bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of within-host spread ofChlamydia trachomatisbetween vagina, endocervix and rectum revealed by comparative genomic analysis
Authors: Joseph Sandeep J. , Bommana Sankhya , Ziklo Noa , Kama Mike , Dean Deborah , Read Timothy D. 
Published: January 2023

AbstractChlamydia trachomatis, a gram-negative obligate intracellular bacterium, commonly causes sexually transmitted infections (STIs). Little is known aboutC. trachomatistransmission within the host, which is important for understanding disease epidemiology and progression. We used RNA-bait enrichment and whole-genome sequencing to compare rectal, vaginal and endocervical samples collected at the same time from 26 study participants who attended Fijian Ministry of Health and Medical Services clinics and tested positive forC. trachomatisat each anatomic site. The 78C. trachomatisgenomes from participants were from two major clades of theC. trachomatisphylogeny (the “prevalent urogenital and anorecta”l clade and “non-prevalent urogenital and anorectal” clade). For 21 participants, genome sequences were almost identical in each anatomic site. For the other five participants, two distinctC. trachomatisstrains were present in different sites; in two cases, the vaginal sample was a mixture of strains. The absence of large numbers of fixed SNPs betweenC. trachomatisstrains within many of the participants could indicate recent acquisition of infection prior to the clinic visit without sufficient time to accumulate significant variation in the different body sites. This model suggests that manyC. trachomatisinfections may be resolved relatively quickly in the Fijian population, possibly reflecting common prescription or over-the-counter antibiotics usage.ImportanceChlamydia trachomatisis a bacterial pathogen that causes millions of sexually transmitted infections (STIs) annually across the globe. BecauseC. trachomatislives inside human cells, it has historically been hard to study. We know little about how the bacterium spreads between body sites. Here, samples from 26 study participants who had simultaneous infections in their vagina, rectum and endocervix were genetically analyzed using an improved method to extractC. trachomatisDNA directly from clinical samples for genome sequencing. By analyzing patterns of mutations in the genomes, we found that 21 participants shared very similarC. trachomatisstrains in all three anatomic sites, suggesting recent infection and spread. For five participants twoC. trachomatisstrains were evident, indicating multiple infections. This study is significant in that improved enrichment methods for genome sequencing provides robust data to genetically trace patterns ofC. trachomatisinfection and transmission within an individual for epidemiologic and pathogenesis interrogations.
CRaTER enrichment for on-target gene-editing enables generation of variant libraries in hiPSCs
Authors: Friedman Clayton E. , Fayer Shawn , Pendyala Sriram , Chien Wei-Ming , Tran Linda , Chao Leslie , Mckinstry Ashley , Karbassi Elaheh , Fenix Aidan M. , Loiben Alexander , Murry Charles E. , Starita Lea M. , Fowler Douglas M. , Yang Kai-Chun 
Published: January 2023

SUMMARYStandard transgenic cell line generation requires screening 100-1000s of colonies to isolate correctly edited cells. We describeCRISPRaOn-TargetEditingRetrieval (CRaTER) which enriches for cells with on-target knock-in of a cDNA-fluorescent reporter transgene by transient activation of the targeted locus followed by flow sorting to recover edited cells. We show CRaTER recovers rare cells with heterozygous, biallelic-editing of the transcriptionally-inactiveMYH7locus in human induced pluripotent stem cells (hiPSCs), enriching on average 25-fold compared to standard antibiotic selection. We leveraged CRaTER to enrich for heterozygous knock-in of a library of single nucleotide variants (SNVs) inMYH7, a gene in which missense mutations cause cardiomyopathies, and recovered hiPSCs with 113 differentMYH7SNVs. We differentiated these hiPSCs to cardiomyocytes and show MYH7 fusion proteins can localize as expected. Thus, CRaTER substantially reduces screening required for isolation of gene-edited cells, enabling generation of transgenic cell lines at unprecedented scale.
Quantum mechanical electronic and geometric parameters for DNA k-mers as features for machine learning
Authors: Masuda Kairi , Abdullah Adib A. , Sahakyan Aleksandr B. 
Published: January 2023

