bluuebunny/crossref_metadata_2025_split huggingface dataset:
A de novo genome assembly and annotation of the southern flying squirrel (Glaucomys volans)
Authors: Wolf J.F. , Bowman J. , Keobouasone S. , Taylor R.S. , Wilson P.J. 
Published: June 2021

ABSTRACTNorthern (Glaucomys sabrinus) and southern (Glaucomys volans) flying squirrels are widespread species distributed across much of North America. Northern flying squirrels are common inhabitants of the boreal forest, also occurring in coniferous forest remnants farther south, whereas the southern flying squirrel range is centered in eastern temperate woodlands. These two flying squirrel species exhibit a hybrid zone across a latitudinal gradient in an area of recent secondary contact.Glaucomyshybrid offspring are viable and can successfully backcross with either parental species, however, the fitness implications of such events are currently unknown. Some populations ofG. sabrinusare endangered, and thus, interspecific hybridization is a key conservation concern in flying squirrels. We sequenced and assembled ade novolong-read genome from aG. volansindividual sampled in southern Ontario, Canada, while four short-read genomes (2G. sabrinusand 2G. volans, all from Ontario) were re-sequenced on Illumina platforms. The final genome assembly consisted of approximately 2.40Gb with a scaffold N50 of 455.26Kb. Benchmarking Universal Single-Copy Orthologs reconstructed 3,742 (91.2%) complete mammalian genes and genome annotation using RNA-seq identified the locations of 19,124 protein-coding genes. The four short-read individuals were aligned to our reference genome to investigate the demographic history of the two species. A Principal Component Analysis clearly separated re-sequenced individuals, while inferring population size history using the Pairwise Sequentially Markovian Coalescent model noted an approximate species split one million years ago, and a single, possibly recently introgressed individual.
Genetic analysis of praziquantel response in schistosome parasites implicates a Transient Receptor Potential channel
Authors: Le Clec’h Winka , Chevalier Frédéric D. , Mattos Ana Carolina A. , Strickland Amanda , Diaz Robbie , McDew-White Marina , Rohr Claudia M. , Kinung’hi Safari , Allan Fiona , Webster Bonnie L , Webster Joanne P , Emery Aidan M , Rollinson David , Djirmay Amadou Garba , Al Mashikhi Khalid M , Yafae Salem Al , Idris Mohamed A , Moné Hélène , Mouahid Gabriel , LoVerde Philip , Marchant Jonathan S. , Anderson Timothy J.C. 
Published: June 2021

AbstractMass treatment with praziquantel (PZQ) monotherapy is the mainstay for schistosomiasis treatment. This drug shows imperfect cure rates in the field and parasites showing reduced PZQ response can be selected in the laboratory, but the extent of resistance in Schistosoma mansoni populations is unknown. We examined the genetic basis of variation in PZQ response in a S. mansoni population (SmLE-PZQ-R) selected with PZQ in the laboratory: 35% of these worms survive high dose (73 µg/mL) PZQ treatment. We used genome wide association to map loci underlying PZQ response. The major chr. 3 peak contains a transient receptor potential (Sm.TRPMPZQ) channel (Smp_246790), activated by nanomolar concentrations of PZQ. PZQ response shows recessive inheritance and marker-assisted selection of parasites at a single Sm.TRPMPZQ SNP enriched populations of PZQ-resistant (PZQ-ER) and sensitive (PZQ-ES) parasites showing >377 fold difference in PZQ response. The PZQ-ER parasites survived treatment in rodents better than PZQ-ES. Resistant parasites show 2.25-fold lower expression of Sm.TRPMPZQ than sensitive parasites. Specific chemical blockers of Sm.TRPMPZQ enhanced PZQ resistance, while Sm.TRPMPZQ activators increased sensitivity. A single SNP in Sm.TRPMPZQ differentiated PZQ-ER and PZQ-ES lines, but mutagenesis showed this was not involved in PZQ-response, suggesting linked regulatory changes. We surveyed Sm.TRPMPZQ sequence variation in 259 parasites from the New and Old World revealing one nonsense mutation that results in a truncated protein with no PZQ-binding site. Our results demonstrate that Sm.TRPMPZQ underlies variation in PZQ response in S. mansoni and provides an approach for monitoring emerging PZQ-resistance alleles in schistosome elimination programs.One Sentence SummaryA transient receptor potential channel determines variation in praziquantel-response in Schistosoma mansoni.
Impact of SNP calling quality on the detection of transmission ratio distortion in goats
Authors: Luigi-Sierra María Gracia , Casellas Joaquim , Martínez Amparo , Delgado Juan Vicente , Álvarez Javier Fernández , Such Francesc Xavier , Jordana Jordi , Amills Marcel 
Published: June 2021

