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The amyloid precursor protein (APP) was discovered in the 1980s as the precursor protein of the amyloid A4 peptide. The amyloid A4 peptide, also known as A-beta (Aβ), is the main constituent of senile plaques implicated in Alzheimer’s disease (AD). In association with the amyloid deposits, increasing impairments in learning and memory as well as the degeneration of neurons especially in the hippocampus formation are hallmarks of the pathogenesis of AD. Within the last decades much effort has been expended into understanding the pathogenesis of AD. However, little is known about the physiological role of APP within the central nervous system (CNS). Allocating APP to the proteome of the highly dynamic presynaptic active zone (PAZ) identified APP as a novel player within this neuronal communication and signaling network. The analysis of the hippocampal PAZ proteome derived from APP-mutant mice demonstrates that APP is tightly embedded in the underlying protein network. Strikingly, APP deletion accounts for major dysregulation within the PAZ proteome network. Ca2+-homeostasis, neurotransmitter release and mitochondrial function are affected and resemble the outcome during the pathogenesis of AD. The observed changes in protein abundance that occur in the absence of APP as well as in AD suggest that APP is a structural and functional regulator within the hippocampal PAZ proteome. Within this review article, we intend to introduce APP as an important player within the hippocampal PAZ proteome and to outline the impact of APP deletion on individual PAZ proteome subcommunities.
Background: Infection is a main cause of morbidity and mortality after heart surgery, with multi-resistant pathogens increasingly representing a challenge. Daptomycin provides bactericidal activity against gram-positive organisms that are resistant to standard treatment including vancomycin.
Methods: A cohort of cardiac surgical patients, treated with daptomycin for major infection at two tertiary care centers, were retrospectively studied with a particular focus on the type of infection, causative pathogens and co-infections, daptomycin dosage, adverse events and outcome in order to provide evidence for the efficiency and safety of daptomycin in a distinct high-risk patient population.
Results: Sixty-five patients (87.7 % males, 60.4 ± 13.5 years) who had undergone aortic surgery (20.0 %), ventricular assist device (VAD) implantation (21.5 %), combined procedures (21.5 %), coronary artery bypass grafting (12.3 %), isolated valve surgery (15.4 %) and heart transplantation (7.7 %) were diagnosed with catheter-related infection (26.1 %), valve endocarditis (18.8 %), sternal wound (13.0 %), VAD-associated (11.6 %), cardiac implantable electrophysiological device (CIED)-associated (4.1 %), respiratory tract (4.3 %), bloodstream (4.3 %) and other infection (4.3 %). In 13.0 %, no focus of infection was identified though symptoms of severe infection were present. The most frequent pathogens were Staphylococcus epidermidis (30.4 %), Staphylococcus aureus (23.1 %) and Enterococcus species (10.1 %). Daptomycin doses ranging from 3 mg/kg every 48 h to 10 mg/kg every 24 h were administered for 15.4 ± 11.8 days. 87.0 % of the cases were classified as success, 7.2 % as treatment failure and 5.8 as non-evaluable. Adverse events were limited to one case of mild and one case of moderate neutropenia with recovery upon termination of treatment.
Conclusion: Daptomycin proved safe and effective in major infection in high-risk cardiac surgical patients.
A small collection of Odonata from Nuku Hiva Island, Marquesas Islands is presented. It adds Anax guttatus as a new species to this oceanic group. Hemicordulia sp. nov. is reported, but not described because the same species has been sampled before and is pending a formal description. A short taxonomic discussion on observed morphological similarity of male anal appendages in taxa presently assigned to Amorphostigma, Hivaagrion and Ischnura east of New Caledonia is provided. Important considerations for biogeography of the Pacific Odonata are discussed too.
New data on Odonata of the Guadalcanal Island, Solomon Islands are provided following a recently completed Rapid Biodiversity Assessment of the Tetena Haiaja ridge. Two new species, Lieftinckia ulunorum and Procordulia valevahalo are described.
