julilili42/papers huggingface dataset:
Inhibition of the ATP synthase sensitizes Staphylococcus aureus towards human antimicrobial peptides
2020-07-09

Abstract Antimicrobial peptides (AMPs) are an important part of the human innate immune system for protection against bacterial infections, however the AMPs display varying degrees of activity against Staphylococcus aureus . Previously, we showed that inactivation of the ATP synthase sensitizes S. aureus towards the AMP antibiotic class of polymyxins. Here we wondered if the ATP synthase similarly is needed for tolerance towards various human AMPs, including human β-defensins (hBD1-4), LL-37 and histatin 5. Importantly, we find that the ATP synthase mutant ( atpA ) is more susceptible to killing by hBD4, hBD2, LL-37 and histatin 5 than wild type cells, while no changes in susceptibility was detected for hBD3 and hBD1. Administration of the ATP synthase inhibitor, resveratrol, sensitizes S. aureus towards hBD4-mediated killing. Neutrophils rely on AMPs and reactive oxygen molecules to eliminate bacteria and the atpA mutant is more susceptible to killing by neutrophils than the WT, even when the oxidative burst is inhibited.These results show that the staphylococcal ATP synthase enhance tolerance of S. aureus towards some human AMPs and this indicates that inhibition of the ATP synthase may be explored as a new therapeutic strategy that sensitizes S. aureus to naturally occurring AMPs of the innate immune system.
Finding karstic caves and rockshelters in the Inner Asian mountain corridor using predictive modelling and field survey
2020-07-09

The area of the Inner Asian Mountain Corridor (IAMC) follows the foothills and piedmont zones around the northern limits of Asia’s interior mountains, connecting two important areas for human evolution: the Fergana valley and the Siberian Altai. Prior research has suggested the IAMC may have provided an area of connected refugia from harsh climates during the Pleistocene. To date, this region contains very few secure, dateable Pleistocene sites, but its widely available carbonate deposits present an opportunity for discovering cave sites, which generally preserve longer sequences and organic remains. Here we present two models for predicting karstic cave and rockshelter features in the Kazakh portion of the IAMC. The 2018 model used a combination of lithological data and unsupervised landform classification, while the 2019 model used feature locations from the results of our 2017-2018 field surveys in a supervised classification using a minimum-distance classifier and morphometric features derived from the ASTER digital elevation model (DEM). We present the results of two seasons of survey using two iterations of the karstic cave models (2018 and 2019), and evaluate their performance during survey. In total, we identified 96 cave and rockshelter features from 2017-2019. We conclude that this model-led approach significantly reduces the target area for foot survey.
Efficient dynamic variation graphs
2020-07-10

Abstract Motivation Pangenomics is a growing field within computational genomics. Many pangenomic analyses use bidirected sequence graphs as their core data model. However, implementing and correctly using this data model can be difficult, and the scale of pangenomic datasets can be challenging to work at. These challenges have impeded progress in this field. Results Here, we present a stack of two C++ libraries, libbdsg and libhandlegraph, which use a simple, field-proven interface, designed to expose elementary features of these graphs while preventing common graph manipulation mistakes. The libraries also provide a Python binding. Using a diverse collection of pangenome graphs, we demonstrate that these tools allow for efficient construction and manipulation of large genome graphs with dense variation. For instance, the speed and memory usage are up to an order of magnitude better than the prior graph implementation in the VG toolkit, which has now transitioned to using libbdsg’s implementations. Availability and implementation libhandlegraph and libbdsg are available under an MIT License from https://github.com/vgteam/libhandlegraph and https://github.com/vgteam/libbdsg.
A molecular and epidemiological study of Vibrio cholerae isolates from cholera outbreaks in southern Ghana
2020-07-10

