bluuebunny/crossref_metadata_2025_split huggingface dataset:
A polytypic species revisited: Phylogenetic and morphological variation, taxonomic status, and geographical distribution ofTrachops(Chiroptera: Phyllostomidae)
Authors: Camacho M. Alejandra , Menéndez-Guerrero Pablo A. , Horváth Balázs , Cadar Dániel , Murienne Jérôme 
Published: January 2024

AbstractThe taxonomic status of the neotropical bat genusTrachopshas been reevaluated through an integrated study that incorporates morphological, morphometric, and molecular data across its extensive geographic range. Our research, which included previously unexamined regions, revealed substantial insights into the diversity withinTrachops. The results support the elevation ofT. cirrhosus ehrhardtito species status, due to genetic and morphological differences in southeastern Brazil specimens. Conversely, our comprehensive analysis found insufficient evidence to maintain the subspecific distinction ofT. c. coffini, which lacks diagnosable morphological characters and is not genetically distinct fromT. c. cirrhosusacross its distribution range. Additionally, our findings challenge the previous belief of a latitudinal differentiation in body size forTrachops cirrhosus, as specimens from western South America and northeastern South America exhibit similar sizes to those from Central America. These results underscore the importance of revising the taxonomic framework for this bat genus, contributing to a more precise understanding of its evolutionary relationships, and further enhancing conservation efforts, considering the potential threats to the newly recognizedT. ehrhardtiin the imperiled Atlantic Forest of Brazil.
FANCJ promotes PARP1 activity during DNA replication that is essential in BRCA1 deficient cells
Authors: Cong Ke , MacGilvary Nathan , Lee Silviana , MacLeod Shannon G. , Calvo Jennifer , Peng Min , Kousholt Arne Nedergaard , Day Tovah , Cantor Sharon B. 
Published: January 2024

SUMMARYSingle-stranded DNA gaps are postulated to be fundamental to the mechanism of anti-cancer drugs. Gaining insights into their induction could therefore be pivotal for advancing therapeutic strategies. For poly (ADP-ribose) polymerase inhibitors (PARPi) to be effective, the presence of FANCJ helicase is required. However, the relationship between FANCJ dependent gaps and PARP1 catalytic inhibition or trapping—both linked to PARPi toxicity in BRCA deficient cells—is yet to be elucidated. Here, we find that the efficacy of PARPi is contingent on S-phase PARP1 activity, which is compromised in FANCJ deficient cells because PARP1, along with MSH2, is “sequestered” by G-quadruplexes. PARP1’s replication activity is also diminished in cells missing a FANCJ-MLH1 interaction, but in such cells, depleting MSH2 can release sequestered PARP1, restoring PARPi-induced gaps and sensitivity. Our observations indicate that sequestered and trapped PARP1 are different chromatin-bound forms, with FANCJ loss increasing PARPi resistance in cells susceptible to canonical PARP1 trapping. However, in BRCA1 null cells, the loss of FANCJ mirrors the effects of PARP1 loss or inhibition, with the common detrimental factor being the loss of PARP1 activity during DNA replication, not trapping. These insights underline the crucial role of PARP1 activity during DNA replication in BRCA deficient cells and emphasize the importance of understanding drug mechanisms for enhancing precision medicine.
Quantifying the Prevalence of Non-B DNA Motifs as a Marker of Non-B Burden in Cancer using NBBC
Authors: Xu Qi , Kowalski Jeanne 
Published: January 2024

AbstractAlternative DNA structures, such as Z-DNA, G-quadruplexes, and mirror repeats, have shown potential involvement in cancer etiology. NBBC (Non-B DNA Burden in Cancer) is a web-based tool designed for quantifying and analyzing non-B DNA motifs within a cancer context. Herein, we provide a step-by-step protocol for employing NBBC, starting with data input and proceeding through the quantification and normalization of non-B DNA motifs that result in calculation of non-B burden. With detailed instructions for performing various motif-centric analyses based on cancer gene signatures, including DNA damage repair and response pathways for exploring genomic stability, and sample-level gene mutation signatures, a user is able to explore non-B associative correlations within current cancer biology. We provide additional detail on input queries into NBBC, interpret the quantitative results, and apply normalization techniques to ensure accurate comparisons across different genomic regions and non-B DNA structures.NBBC offers a powerful and user-friendly interface for the cancer research community. This chapter serves as an essential, enhanced instructional guide for researchers to leverage NBBC in their cancer biomarker investigations for an understanding of the potential role of non-B DNA in contributing to them.
Identification of essential genes that support fitness ofAcinetobacter baumanniiefflux pump overproducers in the presence of fluoroquinolone
Authors: Hamami Efrat , Huo Wenwen , Neal Katherine , Neisewander Isabelle , Geisinger Edward , Isberg Ralph R. 
Published: January 2024