SUMMARYTransmission ratio distortion (TRD) is the preferential transmission of one specific allele to offspring at the expense of the other one. The existence of TRD is mostly explained by the segregation of genetic variants with deleterious effects on the developmental processes that go from the formation of gametes to fecundation and birth. A few years ago, a statistical methodology was implemented in order to detect TRD signals on a genome-wide scale as a first step to uncover the biological basis of TRD and reproductive success in domestic species. In the current work, we have analyzed the impact of SNP calling quality on the detection of TRD signals in a population of Murciano-Granadina goats. Seventeen bucks and their offspring (N=288) were typed with the Goat SNP50 BeadChip, while the genotypes of the dams were lacking. Performance of a genome-wide scan revealed the existence of 36 SNPs showing significant evidence of TRD. When we calculated GenTrain scores for each one of the SNPs, we observed that 25 SNPs showed scores below 0.8. The allele frequencies of these SNPs in the offspring were not correlated with the allele frequencies estimated in the dams with statistical methods, thus evidencing that flawed SNP calling quality might lead to the detection of spurious TRD signals. We conclude that, when performing TRD scans, the GenTrain scores of markers should be taken into account to discriminate SNPs that are truly under TRD from those yielding spurious signals due to technical problems.
Motif-based phosphoproteome clustering improves modeling and interpretation
Authors: Creixell Marc , Meyer Aaron S. 
Published: June 2021

AbstractCell signaling is orchestrated in part through a network of protein kinases and phosphatases. Dysregulation of kinase signaling is widespread in diseases such as cancer and is readily targetable through inhibitors of kinase enzymatic activity. Mass spectrometry-based analysis of kinase signaling can provide a global view of kinase signaling regulation but making sense of these data is complicated by its stochastic coverage of the proteome, measurement of substrates rather than kinase signaling itself, and the scale of the data collected. Here, we implement a dual data and motif clustering strategy (DDMC) that simultaneously clusters substrate peptides into similarly regulated groups based on their variation within an experiment and their sequence profile. We show that this can help to identify putative upstream kinases and supply more robust clustering. We apply this clustering to large-scale clinical proteomic profiling of lung cancer and identify conserved proteomic signatures of tumorigenicity, genetic mutations, and tumor immune infiltration. We propose that DDMC provides a general and flexible clustering strategy for the analysis of phosphoproteomic data.One-sentence SummaryDDMC is a general and flexible strategy for phosphoproteomic analysis by clustering phosphopeptides using both their phosphorylation abundance and sequence motifs.
Imaging of the pial arterial vasculature of the human brain in vivo using high-resolution 7T time-of-flight angiography
Authors: Bollmann Saskia , Mattern Hendrik , Bernier Michaël , Robinson Simon D. , Park Daniel , Speck Oliver , Polimeni Jonathan R. 
Published: June 2021

AbstractThe pial arterial vasculature of the human brain is the only blood supply to the neocortex, but quantitative data on the morphology and topology of these mesoscopic arteries (diameter 50– 300 µm) remains scarce. Because it is commonly assumed that blood flow velocities in these vessels are prohibitively slow, non-invasive time-of-flight MRI angiography (TOF-MRA)—which is well-suited to high 3D imaging resolutions—has not been applied to imaging the pial arteries. Here, we provide a theoretical framework that outlines how TOF-MRA can visualize small pial arteries in vivo, by employing extremely small voxels at the size of individual vessels. We then provide evidence for this theory by imaging the pial arteries at 140-µm isotropic resolution using a 7T MRI scanner and prospective motion correction, and show that pial arteries one voxel-width in diameter can be detected. We conclude that imaging pial arteries is not limited by slow blood flow, but instead by achievable image resolution. This study represents the first targeted, comprehensive account of imaging pial arteries in vivo in the human brain. This ultra-high-resolution angiography will enable the characterization of pial vascular anatomy across the brain to investigate patterns of blood supply and relationships between vascular and functional architecture.
Dietary modulation alters susceptibility to Listeria monocytogenes and Salmonella typhimurium in a gut microbiota-independent manner
Authors: Wolter Mathis , Steimle Alex , Zimmer Jacques , Desai Mahesh S. 
Published: June 2021

