bluuebunny/crossref_metadata_2025_split huggingface dataset:
ComF is a key mediator in single-stranded DNA transport and handling during natural transformation
Authors: Damke Prashant P. , Celma Louisa , Kondekar Sumedha , Guilmi Anne Marie Di , Marsin Stéphanie , Dépagne Jordane , Veaute Xavier , Legrand Pierre , Walbott Hélène , Vercruyssen Julien , Guérois Raphaël , Quevillon-Cheruel Sophie , Radicella J. Pablo 
Published: August 2021

ABSTRACTNatural transformation plays a major role in the spreading of antibiotic resistances and virulence factors. Whilst bacterial species display specificities in the molecular machineries allowing transforming DNA capture and integration into their genome, the ComF(C) protein is essential for natural transformation in all Gram-positive and - negative species studied. Despite this, its role remains largely unknown. Here, we show that Helicobacter pylori ComF is not only involved in DNA transport through the cell membrane, but it also required for the handling of the ssDNA once it is delivered into the cytoplasm. ComF crystal structure revealed the presence of a zinc-finger motif and a putative phosphoribosyl transferase domain, both necessary for its in vivo activity. ComF is a membrane-associated protein with affinity for single-stranded DNA. Collectively, our results suggest that ComF provides the link between the transport of the transforming DNA into the cytoplasm and its handling by the recombination machinery.
LRET-derived HADDOCK structural models describe the conformational heterogeneity required for processivity of the Mre11-Rad50 DNA damage repair complex
Authors: Canny Marella D. , Latham Michael P. 
Published: August 2021

AbstractThe Mre11-Rad50-Nbs1 protein complex is one of the first responders to DNA double strand breaks. Studies have shown that the catalytic activities of the evolutionarily conserved Mre11-Rad50 (MR) core complex depend on an ATP-dependent global conformational change that takes the macromolecule from an open, extended structure in the absence of ATP to a closed, globular structure when ATP is bound. We have previously identified an additional ‘partially open’ conformation using Luminescence Resonance Energy Transfer (LRET) experiments. Here, a combination of LRET and the molecular docking program HADDOCK was used to further investigate this partially open state and identify three conformations of ATP-bound MR in solution: closed, partially open, and open, which are in addition to the extended, apo conformation. These models are supported with mutagenesis and SAXS data that corroborate the presence of these three states and suggest a mechanism for the processivity of the MR complex along the DNA.
Helical Ordering of Envelope Associated Proteins and Glycoproteins in Respiratory Syncytial Virus Filamentous Virions
Authors: Conley Michaela J. , Short Judith M. , Hutchings Joshua , Burns Andrew M. , Streetley James , Bakker Saskia E. , Jaffery Hussain , Stewart Murray , Power B. Joanne , Zanetti Giulia , Fearns Rachel , Vijayakrishnan Swetha , Bhella David 
Published: August 2021

AbstractHuman respiratory syncytial virus (RSV) causes severe respiratory illness in children and the elderly. Treatments for RSV disease are however limited and efforts to produce an effective vaccine have so far been unsuccessful. Understanding RSV virion structure is an important prerequisite for developing interventions to treat or prevent infection but has been challenging because of the fragility of virions propagated in cell culture. Here we show, using cryogenic electron microscopy (cryoEM) and cryogenic electron tomography (cryoET) of RSV particles cultivated directly on transmission electron microscopy (TEM) grids, that there is extensive helical symmetry in RSV filamentous virions. We have calculated a 16 Å resolution three-dimensional reconstruction of the viral envelope, targeting the matrix protein (M) that forms an endoskeleton below the viral membrane. These data define a helical lattice of M proteins, showing how M is oriented relative to the viral envelope and that helical ordering of viral glycoproteins that stud the viral envelope is coordinated by the M layer. Moreover, the helically ordered viral glycoproteins in RSV filamentous virions cluster in pairs, which may have implications for the conformation of fusion (F) glycoprotein epitopes that are the principal target for vaccine and monoclonal antibody development. We also report the presence, in authentic virus infections, of N-RNA rings packaged within RSV filamentous virions. Overall, the structural data obtained provides molecular insight into the organization of the virion and the mechanism of its assembly.
Role of polycomb repressive complex 2 in regulation of human transcription factor gene expression
Authors: Brown Jay C. 
Published: August 2021

