bluuebunny/crossref_metadata_2025_split huggingface dataset:
First report of classical knockdown resistance (kdr) mutation, L1014F, in human head louse Pediculus humanus capitis (Phthiraptera: Anoplura)
Authors: Mallick Prashant K. , Sindhania Ankita , Gupta Toshi , Singh Dhirendra P , Saini Seema , Singh Om P. 
Published: May 2022

AbstractThere are at least three known knockdown resistance (kdr) mutations reported globally in the human head louse Pediculus humanus capitis (Phthiraptera: Anoplura) that are associated with reduced sensitivity to pyrethroids. However, prevalence of kdr mutation is not known in the Indian subcontinent. To identify kdr mutations in the Indian population, the genomic region of the voltage-gated sodium channel gene encompassing IIS1-2 linker to IIS6 segments was PCR-amplified and sequenced from P. humanus capitis samples collected from different geographic localities of India. DNA sequencing revealed the presence of four kdr mutations, i.e., M827I, T929I, L932F and L1014F. The presence of a classical kdr mutation, L1014F, a most widely reported mutation across insect-taxa associated with kdr-trait, is being reported for the first time in P. humanus capitis.
Unique gut microbiome signatures among adult patients with moderate to severe atopic dermatitis in southern Chinese
Authors: Wang Yiwei , Hou Jinpao , Tsui Joseph Chi-Ching , Wang Lin , Zhou Junwei , Chan Un Kei , Lo Claudia Jun Yi , Siu Pui Ling Kella , Loo Steven King Fan , Tsui Stephen Kwok Wing 
Published: May 2022

ABSTRACTImbalance of the immune system caused by alterations of gut microbiome is considered to be a critical factor in the pathogenesis of infant eczema but the exact role of the gut microbiome in adult atopic dermatitis (AD) patients remains to be clarified. To investigate the differences of the gut microbiome between adult AD patients and healthy individuals, stool samples of 234 adults, containing 104 AD patients and 130 healthy subjects were collected for amplicon sequencing. Altered structure and metabolic dysfunctions of the gut microbiome were identified in adult AD patients. Our results illustrated that the adult AD patients were more likely to have allergies, particularly non-food allergies. And the gut microbiome composition of the AD and normal groups were considerably different. Besides, Romboutsia and Clostridium_sensu_stricto_1 was enriched in the normal group, whereas Blautia, Butyricicoccus, Lachnoclostridium, Eubacterium_hallii_group, Erysipelatoclostridium, Megasphaera, Oscillibacter, Flavonifractor were dominated in the AD group. Moreover, purine nucleotide degradation pathways were significantly enriched in the AD group and the enrichment of proteinogenic amino acid biosynthesis pathways was found in the normal group. This study provides insights into new therapeutic strategies targeting the gut microbiome for AD and evidence for the involvement of gut-skin axis in AD patients.
Prevalence of Lung Cancer in Colombia and a New Diagnostic Algorithm Using Health Administrative Databases: A Real-World Evidence Study
Authors: Amaya-Nieto Javier , Torres Gabriel F. , Buitrago Giancarlo 
Published: May 2022

AbstractReliable, timely and detailed information on lung cancer prevalence, mortality and costs from middle-income countries is essential to policy design. Thus, we aimed to develop an electronic algorithm to identify lung cancer prevalent patients in Colombia by using administrative claims databases, as well as to estimate prevalence rates by age, sex and geographic region. We performed a cross-sectional study based on national claim databases in Colombia (Base de datos de suficiencia de la Unidad de Pago por Capitación and Base de Datos Única de Afiliados) to identify lung cancer prevalent patients in 2017. Several algorithms based on the presence or absence of oncological procedures (chemotherapy, radiotherapy and surgery) and a minimum number of months that each individual had lung cancer ICD-10 codes were developed. After testing 16 algorithms, those with the closest prevalence rates to those rates reported by aggregated official sources (Global Cancer Observatory and Cuenta de Alto Costo) were selected. We estimated prevalence rates by age, sex and geographic region. Two algorithms were selected: i) one algorithm that was defined as the presence of ICD-10 codes for 4 months or more (the sensitive algorithm); and ii) one algorithm that was defined by adding the presence of at least one oncological procedure (the specific algorithm). The estimated prevalence rates per 100,000 inhabitants were 15.3 and 9.7 for the sensitive and specific algorithms, respectively. These rates were higher in men (9.9 per 100,000), over 65-years-old (37.1 per 100,000) who lived in Central and Bogota regions (14.7 and 10.9 per 100,000, respectively). Selected algorithms showed similar aggregated prevalence estimations to those rates reported by official sources and allowed us to estimate prevalence rates in specific aging, regional and gender groups for Colombia by using national claims databases. These findings could be useful to identify clinical and economical outcomes related to lung cancer patients by using national individual-level databases.
Topology Adaptive Graph Convolution Network With Heterogeneous Entities For Predicting Adverse Events from Drug-Drug-Interactions
Authors: Bagchi Srijani , Sarkar Anasua , Maulik Ujjwal 
Published: May 2022

