bluuebunny/crossref_metadata_2025_split huggingface dataset:
SNT: A Unifying Toolbox for Quantification of Neuronal Anatomy
Authors: Arshadi Cameron , Günther Ulrik , Eddison Mark , Harrington Kyle I. S. , Ferreira Tiago A. 
Published: July 2020

SummaryQuantification of neuronal morphology is essential for understanding neuronal connectivity and many software tools have been developed for neuronal reconstruction and morphometry. However, such tools remain domain-specific, tethered to specific imaging modalities, and were not designed to accommodate the rich metadata generated by recent whole-brain cellular connectomics. To address these limitations, we created SNT: a unifying framework for neuronal morphometry and analysis of single-cell connectomics for the widely used Fiji and ImageJ platforms.We demonstrate that SNT can be used to tackle important problems in contemporary neuroscience, validate its utility, and illustrate how it establishes an end-to-end platform for tracing, proof-editing, visualization, quantification, and modeling of neuroanatomy.With an open and scriptable architecture, a large user base, and thorough community-based documentation, SNT is an accessible and scalable resource for the broad neuroscience community that synergizes well with existing software.
Collagen (I) homotrimer potentiates the osteogenesis imperfecta (oim) mutant allele and reduces survival in male mice
Authors: Lee Katie J. , Rambault Lisa , Bou-Gharios George , Clegg Peter D. , Akhtar Riaz , Czanner Gabriela , van ‘t Hof Rob , Canty-Laird Elizabeth G. 
Published: July 2020

AbstractType I collagen is the major structural component of bone where it exists as an (α1)2(α2)1heterotrimer in all vertebrates. The osteogenesis imperfecta (oim) mouse model comprising solely homotrimeric (α1)3type I collagen, due to a dysfunctional α2 chain, has a brittle bone phenotype implying that the heterotrimeric form is required for physiological bone function. However, humans with rare null alleles preventing synthesis of the α2 chain have connective tissue and cardiovascular abnormalities (cardiac valvular Ehlers Danlos Syndrome), without evident bone fragility. Conversely a prevalent human single nucleotide polymorphism leading to increased homotrimer synthesis is associated with osteoporosis. Whilst the oim line is well-studied, whether homotrimeric type I collagen is functionally equivalent to the heterotrimeric form in bone has not been demonstrated. Col1a2 null and oim mouse lines were used in this study and bones analysed by microCT and 3-point bending. RNA was also extracted from heterozygote tissues and allelic discrimination analyses performed using qRT-PCR. Here we comprehensively show for the first time that mice lacking the α2(I) chain do not have impaired bone biomechanical or structural properties, unlike oim homozygous mice. However Mendelian inheritance was affected in male mice of both lines and male mice null for the α2 chain exhibited age-related loss of condition. The brittle bone phenotype of oim homozygotes could result from detrimental effects of the oim mutant allele, however, the phenotype of oim heterozygotes is known to be less severe. We used allelic discrimination to show that the oim mutant allele is not downregulated in heterozygotes. We then tested whether gene dosage was responsible for the less severe phenotype of oim heterozygotes by generating compound heterozygotes. Data showed that compound heterozygotes had impaired bone structural properties as compared to oim heterozygotes, albeit to a lesser extent than oim homozygotes. Hence, we concluded that the presence of heterotrimeric collagen-1 in oim heterozygotes alleviates the effect of the oim mutant allele but a genetic interaction between homotrimeric collagen-1 and the oim mutant allele leads to bone fragility.
Super-elasticity of plasma- and synthetic membranes by coupling of membrane asymmetry and liquid-liquid phase separation
Authors: Steinkühler Jan , Bhatia Tripta , Zhao Ziliang , Lipowsky Reinhard , Dimova Rumiana 
Published: July 2020

AbstractBiological cells are contained by a fluid lipid bilayer (plasma membrane, PM) that allows for large deformations, often exceeding 50% of the initial (or projected) PM area. Biochemically isolated lipids self-organize into membranes, but the extraordinary deformability of the plasma membrane is lost. Pure lipid bilayers are prone to rupture at small (<2-4%) area strains and this limits progress for synthetic reconstitution of cellular features such as migration, phagocytosis and division. Here, we show that by preserving PM structure and composition during isolation from cells, vesicles with cell-like elasticity are obtained. We found that these plasma membrane vesicles store significant area in the form of nanotubes in their lumen. These are recruited by mechanical tension applied to the outer vesicle membrane showing an apparent elastic response. This “super-elastic” response emerges from the interplay of lipid liquid-liquid phase separation and membrane asymmetry. This finding allows for bottom-up engineering of synthetic vesicles that appear over one magnitude softer and with three fold larger deformability than conventional lipid vesicles.
Prophage-encoded phage defense proteins with cognate self-immunity
Authors: Owen Siân V. , Wenner Nicolas , Dulberger Charles L. , Rodwell Ella V. , Bowers-Barnard Arthur , Quinones-Olvera Natalia , Rigden Daniel J. , Rubin Eric J. , Garner Ethan C. , Baym Michael , Hinton Jay C. D. 
Published: July 2020