Cholera remains a major global public health threat and continuous emergence of new Vibrio cholerae strains is of major concern. We conducted a molecular epidemiological study to detect virulence markers and antimicrobial resistance patterns of V. cholerae isolates obtained from the 2012-2015 cholera outbreaks in Ghana. Archived clinical isolates obtained from the 2012, 2014 and 2015 cholera outbreaks in Ghana were revived by culture and subjected to microscopy, biochemical identification, serotyping, antibiotic susceptibility testing, molecular detection of distinct virulence factors and Multi-Locus Variable-Number of Tandem-Repeat Analysis (MLVA). Of 277 isolates analysed, 168 (60.6%) were confirmed to be V. cholerae and 109 (39.4%) isolates constituted other bacteria (Escherichia coli, Aeromonas sobria, Pseudomonas aeruginosa, Enterobacter cloacae and Enterococci faecalis). Serotyping the V. cholerae isolates identified 151 (89.9%) as Ogawa, 3 (1.8%) as Inaba and 14 (8.3%) as non-O1/O139 serogroup. The O1 serogroup isolates (154/168, 91.7%) carried the cholera toxin ctxB gene as detected by PCR. Additional virulence genes detected include zot, tcpA, ace, rtxC, toxR, rtxA, tcpP, hlyA and tagA. The most common and rare virulence factors detected among the isolates were rtxC (165 isolates) and tcpP (50 isolates) respectively. All isolates from 2014 and 2015 were multidrug resistant against the selected antibiotics. MLVA differentiated the isolates into 2 large unique clones A and B, with each predominating in a particular year. Spatial analysis showed clustering of most isolates at Ablekuma sub-district. Identification of several virulence genes among the two different genotypes of V. cholerae isolates and resistance to first- and second-line antibiotics, calls for scaleup of preventive strategies to reduce transmission, and strengthening of public health laboratories for rapid antimicrobial susceptibility testing to guide accurate treatment. Our findings support the current WHO licensed cholera vaccines which include both O1 Inaba and Ogawa serotypes.
Mountain linguistics
2020-07-10

Abstract Language use in mountainous areas often exhibits special social dynamics. This contribution sketches some of the most salient patterns of language use in upland Southeast Asia ,the greater Himalayas, the Caucasus, the Central Andes, the New Guinea highlands, and touches upon the Alps and some highland areas of Africa and North America. Accumulated over long time, such patterns of use yield particular—often highly diverse, fragmented, and discontinuous—distributions of languages and language families in geographical space the precise characteristics of which also depend on prevailing local sociolinguistic and socioeconomic conditions. Generalization are still difficult since most observations are anecdotal rather than systematic: as far as language structure is concerned, languages spoken in mountainous regions are traditionally often attributed a “conservative” or “archaic” character, preserving inherited traits and patterns that are lost elsewhere; the inaccessibility of the terrain and the resulting relative social isolation are commonly invoked to explain this situation. More recently, mountain languages have also been claimed to feature peaks in the distribution of some typological properties, whether due to sociogeographical factors or, more controversially, even direct influences of the environment: ejectives, grammatical encoding of elevational or topographic information, and overall high levels of structural complexity.
LDL-AURIS: A computational model, grounded in error-driven learning, for the comprehension of single spoken words
2020-07-10

A computational model for auditory word recognition is presented that enhances the model of Arnold et al. (2017). Real-valued features are extracted from the speech signal instead of discrete features. One-hot encoding for words’ meanings is replaced by real-valued semantic vectors, adding a small amount of noise to safeguard discriminability. Instead of learning with Rescorla-Wagner updating, we use multivariate multiple regression, which captures discrimination learning at the limit of experience. These new design features substantially improve prediction accuracy for words extracted from spontaneous conversations. They also provide enhanced temporal granularity, enabling the modeling of cohort-like effects. Clustering with t-SNE shows that the acoustic form space captures phone-like similarities and differences. Thus, wide learning with high-dimensional vectors and no hidden layers, and no abstract mediating phone-like representations is not only possible but achieves excellent performance that approximates the lower bound of human accuracy on the challenging task of isolated word recognition.
Using Light to Understand How the Brain Works in the Classroom
2020-07-10

Did you know that we can study the brain in the classroom? Many people think that studying the brain is only possible in complex laboratories with huge, complicated devices. Functional near-infrared spectroscopy (fNIRS) is a new technique that uses light to monitor how active the brain is. fNIRS has several advantages that make it particularly good for observing the brains of babies and children. Also, it is one of the best techniques to study brain function in daily life and real situations, such as in the classroom or during a conversation. However, like all other brain measurement techniques, it cannot be used for everything, meaning that it has limitations. In this article, we discuss how fNIRS works and how it can be used, its advantages, and its limitations. We conclude that, when used in the field of Educational Neuroscience, fNIRS can help scientists to understand how children learn.
Metabolite patterns in human myeloid hematopoiesis result from lineage-dependent active metabolic pathways
2020-07-10

