if biological motion processing is disrupted in ADHD. We used 64-channel EEG and spatio-temporal source analysis to assess event-related potentials associated with human motion processing in 21 children and adolescents with ADHD and 21 matched typically developing controls. On the behavioural level, all subjects were able to differentiate between human and scrambled motion. But in response to both scrambled and biological motion, the N200 amplitude was decreased in subjects with ADHD. After a spatio-temporal dipole analysis, a human motion specific activation was observable in occipital-temporal regions with a reduced and more diffuse activation in ADHD subjects. These results point towards neuronal determined alterations in the processing of biological motion in ADHD.
The purpose of this book is to show that the possession cult of Vimbuza presents itself as an oral genre which is part and parcel of African Oral Literature. The ethnolinguistic study which we undertake will permit us to catch a glimpse of its whole complexity. The analysis has a bearing on four principal aspects. Historical developments: a certain number of facts concerning the birth of possession among the Tumbuka; possession: the study attempts to show how the cult articulates itself with its beliefs and the use of divination; the social role: analysis of social functions; the style: an analysis of the linguistic procedures which are characteristic of Vimbuza songs. The presence of rhetorical figures would confirm that we are talking about an oral literary genre.
From his first research there in 1959 until shortly before his death in 2010, Victor Le Vine was a major Cameroon scholar. What he wrote during Cameroon's first half-century of independence carries implications for the years ahead. This volume introduces and presents eight of his short writings, 1961-2007, five never previously published. They demonstrate his mastery of the intricacies and the sweep of the country's governance history, and both his own and Cameroon's importance for African Studies at large.
The implications of delegating fiscal decision making power to sub-national governments has become an area of significant interest over the past two decades, in the expectation that these reforms will lead to better and more efficient provision of public goods and services. The move towards decentralization has, however, not been homogeneously implemented on the revenue and expenditure side: decentralization has materialized more substantially on the latter than on the former, creating "vertical fiscal imbalances". These imbalances measure the extent to which sub-national governments’ expenditures are financed through their own revenues. This mismatch between own revenues and expenditures may have negative consequences for public finances performance, for example by softening the budget constraint of sub-national governments. Using a large sample of countries covering a long time period from the IMF’s Government Finance Statistics Yearbook, this paper is the first to examine the effects of vertical fiscal imbalances on fiscal performance through the accumulation of government debt. Our findings suggest that vertical fiscal imbalances are indeed relevant in explaining government debt accumulation, and call for a degree of caution when promoting fiscal decentralization.
Vegetation of Little Bora Nature Conservation Trust Agreement, North Western Slopes, New South Wales
(2014)
The vegetation of the Little Bora Nature Conservation Trust Agreement property (560 ha in area), 8 km south east of Bingara (lat 29° 55’S long 150° 37’) in the Gwydir Shire and within the Nandewar Bioregion is described. Eight vegetation communities are defined based on flexible UPGMA analysis of cover-abundance scores of all vascular plant taxa. These communities are mapped based on ground truthing, ADS40 imagery interpretation, topography and substrate. Communities described are: 1) Melaleuca bracteata – Eucalyptus melanophloia – Eucalyptus camaldulensis Woodland, 2) Callitris glaucophylla – Eucalyptus melanophloia – Eucalyptus albens Woodland, 3) Callitris glaucophylla – Eucalyptus melanophloia – Brachychiton populneus Woodland, 4) Eucalyptus albens Woodland, 5) Eucalyptus caleyi – Eucalyptus albens – Callitris glaucophylla Woodland, 6) Callitris glaucophylla – Eucalyptus melanophloia – Eucalyptus albens Woodland, 7) Austrostipa verticillata – Austrostipa scabra Derived Grassland, 8) Eucalyptus melliodora – Eucalyptus dealbata Woodland. A total of 232 vascular plant taxa were found of which 14% were considered exotic in origin. 66 ha of listed threatened communities were mapped along with populations of a currently listed Extinct plant (TSC Act) Dodonaea stenophylla.
