julilili42/papers huggingface dataset:
Profiling Cisplatin Resistance in Head and Neck Cancer: A Critical Role of the VRAC Ion Channel for Chemoresistance
2021-09-27

Treatment success of head and neck cancers (HNSCC) is often hindered by tumor relapses due to therapy resistances. This study aimed at profiling cisplatin resistance mechanisms and identifying biomarkers potentially suitable as drug targets and for patient stratification. Bioinformatic analyses of suggested resistance factors in a cohort of 565 HNSCC patients identified the VRAC ion channel as a clinically relevant indicator for recurrent diseases following radiochemotherapy (p = 0.042). Other drug import/export transporters, such as CTR1, OCT1, or MRP1, were found to be less relevant. To experimentally verify VRAC’s critical role for cisplatin resistance, we used CRISPR/Cas9 knockout resulting in cisplatin-resistant HNSCC cells, which could be resensitized by VRAC expression. Next-generation sequencing further underlined VRAC’s importance and identified VRAC-regulated signaling networks, potentially also contributing to cisplatin resistance. CTR1, OCT1, or MRP1 did not contribute to increased cisplatin resistance. In addition to two-dimensional HNSCC models, three-dimensional tumor spheroid cultures confirmed VRAC’s unique role for cisplatin sensitivity. Here, resistance correlated with DNA damage and downstream apoptosis. The cisplatin specificity of the identified VRAC pathway was verified by testing paclitaxel and doxorubicin. Our results were independently confirmed in naturally occurring, cisplatin-resistant HNSCC cancer cell models. Collectively, we here demonstrate VRAC’s role for cisplatin resistance in HNSCC and its relevance as a potential drug target and/or prognostic biomarker for chemotherapy resistance.
Screening ofAzadirachta indicaphytoconstituents as GSK-3β inhibitor and its implication in neuroblastoma: molecular docking, molecular dynamics, MM-PBSA binding energy, and in-vitro study
2021-09-27

Glycogen synthase kinase-3 (GSK-3), a constitutively active serine/threonine kinase, primary regulator of various cellular activities varying from glycogen metabolism to cell proliferation and regulation. GSK-3β is associated with the pathogenesis of numerous human diseases, including cancer, metabolic disorder, and Alzheimer's disease. In this study, <i>Azadirachta indica</i> compounds were selected and further screened on the BOILED-Egg model. The compounds showing good GIT absorption were docked with the crystal structure of GSK-3β. The compounds with high docking score were submitted for the molecular dynamic simulation (MDS) and Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA). Based upon the MDS and MM-PBSA study, gedunin showed the highest binding energy throughout the MDS process. Gedunin was isolated from the <i>Azadirachta indica</i>, and its efficacy on GSK-3β inhibition was studied in the human neuroblastoma (SH-SY5Y) cells. Gedunin induced apoptosis and anti-proliferative activity by arresting G2/M phase, as evident by cell-cycle analysis. From immunoblot study, gedunin significantly enhanced the expression of an inhibitory form of GSK-3β (p-GSK-3β Ser9) in concentration-dependent manner. Our findings demonstrate that gedunin may act as an effective GSK-3β inhibitor suggesting that this compound may be used for the management of neuroblastoma. Further preclinical and clinical investigation is desirable.Communicated by Ramaswamy H. Sarma.
Comparing individuals buried in flexed and extended positions at the Greek colony of Chersonesos (Crimea) using cranial metric, dental metric, and dental nonmetric traits
2021-09-27