Abstract Assessment of hematotoxicity from environmental or xenobiotic compounds is of notable interest and is frequently assessed via the colony forming unit (CFU) assay. Identification of the mode of action of single compounds is of further interest, as such often enables transfer of results across different tissues and compounds. Metabolomics displays one promising approach for identifying such, nevertheless, suitability with current protocols is restricted. Here, we combined an HSPC expansion approach with distinct lineage differentiations, resulting in formation of erythrocytes, dendritic cells and neutrophils. We examined the unique combination of fluxes in glycolysis, glutaminolysis, polyamine synthesis, fatty acid oxidation and synthesis, as well as glycerophospholipid and sphingolipid metabolism. We further assessed their interconnections and essentialness for each lineage formation. By this, we provide further insights into metabolic fluxes during differentiation of HSPC into different lineages, enabling profound understanding of possible metabolic changes in each lineage caused by exogenous compounds.
Comparison of target enrichment strategies for ancient pathogen DNA
2020-07-10

Abstract In ancient DNA research, the degraded nature of the samples generally results in poor yields of highly fragmented DNA, and targeted DNA enrichment is thus required to maximize research outcomes. The three commonly used methods – (1) array-based hybridization capture and in-solution capture using either (2) RNA or (3) DNA baits – have different characteristics that may influence the capture efficiency, specificity, and reproducibility. Here, we compared their performance in enriching pathogen DNA of Mycobacterium leprae and Treponema pallidum of 11 ancient and 19 modern samples. We find that in-solution approaches are the most effective method in ancient and modern samples of both pathogens, and RNA baits usually perform better than DNA baits. Method summary We compared three targeted DNA enrichment strategies used in ancient DNA research for the specific enrichment of pathogen DNA regarding their efficiency, specificity, and reproducibility for ancient and modern Mycobacterium leprae and Treponema pallidum samples. Array-based capture and in-solution capture with RNA and DNA baits were all tested in three independent replicates.
Shape-invariant perceptual encoding of dynamic facial expressions across species
2020-07-10

Abstract Dynamic facial expressions are crucial for communication in primates. Due to the difficulty to control shape and dynamics of facial expressions across species, it is unknown how species-specific facial expressions are perceptually encoded and interact with the representation of facial shape. While popular neural-network theories predict a joint encoding of facial shape and dynamics, the neuromuscular control of faces evolved more slowly than facial shape, suggesting a separate encoding. To investigate this hypothesis, we developed photo-realistic human and monkey heads that were animated with motion-capture data from monkeys and human. Exact control of expression dynamics was accomplished by a Bayesian machine-learning technique. Consistent with our hypothesis, we found that human observers learned cross-species expressions very quickly, where face dynamics was represented independently of facial shape. This result supports the co-evolution of the visual processing and motor-control of facial expressions, while it challenges popular neural-network theories of dynamic expression-recognition.
Mind the Body: An Exploration of Bodily Self-Awareness, by Frédérique de Vignemont
2020-07-10

Frédérique de Vignemont’s Mind the Body is the most comprehensive study of bodily awareness and the sense of body ownership (SoBO) there is. She brings together relevant work from philosophy and from the brain, cognitive, and clinical sciences in a way that is unprecedented. She systematises the debate on SoBO by cataloguing different views and structuring the dialectic. She synthesises her published work into a new overall narrative, with some key changes. The key new developments are the phenomenal contrast argument for a positive phenomenology of SoBO and the bodyguard hypothesis about SoBO. Other highlights include: her critique of the notions of body image and body schema and her suggestions how to move beyond that tired dichotomy, her bold account of how multimodal bodily self-ascriptions can be immune to error through misidentification, and her discussion of why bodily awareness is constitutively multimodal. Anyone interested in these topics will be indebted to her work.
Possible functions for the ‘embryonic’ cholinergic system present in gametes at fertilization
2020-07-10