The first is a new member of the Solomon Islands endemic genus while the second is a new genus for the country and the second validated species from the Corduliidae family known from this Pacific archipelago. As L. ulunorum is found to be very closely related to formerly known L. lairdi Lieftinck, 1963, which was also collected during the field trip, both are described in detail based on mature adults and teneral specimens. Comparison with L. salomonis Kimmins, 1957 (investigated only from figures published in the original species description) and Salomoncnemis gerdae Lieftinck, 1987 (also sampled during this study) were provided as well.
Additional morphological data is given on the following species: Teinobasis bradleyi Kimmins, 1957, female is illustrated here for the first time; Anax sp. cf. gibbosulus, second record of the genus for the country and Gynacantha amphora Marinov & Theischinger, 2012, originally described by a single male, here the description of the female is provided.
All other species collected during the field trip will be published separately in the final expedition report.
The results of a short collecting trip to Perlis in the northwest
of Peninsular Malaysia are reported. Eighty three species were collected, at least 61 of these are new records for the state, and three species are recorded from Malaysia for the first time: Euphaea
masoni Selys, 1879, Archibasis oscillans (Selys, 1877) and Paracercion calamorum (Ris, 1916). A checklist of the Odonata recorded from Perlis is given in an appendix.
This PhD thesis has been carried out within an interdisciplinary cooperational project between the Deutsches Bergbau-Museum Bochum and the Goethe-Universität Frankfurt, which is dedicated to ancient Pb-Ag mining and metal production in the hinterland of the municipium Ulpiana in central Kosovo. Geochemical analysis (OM, XRD, EMP, MC-ICP-MS) of ores, metallurgical (by-) products and metal artefacts allowed to reconstruct the local chaîne opératoire and to decipher significant chronological differences between presumably Roman/late antique and medieval/early modern metallurgical processing. Pb isotope provenance studies documented the relevance of local metal production within the Roman Empire and confirmed the actual existence of a Metalla Dardanica district, which until now solely has been suspected on basis of epigraphy.
The predominant abundance of the by-products matte (Cu, Pb, Fe and Zn sulphides) and speiss (ferrous speiss: Fe-As compounds; base metal speiss: ~(Cu,Ni,Fe,Ag )x(Sb,Sn,As )y ) at smelting sites with a preliminary Roman/late antique dating points to treatment of complex polymetallic ore. Pb isotope analysis demonstrated that the mining district of Shashkoc-Janjevo (partially) supplied six of the ten investigated metallurgical sites. In this mineralisation, parageneses with elevated Cu, As and Sb abundances comprise significant proportions of particularly tennantite-tetrahedrite minerals, chalcopyrite, arsenopyrite and were generated during the early and main stages of ore formation. Later precipitated ore in contrast is marked by a significantly less versatile mineralogy and consists almost exclusively of galena, sphalerite and pyrite/marcasite. Besides increased Cu, As and Sb contents, ore from the main formation stage also exhibits generally higher Ag abundances, which are mainly hosted by fahlore and locally abundant secondary Cu sulphides (chalcocite, digenite and covellite) and oxidised phases (e.g. malachite, azurite). The higher precious metal grades of this ore type, whose geochemical signature (i.e. higher proportions of Cu, As and Sb) is mirrored by the abundance of the metallurgical by-products matte and speiss (almost exclusively found at potentially Roman/late antique smelting sites; see above), presumably were a pivotal factor leading to its preferential exploitation in earlier times. Matte and base metal-rich speiss contain notable amounts of Ag, which are mainly present in Cu-(Fe) sulphides and particularly antimonides ((Cu,Ni)2Sb, Ag3Sb), respectively. While the speiss compounds due to their close association with Pb bullion presumably were cupelled automatically, the metallurgical treatment of matte could not have been proven unambiguously, but overall certainly is highly likely.
