julilili42/papers huggingface dataset:
Did climate determine Late Pleistocene settlement dynamics in the Ach Valley, SW Germany?
2019-05-02

The loss of Neanderthal groups across Western and Central Europe during Oxygen Isotope Stage (OIS) 3 has held the attention of archaeologists for decades. The role that climatic change, genetic interbreeding, and interspecies competition played in the extinction of Neanderthal groups is still debated. Hohle Fels is one of several important Middle and Upper Paleolithic sites from the Ach Valley in southwestern Germany which documents the presence of Neanderthals and modern humans in the region. Chronological and stratigraphic records indicate that these two groups occupied the site with little to no overlap or interaction. This provides the opportunity to examine the behavioural variability of Swabian Neanderthal populations without the complication of cross-cultural influence. In this study we contribute a terrestrial paleoenvironmental record derived from the small mammal material from Hohle Fels Cave to the ever-growing archaeological record of this period. By reconstructing the climate and landscape of the Ach Valley during this time we can identify the effect that the OIS 3 environment had on the presence of Neanderthals in the region. Based on indicator taxa and the habitat weighing method, the small mammal record, which includes rodents, insectivores, and bats, from Hohle Fels shows that the earliest Neanderthal occupation took place on a landscape characterized by substantial woodland and forest, rivers and ponds, as well as moist meadows and grasslands. A gradual increase in cold tundra and arctic environments is clear towards the end of the Middle Paleolithic, extending to the end of the early Aurignacian which may correlate with the onset of the Heinrich 4 event (~42,000 kya). Our taphonomic analysis indicates the material was accumulated primarily by opportunistic predators such as the great grey owl, snowy owl, and European eagle owl, and therefore reflects the diversity of landscapes present around the site in the past. Importantly, at the time Neanderthals abandoned the Ach Valley we find no indication for dramatic climatic deterioration. Rather, we find evidence of a gradual cooling of the Swabian landscape which may have pushed Neanderthal groups out of the Ach Valley prior to the arrival of modern human Aurignacian groups.
Choice of link and variance function for generalized linear mixed models: a case study with binomial response in proteomics
2019-05-02

Non-normality is a common phenomenon in data from agricultural and biological research, especially in molecular data (for example; -omics, RNAseq, flow cytometric data, etc.). For over half a century, the leading paradigm called for using analysis of variance (ANOVA) after applying a data transformation. The introduction of generalized linear mixed models (GLMM) provides a new way of analyzing non-normal data. Selecting an apt link function in GLMM can be quite influential, however, and is as critical as selecting an appropriate transformation for ANOVA. In this paper, we assess the performance of different parametric link families available in literature. Then, we propose a new estimation method for selecting an appropriate link function with a suitable variance function in a quasi-likelihood framework. We apply these methods to a proteomics data set, showing that GLMMs provide a very flexible framework for analyzing these kinds of data.
Lying, Denying, or Justifying?
2019-05-02

In Tunisia under Ben Ali (1987–2011), marked human rights rhetoric coincided with intense repression. This points to a more general puzzle: what happens when authoritarian regimes uphold their repressive power maintenance agendas while simultaneously trying to avoid negative international consequences? This article argues that authoritarian decision-makers attempt to evade negative consequences from international audiences by applying cushioning strategies in the form of obfuscation, rhetorical justification and/or procedural justification. In that way, they adapt their repressive tactics and manipulate the visibility and perception of their repressive behavior. Ben Ali’s main strategy was to obfuscate, i.e. to deny and cover repression. However, as international audiences are far from applying the same yardstick to all human rights violations, ruling elites often repress targets differently depending on whether audiences have links and sympathy. Again, this becomes apparent in the Tunisian case study, from which hypotheses are generated for future research.
Intrinsically aggregation-prone proteins form amyloid-like aggregates and contribute to tissue aging in Caenorhabditis elegans
2019-05-03