AbstractFood safety has considerably improved worldwide, yet infections with food-borne human enteric pathogens, such as Listeria spp. and Salmonella spp., still cause numerous hospitalizations and fatalities. Thus, the need to shed more light on the mechanisms of enteropathogenesis is apparent. Since dietary alterations, including fiber deficiency, might impact the colonization resistance by the gut microbiota, studying diet–microbiota–pathogen axis holds promise in further understanding the pathogenesis mechanisms. Using a gnotobiotic mouse model containing a 14-member synthetic human gut microbiota (14SM), we have previously shown that dietary fiber deprivation promotes proliferation of mucin-degrading bacteria leading to a microbiota-mediated erosion of the colonic mucus barrier, which results in an increased susceptibility towards the rodent enteric pathogen Citrobacter rodentium. Here, we sought to understand how low-fiber diet affects susceptibility to Listeria monocytogenes and Salmonella typhimurium infections in our 14SM gnotobiotic mouse model, in BALB/c and C57BL/6N backgrounds, respectively. Intriguingly and in contrast to our results with C. rodentium, we observe that depriving mice of dietary fiber protected them from infections with the pathogens compared to mice fed a standard chow. The microbiota delayed the overall pathogenicity as compared to the onset of disease observed in germ-free control mice; nevertheless, we observe the same effect of diet in germ-free mice, suggesting that the susceptibility is microbiota independent. Our study points out an important observation that dietary fiber plays a crucial role on either the host susceptibility, the virulence of these pathogens, or both, which would be judicious to design and interpret future studies.ImportanceHuman enteric pathogens Listeria monocytogenes and Salmonella typhimurium are employed as classical models in rodent hosts to understand the pathogenesis mechanisms of food-borne pathogens. Research in the past decade has stressed importance of the composition of the gut microbiota in modulating susceptibility to these pathogens. Our results—using gnotobiotic mice and germ-free control animals—additionally suggest that the dietary fiber components dominate the impact of enteropathogenic virulence over the pathogenicity-modulating properties of the gut microbiota. The significance of our research is in the need to carefully choose a certain chow when performing the enteropathogen-associated mouse experiments and to cautiously match the rodent diets when trying to replicate experiments across different laboratories. Finally, our data underscore the importance of germ-free control animals to study these pathogens, as our findings would have been prone to misinterpretation in the absence of these controls.
Equine intestinal O-seroconverting temperate coliphage Hf4s: genomic and biological characterization
Authors: Kulikov Eugene E. , Golomidova Alla K. , Efimov Alexandr D. , Belalov Ilya S. , Letarova Maria A. , Zdorovenko Evelina L. , Knirel Yuriy A. , Dmitrenok Andrey S. , Letarov Andrey V. 
Published: June 2021

Tailed bacteriophages constitute the bulk of the intestinal viromes of the vertebrate animals. However, the relationships between lytic and lysogenic lifestyles of the phages in these ecosystems are not always clear and may vary between the species or even between the individuals. The human intestinal (fecal) viromes are believed to be dominated by temperate phages, while in the horse feces the virulent phages are more prevalent. Almost all the isolates of horse fecal coliphages are virulent. Phage Hf4s is the first temperate equine intestinal coliphage characterized. It was isolated from the horse feces on the indigenous equine E. coli 4s strain. It is a podovirus, related to Lederbergvirus genus (including the well–characterized Salmonella phage P22). Hf4s recognizes the host O antigen as its primary receptor and possesses a functional O-antigen seroconversion cluster that renders the lysogens protected from the superinfection by the same phage and also abolishes the adsorption of some indigenous equine virulent coliphages, such as DT57C, while the other phages, such as G7C or phiKT retain the ability to infect E. coli 4s (Hf4s) lysogens.ImportanceThe relationships between virulent and temperate bacteriophages and their impact on high-density symbiotic microbial ecosystems of the animal are not always clear and may vary between the species or even between the individuals. The horse intestinal virome is dominated by the virulent phages, and Hf4s is the first temperate equine intestinal coliphage characterized. It recognizes the host O antigen as its primary receptor and possesses a functional O-antigen seroconversion cluster that renders the lysogens protected from the superinfection by some indigenous equine virulent coliphages, such as DT57C, while the other phages, such as G7C or phiKT retain the ability to infect E. coli 4s (Hf4s) lysogens. microbial viruses in the mammal intestinal ecosystems.
Amyloid aggregation of Streptococcus mutans Cnm influences its collagen-binding activity
Authors: de Mojana di Cologna Nicholas , Samaddar Sandip , Valle Carolina A. , Vargas Jonathan , Aviles-Reyes Alejandro , Morales Joyce , Ganguly Tridib , Pileggi Roberta , Brady L. Jeannine , Lemos José A. , Abranches Jacqueline 
Published: June 2021