AbstractIn times like this, it is imperative to be cautious about the effects of drugs or vaccination doses on patients who are already suffering from other serious diseases. It’s not only the virus which can affect the body metabolisms, drugs to encounter the virus may also end up having unwanted negative effects. Therapeutic activities of drugs are often influenced by co-administration of drugs that may cause inevitable drug-drug interactions and inadvertent side effects. Therefore, prediction and identification of DDIs are extremely vital for patient safety and treatment modalities. In this context, we intend to develop a computational method based on functional similarity of drugs. Our objective has been enhanced by the usage of knowledge graphs which allows capturing underlying information embeddings in a biological network with heterogenous entities. On providing this knowledge graph as the input to a Topology Adaptive Graph Convolution Network which performs topologically-aware flexible convolutions, we achieve improvements on priorly proposed GCN models that has been shown as comparison.
Sexual selection and pseudogenization in primate fertilization
Authors: Carlisle Jolie A. , Bickell Andrew L. , Hart Michael W. 
Published: May 2022

AbstractThe mouse sperm protein ZP3R interacts with proteins in the egg coat and mediates sperm–egg adhesion in a species-specific manner. Understanding the function and evolution of such genes has important implications for studies of speciation, reproductive success, and infertility. A recent analysis showed that (1) the human pseudogeneC4BPAP1is the ortholog ofZp3r, (2)ZP3Rpseudogenization evolved independently in parallel among several primate lineages, and (3) functionalZP3Rgenes evolve under positive selection among other primate species. The causes of this pseudogenization ofZP3Rare unknown. To explore one plausible cause (changes in sexual selection on males), we searched forZP3Rpseudogenes in recently published genomes, then compared sexually selected male traits among lineages with and without a functionalZP3R. We found that traits associated with more intense sexual selection on males (large male body size, larger male canines, larger testes) were associated with functionalZP3Rexpression, and suggest that a relaxation of sexual selection may be associated with selection forZP3Rpseudogenization. This proposed causal relationship implies an evolutionary cost to maintaining redundancy in the suite of primate fertilization genes.Lay summaryIn sexual interactions more is often assumed to be better. But the evolution of animal genomes suggests that sometimes less is more: the adaptive loss of genes that function in sex may be favored by selection. How could this happen? One surprising answer comes from analyzing humans and some other primate species that have turned off a key gene calledZP3Rthat helps sperm bind to eggs. The loss of that gene function in some primates is associated with male traits (smaller bodies, smaller canines, smaller testes) that often indicate less vigorous selection on males to compete for matings with females. That correlation implies that the same selection acting on male morphological traits may also act on sperm molecular traits. The correlation also implies that it’s expensive to keep some genes turned on, and that when they’re no longer helpful it’s adaptive to turn them off or allow them to become fallow. This economy of gene expression in sex is an under-explored area of research.
On the interplay between lipids and asymmetric dynamics of an NBS degenerate ABC transporter
Authors: Tóth Ágota , Janaszkiewicz Angelika , Crespi Veronica , Di Meo Florent 
Published: May 2022