SummaryTemperate phages are pervasive in bacterial genomes, existing as vertically-inherited islands called prophages. Prophages are vulnerable to the predation of their host bacterium by exogenous phages. Here we identify BstA, a novel family of prophage-encoded phage defense proteins found in diverse Gram-negative bacteria. BstA drives potent suppression of phage epidemics through abortive infection. During lytic replication, thebstA-encoding prophage is not itself inhibited by BstA due to a self-immunity mechanism conferred by the anti-BstA (aba) element, a short stretch of DNA within thebstAlocus. Inhibition of phage replication by distinct BstA proteins fromSalmonella, KlebsiellaandEscherichiaprophages is functionally interchangeable, but each possesses a cognateabaelement. The specificity of theabaelement ensures that immunity is exclusive to the replicating prophage, and cannot be exploited by heterologous BstA-encoding phages. BstA allows prophages to defend host cells against exogenous phage attack, without sacrificing their own lytic autonomy.
Active fatty acid oxidation defines the cellular response towards reactive oxygen species
Authors: Kaiser Lars , Quint Isabel , Csuk René , Jung Manfred , Deigner Hans-Peter 
Published: July 2020

AbstractEndocrine disrupting compounds (EDC) are ubiquitous in the human environment, displaying a highly relevant research topic. The impact of EDC on the differentiation of primitive cells, e.g. in hematopoiesis, is of particular interest. We found profound inhibitory effects of di-2-ethylhexyl phthalate (DEHP) on erythropoiesis and dendropoiesis, mediated via reactive oxygen species (ROS) generation. Neutrophil differentiation, however, was not affected by DEHP. ROS leads to a shift from glycolysis to the pentose phosphate pathway and diminishes ATP generation from glycolysis, ultimately resulting in apoptosis in both cell types. In neutrophils, ATP generation is held constant by active fatty acid oxidation (FAO), rendering these cells highly resistant against ROS. This relationship also holds true in HUVEC and HepG2 cells, also in combination with other organic peroxides. We, therefore, uncover a key mechanism for ROS quenching which further explains the distinct ROS quenching ability of different tissues.
Regulations of mitochondrial DNA repair by poly(ADP-Ribose) Polymerase 1
Authors: Herrmann Geoffrey K. , Yin Y. Whitney 
Published: July 2020

ABSTRACTFormation of a repair enzyme complex is beneficial to DNA repair. Despite the fact that mitochondrial base excision repair (mtBER) enzymes DNA polymerase gamma (Pol γ) and poly(ADP-ribose) polymerase 1 (PARP1) were found in the same complex, the functional role of the interaction in mtBER has not been characterized. We report studies that PARP1 regulates Pol γ activity during DNA repair in a metabolic cofactor NAD+(nicotinamide adenosine dinucleotide)-dependent manner. In the absence of NAD+, PARP1 completely inhibits Pol γ, while increasing NAD+level to physiological concentration enables Pol γ to resume maximum repair activity. Pol γ is PARylated when bound to DNA repair intermediates, and PARylation is essential for Pol γ repair activity. The PARP1 inhibitor Olaparib that abolishes PARP1 catalytic activity suppresses Pol γ gap-filling synthesis at physiological concentrations of NAD+, suggesting inhibiting PARP1 activity would increase mtDNA mutations. Because NAD+cellular levels are linked to metabolism and to ATP production via oxidative phosphorylation, our results suggest that mtDNA damage repair is correlated with cellular metabolic state and integrity of the respiratory chain. Our results revealed a molecular basis of drug toxicity from prolonged usage of PARP1 inhibitors in treating cardiac dysfunctions
The dimerisable Cre recombinase allows conditional genome editing in the mosquito stages ofPlasmodium berghei
Authors: Fernandes Priyanka , Briquet Sylvie , Patarot Delphine , Loubens Manon , Hoareau-Coudert Bénédicte , Silvie Olivier 
Published: July 2020