ABSTRACTWith the development of advanced predictive modelling techniques, we are witnessing a steep increase in model development initiatives in genomics that employ high-end machine learning methodologies. Of particular interest are models that predict certain genomic or biological characteristics based solely on DNA sequence information. These models, however, treat the DNA sequence as a mere collection of four, A, T, G and C, letters, thus dismissing the past physico-chemical advancements in science that can enable the use of more intricate information about nucleic acid sequences. Here, we provide a comprehensive database of quantum mechanical and geometric features for all the permutations of 7-meric DNA in their representative B, A and Z conformations. The database is generated by employing the applicable high-cost and time-consuming quantum mechanical methodologies. This can thus make it seamless to associate a wealth of novel molecular features to any DNA sequence, by scanning it with a matching k-meric window and pulling the pre-computed values from our database for further use in modelling. We demonstrate the usefulness of our deposited features through their exclusive use in developing a model for A to C mutation rate constants.
Item-specific memory reactivation during sleep supports memory consolidation in humans
Authors: Liu Jing , Xia Tao , Chen Danni , Yao Ziqing , Zhu Minrui , Antony James W. , Lee Tatia M.C. , Hu Xiaoqing 
Published: January 2023

AbstractMemory consolidation stabilizes newly acquired information. Understanding how individual memories are reactivated during sleep is essential in theorizing memory consolidation. Via unobtrusively re-playing auditory memory cues to sleeping human participants, we identified the reactivation of individual memories during slow-wave sleep (SWS). Using representational similarity analysis (RSA) on cue-elicited electroencephalogram (EEG), we found functionally segregated item-specific representations: the early post-cue EEG activity (0-2 seconds) contained comparable representations for memory cues and for non-memory control cues, thus reflecting sensory processing. Critically, the later EEG activity (2.5-3 s) showed greater item-specific representations for post-sleep remembered items than for forgotten and control cues, demonstrating the reactivation and consolidation of individual memories. Moreover, spindles preferentially supported item-specific memory reactivation for items that were not tested before sleep. These findings delineated how cue-triggered item-specific memory reactivation, subserved by spindles during SWS, contributed to memory consolidation. These results will benefit future research aiming to perturb specific memory episodes during sleep.
Characterizing the microbiome of patients with myeloproliferative neoplasms during a Mediterranean diet intervention
Authors: Avelar-Barragan Julio , Mendez Luque Laura F. , Nguyen Jenny , Nguyen Hellen , Odegaard Andrew O. , Fleischman Angela G. , Whiteson Katrine L. 
Published: January 2023

AbstractMyeloproliferative neoplasms (MPN) are a class of hematological malignancies which result in the overproduction of myeloid lineage cells. These malignancies result in increased cytokine production and inflammation, which correlate with worsened symptom burden and prognosis. Other than bone marrow transplantation, there is no cure for myeloproliferative neoplasms. As such, treatments focus on reducing thrombotic risk, inflammation, and symptom burden. Because current pharmacological treatments carry significant side-effects, there is a need to explore low-risk therapies. One alternative is the Mediterranean diet, which is rich in anti-inflammatory foods, reduces inflammatory biomarkers, and beneficially alters the gut microbiome. Here, we performed a 15-week clinical trial of 28 individuals with MPN who were randomized to dietary counseling based on either a Mediterranean diet or standard U.S. Guidelines for Americans. Our primary objective was to determine if MPN patients were able to adopt a Mediterranean eating style when supported with dietician counseling. As exploratory endpoints, we investigated the impact of diet and inflammation on the gut microbiome. Using shotgun metagenomic sequencing, we found that microbiome diversity and composition were stable throughout the study duration in both cohorts. Furthermore, we discovered significant differences in the microbiomes between MPN subtypes, such as increased beta-dispersion in subjects with myelofibrosis. Lastly, we found several significant correlations between the abundances of multiple bacterial taxa and cytokine levels. Together, this study provides insight into the interaction between diet, inflammation, and the gut microbiome.ImportanceThe gut microbiome serves as an interface between the host and diet. Diet and the gut microbiome both play important roles in managing inflammation, which is a key aspect of MPN. Studies have shown that a Mediterranean diet can reduce inflammation. Therefore, we longitudinally characterized the gut microbiomes of MPN patients in response to Mediterranean or US-style dietary counseling to determine whether there were microbiome-associated changes in inflammation. We did not find significant changes in the gut microbiome associated with diet, but we did find several associations with inflammation. This research paves the way for future studies by identifying potential mechanistic targets implicated in inflammation within the MPN gut microbiome.
Bayesian modeling of the impact of antibiotic resistance on the efficiency of MRSA decolonization
Authors: Ojala Fanni , Abdul Sater Mohamad R. , Miller Loren G. , McKinnell James A. , Huang Susan S. , Grad Yonatan H. , Marttinen Pekka 
Published: January 2023