AbstractMultidrug resistance-associated proteins are ABC C-family exporters. They are crucial in pharmacology as they transport various substrates across membranes. However, the role of the degenerate nucleotide-binding site (NBS) remains unclear likewise the interplay with the surrounding lipid environment. Here, we propose a dynamic and structural overview of MRP1 fromca. 110 µs molecular dynamics simulations. ATP binding to NBS1 is likely maintained along several transport cycles. Asymmetric NBD behaviour is ensured by lower signal transduction from NBD1 to the rest of the protein owing to the absence of ball-and-socket conformation between NBD1 and coupling helices. Even though surrounding lipids play an active role in the allosteric communication between the substrate-binding pocket and NBDs, our results suggest that lipid composition has a limited impact, mostly by affecting transport kinetics. We believe that our work can be extended to other degenerate NBS ABC proteins and provide hints for deciphering mechanistic differences among ABC transporters.
The genomic and bioclimatic characterization of Ethiopian barley (Hordeum vulgare L.) unveils challenges and opportunities to adapt to a changing climate
Authors: Lakew Basazen F. , Caproni Leonardo , Kassaw Seyoum A. , Miculan Mara , Ahmed Jemal Seid , Grazioli Simona , Kidane Yosef Gebrehawaryat , Fadda Carlo , Pè Mario Enrico , Dell’Acqua Matteo 
Published: May 2022

AbstractThe climate crisis is impacting agroecosystems of the global South, threatening the food security of millions of smallholder farmers. Understanding the effect of current and future climates on crop agrobiodiversity may guide breeding efforts and adaptation strategies to sustain the livelihoods of farmers cropping in challenging conditions. Here, we combine a genomic and climatic characterization of a large collection of traditional barley varieties from Ethiopia, key to food security in local smallholder farming systems. We employ data-driven approaches to characterize their local adaptation to current and future climates and identify barley genomic regions with potential for breeding for local adaptation. We used a sequencing approach to genotype at high- density 436 barley varieties, finding that their genetic diversity can be traced back to geography and environmental diversity in Ethiopia. We integrate this information in a genome-wide association study targeting phenology traits measured in common garden experiments as well as climatic features at sampling points of traditional varieties, describing 106 genomic loci associated with local adaptation. We then employ a machine learning approach to link barley genomic diversity with climate variation, estimating barley genomic offset in future climate scenarios. Our data show that the genomic characterization of traditional agrobiodiversity coupled with climate modelling may contribute to the mitigation of the climate crisis effects on smallholder farming systems.
Phage resistance profiling identifies new genes required for biogenesis and modification of the corynebacterial cell envelope
Authors: McKitterick Amelia C. , Bernhardt Thomas G. 
Published: May 2022

ABSTRACTBacteria of the order Corynebacteriales including pathogens such as Mycobacterium tuberculosis and Corynebacterium diphtheriae are characterized by their complex, multi-layered envelope. In addition to a peptidoglycan layer, these organisms possess an additional polysaccharide layer made of arabinogalactan and an outer membrane layer composed predominantly of long-chain fatty acids called mycolic acids. This so-called mycolata envelope structure is both a potent barrier against antibiotic entry into cells and a target of several antibacterial therapeutics. A better understanding of the mechanisms underlying mycolata envelope assembly therefore promises to reveal new ways of disrupting this unique structure for the development of antibiotics and antibiotic potentiators. Because they engage with receptors on the cell surface during infection, bacteriophages have long been used as tools to uncover important aspects of host envelope assembly. However, surprisingly little is known about the interactions between Corynebacteriales phages and their hosts. We therefore made use of the phages Cog and CL31 that infect Corynebacterium glutamicum (Cglu), a model member of the Corynebacteriales, to discover host factors important for phage infection. A high-density transposon library of Cglu was challenged with these phages followed by transposon sequencing to identify resistance loci. The analysis identified an important role for mycomembrane porins in phage infection as well as components of the arabinogalactan and mycolic acid synthesis pathways. Importantly, the approach also implicated a new gene (cgp_0396) in the process of arabinogalactan modification and identified a conserved new factor (AhfA, Cpg_0475) required for mycolic acid synthesis in Cglu.
Clonally selected lines after CRISPR/Cas editing are not isogenic
Authors: Panda Arijit , Suvakov Milovan , Mariani Jessica , Drucker Kristen L. , Park Yohan , Jang Yeongjun , Kollmeyer Thomas M. , Sarkar Gobinda , Bae Taejeong , Kim Jean J. , Yoon Wan Hee , Jenkins Robert B. , Vaccarino Flora , Abyzov Alexej 
Published: May 2022