The beneficiated ore (i.e. crushed and sorted, potentially also treated by more lavish techniques such as grinding, sieving or wet-mechanical methods) possibly was partially roasted and subsequently together with fluxes and charcoal submitted to the furnaces. The working temperatures approximately ranged between 1100 and 1400 °C. Slags from all presumably Roman/late antique dated and few of their potentially medieval/early modern analogues were produced from smelting of (partially roasted) ore with charcoal and added siliceous material, thus resulting in fayalite-dominant phase assemblages or rarely observed glassy parageneses. Even though several subtypes of fayalite slags have been established on basis of the abundance of Fe-rich oxide phases (i.e. spinel ss and wüstite), late clinopyroxene and the general solidification sequence of the slags, the process conditions (i.e. temperature, fO2, added fluxing agents) must have been widely similar; chemical variations could be explained by varying degrees of interaction of the slag melt with charcoal ash and furnace material. The other investigated metallurgical remains indicate employment of a calcareous flux, which led to formation of Ca-rich olivine-, olivine+clinopyroxene-, clinopyroxene- or melilite-type slags. These types as well as glassy slags were generated at more oxidising conditions outside the fayalite stability field (FMQ buffer equilibrium, cf. Lindsley, 1976) than their olivine-dominant analogues. Conclusions on the furnace construction could be drawn on basis of the typology of the slags, which mostly were tapped into a basin located outside the furnace, but partially (at two presumably medieval/early modern sites) also accumulated in a reservoir within the smelter.
Lead artefacts excavated in Ulpiana could be isotopically related to ores from mineralisations in its vicinity and demonstrate that the resources were at least utilised for local metal production. However, also ship wreck cargo from Israel - including several lead ingots with the inscription 'MET DARD' (Raban, 1999) - and late antique lead-glazed pottery from Serbia and Romania (Walton & Tite, 2010) could be related to a possible Kosovarian/Serbian provenance of the raw material and thus indicate flourishing trade of metal from the Metalla Dardanica district within the Roman Empire.
References:
Lindsley, D. H. (1976). Experimental studies of oxide minerals. In D. Rumble, III (Hrsg.), Oxide minerals (61-88). Reviews in Mineralogy, Volume 3. Washington, DC: Mineralogical Society of America.
Raban, A. (1999). The lead ingots from the wreck site (area K8). Journal of Roman Archaeology, Supplementary Series, 35, 179-188.
Walton, M. S., & Tite, M. S. (2010). Production technology of Roman lead-glazed pottery and its continuance into late antiquity. Archaeometry, 52(5), 733-759.
Records of Odonata collected in the vicinity of the Borneo Highlands Resort on Gunung Penrissen in south western Sarawak in the period 2014-2016 are presented.
Notable records include new species of Telosticta Dow & Orr, 2012, Rhinocypha Rambur, 1842 and Leptogomphus Selys, 1878, as well as the first record of the recently described genus Borneogomphus Karube & Sasamoto, 2014 from Sarawak.
We compare the cost effectiveness of two pronatalist policies:
(a) child allowances; and
(b) daycare subsidies.
We pay special attention to estimating how intended fertility (fertility before children are born) responds to these policies. We use two evaluation tools:
(i) a dynamic model on fertility, labor supply, outsourced childcare time, parental time, asset accumulation and consumption; and
(ii) randomized vignette-survey policy experiments.
We implement both tools in the United States and Germany, finding consistent evidence that daycare subsidies are more cost effective. Nevertheless, the required public expenditure to increase fertility to the replacement level might be viewed as prohibitively high.
We extend the classical ”martingale-plus-noise” model for high-frequency prices by an error correction mechanism originating from prevailing mispricing. The speed of price reversal is a natural measure for informational efficiency. The strength of the price reversal relative to the signal-to-noise ratio determines the signs of the return serial correlation and the bias in standard realized variance estimates. We derive the model’s properties and locally estimate it based on mid-quote returns of the NASDAQ 100 constituents. There is evidence of mildly persistent local regimes of positive and negative serial correlation, arising from lagged feedback effects and sluggish price adjustments. The model performance is decidedly superior to existing stylized microstructure models. Finally, we document intraday periodicities in the speed of price reversion and noise-to-signal ratios.