Natural vegetation of freely draining beach sand ridges in the valley of the Upper Myall River on the lower North Coast of NSW is sclerophyllous open forest or woodland. Based on previous experience on the nearby Eurunderee area, the vegetation on the sand ridges was classified into three types. These were mapped using aerial photographs and field observation. In transects, each 50 m long, the presence of species was scored in 10, 5 X 5 m quadrats. 48 such transects were used sampling all three types of vegetation on the sand ridges and also vegetation in periodically waterlogged sites adjacent to the ridges. Data from the transects, subjected to an ordination using principal components analysis, revealed clear separation between vegetation of the ridges and that of periodically waterlogged sites. In the ordination, vegetation of the ridges formed a continuum with the three types occupying characteristic parts of the continuum, reflecting their respective distributions on sands with different geomorphological histories. The most grassy, tallest forest, termed Dry Sclerophyll Forest (DSF) is on sands either recently disturbed or deposited (Holocene) or closely overlying other substrates. Banksia serrata occurs in DSF. The least grassy, most sclerophyllous, lowest forest or woodland, termed Dry Heath Forest (DHF), occurs on sands apparently little disturbed since they were laid down in the Pleistocene. Banksia aemula occurs in DHF. An intermediate forest, in which Banksia aemula and Banksia serrata occur together, Intermediate Dry Forest (IDF), is most widely found on the sand mass close to Bombah Broadwater. This sand is postulated to have been reworked during the last Glacial Period. In short, the vegetation of these sand ridges largely varies with time since they were laid down or last disturbed in a major way. Preliminary observations indicate the degree of podsolization of their soils is similarly related to this variation in time.
A newly discovered population of Xystocheir brachymacris Shelley, 1996 (Polydesmida: Xystodesmidae: Xystocheirini), in Placer County (Co.), California, exhibits an unusual grayish-black color dorsally with mottled, ovoid patches at paranotal bases; it cons titutes northern generic and specifi c range extensions of ~28.4 km (17.6 mi). The gonopods differ from those in the El Dorado Co. population in having shorter/acuminate prefemoral processes and blade-like, rather than spatulate, processes “B” that angle away from the solenomere instead of overhanging it. Additionally, a strong distomedial prefemoral lobe, absent from the El Dorado population, arises from the stem in Placer Co. males. Authorship of Xystocheirini is properly attributed to Hoffman, 1980.
Silva, Roberta Lane de Oliveira ; Silva, Manassés Daniel ; Ferreira Neto, José Ribamar Costa ; Nardi, Claudia Huerta de ; Chabregas, Sabrina Moutinho ; Burnquist, William Lee ; Kahl, Günter ; Benko-Iseppon, Ana Maria ; Kido, Ederson Akio
One of the most challenging aspects of RT-qPCR data analysis is the identification of reliable reference genes. Ideally, they should be neither induced nor repressed under different experimental conditions. To date, few reference genes have been adequately studied for sugarcane (Saccharum spp.) using statistical approaches. In this work, six candidate genes (αTUB, GAPDH, H1, SAMDC, UBQ, and 25S rRNA) were tested for gene expression normalization of sugarcane root tissues from drought-tolerant and -sensitive accessions after continuous dehydration (24 h). By undergoing different approaches (GeNorm, NormFinder, and BestKeeper), it was shown that most of them could be used in combinations for normalization purposes, with the exception of SAMDC. Nevertheless three of them (H1, αTUB, and GAPDH) were considered the most reliable reference genes. Their suitability as reference genes validated the expression profiles of two targets (AS and PFPα1), related to SuperSAGE unitags, in agreement with results revealed by previous in silico analysis. The other two sugarcane unitags (ACC oxidase and PIP1-1), after salt stress (100 mM NaCl), presented their expressions validated in the same way. In conclusion, these reference genes will be useful for dissecting gene expression in sugarcane roots under abiotic stress, especially in transcriptomic studies using SuperSAGE or RNAseq approaches.