AbstractThe CRISPR-Cas9 system has enabled researchers to precisely modify/edit the sequence of a genome. A typical editing experiment consists of two steps: (i) editing cultured cells; (ii) cell cloning and selection of clones with and without intended edit, presumed to be isogenic. The application of CRISPR-Cas9 system may result in off-target edits, while cloning will reveal culture-acquired mutations. We analyzed the extent of the former and the latter by whole genome sequencing in three experiments involving separate genomic loci and conducted by three independent laboratories. In all experiments we hardly found any off-target edits, while detecting hundreds to thousands of single nucleotide mutations unique to each clone after relatively short culture of 10-20 passages. Notably, clones also differed in copy number alterations that were several kb to several mb in size and represented the largest source of genomic divergence among clones. We suggest that screening of clones for mutations and copy number alterations acquired in culture is a necessary step to allow correct interpretation of DNA editing experiments. Furthermore, since culture associated mutations are inevitable, we propose that experiments involving derivation of clonal lines should compare a mix of multiple unedited lines and a mix of multiple edited lines.
Emergent low-frequency activity in cortico-cerebellar networks with motor skill learning
Authors: Fleischer Pierson J. , Abbasi Aamir , Fealy Andrew W. , Danielsen Nathan P. , Sandhu Ramneet , Raj Philip R. , Gulati Tanuj 
Published: May 2022

AbstractThe motor cortex controls skilled arm movement by recruiting a variety of targets in the nervous system, and it is important to understand the emergent activity in these regions as refinement of a motor skill occurs. One fundamental projection of the motor cortex is to the cerebellum. However, the emergent activity in the motor cortex and the cerebellum that appears as a dexterous motor skill is consolidated is incompletely understood. Here, we report on low-frequency oscillatory (LFO) activity that emerges in cortico-cerebellar networks with learning the reach-to-grasp motor skill. We chronically recorded the motor and the cerebellar cortices in rats which revealed the emergence of coordinated movement-related activity in the local-field potentials (LFPs) as the reaching skill consolidated. We found that the local and cross-area spiking activity was coordinated with LFOs. Finally, we also found that these neural dynamics were more prominently expressed during accurate behavior. This work furthers our understanding on emergent dynamics in the cortico-cerebellar loop that underlie learning and execution of precise skilled movement.
The archaeological potential of the northern Luangwa Valley, Zambia: the Luwumbu basin
Authors: Burke A. , Bisson M. , Schilt F. , Tolan S. , Drapeau M. , Aleman J. , Peros M. 
Published: May 2022

AbstractThe Luangwa Basin, Zambia, which forms part of the Zambezi drainage, is strategically located between the Central African plateau and the East African Rift system. The Luangwa River and major tributaries, such as the Luwumbu River, are perennial water sources supporting essential resources that sustain human communities and a rich and diverse fauna and flora. The archaeological record of Luangwa is relatively unknown, despite early archaeological exploration hinting at its potential. Recent research in the southern Luangwa valley, however, suggests that it preserves a long record of hominin occupation spanning the Early to Late Stone Age. The research described here details fieldwork carried out in northeastern Luangwa, in the Luwumbu Basin, that confirms that a relatively deep package of Quaternary deposits, containing evidence of the Stone Age occupation of the region persists in the upper piedmont zone.
Distinct nano-structures support a multifunctional role of actin at presynapses
Authors: Bingham Dominic , Wernert Florian , Costa Moura Julie Da , Boroni-Rueda Fanny , van Bommel Nikki , Caillol Ghislaine , Papandréou Marie-Jeanne , Leterrier Christophe 
Published: May 2022