ABSTRACTThe study described here was pursued with the idea that information about control of human gene expression might result from comparing the promoter regions of a highly expressed gene population with that of a related population that is weakly expressed. Systematic differences in the two promoter populations would be candidates for a role in causing the distinct expression levels observed. The results reported here were obtained with human genes encoding transcription factors (TF). Among TF genes, those with wide tissue transcription are strongly expressed while those expressed in one or only a few tissues are weakly transcribed in most cases. The promoter regions of the two populations were compared using the results of ChIP-seq experiments. Results demonstrated that the promoter region of broadly expressed TF genes is enriched in binding sites for POLR2A, a component of RNA polymerase II while promoters of tissue targeted genes are enriched in EZH2, a subunit of polycomb repressive complex 2 (PRC2). It was rare to observe promoters with binding sites for both POLR2A and EZH2 or for neither one. The findings are interpreted to indicate that strong expression of broadly expressed TF genes is due to the presence of RNA polymerase II at the promoter while weak expression of tissue targeted promoters results from the presence of PRC2. Finally, transcription factor families were compared in the proportion of broadly expressed and tissue targeted genes. The results demonstrated that most families possess both broadly expressed and tissue targeted members. For instance, this was the case with 16 of 20 TF families. The results are interpreted to indicate that while individual TFs such as EZH2 may be specific for broadly expressed or tissue targeted genes, this is not a property of most TF families. Most have both broadly expressed and tissue targeted members.
Regulators of male and female sexual development critical for transmission of a malaria parasite
Authors: Russell Andrew J C , Sanderson Theo , Bushell Ellen , Talman Arthur M , Anar Burcu , Girling Gareth , Hunziker Mirjam , Kent Robyn S , Metcalf Tom , Montandon Ruddy , Pandey Vikash , Brett Roberts A , Sayers Claire , Schwach Frank , Rayner Julian C , Voet Thierry , Modrzynska Katarzyna K , Waters Andrew P. , Lawniczak Mara K N , Billker Oliver 
Published: August 2021

SummaryThe transmission of malaria parasites from vertebrate host to mosquito vector requires a developmental switch in asexually dividing blood-stage parasites to sexual reproduction. In Plasmodium berghei the transcription factor AP2-G is required and sufficient for this switch, but how a particular sex is determined in a haploid parasite remains unknown. Using a global screen of barcoded mutants, we here identify ten genes essential for the formation of either male or female sexual forms and validate their importance for transmission. High-resolution single-cell transcriptomics of wild-type and mutant parasites portrays the developmental bifurcation and reveals a regulatory cascade of putative gene functions in determination and subsequent differentiation of each sex. A male-determining gene with a LOTUS/OST-HTH domain points towards unexpected conservation of molecular mechanisms of gametogenesis in animals and a distantly related eukaryotic parasite.
Identifying genomic regions and candidate genes selected during the breeding of rice in Vietnam
Authors: Higgins Janet , Santos Bruno , Khanh Tran Dang , Trung Khuat Huu , Duong Tran Duy , Phuong Doai Nguyen Thi , Hall Anthony , Dyer Sarah , Ham Le Huy , Caccamo Mario , De Vega Jose 
Published: August 2021