Knowledge about useful plants and their various applications in West Africa is scattered over many publications and often in form of grey literature difficult to access. Several online-databases compile large scale information from these sources and provide comprehensive summarized descriptions of plant usages. Our aim is to additionally build up a database (UseDa) for primary ethnobotanical interview data. Thus, quantitative data can be extracted and synthesized and data sets can be treated according to different research questions analyzing for example uses in specific areas, of different ethnic groups or user groups, which is essential for practical applications on a local level. In this article we give an overview on the technical structure and the content of the database and discuss at the end the possible output for practical application. The database was set up in the frame of the EU-funded Project UNDESERT.
Use of drug-eluting balloon coronary intervention prior to living donor kidney transplantation
(2014)
Kammerer, Tobias ; Beiras Fernández, Andrés ; Rehm, Markus ; Stangl, Manfred ; Guba, Markus ; Kupatt-Jeremias, Christian ; Weis, Florian
Background: Kidney transplantation is the gold standard of therapy in patients with terminal renal insufficiency. Living donor transplantation is a well-established option in this field. Enlarging the donor's pool implicates the acceptance of an increased rate of comorbidities. Among them, coronary artery disease is a growing problem. An increasing number of patients, undergoing living donation, receive antiplatelet therapies due to coronary disease.
Case presentation: Here we report about the perioperative treatment with a drug-eluting balloon in a patient with major cardiac risk factors who underwent kidney transplantation.
Conclusion: At the current time no recommendation can be given for the routine use of drug-eluting balloons.
The disintegrin and metalloproteinases ADAM10 and ADAM17 are regarded as the most important α-secretases involved in the physiological processing of amyloid precursor protein (APP) in brain. Since it has been suggested that processing of APP by α-secretases could be involved in the reorganization of the brain following injury, we studied mRNA expression of the two α-secretases Adam10 and Adam17, the ß-secretase Bace1, and the App-gene family (App, Aplp1, Aplp2) in the dentate gyrus of the mouse following entorhinal denervation. Using laser microdissection, tissue was harvested from the outer molecular layer and the granule cell layer of the denervated dentate gyrus. Expression levels of candidate genes were assessed using Affymetrix GeneChip Mouse Gene 1.0 ST arrays and reverse transcription-quantitative PCR, revealing an upregulation of Adam10 mRNA and Adam17 mRNA in the denervated outer molecular layer and an upregulation of Adam10 mRNA and App mRNA in the dentate granule cell layer. Immunolabeling for ADAM10 or ADAM17 in combination with markers for astro- and microglia revealed an increased labeling of ADAM10 and ADAM17 in the denervated outer molecular layer that was associated with reactive astrocytes but not with microglia. Collectively, these data show that denervation affects the expression level of APP and its two most important α-secretases. This suggests that APP-processing could be shifted towards the non-amyloidogenic pathway in denervated areas of the brain and, thus, towards the formation of neuroprotective APP cleavage products, such as APPsα.
Pinnaspis chamaecyparidis Takagi, Pinnaspis hikosana Takagi and Pinnaspis uniloba (Kuwana), occurring on Chamaecyparis obtusa Endl., Styrax japonica S. et Z. and Cleyera japonica Thunb. are newly documented in the Korean fauna of armored scales (Diaspididae). The characters of these species are here redescribed with illustrative photographs and information on distribution and hosts along with a dichotomous key to the species of Pinnaspis for correct species identifi cation. In addition, the paper discusses the current status of Pinnaspis buxi (Bouché) and Pinnaspis strachani (Cooley) which are known as native armored scale insects of Korea by analyzing information on the result of the survey.