Reduced protein homeostasis leading to increased protein instability is a common molecular feature of aging, but it remains unclear whether this is a cause or consequence of the aging process. In neurodegenerative diseases and other amyloidoses, specific proteins self-assemble into amyloid fibrils and accumulate as pathological aggregates in different tissues. More recently, widespread protein aggregation has been described during normal aging. Until now, an extensive characterization of the nature of age-dependent protein aggregation has been lacking. Here, we show that age-dependent aggregates are rapidly formed by newly synthesized proteins and have an amyloid-like structure resembling that of protein aggregates observed in disease. We then demonstrate that age-dependent protein aggregation accelerates the functional decline of different tissues in C. elegans. Together, these findings imply that amyloid-like aggregates contribute to the aging process and therefore could be important targets for strategies designed to maintain physiological functions in the late stages of life.
Efficient Ytterbium Near-Infrared Luminophore Based on a Nondeuterated Ligand
2019-05-03

A novel molecular ytterbium complex is reported with a new tetradentate ligand based on the 2,2'-bipyridine-6,6'-dicarboxylic acid scaffold. The photophysical properties are investigated, especially with respect to near-infrared luminescence. The ytterbium complex shows a rather high absolute luminescence quantum yield of Φ = 3.0% and a luminescence lifetime of τ<sub>obs</sub> = 72 μs at room temperature in CD<sub>3</sub>OD solution.
Effects of climate change and horticultural use on the spread of naturalized alien garden plants in Europe
2019-05-03

Climate warming is supposed to enlarge the area climatically suitable to the naturalization of alien garden plants in temperate regions. However, the effects of a changing climate on the spread of naturalized ornamentals have not been evaluated by spatially and temporarily explicit range modelling at larger scales so far. Here, we assess how climate change and the frequency of cultivation interactively determine the spread of 15 ornamental plants over the 21st century in Europe. We coupled species distribution modelling with simulations of demography and dispersal to predict range dynamics of these species in annual steps across a 250 × 250 m raster of the study area. Models were run under four scenarios of climate warming and six levels of cultivation intensity. Cultivation frequency was implemented as size of the area used for planting a species. Although the area climatically suitable to the 15 species increases, on average, the area predicted to be occupied by them in 2090 shrinks under two of the three climate change scenarios. This contradiction obviously arises from dispersal limitations that were pronounced although we assumed that cultivation is spatially adapting to the changing climate. Cultivation frequency had a much stronger effect on species spread than climate change, and this effect was non‐linear. The area occupied increased sharply from low to moderate levels of cultivation intensity, but levelled off afterwards. Our simulations suggest that climate warming will not necessarily foster the spread of alien garden plants in Europe over the next decades. However, climatically suitable areas do increase and hence an invasion debt is likely accumulating. Restricting cultivation of species can be effective in preventing species spread, irrespective of how the climate develops. However, for being successful, they depend on high levels of compliance to keep propagule pressure at a low level.
No Association of Variants of the NPY-System With Obsessive-Compulsive Disorder in Children and Adolescents
2019-05-03

Obsessive-compulsive disorder (OCD) causes severe distress and is therefore counted by the World Health Organisation (WHO) as one of the 10 most impairing illnesses. There is evidence for a strong genetic underpinning especially in early onset OCD (eoOCD). Though several genes involved in neurotransmission have been reported as candidates, there is still a need to identify new pathways. In this study, we focussed on genetic variants of the Neuropeptide Y (NPY) system. NPY is one of the most abundant neuropeptides in the human brain with emerging evidence of capacity to modulate stress response, which is of high relevance in OCD. We focussed on tag-SNPs of NPY and its receptor gene NPY1R in a family-based approach. The sample comprised 86 patients (children and adolescents) with eoOCD with both their biological parents. However, this first study on genetic variants of the NPY-system could not confirm the association between the investigated SNPs and eoOCD. Based on the small sample size results have to be interpreted as preliminary and should be replicated in larger samples. However, also in an additional GWAS analysis in a large sample, we could not observe an associations between NPY and OCD. Overall, these preliminary results point to a minor role of NPY on the stress response of OCD.
Efficient small-world and scale-free functional brain networks at rest using k-nearest neighbors thresholding
2019-05-05