AbstractBackground and aimsVietnam harnesses a rich diversity of rice landraces adapted to a broad range of conditions, which constitute a largely untapped source of genetic diversity for the continuous improvement of rice cultivars. We previously identified a strong population structure in Vietnamese rice, which is captured in five Indica and four Japonica subpopulations, including an outlying Indica-5 group. Here, we leveraged on that strong differentiation, and the 672 rice genomes generated, to identify genes within genomic regions putatively selected during domestication and breeding of rice in Vietnam.MethodologyWe identified significant distorted patterns in allele frequency (XP-CLR method) and population differentiation scores (FST), resulting from differential selective pressures between native subpopulations, and compared them with QTLs previously identified by GWAS in the same panel. We particularly focused on the outlying Indica-5 subpopulation because of its likely novelty and differential evolution.ResultsWe identified selection signatures in each of the Vietnamese subpopulations and carried out a comprehensive annotation of the 52 regions selected in Indica-5, which represented 8.1% of the rice genome. We annotated the 4,576 genes in these regions, verified the overlap with QTLs identified in the same diversity panel and the comparison with a FST analysis between subpopulations, to select sixty-five candidate genes as promising breeding targets, several of which harboured alleles with non-synonymous substitutions.ConclusionsOur results highlight genomic differences between traditional Vietnamese landraces, which are likely the product of adaption to multiple environmental conditions and regional culinary preferences in a very diverse country. We also verified the applicability of this genome scanning approach to identify potential regions harbouring novel loci and alleles to breed a new generation of sustainable and resilient rice.Key MessageWe localised regions in the rice genome selected during breeding by comparing allele frequency patterns among Vietnamese rice subpopulations. We characterised candidate genes in the Indica-5 subpopulation with breeding potential.
Transcranial Ultrasound Stimulation in Anterior Cingulate Cortex Impairs Information Sampling and Learning in Loss Contexts
Authors: Boroujeni Kianoush Banaie , Sigona Michelle K , Treuting Robert Louie , Manuel Thomas J. , Caskey Charles F. , Womelsdorf Thilo 
Published: August 2021

ABSTRACTNeuronal subgroups in anterior cingulate cortex (ACC) and the anterior striatum (STR) encode the reward structure of a given environment. But whether or how this reward information is used to guide information sampling, optimize decision making, or motivate behavior in cognitively challenging situations has remained elusive. Here, we causally tested these scenarios by transiently disrupting ACC and STR of rhesus monkeys with transcranial ultrasound with a learning task that independently varied cognitive and motivational demands. We found that disrupting the ACC, but not the STR, prolonged information sampling and reduced learning efficiency whenever the motivational payoff was low. These impairments were most pronounced at high cognitive demands and based on an inability to use loss experiences to improve performance. These results provide causal evidence that the ACC is necessary for motivation, to overcome anticipated costs from negative (loss) outcomes, and for cognition, to enhance visual information sampling during adaptive behavior.HIGHLIGHTSTranscranial ultrasound stimulation of the anterior cingulate cortex disrupts learning after loss experience.The ultrasound-induced learning deficit is exacerbated at high cognitive load.The ultrasound-induced learning deficit is accompanied by inefficient fixational information sampling.Anterior cingulate cortex causally supports credit assignment of aversive outcomes to visual features.
Genomic diversity of bacteriophages infecting Rhodobacter capsulatus and their relatedness to its gene transfer agent RcGTA
Authors: Rapala Jackson , Miller Brenda , Garcia Maximiliano , Dolan Megan , Bockman Matthew , Hansson Mats , Russell Daniel A. , Garlena Rebecca A. , Cresawn Steven G. , Westbye Alexander B. , Beatty J. Thomas , Alvey Richard M. , Bollivar David W. 
Published: August 2021

AbstractThe diversity of bacteriophages is likely unparalleled in the biome due to the immense variety of hosts and the multitude of viruses that infect them. Recent efforts have led to description at the genomic level of numerous bacteriophages that infect the Actinobacteria, but relatively little is known about those infecting other prokaryotic phyla, such as the purple non-sulfur photosynthetic α-proteobacterium Rhodobacter capsulatus. This species is a common inhabitant of freshwater ecosystems and has been an important model system for the study of photosynthesis. Additionally, it is notable for its utilization of a unique form of horizontal gene transfer via a bacteriophage-like element known as the gene transfer agent (RcGTA). Only three bacteriophages of R. capsulatus had been sequenced prior to this report. Isolation and characterization at the genomic level of 26 new bacteriophages infecting this host advances the understanding of bacteriophage diversity and the origins of RcGTA. These newly discovered isolates can be grouped along with three that were previously sequenced to form six clusters with four remaining as single representatives. These bacteriophages share genes with RcGTA that seem to be related to host recognition. One isolate was found to cause lysis of a marine bacterium when exposed to high titer lysate. Although some clusters are more highly represented in the sequenced genomes, it is evident that many more bacteriophage types that infect R. capsulatus are likely to be found in the future.
Statistical potentials from the Gaussian scaling behaviour of chain fragments buried within protein globules
Authors: Zamuner Stefano , Seno Flavio , Trovato Antonio 
Published: August 2021