The study of the Portuguese marine ichthyofauna has a long historical tradition, rooted back in the 18th Century. Here we present an annotated checklist of the marine fishes from Portuguese waters, including the area encompassed by the proposed extension of the Portuguese continental shelf and the Economic Exclusive Zone (EEZ). The list is based on historical literature records and taxon occurrence data obtained from natural history collections, together with new revisions and occurrences. It comprises a total of 1191 species, distributed among 3 superclasses, 4 classes, 42 orders, 212 families and 617 genera. If considering only the EEZ and present territorial waters, this list represents an increase of 230 species (27.8%) and of 238 species (29.0%), when compared to the information available in FishBase (2012) and in the last checklist of marine and estuarine fishes of Portugal (1993), respectively. The order Perciformes shows the highest diversity, with 54 families, 162 genera and 299 species. Stomiidae (80 species), Myctophidae (71 species) and Macrouridae (37 species) are the richest families. From the listed species, 734 are present off mainland Portugal, 857 off the Azores and 766 off Madeira. Within the limits of the examined area, three species are reported for the first time in mainland Portugal and twenty-nine records are identified as doubtful. A total of 133 species have been recorded from the extended Portuguese continental shelf (2 off mainland Portugal, 117 off the Azores and 14 off Madeira), two of which are common to the Azores and Madeira extensions. Biogeographically, the Atlantic group is the most important (548 species – 46.01%), followed by the Lusitanian group (256 species – 21.49%), the African group (71 species – 5.96%), the Boreal group (34 species – 2.85%), the Mediterranean group (31 species – 2.60%), the Macaronesian group (21 species – 1.76%), the Atlantic/African group (19 species – 1.60%) and the Mediterranean/African and the Arctic groups, each with only 1 species (0.08%). Regarding the preferences for vertical habitat, the demersal fishes are the most important group (305 species – 25.61%), followed by the mesopelagic group (228 species – 19.14%), the bathypelagic group (164 species – 13.77%), the benthopelagic group (147 species – 12.34%), the bathydemersal group (115 species – 9.66%), the reef-associated group (88 species – 7.39%), the pelagic group (74 species – 6.21%), the epipelagic group (58 species – 4.87%) and 1 species (0.08%) of the benthic group. The oceanic habitat is the best represented group comprising 446 species (37.45%), followed by the shelf group (199 species – 16.71%), the slope group (164 species – 13.77%), the inner shelf group (89 species – 7.47%), the coastal group (70 species – 5.88%), the outer shelf group (29 species – 2.43%) and the oceanic/shelf group (7 species – 0.59%).
Aru, Juhan ; Aru, Jaan ; Priesemann, Viola ; Wibral, Michael ; Lana, Luiz ; Pipa, Gordon ; Singer, Wolf ; Vicente, Raul
Cross-frequency coupling (CFC) has been proposed to coordinate neural dynamics across spatial and temporal scales. Despite its potential relevance for understanding healthy and pathological brain function, the standard CFC analysis and physiological interpretation come with fundamental problems. For example, apparent CFC can appear because of spectral correlations due to common non-stationarities that may arise in the total absence of interactions between neural frequency components. To provide a road map towards an improved mechanistic understanding of CFC, we organize the available and potential novel statistical/modeling approaches according to their biophysical interpretability. While we do not provide solutions for all the problems described, we provide a list of practical recommendations to avoid common errors and to enhance the interpretability of CFC analysis.
Ultrafast protein dynamics are of great interest for understanding the molecular basis of biochemical function. One method to study structural changes with highest time-resolution starting in the femtosecond regime is 2D-IR spectroscopy. However its application to investigate protein dynamics both with high temporal and spatial resolution is currently limited to few biological systems with intrinsic chromophores. Spectral congestion, the contribution of many similar oscillators to the same signals, makes it difficult to draw conclusions about local structural dynamics in most other proteins.
The aim of this thesis is to extend the application of 2D-IR spectroscopy to a wider range of proteins by introducing unnatural amino acids (UAAs) with azide or nitrile groups as site-specific vibrational probes, which absorb in the free spectral window between 1800 to 3000 cm-1 by using methods from chemical biology.
In a comparative experimental study using FTIR and 2D-IR spectroscopy of single amino acids azidohomoalanine (Aha), a methionine analogue, was identified as preferred label. To demonstrate the application potential of UAAs as site-specific probes, Aha was then incorporated into different positions in a small globular protein. By using both FTIR and ultrafast 2D-IR it was shown, that indeed the local microenvironment as well as conformational fluctuations on picosecond timescale could be monitored with high spatial information. The azide moiety shows a shift of its absorption frequency depending on the polarity of its surrounding. Using this approach, different subensembles for the protein conformations with more polar and less polar environment around the vibrational probe can be distinguished.