Abstract In recent years, there has been a massive effort to analyze the topological properties of brain networks. Yet, one of the challenging questions in the field is how to construct brain networks based on the connectivity values derived from neuroimaging methods. From a theoretical point of view, it is plausible that the brain would have evolved to minimize energetic costs of information processing, and therefore, maximizes efficiency as well as to redirect its function in an adaptive fashion, that is, resilience. A brain network with such features, when characterized using graph analysis, would present small-world and scale-free properties. In this paper, we focused on how the brain network is constructed by introducing and testing an alternative method: k-nearest neighbor (kNN). In addition, we compared the kNN method with one of the most common methods in neuroscience: namely the density threshold. We performed our analyses on functional connectivity matrices derived from resting state fMRI of a big imaging cohort (N=434) of young and older healthy participants. The topology of networks was characterized by the graph measures degree, characteristic path length, clustering coefficient and small world. In addition, we verified whether kNN produces scale-free networks. We showed that networks built by kNN presented advantages over traditional thresholding methods, namely greater values for small-world (linked to efficiency of networks) than those derived by means of density thresholds and moreover, it presented also scale-free properties (linked to the resilience of networks), where density threshold did not. A brain network with such properties would have advantages in terms of efficiency, rapid adaptive reconfiguration and resilience, features of brain networks that are relevant for plasticity and cognition as well as neurological diseases as stroke and dementia. Highlights A novel thresholding method for brain networks based on k-nearest neighbors (kNN) kNN applied on resting state fMRI from a big cohort of healthy subjects BASE-II kNN built networks present greater small world properties than density threshold kNN built networks present scale-free properties whereas density threshold did not
Inhibiting pathologically active ADAM10 rescues synaptic and cognitive decline in Huntington’s disease
2019-05-06

A disintegrine and metalloproteinase 10 (ADAM10) is implicated in synaptic function through its interaction with postsynaptic receptors and adhesion molecules. Here, we report that levels of active ADAM10 are increased in Huntington's disease (HD) mouse cortices and striata and in human postmortem caudate. We show that, in the presence of polyglutamine-expanded (polyQ-expanded) huntingtin (HTT), ADAM10 accumulates at the postsynaptic densities (PSDs) and causes excessive cleavage of the synaptic protein N-cadherin (N-CAD). This aberrant phenotype is also detected in neurons from HD patients where it can be reverted by selective silencing of mutant HTT. Consistently, ex vivo delivery of an ADAM10 synthetic inhibitor reduces N-CAD proteolysis and corrects electrophysiological alterations in striatal medium-sized spiny neurons (MSNs) of 2 HD mouse models. Moreover, we show that heterozygous conditional deletion of ADAM10 or delivery of a competitive TAT-Pro-ADAM10709-729 peptide in R6/2 mice prevents N-CAD proteolysis and ameliorates cognitive deficits in the mice. Reduction in synapse loss was also found in R6/2 mice conditionally deleted for ADAM10. Taken together, these results point to a detrimental role of hyperactive ADAM10 at the HD synapse and provide preclinical evidence of the therapeutic potential of ADAM10 inhibition in HD.
Synthetic Lugdunin Analogues Reveal Essential Structural Motifs for Antimicrobial Action and Proton Translocation Capability
2019-05-06

Abstract Lugdunin, a novel thiazolidine cyclopeptide, exhibits micromolar activity against methicillin‐resistant Staphylococcus aureus (MRSA). For structure–activity relationship (SAR) studies, synthetic analogues obtained from alanine and stereo scanning as well as peptides with modified thiazolidine rings were tested for antimicrobial activity. The thiazolidine ring and the alternating d ‐ and l ‐amino acid backbone are essential. Notably, the non‐natural enantiomer displays equal activity, thus indicating the absence of a chiral target. The antibacterial activity strongly correlates with dissipation of the membrane potential in S. aureus. Lugdunin equalizes pH gradients in artificial membrane vesicles, thereby maintaining membrane integrity, which demonstrates that proton translocation is the mode of action (MoA). The incorporation of extra tryptophan or propargyl moieties further expands the diversity of this class of thiazolidine cyclopeptides.
Functionalized gold nanoparticles for sample preparation: A review
2019-05-06