ABSTRACTThe glycosylated collagen- and laminin-binding surface adhesin Cnm is present in approximately 20% of S. mutans clinical isolates and is associated with systemic infections and increased caries risk. Other surface-associated collagen-binding proteins of S. mutans such as P1 and WapA have been demonstrated to form an amyloid quaternary structure with functional implications within biofilms. In silico analysis predicted that the β-sheet rich N-terminal collagen-binding domain (CBD) of Cnm has propensity for amyloid aggregation, whereas the threonine-rich C-terminal domain was predicted to be disorganized. In this study, thioflavin-T fluorescence and electron microscopy were used to show that Cnm forms amyloids either in its native glycosylated or recombinant non-glycosylated forms and that the CBD of Cnm is the main amyloidogenic unit of Cnm. We then performed a series of in vitro, ex vivo and in vivo assays to characterize the amylogenic properties of Cnm. In addition, Congo red birefringence indicated that Cnm is a major amyloidogenic protein of S. mutans biofilms. Competitive binding assays using collagen-coated microtiter plates and dental roots, a substrate rich in collagen, revealed that Cnm monomers inhibit S. mutans binding to collagenous substrates whereas Cnm amyloid aggregates lose this property. Thus, while Cnm contributes to recognition and initial binding of S. mutans to collagen-rich surfaces, Cnm amyloid aggregation appears to represent a mechanism to modulate this activity in mature biofilms.IMPORTANCEStreptococcus mutans is a keystone pathogen that promotes caries by acidifying the dental biofilm milieu. The collagen- and laminin-binding glycoprotein Cnm is a virulence factor found in about 20% of the clinical isolates of S. mutans. Expression of Cnm by S. mutans is associated with niche expansion, allowing colonization of multiple sites in the body including collagen-rich surfaces such as dentin and heart valves. Here, we demonstrate for the first time that Cnm function appears to be modulated by its aggregation status. As a monomer, its primary function is to promote attachment to collagenous substrates via its collagen binding domain (CBD). However, in later stages of biofilm maturation, the same CBD of Cnm self-assembles into amyloid fibrils, losing the ability to bind to collagen and likely becoming a component of the biofilm matrix. Our findings shed light into the role of functional amyloids in S. mutans pathobiology and ecology.
A high content microscopy screening identifies new genes involved in cell width control inBacillus subtilis
Authors: Juillot Dimitri , Cornilleau Charlène , Deboosere Nathalie , Billaudeau Cyrille , Evouna-Mengue Parfait , Lejard Véronique , Brodin Priscille , Carballido-López Rut , Chastanet Arnaud 
Published: June 2021

AbstractHow cells control their shape and size is a fundamental question of biology. In most bacteria, cell shape is imposed by the peptidoglycan (PG) polymeric meshwork that surrounds the cell. Thus, bacterial cell morphogenesis results from the coordinated action of the proteins assembling and degrading the PG shell. Remarkably, during steady-state growth, most bacteria maintain a defined shape along generations, suggesting that error-proof mechanisms tightly control the process. In the rod-shaped model for Gram-positive bacteriaBacillus subtilis, the average cell length varies as a function of the growth rate but the cell diameter remains constant throughout the cell cycle and across growth conditions. Here, in an attempt to shed light on the cellular circuits controlling bacterial cell width, we developed a screen to identify genetic determinants of cell width inB. subtilis. Using high-content screening (HCS) fluorescence microscopy and semi-automated measurement of single-cell dimensions, we screened a library of ~ 4000 single knockout mutants. We identified 13 mutations significantly altering cell diameter, in genes that belong to several functional groups. In particular, our results indicate that metabolism plays a major role in cell width control inB. subtilis.
In vitro culture of freshly isolated Trypanosoma brucei brucei bloodstream forms results in gene copy-number changes
Authors: Mulindwa Julius , Ssentamu Geofrey , Matovu Enock , Marucha Kevin Kamanyi , Aresta-Branco Francisco , Helbig Claudia , Clayton Christine 
Published: June 2021