ABSTRACTAsexual blood stages of the malaria parasite are readily amenable to genetic modification via homologous recombination, allowing functional studies of parasite genes that are not essential in this part of the life cycle. However, conventional reverse genetics cannot be applied for the functional analysis of genes that are essential during asexual blood-stage replication. Various strategies have been developed for conditional mutagenesis ofPlasmodium, including recombinase-based gene deletion, regulatable promoters, and mRNA or protein destabilization systems. Among these, the dimerisable Cre (DiCre) recombinase system has emerged as a powerful approach for conditional gene targeting inP. falciparum. In this system, the bacteriophage Cre is expressed in the form of two separate, enzymatically inactive polypeptides, each fused to a different rapamycin-binding protein. Rapamycin-induced heterodimerization of the two components restores recombinase activity. We have implemented the DiCre system in the rodent malaria parasiteP. berghei, and show that rapamycin-induced excision of floxed DNA sequences can be achieved with very high efficiency in both mammalian and mosquito parasite stages. This tool can be used to investigate the function of essential genes not only in asexual blood stages, but also in other parts of the malaria parasite life cycle.
Beat gestures influence which speech sounds you hear
Authors: Bosker Hans Rutger , Peeters David 
Published: July 2020

ABSTRACTBeat gestures – spontaneously produced biphasic movements of the hand – are among the most frequently encountered co-speech gestures in human communication. They are closely temporally aligned to the prosodic characteristics of the speech signal, typically occurring on lexically stressed syllables. Despite their prevalence across speakers of the world’s languages, how beat gestures impact spoken word recognition is unclear. Can these simple ‘flicks of the hand’ influence speech perception? Across six experiments, we demonstrate that beat gestures influence the explicit and implicit perception of lexical stress (e.g., distinguishingOBjectfromobJECT), and in turn, can influence what vowels listeners hear. Thus, we provide converging evidence for amanual McGurk effect: even the simplest ‘flicks of the hands’ influence which speech sounds we hear.SIGNIFICANCE STATEMENTBeat gestures are very common in human face-to-face communication. Yet we know little about their behavioral consequences for spoken language comprehension. We demonstrate that beat gestures influence the explicit and implicit perception of lexical stress, and, in turn, can even shape what vowels we think we hear. This demonstration of amanual McGurk effectprovides some of the first empirical support for a recent multimodal, situated psycholinguistic framework of human communication, while challenging current models of spoken word recognition that do not yet incorporate multimodal prosody. Moreover, it has the potential to enrich human-computer interaction and improve multimodal speech recognition systems.
The heat shock transcription factor HSF-1 protectsCaenorhabditis elegansfrom peroxide stress
Authors: Servello Francesco A. , Apfeld Javier 
Published: July 2020

AbstractCells induce conserved defense mechanisms that protect them from oxidative stress. How these defenses are regulated in multicellular organisms is incompletely understood. Using the nematodeCaenorhabditis elegans, we show that the heat shock transcription factor HSF-1 protects the nematode from the oxidative stress induced by environmental peroxide. In response to a heat shock or a mild temperature increase, HSF-1 protects the nematodes from subsequent oxidative stress in a manner that depends on HSF-1’s transactivation domain. At constant temperature, HSF-1 protects the nematodes from oxidative stress independently of its transactivation domain, likely by inducing the expression ofasp-4/cathepsin Danddapk-1/dapk. Thus, two distinct HSF-1-dependent processes protectC. elegansfrom oxidative stress.
Microbiome Dynamics of Bovine Mastitis Progression and Genomic Determinants
Authors: Hoque M. Nazmul , Istiaq Arif , Rahman M. Shaminur , Islam M. Rafiul , Anwar Azraf , Siddiki AMAM Zonaed , Sultana Munawar , Crandall Keith A. , Hossain M. Anwar 
Published: July 2020