The presence and function of cholinergic molecules (acetyl-choline, acetylcholinesterase, cholin-acetyltransferase and acetylcholine receptors) in fertilization events is shown by cytochemical, immunocyto-chemical methods and electrophysiological recordings in gametes and early embryos of the sea urchin Paracentrotus lividus.
Faculty Opinions recommendation of Single-particle cryo-EM at atomic resolution
2020-07-10

The three-dimensional positions of atoms in protein molecules define their structure and provide mechanistic insights into the roles they perform in complex biological processes. The more precisely atomic coordinates are determined, the more chemical information can be derived and the more knowledge about protein function may be inferred. With breakthroughs in electron detection and image processing technology, electron cryo-microscopy (cryo-EM) single-particle analysis has yielded protein structures with increasing levels of detail in recent years 1,2 . However, obtaining cryo-EM reconstructions with sufficient resolution to visualise individual atoms in proteins has thus far been elusive. Here, we show that using a new electron source, energy filter and camera, we obtained a 1.7 Å resolution cryo-EM reconstruction for a prototypical human membrane protein, the β3 GABA A receptor homopentamer3. Such maps allow a detailed understanding of small molecule coordination, visualisation of solvent molecules and alternative conformations for multiple amino acids, as well as unambiguous building of ordered acidic side chains and glycans. Applied to mouse apo-ferritin, our strategy led to a 1.2 Å resolution reconstruction that, for the first time, offers a genuine atomic resolution view of a protein molecule using single particle cryo-EM. Moreover, the scattering potential from many hydrogen atoms can be visualised in difference maps, allowing a direct analysis of hydrogen bonding networks. Combination of the technological advances described here with further approaches to accelerate data acquisition and improve sample quality provide a route towards routine application of cryo-EM in high-throughput screening of small molecule modulators and structure-based drug discovery.
High‐protein diet more effectively reduces hepatic fat than low‐protein diet despite lower autophagy and FGF21 levels
2020-07-11

Abstract Background and aims Non‐alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent and nutrition intervention remains the most important therapeutic approach for NAFLD. Our aim was to investigate whether low‐ (LP) or high‐protein (HP) diets are more effective in reducing liver fat and reversing NAFLD and which mechanisms are involved. Methods 19 participants with morbid obesity undergoing bariatric surgery were randomized into two hypocaloric (1500‐1600 kcal/day) diet groups, a low protein (10E% protein) and a high protein (30E% protein), for three weeks prior to surgery. Intrahepatic lipid levels (IHL) and serum fibroblast growth factor 21 (FGF21) were measured before and after the dietary intervention. Autophagy flux, histology, mitochondrial activity and gene expression analyses were performed in liver samples collected during surgery. Results IHL levels decreased by 42.6% in the HP group, but were not significantly changed in the LP group despite similar weight loss. Hepatic autophagy flux and serum FGF21 increased by 66.7% and 42.2%, respectively, after 3 weeks in the LP group only. Expression levels of fat uptake and lipid biosynthesis genes were lower in the HP group compared with those in the LP group. RNA‐seq analysis revealed lower activity of inflammatory pathways upon HP diet. Hepatic mitochondrial activity and expression of β‐oxidation genes did not increase in the HP group. Conclusions HP diet more effectively reduces hepatic fat than LP diet despite of lower autophagy and FGF21. Our data suggest that liver fat reduction upon HP diets result primarily from suppression of fat uptake and lipid biosynthesis.
Issues of theory and method in the analysis of Paleolithic mortuary behavior: A view from Shanidar Cave
2020-07-11

Abstract Mortuary behavior (activities concerning dead conspecifics) is one of many traits that were previously widely considered to have been uniquely human, but on which perspectives have changed markedly in recent years. Theoretical approaches to hominin mortuary activity and its evolution have undergone major revision, and advances in diverse archeological and paleoanthropological methods have brought new ways of identifying behaviors such as intentional burial. Despite these advances, debates concerning the nature of hominin mortuary activity, particularly among the Neanderthals, rely heavily on the rereading of old excavations as new finds are relatively rare, limiting the extent to which such debates can benefit from advances in the field. The recent discovery of in situ articulated Neanderthal remains at Shanidar Cave offers a rare opportunity to take full advantage of these methodological and theoretical developments to understand Neanderthal mortuary activity, making a review of these advances relevant and timely.
Normalized Indices Derived from Visceral Adipose Mass Assessed by Magnetic Resonance Imaging and Their Correlation with Markers for Insulin Resistance and Prediabetes
2020-07-11