AbstractMethicillin-resistantStaphylococcus aureus(MRSA) is a major cause of morbidity and mortality and one of the most serious infectious disease threats. Colonization by MRSA increases the risk of infection and transmission, underscoring the importance of decolonization efforts. However, success of these decolonization protocols varies, raising the possibility that some MRSA strains may be more persistent than others. Here, we studied how the persistence of MRSA colonization correlates with genomic presence of antibiotic resistance genes. Our analysis using a Bayesian mixed effects survival model found that high-level resistance to mupirocin was strongly associated with failure of the decolonization protocol. However, we did not see a similar effect with resistance to chlorhexidine or other antibiotics. Including strain-specific random effects improved the predictive performance, indicating that some strain characteristics other than resistance also contributed to persistence. Study subject-specific random effects did not improve the model. Our results highlight the need to consider the properties of the colonizing MRSA strain when deciding which treatments to include in the decolonization protocol.Author summaryMethicillin-resistantStaphylococcus aureus(MRSA) is responsible for a high burden of morbidity and mortality. MRSA colonization incurs risk of MRSA infection and transmission, highlighting the need for highly effective decolonization protocols. However, decolonization protocols have had mixed success. The extent to which this mixed success is attributable to MRSA strain variations and their resistance to antibiotics, including those like mupirocin that are commonly used for decolonization, versus study subject factors, has been unclear. Here, we characterized the effect of antibiotic resistance genes on the efficiency of an MRSA decolonization protocol. We found that mupirocin resistance and strain-specific effects were associated with reduced effectiveness of an MRSA decolonization protocol, but that resistance to other antibiotics, including purported chlorhexidine resistance genes, and subject-specific effects had no discernible impact on protocol success. Our results highlight the need to consider the properties of the colonizing MRSA strain when deciding which treatments to include in the decolonization protocol.
Prevalence of BovineCysticercosis, Human Taeniasis and Asociated Risk Factors in Selected Towns of Silte Zone, Southern Ethiopia
Authors: mussa Solomon musema 
Published: January 2023