Abstract The Greek colony of Chersonesos was founded in the 5th century BC on the coast of the Crimean Peninsula in the northern Black Sea region. Extensive archeological research has investigated the timing and mode of the Greek land seizure and the responses of the local Taurian tribes, focusing on a large necropolis dating to the earliest period of the colony, somewhere between the 5th and the 4th century BC. Relying on burial traditions as an indicator of the biogeographic origin of the deceased, it was hypothesized that individuals buried in flexed positions were Taurian whereas individuals buried in extended positions were Greek. Here, we test the hypothesis that individuals in flexed and extended burial positions are biologically different by directly analyzing the human skeletal remains. For this, we collected three different types of phenotypic data commonly used for biodistance analysis, namely, (1) cranial measurements, (2) dental measurements, and (3) dental nonmetric traits, recorded for 47 individuals. Using Gower distance coefficients, we combine the three data types in a single analysis and estimate biological relationships among a subset of well‐preserved individuals with documented flexed ( n = 8) and extended ( n = 13) burial position. The estimated distances show a large amount of overlap between the two groups, with the exception of two individuals that are more divergent. To statistically corroborate this finding, we use distance‐based permutational multivariate analyses of variance (PERMANOVA) and dispersion (PERMDISP). Both analyses reveal no statistically significant differences between the groups, neither in group centroids nor in group dispersions. Our results therefore contradict the idea that burial position was determined by ancestry of the deceased. This has implications for future archeological research at Chersonesos and other Greek colonies of the northern Black Sea region.
Many-Joint Robot Arm Control with Recurrent Spiking Neural Networks
2021-09-27

In the paper, we show how scalable, low-cost trunk-like robotic arms can be\\nconstructed using only basic 3D-printing equipment and simple electronics. The\\ndesign is based on uniform, stackable joint modules with three degrees of\\nfreedom each. Moreover, we present an approach for controlling these robots\\nwith recurrent spiking neural networks. At first, a spiking forward model\\nlearns motor-pose correlations from movement observations. After training,\\nintentions can be projected back through unrolled spike trains of the forward\\nmodel essentially routing the intention-driven motor gradients towards the\\nrespective joints, which unfolds goal-direction navigation. We demonstrate that\\nspiking neural networks can thus effectively control trunk-like robotic arms\\nwith up to 75 articulated degrees of freedom with near millimeter accuracy.\\n
Is Alteration of Magnetite During Rock Weathering Climate‐Dependent?
2021-09-27

Abstract Magnetic records in sedimentary sequences are often used as paleoclimate proxies. Climate‐specific alteration of magnetite during rock weathering in the catchment might contribute to proxy variations in sediment sinks. In an actualistic study, we investigated the effects of magnetite alteration using weathered pebble material on basaltic parent rock. We collected samples from the Deccan basalts (India) across a large difference of mean annual precipitation (MAP; ∼800–3,200 mm), and also from the Emeishan basalts (SW‐China) to compare alteration effects at similar MAP (∼1,100 mm) but ∼12°C–15°C lower mean annual temperature (MAT). We used rocks with lamellar magnetite‐ilmenite texture to ensure the best possible uniform parent rock magnetic mineralogy. We separated the weathered material into five groups by grain size, assuming that alteration increases in finer pebbles. Only magnetic susceptibility ( χ ) shows a systematic change, with an increase that is weakly stronger for higher MAP. Consistent with a simplified model, the χ ‐increase may represent progressive maghemitization. For the Emeishan basalts, we found a significantly stronger degree of alteration, including loss of magnetite. We explain this effect, which is surprising regarding the clearly lower MAT, by frost‐induced micro‐cracks due to physical weathering that opens pathways for oxygen and humidity into particle interiors. Based on these findings, we conclude that climate‐related alteration effects of magnetite during rock weathering are in most cases outweighed by parent rock heterogeneity, and magnetic proxy records in derived sediment archives are unlikely to record climate‐related magnetite alteration acquired during rock weathering, at least for catchment with basalts.
Synthesis and crystal structure of Pb14.66Sn7.34Br26(CN2)7O2, a complex member of group 14 carbodiimides
2021-09-27