AbstractMost researchers who study unicellular eukaryotes work with an extremely limited number of laboratory-adapted isolates that were obtained from the field decades ago, but the effects of passage in laboratory rodents, and adaptation to in vitro culture, have been little studied. For example, the vast majority of studies of Trypanosoma brucei biology have concentrated on just two strains, Lister 427 and EATRO1125, which were taken from the field over half a century ago and have since have undergone innumerable passages in rodents and culture. We here describe two new Trypanosoma brucei brucei strains. MAK65 and MAK98, which have undergone only 3 rodent passages since isolation from Ugandan cattle. High-coverage sequencing revealed that adaptation of the parasites to culture was accompanied by changes in gene copy numbers. T. brucei has so far been considered to be uniformly diploid, but we also found trisomy of chromosome 5 not only in one Lister 427 culture, but also in the MAK98 field isolate. Trisomy of chromosome 6, and increased copies of other chromosome segments, were also seen in established cultured lines. The two new T. brucei strains should be useful to researchers interested in trypanosome differentiation and pathogenicity. Initial results suggested that the two strains have differing infection patterns in rodents. MAK65 is uniformly diploid and grew more reproducibly in bloodstream-form culture than MAK98.
Changes In Ploidy Affect Vascular Allometry And Hydraulic Function In Trees
Authors: Barceló-Anguiano M , Holbrook NM , Hormaza JI , Losada JM 
Published: June 2021

SummaryThe enucleated vascular elements of the xylem and the phloem offer an excellent system to test the effect of ploidy on plant function because variation in vascular geometry has a direct influence on transport efficiency. However, evaluations of conduit sizes in polyploid plants have remained elusive, most remarkably in woody species.We used a combination of molecular, physiological, and microscopy techniques to model the hydraulic resistance between source and sinks in tetraploid and diploid mango trees.Tetraploids exhibited larger chloroplasts, mesophyll cells, and stomatal guard cells, resulting in higher leaf elastic modulus and lower dehydration rates despite the high water potentials of both ploidies in the field. Both the xylem and the phloem displayed a scaling of conduits with ploidy, revealing attenuated hydraulic resistance in tetraploids.Conspicuous wall hygroscopic moieties in the cells involved in processes of transpiration and transport advocates a role in volumetric adjustments due to turgor change in polyploids, which, together with the enlargement of organelles, cells, and tissues that are critical for water and photo assimilate transport at long distances, imply major physiological novelties of polyploidy.
Biological, Molecular and Phiysiological
Characterization of Four Soybean mosaic
virus Isolates Present in Argentine Soybean
Crops
Authors: Maugeri Suarez M , Rodríguez M , Bejerman N , Laguna I. G , Rodríguez Pardina P 
Published: June 2021

ABSTRACT
Soybean mosaic
virus (SMV) causes systemic
infections in soybean plants, leading to chlorotic
mosaic and producing significant yield losses. The
virus is widely distributed in all soybean
production areas in the world. In Argentina, three
geographical isolates were identified: Marcos
Juárez (MJ), Manfredi (M), and North Western
Argentina (NOA), and another isolate named “Planta
Vinosa” (PV), which causes severe necrosis
symptoms in some cultivars. Here, the biological,
molecular and physiological characterization of
these isolates was performed for the first time.
Three of the four isolates showed a low genetic
divergence in the evaluated genes (P1, CI and CP).
Although SMV-NOA and SMV-PV had high homology at
the sequence level, they showed wide differences
in pathogenicity, seed mottling and the ability of
transmission by seeds or aphids, as well as in
physiological effects. SMV-NOA caused early
alterations (before symptom appearance, BS) in
ΦPSII and MDA content in leaves with respect to
the other isolates. After the appearance of
macroscopic symptoms (late symptoms, LS), SMV-M
caused a significant increase in the content of
MDA, total soluble sugars, and starch with respect
to the other isolates. Thus, early alterations of
ΦPSII and soluble sugars might have an impact on
late viral symptoms. Likewise, SMV-MJ developed
more severe symptoms in the susceptible Davis
cultivar than in DM 4800. Therefore, our results
show differences in genome, biological properties
and physiological effects among SMV isolates as
well as different interactions of SMV-MJ with two
soybean cultivars.