AbstractThe milk of lactating cows presents a complex ecosystem of interconnected microbial communities which can impose a significant influence on the pathophysiology of mastitis. Previously, we reported the alteration of microbiome (bacteria, archaea, virus) composition between clinical mastitis (CM) and healthy (H) milk. We hypothesized possible dynamic shifts of microbiome compositions with the progress of different pathological states of mastitis (CM, Recurrent CM; RCM, Subclinical Mastitis; SCM) determined by its favoring genomic potentials. To evaluate this hypothesis, we employed whole metagenome sequencing (WMS) in 20 milk samples (CM = 5, RCM = 6, SCM = 4, H = 5) to unravel the microbiome dynamics, interrelation, and relevant metabolic functions. PathoScope (PS) and MG-RAST (MR) analyses mapped the WMS data to 442 bacterial, 58 archaeal and 48 viral genomes with distinct variation in microbiome composition and abundances across these metagenomes (CM>H>RCM>SCM). PS analysis identified 385, 65, 80 and 144 bacterial strains in CM, RCM, SCM, and H milk, respectively, with an inclusion of 67.19% previously unreported opportunistic strains in mastitis metagenomes. Moreover, MR detected 56, 13, 9 and 46 archaeal, and 40, 24, 11 and 37 viral genera in CM, RCM, SCM and H-milk metagenomes, respectively. The CM-microbiomes had closest association with RCM-microbiomes followed by SCM, and H-microbiomes. Furthermore, we identified 333, 304, 183 and 50 virulence factors-associated genes (VFGs), and 48, 31, 11 and 6 antibiotic resistance genes (AGRs) in CM, RCM, SCM, and H-microbiomes, respectively, showing a significant correlation between the relative abundances of VFGs (p = 0.001), ARGs (p = 0.0001), and associated bacterial taxa. We also detected correlated variations in the presence and abundance of several metabolic functional genes related to bacterial colonization, proliferation, chemotaxis, motility and invasion, oxidative stress, virulence and pathogenicity, phage integration and excision, biofilm-formation, and quorum-sensing to be associated with different episodes of mastitis. Therefore, profiling the dynamics of microbiome in different states of mastitis, concurrent VFGs, ARGs, and genomic functional correlations will contribute to developing microbiome-based diagnostics and therapeutics for bovine mastitis, and carries significant implications on curtailing the economic fallout from this disease.
Comprehensive genotyping of Brazilian Cassava (Manihot esculentaCrantz) Germplasm Bank: insights into diversification and domestication
Authors: Ogbonna Alex C. , de Andrade Luciano Rogerio Braatz , de Oliveira Eder Jorge , Mueller Lukas A. , Bauchet Guillaume J. 
Published: July 2020

AbstractCassava (Manihot esculentaCrantz) is a major staple root crop of the tropics, originating from the Amazonas region. In this study, 3,354 cassava landraces and modern breeding lines from the Embrapa Cassava Germplasm Bank (CGB) were characterized. All individuals were subjected to genotyping-by-sequencing (GBS), identifying 27,045 Single Nucleotide Polymorphisms (SNPs). Identity-by-state and population structure analyses revealed a unique set of 1,536 individuals and 10 distinct genetic groups with heterogeneous linkage disequilibrium (LD). On this basis, 1,300 to 4,700 SNP markers were selected for large quantitative trait loci (QTL) detection. Identified genetic groups were further characterized for population genetics parameters including minor allele frequency (MAF), observed heterozygosity (Ho), effective population size estimateand polymorphism information content (PIC). Selection footprints and introgressions ofM. glazioviiwere detected. Spatial population structure analysis revealed five ancestral populations related to distinct Brazilian ecoregions. Estimation of historical relationships among identified populations suggest earliest population split from Amazonas to Atlantic forest and Caatinga eco-regions and active gene flows. This study provides a thorough genetic characterization ofex situgermplasm resources from cassava center of origin, South America, with results shedding light on Brazilian cassava characteristics and its biogeographical landscape. These Findings support and facilitate the use of genetic resources in modern breeding programs including implementation of association mapping and genomic selection strategies.Key messageBrazilian cassava diversity was characterized through population genetics and clustering approaches, highlighting contrasted genetic groups, and spatial genetic differentiation.
Insecticide resistance status of malaria vectorsAnopheles gambiae s.lof southwest Burkina Faso and residual efficacy of indoor residual spraying with microencapsulated pirimiphos-methyl insecticide
Authors: Soma Dieudonné D. , Zogo Barnabas M. , Hien François D. , Hien Aristide S. , Kaboré Didier P.A. , Kientega Mahamadi , Ouédraogo Anicet G. , Pennetier Cédric , Koffi Alphonsine A. , Moiroux Nicolas , Dabiré Roch K. 
Published: July 2020