Abstract A mixed lead/tin bromide carbodiimide oxide was synthesized by solid‐state reaction between Pb(CN 2 ), PbBr 2 , SnBr 2 and SnO at 400 °C. Its monoclinic crystal structure was solved and refined in the space group C 2/ m by single‐crystal X‐ray diffraction from a yellow single crystal. One crystallographic site was found to be occupied by both tin and lead, in agreement with the results of energy‐dispersive X‐ray spectroscopy (EDX). The crystal structure comprises a complex network of tin/lead tetrahedra and tin/lead trigonal bipyramids linked by NCN units. In contrast to Pb(CN 2 ), where the NCN ion is present as a cyanamide moiety, IR‐spectroscopy of the title compound revealed the carbodiimide character of the NCN ion.
Blowing Hot and Cold: Body Temperature and the Microbiome
2021-09-28

The intestinal microbiome influences host health, and its responsiveness to diet and disease is increasingly well studied. However, our understanding of the factors driving microbiome variation remain limited.
White paper on peanut allergy – part 1: Epidemiology, burden of disease, health economic aspects
2021-09-28

Abstract Peanuts are Leguminosae, commonly known as the legume or pea family, and peanut allergy is among the most common food allergies and the most common cause of fatal food reactions and anaphylaxis. The prevalence of peanut allergy increased 3.5-fold over the past two decades reaching 1.4–2% in Europe and the United States. The reasons for this increase in prevalence are likely multifaceted. Sensitization via the skin appears to be associated with the development of peanut allergy and atopic eczema in infancy is associated with a high risk of developing peanut allergy. Until recently, the only possible management strategy for peanut allergy was strict allergen avoidance and emergency treatment including adrenaline auto-injector in cases of accidental exposure and reaction. This paper discusses the various factors that impact the risks of peanut allergy and the burden of self-management on peanut-allergic children and their caregivers.
Beyond rules: How institutional cultures and climate governance interact
2021-09-28

Abstract Institutions have a central role in climate change governance. But while there is a flourishing literature on institutions' formal rules, processes, and organizational forms, scholars lament a relative lack of attention to institutions' informal side; their cultures. It is important to study institutions' cultures because it is through culture that people relate to institutional norms and rules in taking climate action. This review uncovers what work has been done on institutional cultures and climate change, discerns common themes around which this scholarship coheres, and advances and argument for why institutional cultures matter. We employed a systematic literature review to assemble a set of 54 articles with a shared concern for how climate change and institutional cultures concurrently affect each other. The articles provided evidence of a nascent field, emerging over the past 5–10 years and fragmented across literatures. This field draws on diverse concepts of institutionalism for revealing quite different expressions of culture, and is mostly grounded in empirical studies. These disparate studies compellingly demonstrate, from different perspectives, that institutional cultures do indeed matter for implementing climate governance. Indeed, the articles converge in providing empirical evidence of eight key sites of interaction between climate change and institutional cultures: worldviews, values, logics, gender, risk acceptance, objects, power, and relationality. These eight sites are important foci for examining and effecting changes to institutions and their cultures; showing how institutional cultures shape responses to climate change, and how climate change shapes institutional cultures. This article is categorized under: The Social Status of Climate Change Knowledge &gt; Knowledge and Practice
Species stress tolerance and community competitive effects drive differences in species composition between calcareous and siliceous plant communities
2021-09-28