A second major application of site-specific labels is the study of vibrational energy transfer processes (VET), predicted to be relevant for allosteric communication in protein domains such as the PDZ domain. VET can be tracked with high spatial resolution using time-resolved IR spectroscopy by exciting a localized vibrational mode and probing separate modes in a two-colour 2D-IR experiment. To extend this kind of experiment to proteins, a specific donor-acceptor pair of two UAAs was introduced. It uses an azulene moiety as donor that can be excited in the visible range but deposits the excess energy by internal conversion into the vibrational modes of the ground state. In small peptides this VET pair was applied successfully, showing a distance-dependent energy transfer induced signal for VET through covalent bonds. These findings bare great promise for the direct observation of vibrational energy flow in proteins in real-time.
Overall this thesis is the basis for extending the usability of 2D-IR spectroscopy to study structural dynamics in a wide range of proteins systems both with high temporal and spatial resolution.
Understanding the diverging opinions of academic experts, stakeholders and the public is important for effective conservation management. This is especially so when a consensus is needed for action to minimize future risks but the knowledge upon which to base this action is uncertain or missing. How to manage non-native, invasive species (NIS) is an interesting case in point: the issue has long been controversial among stakeholders, but publicly visible, major disagreement among experts is recent. To characterize the multitude of experts’ understanding and valuation of non-native, NIS we performed structured qualitative interviews with 26 academic experts, 13 of whom were invasion biologists and 13 landscape experts. Within both groups, thinking varied widely, not only about basic concepts (e.g., non-native, invasive) but also about their valuation of effects of NIS. The divergent opinions among experts, regarding both the overall severity of the problem in Europe and its importance for ecosystem services, contrasted strongly with the apparent consensus that emerges from scientific synthesis articles and policy documents. We postulate that the observed heterogeneity of expert judgments is related to three major factors: (1) diverging conceptual understandings, (2) lack of empirical information and high scientific uncertainties due to complexities and contingencies of invasion processes, and (3) missing deliberation of values. Based on theory from science studies, we interpret the notion of an NIS as a boundary object, i.e., concepts that have a similar but not identical meaning to different groups of experts and stakeholders. This interpretative flexibility of a concept can facilitate interaction across diverse groups but bears the risk of introducing misunderstandings. An alternative to seeking consensus on exact definitions and risk assessments would be for invasive species experts to acknowledge uncertainties and engage transparently with stakeholders and the public in deliberations about conflicting opinions, taking the role of honest brokers of policy alternatives rather than of issue advocates.
In this thesis, Planck size black holes are discussed. Specifically, new families of black holes are presented. Such black holes exhibit an improved short scale behaviour and can be used to implement gravity self-complete paradigm. Such geometries are also studied within the ADD large extra dimensional scenario. This allows black hole remnant masses to reach the TeV scale. It is shown that the evaporation endpoint for this class of black holes is a cold stable remnant. One family of black holes considered in this thesis features a regular de Sitter core that counters gravitational collapse with a quantum outward pressure. The other family of black holes turns out to nicely fit into the holographic information bound on black holes, and lead to black hole area quantization and applications in the gravitational entropic force. As a result, gravity can be derived as emergent phenomenon from thermodynamics.
The thesis contains an overview about recent quantum gravity black hole approaches and concludes with the derivation of nonlocal operators that modify the Einstein equations to ultraviolet complete field equations.