Abstract Sample preparation is a crucial step for the reliable and accurate analysis of both small molecule and biopolymers which often involves processes such as isolation, pre‐concentration, removal of interferences (purification), and pre‐processing (e.g., enzymatic digestion) of targets from a complex matrix. Gold nanoparticle (GNP)‐assisted sample preparation and pre‐concentration has been extensively applied in many analytical procedures in recent years due to the favorable and unique properties of GNPs such as size‐controlled synthesis, large surface‐to‐volume ratio, surface inertness, straightforward surface modification, easy separation requiring minimal manipulation of samples. This review article primarily focuses on applications of GNPs in sample preparation, in particular for bioaffinity capture and biocatalysis. In addition, their most common synthesis, surface modification and characterization methods are briefly summarized. Proper surface modification for GNPs designed in accordance to their target application directly influence their functionalities, e.g., extraction efficiencies, and catalytic efficiencies. Characterization of GNPs after synthesis and modification is worthwhile for monitoring and controlling the fabrication process to ensure proper quality and functionality. Parameters such as morphology, colloidal stability, and physical/chemical properties can be assessed by methods such as surface plasmon resonance, dynamic light scattering, ζ‐potential determinations, transmission electron microscopy, Taylor dispersion analysis, and resonant mass measurement, among others. The accurate determination of the surface coverage appears to be also mandatory for the quality control of functionality of the nanoparticles. Some promising applications of (functionalized) GNPs for bioanalysis and sample preparation are described herein.
Evidence for Magma–Wall Rock Interaction in Carbonatites from the Kaiserstuhl Volcanic Complex (Southwest Germany)
2019-05-06

Abstract The mineralogy and mineral chemistry of the four major sövite bodies (Badberg, Degenmatt, Haselschacher Buck and Orberg), calcite foidolite/nosean syenite xenoliths (enclosed in the Badberg sövite only) and rare extrusive carbonatites of the Kaiserstuhl Volcanic Complex in Southern Germany provide evidence for contamination processes in the carbonatitic magma system of the Kaiserstuhl. Based on textures and composition, garnet and clinopyroxene in extrusive carbonatites represent xenocrysts entrained from the associated silicate rocks. In contrast, forsterite, monticellite and mica in sövites from Degenmatt, Haselschacher Buck and Orberg probably crystallized from the carbonatitic magma. Clinopyroxene and abundant mica crystallization in the Badberg sövite, however, was induced by the interaction between calcite foidolite xenoliths and the carbonatite melt. Apatite and micas in the various sövite bodies reveal clear compositional differences: apatite from Badberg is higher in REE, Si and Sr than apatite from the other sövite bodies. Mica from Badberg is biotite- and comparatively Fe2+-rich (Mg# = 72–88). Mica from the other sövites, however, is phlogopite (Mg# up to 97), as is typical of carbonatites in general. The typical enrichment of Ba due to the kinoshitalite substitution is observed in all sövites, although it is subordinate in the Badberg samples. Instead, Badberg biotites are strongly enriched in IVAl (eastonite substitution) which is less important in the other sövites. The compositional variations of apatite and mica within and between the different sövite bodies reflect the combined effects of fractional crystallization and carbonatite-wall rock interaction during emplacement. The latter process is especially important for the Badberg sövites, where metasomatic interaction released significant amounts of K, Fe, Ti, Al and Si from earlier crystallized nosean syenites. This resulted in a number of mineral reactions that transformed these rocks into calcite foidolites. Moreover, this triggered the crystallization of compositionally distinct mica and clinopyroxene crystals around the xenoliths and within the Badberg sövite itself. Thus, the presence and composition of clinopyroxene and mica in carbonatites may be useful indicators for contamination processes during their emplacement. Moreover, the local increase of silica activity during contamination enabled strong REE enrichment in apatite via a coupled substitution involving Si, which demonstrates the influence of contamination on REE mineralization in carbonatites.
Are skin senescence and immunosenescence linked within individuals?
2019-05-06