AbstractSynapses are the nexus of signal transmission in the nervous system. Despite decades of work, the architecture of the actin cytoskeleton that concentrates at presynapses remain poorly known, hindering our comprehensive understanding of its roles in presynaptic physiology. In this work, we take advantage of a validated model of bead-induced presynapses to measure and visualize isolated presynaptic actin by diffraction-limited and super-resolution microscopy. We first identify a major population of actin-enriched presynapses that concentrates more presynaptic components, and shows higher synaptic vesicle cycling than their non-enriched counterparts. Using pharmacological perturbations, we determine that an optimal amount of actin is necessary for this effect of actin enrichment. Modulation of this effect by actin nucleation inhibitors indicates its dependance on distinct presynaptic actin assemblies. Using Single Molecule Localization Microscopy (SMLM), we directly visualize these nano-structures in isolated presynapses, defining an actin mesh at the active zone, actin rails between the active zone and deeper reserve pools, and actin corrals around the whole presynaptic compartment. We finally show that these three types of presynaptic actin nano-structures are differentially affected by actin nucleation inhibitors, consistent with their effect on presynaptic component concentration and on synaptic vesicle cycling.
Modeling clonal evolution and oncogenic dependency in vivo in the context of hematopoietic transformation
Authors: Bowman Robert L. , Dunbar Andrew , Mishra Tanmay , Xiao Wenbin , Waarts Michael R. , Maestre Inés Fernández , Eisman Shira E. , Cai Louise , Cai Sheng F. , Vela Pablo Sanchez , Mowla Shoron , Martinez Benitez Anthony R. , Park Young , Csete Isabelle S. , Krishnan Aishwarya , Lee Darren , Boorady Nayla , Potts Chad R. , Jenkins Matthew T. , Carroll Martin P. , Meyer Sara E. , Miles Linde A. , Ferrell P. Brent , Trowbridge Jennifer J. , Levine Ross L. 
Published: May 2022

SummaryCancer evolution is a multifaceted process involving the acquisition of somatic mutations and progressive epigenetic dysregulation of cellular fate. Both cell-intrinsic mechanisms and environmental interactions provide selective pressures capable of promoting clonal evolution and expansion, with single-cell and bulk DNA sequencing offering increased resolution into this process1-4. Advances in genome editing, single-cell biology and expressed lentiviral barcoding have enabled new insights into how transcriptional/epigenetic states change with clonal evolution5,6. Despite the extensive catalog of genomic alterations revealed by resequencing studies7,8, there remain limited means to functionally model and perturb this evolutionary process in experimental systems9. Here we integrated multi-recombinase (Cre, Flp, and Dre) tools for modeling reversible, sequential mutagenesis from premalignant clonal hematopoiesis to acute myeloid leukemia. We demonstrate that somatic acquisition of Flt3 activating mutations elicits distinct phases of acute and chronic activation resulting in differential cooperativity with Npm1 and Dnmt3a disease alleles. We next developed a generalizable allelic framework allowing for the reversible expression of oncogenic mutations at their endogenous loci. We found that reversal of mutant Flt3 resulted in rapid leukemic regression with distinct alterations in cellular compartments depending upon co-occurring mutations. These studies provide a path to model sequential mutagenesis and deterministically investigate mechanisms of transformation and oncogenic dependency in the context of clonal evolution.
Assessing the value relevance of fair value measurements: a South African perspective
Authors: Matsane Ayanda , Nakpodia Franklin , Areneke Geofry 
Published: May 2022

Purpose
This paper aims to explore whether fair value Levels 1 and 2 measurements are more value relevant than Level 3 fair value measurements in a less-active market. Specifically, this research addresses two objectives. Firstly, it examines the value relevance of fair value measures for each disclosure level of fair value. Secondly, it assesses the impact of corporate governance on the value relevance of less observable fair value disclosures (Levels 2 and 3).

Design/methodology/approach
Drawing insights from agency theorising, this research adopts a quantitative approach (regression analysis) that investigates data from a less active financial market (South Africa).

Findings
Contrary to agency theory suppositions, the results show that investors in a less active market value management inputs more than market (more transparent) information. The authors also observe that investors pay limited interest to corporate governance structures when pricing fair value measurement, implying that they rely on factors beyond corporate governance mechanisms.

Originality/value
The authors’ findings offer useful evidence to standard setters and preparers of financial information. While the International Accounting Standard Board suggests that investors value transparent financial information, the data shows that investors in less-active markets value management’s inputs more than those of the market.