Tynommatidae, n. stat., elevated from Tynommatinae, is established as a schizopetalidean family encompassing the western North American callipodidans previously assigned to the Mediterranean Schizopetalidae. It is considered a valid taxon despite somewhat anatomically dissimilar subfamilies, and Colactidinae, Texophoninae, Diactidinae, and Aspidiophoninae constitute tribal elevations and additional new statuses. With a subbasal telopodal prefemoral process, Diactis hedini, n. sp., requires rediagnoses of all three diactidine genera, Diactis Loomis, 1937, and Florea and Caliactis, both by Shelley, 1996, and suggests that telopodal branches ‘B’ in congeners and Florea represent distal relocations of the process along the stem. Similarities in the sizes and shapes of the pleurotergal carinae suggest a sister-group relationship with the other, and partly sympatric, New World family, Abacionidae, which is supported by gonopodal similarities between Colactidinae and Abacion Rafi nesque, 1820. The Western Interior Seaway of the Cretaceous Period, Mesozoic Era, ~141–66 million years ago, appears to have fueled divergence by isolating “proto-abacionid stock” in “Appalachia,” the Eastern North American land mass, which has subsequently spread well into previously inundated areas. The allopatric position of Texophoninae, on the Gulf Coast of south Texas around 1,136 km (710 mi) east of the most proximate familial records, is attributed to this waterway, which eradicated faunal linkages with “proto-Tynommatidae” in “Laramidia,” the Western North American land mass. Texophoninae probably survived the Cretaceous on insular refugia; however, it is rarely encountered anymore and seems destined for imminent extinction. Representatives of the east-Asian families, Caspiopetalidae, Paracortinidae, and Sinocallipodidae, also possess demarcated pleurotergal crests and, implausible though it seems, may share ancestry with the North American taxa vis-à-vis the “Asiamerica” and or “Boreotropic” concepts.
Examination of the type series of Schizotus gibbifrons Lewis 1887 and Pyrochroa higoniae Lewis 1895, together with examination of the historical Lewis collection of Pseudopyrochroa japonica (Heyden 1879), provide hints as to the conspecifi city of these binomials. This evidence, together with concurrent collection events spanning more than 100 years and general anatomy suggests Pseudopyrochroa japonica (Heyden 1879) and Pseudopyrochroa gibbifrons (Lewis 1887) are conspecifi c. Schizotus gibbifrons Lewis is proposed as a new junior synonym of Pyrochroa japonica Heyden, where it joins the established synonym, Pyrochroa higoniae Lewis (1895). Schizotus theresae Pic 1911 is also proposed as a new junior synonym of Pyrochroa basalis Pic 1906, where it joins a long list of synonyms. Complete synonymies are presented for both species.
Two new species of pselaphine staphylinids in the genus Batrisodes are described: B. (Declivodes) dorothae Ferro and Carlton from Feliciana Preserve, Louisiana; and B. (Babnormodes) spretoides Ferro and Carlton from Great Smoky Mountains National Park, Tennessee. They differ from all other described Batrisodes species in secondary male characters, especially details of the frontal region of the head. These two species bring the total diversity of the genus in North America to 88 species. Specimens were imaged using light microscopy, scanning electron microscopy, and X-ray microtomography (micro-CT) techniques. Utility of multiple imaging techniques, especially micro-CT, is discussed.
Two new species and a new genus of Cerambycidae are described from South America: Cotyclytus arriagadai sp. nov., from Bolivia; and Lembu dieguezi, gen. nov., sp. nov., from Paraguay. Orthomegas irroratus (Lameere, 1915) is redescribed, based on the second and third known specimens, and its distribution is expanded to include Ecuador. The male of Jamesia fuscofasciata Dillon and Dillon, 1952 is described and illustrated for the fi rst time, and the distribution of the species is expanded to Peru. Thirty-two new country records (twelve for Paraguay, fi fteen for Peru, two for Ecuador, three for Bolivia) and one new province record (Argentina) are presented.
This paper analyzes two contemporary, „third-generation“ perspectives within critical theory - Nancy Fraser’s and Axel Honneth’s - with the aim of examining the degree to which the two authors succeed in grounding the normative criteria of social critique in the perspectives of ’ordinary’ social actors, as opposed to speculative social theory. To that end, the author focuses on the influential debate between Fraser and Honneth Redistribution or Recognition? which concerns the appropriate normative foundations of a „post-metaphysical“ critical theory, and attempts to reconstruct the fundamental 29 disagreements between Fraser and Honneth over the meaning and tasks of critical theory. The author concludes that both critical theorists ultimately secure the normative foundations of critique through substantive theorizations of the social, which frame the two authors’ „reconstructions“ of the normativity of everyday social action, but argues that post-metaphysical critical theory does not have to abandon comprehensive social theory in order to be epistmologically „non-authoritarian“.