AbstractThe rapid spread of insecticide resistance in malaria vectors and the rebound in malaria cases observed recently in some endemic areas underscore the urgent need to evaluate and deploy new effective control interventions. A randomized control trial was conducted with the aim to investigate the benefit of deploying complementary strategies, including indoor residual spraying (IRS) with pirimiphos-methyl, in addition to long-lasting insecticidal nets (LLINs) in Diébougou, southwest Burkina Faso. We measured the susceptibility ofAnopheles gambiae s.l.population from Diébougou to conventional insecticides. We further monitored the efficacy and residual activity of pirimiphos-methyl on both cement and mud walls using a laboratory susceptible strain (Kisumu) and the localAn. gambiae s.l.population.An. Gambiae s.l.from Diébougou was resistant to pyrethroids (deltamethrin, permethrin and alphacypermethrin) and bendiocarb but showed susceptibility to organophosphates (pirimiphos-methyl and chlorpyrimiphos-methyl). A mixed-effect generalized linear model predicted that pirimiphos-methyl applied on cement or mud walls was effective for 210 days against the laboratory susceptible strain and 247 days against the local population. The residual efficacy of pirimiphos-methyl against the local population on walls made of mud was similar to that of cement (OR=0.792, [0.55-1.12], Tukey’s test p-value =0.19). This study showed that one round of IRS with pirimiphos-methyl CS has the potential to control the multi-resistantAn. gambiae s.l.population from Southwest Burkina Faso for at least 7 months, regardless of the type of wall.
Contrasting effects of nutrients and consumers on tree colonization and growth during secondary succession
Authors: Heckman Robert W. , Halliday Fletcher W. , Wilfahrt Peter A. 
Published: July 2020

AbstractFor succession to proceed from herbaceous to woody dominance, trees must colonize herbaceous communities and grow. Success across these two phases of succession might result from different interactions with the herbaceous community. First, colonizing trees must compete against larger, established herbs, while subsequent growth occurs among similarly sized or smaller herbs. This shift from colonization to growth may cause three drivers of secondary succession— nutrients, consumers, and herbaceous diversity—to differentially affect tree colonization and growth. Initially, these drivers should favor larger, established herbs, reducing colonization. Later, when established trees can better compete with herbs, these drivers should benefit trees and increase their growth. In a four-year study, we added nutrients to, excluded aboveground consumers from, and manipulated initial richness of, the herbaceous community, then allowed trees to naturally colonize these communities (from intact seedbanks or as seed-rain) and grow. Nutrients and consumers had opposing effects on tree colonization and growth: adding nutrients and excluding consumers reduced tree colonization, but later increased established tree growth (height, basal diameter). Together, this shows stage-specific impacts of nutrients and consumers that may improve predictions of the rate and trajectory of succession: factors that initially limited tree colonization later helped established trees to grow.
Updates on enzymatic and structural properties of human glutamine: fructose-6-phosphate amidotransferase 2 (hGFAT2)
Authors: Oliveira Isadora A. , Allonso Diego , Fernandes Tácio V. A. , Lucena Daniela M. S. , Ventura Gustavo T. , Dias Wagner B. , Mohana-Borges Ronaldo S. , Pascutti Pedro G. , Todeschini Adriane R. 
Published: July 2020

AbstractGlycoconjugates play a central role in several cellular processes and alteration in their composition is associated to human pathologies. The hexosamine biosynthetic pathway is a route through which cells obtain substrates for cellular glycosylation, and is controlled by the glutamine: fructose-6-phosphate amidotransferase (GFAT). Human isoform 2 GFAT (hGFAT2) has been implicated in diabetes and cancer, however, there is no information about structural and enzymatic properties of this enzyme. Here, we report a successful expression and purification of a catalytically active recombinant hGFAT2 (rhGFAT2) in E. coli cells fused or not to a HisTag at the C-terminal end. Our enzyme kinetics data suggest that hGFAT2 does not follow the ordered bi-bi mechanism, and performs the glucosamine-6-phosphate synthesis much slowly than previously reported for other GFATs. In addition, hGFAT2 is able to isomerase fructose-6-phosphate into glucose-6-phosphate even in presence of equimolar amounts of glutamine, in an unproductive glutamine hydrolysis. Structural analysis of the generated three-dimensional model rhGFAT2, corroborated by circular dichroism data, indicated the presence of a partially structured loop in glutaminase domain, whose sequence is present in eukaryotic enzymes but absent in the E. coli homolog. Molecular dynamics simulations show such loop as the most flexible portion of the protein, which interacts with the protein mainly through the interdomain region, and plays a key role on conformational states of hGFAT2. Altogether, our study provides the first comprehensive set of data on the structure, kinetics and mechanics of hGFAT2, which will certainly contribute for further studies focusing on drug development targeting hGFAT2.