Visceral adipose tissue (VAT) plays an important role in the pathogenesis of insulin resistance (IR), prediabetes and type 2 diabetes. However, VAT volume alone might not be the best marker for insulin resistance and prediabetes or diabetes, as a given VAT volume may impact differently on these metabolic traits based on body height, gender, age and ethnicity. In a cohort of 1295 subjects from the Tübingen Diabetes Family Study (TDFS) and in 9978 subjects from the UK Biobank (UKBB) undergoing magnetic resonance imaging for quantification of VAT volume, total adipose tissue (TAT) in the TDFS, total abdominal adipose tissue (TAAT) in the UKBB, and total lean tissue (TLT), VAT volume and several VAT-indices were investigated for their relationships with insulin resistance and glycemic traits. VAT-related indices were calculated by correcting for body height (VAT/m:VAT/body height; VAT/m2:VAT/(body height)2, and VAT/m3:VAT/(body height)3), TAT (%VAT), TLT (VAT/TLT) and weight (VAT/WEI), with closest equivalents used within the UKBB dataset. Prognostic values of VAT and VAT-related indices for insulin sensitivity, HbA1c levels and prediabetes/diabetes were analyzed for males and females. Males had higher VAT volume and VAT-related indices than females in both cohorts (p &lt; 0.0001) and VAT volume has shown to be a stronger determinant for insulin sensitivity than anthropometric variables. Among the parameters uncorrected VAT and derived indices, VAT/m3 most strongly correlated negatively with insulin sensitivity and positively with HbA1c levels and prediabetes/diabetes in the TDFS (R2 = 0.375/0.305 for females/males for insulin sensitivity, 0.178/0.148 for HbA1c levels vs., e.g., 0.355/0.293 and 0.144/0.133 for VAT, respectively) and positively with HbA1c (R2 = 0.046/0.042) in the UKBB for females and males. Furthermore, VAT/m3 was found to be a significantly better determinant of insulin resistance or prediabetes than uncorrected VAT volume (p &lt; 0.001/0.019 for females/males regarding insulin sensitivity, p &lt; 0.001/&lt; 0.001 for females/males regarding HbA1c). Evaluation of several indices derived from VAT volume identified VAT/m3 to correlate most strongly with insulin sensitivity and glucose metabolism. Thus, VAT/m3 appears to provide better indications of metabolic characteristics (insulin sensitivity and pre-diabetes/diabetes) than VAT volume alone.
Impact of Helminth Infections during Pregnancy on Vaccine Immunogenicity in Gabonese Infants
2020-07-11

Helminth infections are common in sub-Saharan Africa. Besides direct clinical effects, a bias towards a T helper type 2 (Th2) cell immune response is observed. The consequences of parasite infection during pregnancy for the mother and particularly for the fetus and the newborn can be severe and may include impaired immune response during acute infection and vaccination. Here, we present data of immune responses to vaccines given within the expanded program on immunization (EPI) of infants born to helminth infected or non-infected mothers. The study was conducted in Lambaréné and surroundings, Gabon. Maternal helminth infection was diagnosed microscopically using the Kato-Katz method for soil-transmitted helminths (STH), urine filtration for Schistosoma haematobium infections and the saponin-based method for filarial infections. Plasma antibody levels to different vaccine antigens were measured in mothers and their offspring by enzyme-linked immunosorbent assay (ELISA) at different timepoints. We found 42.3% of the mothers to be infected with at least one helminth species. Significantly lower anti-tetanus toxoid immunoglobulin (Ig) G was detected in the cord blood of infants born to helminth infected mothers. Following vaccination, immune responses of the infants to EPI vaccines were similar between the two groups at nine and 12 months. Even though infection with helminths is still common in pregnant women in Gabon, in our setting, there was no evidence seen for a substantial effect on infants’ immune responses to vaccines given as part of the EPI.