AbstractKnowledge-based approaches use the statistics collected from protein data-bank structures to estimate effective interaction potentials between amino acid pairs. Empirical relations are typically employed that are based on the crucial choice of a reference state associated to the null interaction case. Despite their significant effectiveness, the physical interpretation of knowledge-based potentials has been repeatedly questioned, with no consensus on the choice of the reference state. Here we use the fact that the Flory theorem, originally derived for chains in a dense polymer melt, holds also for chain fragments within the core of globular proteins, if the average over buried fragments collected from different non-redundant native structures is considered. After verifying that the ensuing Gaussian statistics, a hallmark of effectively non-interacting polymer chains, holds for a wide range of fragment lengths, we use it to define a ‘bona fide’ reference state. Notably, despite the latter does depend on fragment length, deviations from it do not. This allows to estimate an effective interaction potential which is not biased by the presence of correlations due to the connectivity of the protein chain. We show how different sequence-independent effective statistical potentials can be derived using this approach by coarse-graining the protein representation at varying levels. The possibility of defining sequence-dependent potentials is explored.
Retinoic acid treatment recruits macrophages and increases axonal regeneration after optic nerve injury in the frog Rana pipiens
Authors: De La Rosa-Reyes Valeria , Duprey-Díaz Mildred V. , Blagburn Jonathan M. , Blanco Rosa E. 
Published: August 2021

AbstractRetinoic acid (RA) plays major roles during nervous system development, and during regeneration of the adult nervous system. We have previously shown that components of the RA signaling pathway are upregulated after optic nerve injury, and that exogenous application of all-trans retinoic acid (ATRA) greatly increases the survival of axotomized retinal ganglion cells (RGCs). The objective of the present study is to investigate the effects of ATRA application on the macrophages in the optic nerve after injury, and to determine whether this affects axonal regeneration. The optic nerve was crushed and treated with PBS, ATRA and/or clodronate-loaded liposomes. Nerves were examined at one and two weeks after axotomy with light microscopy, immunocytochemistry and electron microscopy. ATRA application to the optic nerve caused transient increases in the number of macrophages and microglia one week after injury. The macrophages are consistently labeled with M2-type markers, and have considerable phagocytic activity. ATRA increased ultrastructural features of ongoing phagocytic activity in macrophages at one and two weeks. ATRA treatment also significantly increased the numbers of regenerating GAP-43-labeled axons. Clodronate liposome treatment depleted macrophage numbers by 80%, completely eliminated the ATRA-mediated increase in axonal regeneration, and clodronate treatment alone decreased axonal numbers by 30%. These results suggest that the success of axon regeneration is partially dependent on the presence of debris-phagocytosing macrophages, and that the increases in regeneration caused by ATRA are in part due to their increased numbers. Further studies will examine whether macrophage depletion affects RGC survival.
Change in the bladder function of rats with focal cerebral infarction induced by photochemically-induced thrombosis
Authors: Ota Yuya , Kubota Yasue , Hotta Yuji , Matsumoto Mami , Matsuyama Nayuka , Kato Taiki , Hamakawa Takashi , Kataoka Tomoya , Kimura Kazunori , Sawamoto Kazunobu , Yasui Takahiro 
Published: August 2021