Abstract Both chemical and physical properties of soils have been used for two centuries for explaining differences in species composition and diversity between plant communities from calcareous and siliceous soils. Here, we examine the prediction from the ‘physical hypothesis’, which proposes that species from siliceous soils are absent from calcareous soils because of high drought stress, while species from calcareous soils are absent from siliceous soils because of high competition due to higher water availability. This hypothesis therefore predicts a trade‐off between stress tolerance and competitive response that allows calcareous and siliceous species to dominate their respective communities. There has been no attempt to experimentally assess these predictions. We cross‐transplanted with and without neighbours using a removal experiment, two dominant species from calcareous soils ( Bromus erectus and Brachypodium sylvaticum ) and two species from siliceous soils ( Pseudarrhenatherum longifolium and Deschampsia flexuosa ) in herbaceous communities from the two soils types. We repeated the experiment 4 years, taking advantage of inter‐annual climatic variability to test the interplay between year quality (dry vs. wet years) and soil types on survival responses with and without neighbours. We quantified species stress tolerances, their competitive responses and the competitive effect of the two community types. In the absence of neighbours, species from siliceous soils had much lower survival than species from calcareous soils during dry years, in particular on calcareous soils. It indicates a lower stress tolerance of siliceous species and a higher level of stress occurring on calcareous soils. Competition strongly reduced the survival of calcareous but not siliceous species, indicating a greater competitive response of the latter and competition was more important on siliceous soils than on calcareous soils during wet years. However, we found that species stress tolerances were more important than competitive effect of neighbours in driving differences in species composition. Synthesis . The contrasting responses found for dominant species from calcareous and siliceous soils support the trade‐off between stress tolerance and competitive response proposed by the physical hypothesis. Our results bring additional evidence that differences in water availability and stress between the two soil types are driving species responses to bedrock types.
Fast Rotating Neutron Stars: Oscillations and Instabilities
2021-09-28

In this review article, we present the main results from our most recent research concerning the oscillations of fast rotating neutron stars. We derive a set of time evolution equations for the investigation of non-axisymmetric oscillations of rapidly rotating compact objects in full general relativity, taking into account the contribution of a dynamic spacetime. Using our code, which features high accuracy at comparably low computational expense, we are able to extract the frequencies of non-axisymmetric modes of compact objects with rotation rates up to the Kepler limit. We propose various universal relations combining bulk properties of isolated neutron stars as well as of binary systems before and after merger; these relations are independent of the true equation of state and may serve as a valuable tool for gravitational wave asteroseismology. We also present an introductory example using a Bayesian analysis.
Performance and automation of ancient DNA capture with RNA hyRAD probes
2021-09-28

Abstract DNA hybridization‐capture techniques allow researchers to focus their sequencing efforts on preselected genomic regions. This feature is especially useful when analysing ancient DNA (aDNA) extracts, which are often dominated by exogenous environmental sources. Here, we assessed, for the first time, the performance of hyRAD as an inexpensive and design‐free alternative to commercial capture protocols to obtain authentic aDNA data from osseous remains. HyRAD relies on double enzymatic restriction of fresh DNA extracts to produce RNA probes that cover only a fraction of the genome and can serve as baits for capturing homologous fragments from aDNA libraries. We found that this approach could retrieve sequence data from horse remains coming from a range of preservation environments, including beyond radiocarbon range, yielding up to 146.5‐fold on‐target enrichment for aDNA extracts showing extremely low endogenous content (&lt;1%). Performance was, however, more limited for those samples already characterized by good DNA preservation (&gt;20%–30%), while the fraction of endogenous reads mapping on‐ and off‐target was relatively insensitive to the original endogenous DNA content. Procedures based on two instead of a single round of capture increased on‐target coverage up to 3.6‐fold. Additionally, we used methylation‐sensitive restriction enzymes to produce probes targeting hypomethylated regions, which improved data quality by reducing post‐mortem DNA damage and mapping within multicopy regions. Finally, we developed a fully automated hyRAD protocol utilizing inexpensive robotic platforms to facilitate capture processing. Overall, our work establishes hyRAD as a cost‐effective strategy to recover a set of shared orthologous variants across multiple ancient samples.
Sexual dysfunction and depression in Behçet’s disease in comparison to healthy controls
2021-09-28