ABSTRACTBovine cysticercosis is an infection of cattle caused by the larval stage of Cysticercus Bovis, the human intestinal cestodes and it has economic important and public health importance. Across-sectional study was conducted from March 2022 to August 2022 to determine the prevalence of Bovine Cysticercosis, Human Taeniasis and associated risk factors in selected towns of Silte zone. The study was conducted in Silte zone municipal abbatoir, Southern Ethiopia in cattle slaughtered randomly selected towns,namely, at Kilto,Kutery,Kirate and Werabe Tawon municipal abattoirs. Systematic random sampling technique was used to collect all the necessary data from abattoir survey of the study animals and questionnaire survey collected data stored by using in Epi data software and analyzed using (SPSS-22) software program. The sample size required for this study was determined to be based on the expected prevalence (50%) of C. bovis and the 5% desired absolute precision and 95% CI. Out of 422 carcasses examined during the study period in 4 municipality abattoirs, 36 % were infected with C.bovis. A prevalence of 35.7%, 35.92%, 37.96% and 34.11% were Kilto,Kutery,Kirate and Werabe Tawon were observed, respectively. Among considered risk factors, sex, body condition and breed showed statistically significant difference in prevalence of C. bovis in study area. Regarding the anatomical distribution of the cysts, shoulder muscle showed highest prevalence 28.44%, was followed by tongue 20.79% tricepsbrachi muscle 18.35%, masseter muscle 17.74%, heart 12.84%, and Liver 1.8%,. Out of 110 respondents, 64.5% had contracted T.saginata. Among considered risk factors, sex, age, occupation, education status, raw meat consumption and knowledge about the disease showed statistically significant difference in prevalence of T.saginata in study area. The findings of this study indicated that importance of Bovine Cysticercosis and Taeniasis in the study area. Therefore, attention should be given to the public awareness, detailed meat inspection to be safe to public health, consumption of well-cooked cattle meat should be implemented for breaking the cycle of the diseases and promote meat industry in the country.
Aspergillus fumigatustranscription factor ZfpA regulates hyphal development and alters susceptibility to antifungals and neutrophil killing during infection
Authors: Schoen Taylor J. , Calise Dante G. , Bok Jin Woo , Nwagwu Chibueze D. , Zarnowski Robert , Andes David , Huttenlocher Anna , Keller Nancy P. 
Published: January 2023

AbstractHyphal growth is essential for host colonization duringAspergillusinfection. The transcription factor ZfpA regulatesA. fumigatushyphal development including branching, septation, and cell wall composition. However, how ZfpA affects fungal growth and susceptibility to host immunity during infection has not been investigated. Here, we use the larval zebrafish-Aspergillusinfection model and primary human neutrophils to probe how ZfpA affectsA. fumigatuspathogenesis and response to antifungal drugsin vivo. ZfpA deletion promotes fungal clearance and attenuates virulence in wild-type hosts and this virulence defect is abrogated in neutrophil-deficient zebrafish. ZfpA deletion also increases susceptibility to human neutrophilsex vivowhile overexpression impairs fungal killing. Overexpression of ZfpA confers protection against the antifungal caspofungin by increasing chitin synthesis during hyphal development, while ZfpA deletion reduces cell wall chitin and increases caspofungin susceptibility in neutrophil-deficient zebrafish. These findings suggest a protective role for ZfpA activity in resistance to the innate immune response and antifungal treatment duringA. fumigatusinfection.Author SummaryAspergillus fumigatusis a common environmental fungus that can infect immunocompromised people and cause a life-threatening disease called invasive aspergillosis. An important step during infection is the development ofA. fumigatusfilaments known as hyphae.A. fumigatususes hyphae to acquire nutrients and invade host tissues, leading to tissue damage and disseminated infection. In this study we report that a regulator of gene transcription inA. fumigatuscalled ZfpA is important for hyphal growth during infection. We find that ZfpA activity protects the fungus from being killed by innate immune cells and decreases the efficacy of antifungal drugs during infection by regulating construction of the cell wall, an important protective layer for fungal pathogens. Our study introduces ZfpA as an important genetic regulator of stress tolerance during infection that protectsA. fumigatusfrom the host immune response and antifungal drugs.
The infectious salmon anaemia virus esterase prunes erythrocyte surfaces in infected Atlantic salmon and exposes terminal sialic acids to lectin recognition
Authors: Fosse Johanna Hol , Andresen Adriana Magalhaes Santos , Ploss Frieda Betty , Weli Simon Chioma , Heffernan Inger , Sapotka Subash , Lundgård Krister , Kuiper Raoul Valentin , Solhaug Anita , Falk Knut 
Published: January 2023