Abstract With advancing age, many organs exhibit functional deterioration. The age‐associated accumulation of senescent cells is believed to represent one factor contributing to this phenomenon. While senescent cells are found in several different organ systems, it is not known whether they arise independently in each organ system or whether their prevalence within an individual reflects that individual's intrinsic aging process. To address this question, we studied senescence in two different organ systems in humans, namely skin and T cells in 80 middle‐aged and older individuals from the Leiden Longevity Study. Epidermal p16INK4a positivity was associated with neither CD4 + nor CD8 + T‐cell immunosenescence phenotype composites (i.e., end‐stage differentiated/senescent T cells, including CD45RA + CCR7 ‐ CD28 ‐ CD27 ‐ CD57 + KLRG1 + T cells). Dermal p16INK4a positivity was significantly associated with the CD4 + , but not with the CD8 + immunosenescence composite. We therefore conclude that there is limited evidence for a link between skin senescence and immunosenescence within individuals.
Estonian case inflection made simple. A case study in Word and Paradigm morphology with Linear Discriminative Learning.
2019-05-06

According to Word and Paradigm Morphology (Matthews, 1974; Blevins, 2016), the word is the basic cognitive unit over which paradigmatic analogy operates to predict form and meaning of novel forms. Baayen et al. (2019b, 2018) introduced a computational formalization of word and paradigm morphology which makes it possible to model the production and comprehension of complex words without requiring exponents, morphemes, inflectional classes, and separate treatment of regular and irregular morphology. This computational model, Linear Discriminative Learning (LDL), makes use of simple matrix algebra to move from words’ forms to meanings (comprehension) and from words’ meanings to their forms (production). In Baayen et al. (2018), we showed that LDL makes accurate predictions for Latin verb conjugations. The present study reports results for noun declension in Estonian. Consistent with previous findings, the model’s predictions for comprehension and production are highly accurate. Importantly, the model achieves this high accuracy without being informed about stems, exponents, and inflectional classes. The speech errors produced by the model look like errors that native speakers might make. When the model is trained on incomplete paradigms, comprehension accuracy for unseen forms is hardly affected, but production accuracy decreases, reflecting the well-known asymmetry between comprehension and production. Unseen principal parts (i.e., nominative, genitive, and partitive singulars) are particularly difficult to produce, possibly due to their more distinctive forms. Removing principal parts from training, however, does not affect accuracy for other case forms. Model performance does not degrade either when the training data includes the alternative forms that are ubiquitous in Estonian. These results are consistent with the claim of Blevins (2008) that Estonian number and case inflection is organized in a way that facilitates the deduction of full paradigms from only a small number of forms.
Mutation spectrum and clinical investigation of achromatopsia patients with mutations in the GNAT2 gene
2019-05-06

Achromatopsia (ACHM) is a hereditary cone photoreceptor disorder characterized by the inability to discriminate colors, nystagmus, photophobia, and low-visual acuity. Six genes have been associated with this rare autosomal recessively inherited disease, including the GNAT2 gene encoding the catalytic α-subunit of the G-protein transducin which is expressed in the cone photoreceptor outer segment. Out of a cohort of 1,116 independent families diagnosed with a primary clinical diagnosis of ACHM, we identified 23 patients with ACHM from 19 independent families with likely causative mutations in GNAT2, representing 1.7% of our large ACHM cohort. In total 22 different potentially disease-causing variants, of which 12 are novel, were identified. The mutation spectrum also includes a novel copy number variation, a heterozygous duplication of exon 4, of which the breakpoint matches exactly that of the previously reported exon 4 deletion. Two patients carry just a single heterozygous variant. In addition to our previous study on GNAT2-ACHM, we also present detailed clinical data of these patients.