ABSTRACTThe photochemically-induced thrombosis(photothrombosis) method can create focal cerebral infarcts anywhere in the relatively superficial layers of the cerebrum; it is easy to implement and minimally invasive. Taking advantage of this versatility, we aimed to establish a new rat model of urinary frequency with focal cerebral infarction, which was characterized by its simplicity, nonlethal nature, and high reproducibility. The prefrontal cortex and the anterior cingulate cortex, which are urinary centers, were targeted for focal cerebral infarction, and urinary parameters were measured by cystometrogram. Cystometric analysis indicated that micturition intervals significantly shortened in photothrombosis-treated rats compared with those in the sham operative group on Days 1 and 7 (P < 0.01), but prolonged after 14 days, with no difference between the two groups. Immunopathological evaluation showed an accumulation of activated microglia, followed by an increase in reactive astrocytes at the peri-infarct zone after photothrombotic stroke. Throughout this study, all postphotothrombosis rats showed cerebral infarction in the prefrontal cortex and anterior cingulate cortex; there were no cases of rats with fatal cerebral infarction. This model corresponded to the clinical presentation, in that the micturition status changed after stroke. In conclusion, this novel model combining nonlethality and high reproducibility may be a suitable model of urinary frequency after focal cerebral infarction.
The creation of functioning gastrojejunostomy following magnetic compression
Authors: Qiao Wei , Lv Yi , Du Zhaoqing , Li Hui , Du Lixue , Hu Haitian , Li Dichen 
Published: August 2021

AbstractBackgroundMagnetic compression for creating gastrojejunostomy has many advantages according to previous studies. However, following mechanical device release after healing, the anastomotic stenosis becomes the pivotal point.MethodsRectangle-shaped magnets were used for magnetic compression in rabbits. Both paclitaxel-loaded magnets and a strategy of pyloric ligation were chosen to improve the gastrojejunostomy. Based on these choices, the half-capsule was applied to occlude the pylorus after anastomotic formation. The size and patency of the anastomoses were analyzed to evaluate the efficacy of these approaches. A histological examination was also performed.ResultsThe positive effect of ligating the pylorus on gastrojejunostomy was significantly greater than that achieved using paclitaxel-loaded magnets during either short- or long-term follow-up. There were fewer scar tissue and collagen fibers at the anastomotic site in the treatment group than in the control group. The anastomotic aperture was of great interest at 9 months after the ligation of the pylorus following magnetic compression. In the view of the jejunum, although the aperture was barely visible, gastric juice was continuously spilling through it like a spring, and the aperture was clearly visible from the stomach side. All half-capsules failed to block the pylorus.ConclusionThe effect of paclitaxel on maintaining gastrojejunostomy patency was temporary. The ligation of the pylorus ensured the long-term patency of gastrojejunostomy, and the aperture was comparable to the pylorus which could play an anti-reflux role. Further studies for the sort of gastrointestinal aperture are being planned.
Evaluation of freshness and physicochemical characteristics of blankets of pirarucu (Arapaima gigas) bred in captivity at different ages in relation to the seasons
Authors: de Rosa Krishna R. , da Silva Alessandra A. , de Barros Wander M. , Pedroso Anaqueli L. , Ferreira Maria Fernanda E. , Savay-da-Silva Luciana K. , de F. Mateus Lucia Aparecida , Kubota Ernesto H. 
Published: August 2021

AbstractThis study aimed to evaluate the freshness and physicochemical characterization of pirarucu blankets at different ages bred in captivity in excavated tanks in northern Mato Grosso State, Brazil, in different seasons (rain and dry seasons). Four harvests were performed in two different tanks and five specimens obtained in each evaluated period, with animals aged 18 and 24 months, respectively, at the beginning of the experiment. The animals were slaughtered in a local establishment that had an inspection service following humane standards, and the blankets were later sent to analysis. The samples were analyzed for freshness via total volatile nitrogenous bases and physicochemical characteristics (pH in 24 h, water activity, water retention capacity, dripping loss, cooking loss, and shear force). There was a statistical difference for total nitrogenous volatile bases and shear force with higher values in the rainy season (24 month-of-old animals). Additionally, pH and water activity differed statistically at 24 h in the same period, albeit for 18-month-of-old animals. It was possible to conclude that climate variation affected the freshness and physicochemical characteristics of the pirarucu blankets while age did not.