Tuning and optimization of the field distribution for 4-rod radio frequency quadrupole linacs
(2014)
In this thesis, the tuning process of the 4-rod Radio Frequency Quadrupole has been analyzed and a theory for the prediction of the tuning plate's influence on the longitudinal voltage distribution was developed together with RF design options for the optimization of the fringe fields.
The basic principles of the RFQ's particle dynamics and resonant behavior are introduced in the theory part of this thesis. All studies that are presented are based on the work on four RFQs of recent linac projects. These RFQs are described in one chapter. Here, the projects are introduced together with details about the RFQ parameters and performance. In the meantime two of these RFQs are in full operation at NSCL at MSU and FNAL. One is operating in the test phase of the MedAustron Cancer Therapy Center and the fourth one for LANL is about to be built. The longitudinal voltage distribution has been studied in detail with a focus on the influence of the RF design with tuning elements and parameters like the electrodes overlap or the distance between stems. The theory for simulation methods for the field flatness that were developed as part of this thesis, as well as its simulation with CST MWS have been analyzed and compared to measurements. The lumped circuit model has proven to predict results with an accuracy that can be used in the tuning process of 4-rod RFQs. Together with results from the tuning studies, the studies on the fringe fields of the 4-rod structure lead to a proposal for a 4-rod RFQ model with an improved field distribution in the transverse and longitudinal electric field.
Harter, Patrick Nikolaus ; Blank, Anna-Eva ; Weide, Benjamin ; Beschorner, Rudi ; Bernatz, Simon ; Baumgarten, Peter ; Braczynski, Anne Kristin ; Hattingen, Elke ; Ronellenfitsch, Michael Wilfried ; Schwarz, Herbert ; Mittelbronn, Michel Guy André
Aim: The cytokine receptor tumor necrosis factor receptor superfamily member 9 (TNFRSF9) is mainly considered to be a co-stimulatory activation marker in hematopoietic cells. Several preclinical models have shown a dramatic beneficial effect of treatment approaches targeting TNFRSF9 with agonistic antibodies. However, preliminary clinical phase I/II studies were stopped after the occurrence of several severe deleterious side effects. In a previous study, it was demonstrated that TNFRSF9 was strongly expressed by reactive astrocytes in primary central nervous system (CNS) tumors, but was largely absent from tumor or inflammatory cells. The aim of the present study was to address the cellular source of TNFRSF9 expression in the setting of human melanoma brain metastasis, a highly immunogenic tumor with a prominent tropism to the CNS.
Methods: Melanoma brain metastasis was analyzed in a cohort of 78 patients by immunohistochemistry for TNFRSF9 and its expression was correlated with clinicopathological parameters including sex, age, survival, tumor size, number of tumor spots, and BRAF V600E expression status.
Results: Tumor necrosis factor receptor superfamily member 9 was frequently expressed independently on both melanoma and endothelial cells. In addition, TNFRSF9 was also present on smooth muscle cells of larger vessels and on a subset of lymphomonocytic tumor infiltrates. No association between TNFRSF9 expression and patient survival or other clinicopathological parameters was seen. Of note, several cases showed a gradual increase in TNFRSF9 expression on tumor cells with increasing distance from blood vessels, an observation that might be linked to hypoxia-driven TNFRSF9 expression in tumor cells.
Conclusion: The findings indicate that the cellular source of TNFRSF9 in melanoma brain metastasis largely exceeds the lymphomonocytic pool, and therefore further careful (re-) assessment of potential TNFRSF9 functions in cell types other than hematopoietic cells is needed. Furthermore, the hypothesis of hypoxia-driven TNFRSF9 expression in brain metastasis melanoma cells requires further functional testing.