AbstractMany sialic acid-binding viruses express a receptor-destroying enzyme (RDE) that removes the virus-targeted receptor and limits viral interactions with the host cell surface. Despite a growing appreciation of how the viral RDE promotes viral fitness, little is known about its direct effects on the host. Infectious salmon anaemia virus (ISAV) attaches to 4-O-acetylated sialic acids on the surface of Atlantic salmon epithelial, endothelial, and red blood cells. ISAV receptor binding and destruction are effectuated by the same surface molecule, the haemagglutinin esterase (HE). We recently discovered a global loss of vascular 4-O-acetylated sialic acids in ISAV-infected fish. The loss correlated with the expression of viral proteins, giving rise to the hypothesis that it was mediated by the HE.Here, we report that the capacity to bind new ISAV particles is also progressively lost from circulating erythrocytes in infected fish. Furthermore, salmon erythrocytes exposed to ISAVex vivolost their capacity to bind new ISAV particles. The loss of ISAV binding was not associated with receptor saturation. Moreover, upon loss of the ISAV receptor, erythrocyte surfaces became more available to the lectin wheat germ agglutinin, suggesting a potential to alter interactions with endogenous lectins of similar specificity. The pruning of erythrocyte surfaces was inhibited by an antibody that prevented ISAV attachment. Furthermore, recombinant HE, but not an esterase-silenced mutant, was sufficient to induce the observed surface modulation. Our results directly link the ISAV-induced erythrocyte modulation to the hydrolytic activity of the HE and show that the observed effects are not mediated by endogenous esterases.Our findings are the first to directly link a viral esterase to extensive host cell surface modulation in infected individuals. This raises the question of how common the phenomenon is among sialic acid-binding viruses. It is also relevant to ask if the altered sialic acid landscape of the affected cells influences host biological functions with relevance to viral disease.
Summary tests of introgression are highly sensitive to rate variation across lineages
Authors: Frankel Lauren E. , Ané Cécile 
Published: January 2023

AbstractThe evolutionary implications and frequency of hybridization and introgression are increasingly being recognized across the tree of life. To detect hybridization from multi-locus and genome-wide sequence data, a popular class of methods are based on summary statistics from subsets of 3 or 4 taxa. However, these methods often carry the assumption of a constant substitution rate across lineages and genes, which is commonly broken in many groups. In this work, we quantify the effects of rate variation on theD-statistic (also known as ABBA-BABA test), theD3statistic, and HyDe. All three tests are used widely across a range of taxonomic groups, in part because they are very fast to compute. We consider rate variation across species lineages, across genes, their lineage-by-gene interaction, and rate variation across gene-tree edges. We simulated species networks according to a birth-death-hybridization process so as to capture a range of realistic species phylogenies. For all three methods tested, we found a marked increase in the false discovery of reticulation (type-1 error rate) when there is rate variation across species lineages. TheD3statistic was the most sensitive, with around 80% type-1 error, such thatD3appears to more sensitive to a departure from the clock than to the presence of reticulation. For all three tests, the power to detect hybridization events decreased as the number of hybridization events increased, indicating that multiple hybridization events can “hide” one another if they occur within a small subset of taxa. Our study highlights the need to consider rate variation when using site-based summary statistics, and points to the advantages of methods that do not require assumptions on evolutionary rates across lineages or across genes.
Clonal cell states link Barrett’s esophagus and esophageal adenocarcinoma
Authors: Gier Rodrigo A. , Hueros Raúl A. Reyes , Rong Jiazhen , DeMarshall Maureen , Karakasheva Tatiana A. , Muir Amanda B. , Falk Gary W. , Zhang Nancy R. , Shaffer Sydney M. 
Published: January 2023

AbstractBarrett’s esophagus is a common type of metaplasia and a precursor of esophageal adenocarcinoma. However, the cell states and lineage connections underlying the origin, maintenance, and progression of Barrett’s esophagus have not been resolved in humans. To address this, we performed single-cell lineage tracing and transcriptional profiling of patient cells isolated from metaplastic and healthy tissue. Our analysis revealed discrete lineages in Barrett’s esophagus, normal esophagus, and gastric cardia. Transitional basal progenitor cells of the gastroesophageal junction were unexpectedly related to both esophagus and gastric cardia cells. Barrett’s esophagus was polyclonal, with lineages that contained all progenitor and differentiated cell types. In contrast, precancerous dysplastic foci were initiated by the expansion of a single molecularly aberrant Barrett’s esophagus clone. Together, these findings provide a comprehensive view of the cell dynamics of Barrett’s esophagus, linking cell states along the full disease trajectory, from its origin to cancer.