Abstract Behçet’s disease (BD) can affect the genital system and is more common in Middle Eastern countries and Asia but also occurs in Caucasian people. Aim of this study was to evaluate the prevalence of sexual dysfunction (SD) and depression in patients with BD compared to a healthy control group (HCG). In addition, differences with regard to depression and patients’ origin were evaluated. This prospective, monocentric study included 106 consecutive patients from our specialized BD outpatient clinic. Patients were asked to fill out the paper based standardized and validated questionnaires International Index of Erectile Function (IIEF), the Female Sexual Function Index (FSFI) and the Beck Depression Inventory (BDI). In addition, 206 healthy controls were asked to fill out the questionnaires. 106 patients with BD were evaluated and 206 participants in the HCG. The mean age in BD group was 40.5 years as compared to 44.4 years in the HCG. Half of the patients had Middle Eastern and half Caucasian origin. SD was found in 24.5% of all subjects. Only 6.9% of male patients showed signs of SD, while half of the women’s group was suffering from SD. The prevalence for SD was significantly higher in women with Middle Eastern ethnic origin compared to women with Caucasian origin (75 vs. 33.3%, p = 0.024). Erectile Dysfunction occurred in 55% of all male patients which was not statistical different from the HCG. Genital ulcers affected 73.6% of all patients. Depression was found in 36.7% of all subjects as compared to 6.25% in the HCG ( p &lt; 0.001). Both, SD and depression correlated positively in males ( p = 0.017) and females ( p = 0.013). SD and depression are very common problems in BD and should be addressed by the treating physician. Both manifestations are intensifying each other. Depression especially is more prevalent compared to the healthy population.
Bat phylogenetic responses to regenerating Amazonian forests
2021-09-28

Abstract Throughout the tropics, regenerating secondary forests occupy vast areas previously cleared for agriculture and cattle ranching. However, despite the importance of regenerating forests in mitigating the pervasive negative consequences of forest loss and fragmentation on forest‐associated biodiversity, longitudinal studies on species' phylogenetic responses to matrix regeneration are rare. We surveyed bats in continuous primary forest, primary forest fragments and in the regenerating secondary forest matrix of a whole‐ecosystem Amazonian fragmentation experiment, ~15 and ~30 years after forest clearance, to investigate how changes in matrix quality through forest recovery affect phylogenetic α ‐ and β ‐diversity. We found that temporal changes in phylogenetic α ‐richness were more marked in the secondary forest matrix than in forest fragments and continuous forest, evidencing a significant increase in total evolutionary history over time. However, when the effects of species richness were accounted for, the phylogenetic structure of each assemblage was reduced close to zero, evincing a random pattern of lineages in all habitat types. Temporal differences in phylogenetic β ‐diversity were driven mainly by β replacement in secondary forest and continuous forest ~30 years after forest clearance. Both habitats also clustered together in terms of β richness , indicating similar levels of evolutionary heritage. Consequently, regenerating secondary forest showed a reduction in the extinction probability of lineages over time. Synthesis and applications . Approximately 30 years of secondary forest regeneration were sufficient for phylogenetic richness to recover to levels similar to those observed in continuous forest. Promoting forest succession on degraded land through a combination of natural and active restoration, while ensuring the long‐term protection of secondary forests regardless of their age, is of key importance for conserving tropical bat diversity and their associated ecosystem services. Such restoration measures would stimulate the recolonization of fragments and matrix habitats by evolutionarily distinct bat species, safeguarding phylogenetically diverse assemblages and ecological functions. Our study suggests that forest restoration in tropical degraded areas should be encouraged and secondary forests be protected by law, especially in countryside ecosystems with high primary forest cover, and in the surroundings of protected areas.
The Effects of Situational and Individual Factors on Algorithm Acceptance in COVID-19-Related Decision-Making: A Preregistered Online Experiment
2021-09-28

In times of the COVID-19 pandemic, difficult decisions such as the distribution of ventilators must be made. For many of these decisions, humans could team up with algorithms; however, people often prefer human decision-makers. We examined the role of situational (morality of the scenario; perspective) and individual factors (need for leadership; conventionalism) for algorithm preference in a preregistered online experiment with German adults (n = 1,127). As expected, algorithm preference was lowest in the most moral-laden scenario. The effect of perspective (i.e., decision-makers vs. decision targets) was only significant in the most moral scenario. Need for leadership predicted a stronger algorithm preference, whereas conventionalism was related to weaker algorithm preference. Exploratory analyses revealed that attitudes and knowledge also mattered, stressing the importance of individual factors.