AbstractAcinetobacter baumanniiis a nosocomial pathogen often associated with multidrug resistance (MDR) infections. Fluoroquinolone resistance (FQR) due to drug target site mutations and elevated expression of RND drug transporters is common among clinical isolates. We describe here a CRISPRi platform that identifies hypomorphic mutations that preferentially altered drug sensitivity in RND pump overproducers. An sgRNA library against essential genes ofA. baumanniiwas constructed with single and double nucleotide mutations that produced titratable knockdown efficiencies and introduced into multiple strain backgrounds. Other thannusGdepletions, there were few candidates in the absence of drug treatment that showed lowered fitness specifically in strains overexpressing clinically relevant RND efflux pumps AdeAB, AdeIJK, or AdeFGH. In the presence of ciprofloxacin, the hypomorphs causing hypersensitivity were predicted to result in outer membrane dysfunction, to which the AdeFGH overproducer appeared particularly sensitive. Depletions of either the outer membrane assembly BAM complex, LOS biogenesis proteins, or Lpt proteins involved in LOS transport to the outer membrane caused drug hypersensitivity in at least two of the three pump overproducers. On the other hand, depletions of translation-associated proteins, as well as components of the proton-pumping ATP synthase pump resulted in fitness benefits for at least two pump-overproducing strains in the presence of the drug. Therefore, pump overproduction exacerbated stress caused by defective outer membrane integrity, while the efficacy of drug resistance in efflux overproducers was enhanced by slowed translation or defects in ATP synthesis linked to the control of proton movement across the bacterial membrane.
Predicting the subcellular location of prokaryotic proteins with DeepLocPro
Authors: Moreno Jaime , Nielsen Henrik , Winther Ole , Teufel Felix 
Published: January 2024

AbstractProtein subcellular location prediction is a widely explored task in bioinformatics because of its importance in proteomics research. We propose DeepLocPro, an extension to the popular method DeepLoc, tailored specifically to archaeal and bacterial organisms. DeepLocPro is a multiclass subcellular location prediction tool for prokaryotic proteins, trained on experimentally verified data curated from UniProt and PSORTdb. DeepLocPro compares favorably to the PSORTb 3.0 ensemble method, surpassing its performance across multiple metrics on our benchmark experiment. The DeepLocPro prediction tool is available online athttps://ku.biolib.com/deeplocproandhttps://services.healthtech.dtu.dk/services/DeepLocPro-1.0/.
Checkpoint-independent association of Mad3BUBR1with Stu1CLASPdirects homolog alignment in meiosis I
Authors: Mukherjee Anuradha , Spanos Christos , Marston Adele L. 
Published: January 2024

SummaryGametes are produced via meiosis, a specialized cell division associated with frequent errors which cause birth defects and infertility. Uniquely in meiosis I, homologous chromosomes segregate to opposite poles, usually requiring their linkage by chiasmata, the products of crossover recombination1. The spindle checkpoint delays cell cycle progression until all chromosomes are properly attached to microtubules2but the steps leading to the capture and alignment of chromosomes on the meiosis I spindle remain poorly understood. In budding yeast meiosis I, Mad2 and Mad3BUBR1are equally important for spindle checkpoint delay, but biorientation of homologs on the meiosis I spindle requires Mad2, but not Mad3BUBR13,4. Here we show that Mad3BUBR1promotes accurate meiosis I homolog segregation outside its canonical checkpoint role, independently of Mad2. We find that Mad3BUBR1associates with the TOGL1 domain of Stu1CLASP, a conserved plus-end microtubule protein which is important for chromosome capture onto the spindle. Homologous chromosome pairs that are proficient in crossover formation, but which fail to biorient, rely on Mad3BUBR1-Stu1CLASPto ensure their efficient attachment to microtubules and segregation during meiosis I. Furthermore, we show that Mad3BUBR1-Stu1CLASPare essential to rescue the segregation of mini-chromosomes lacking crossovers. Our findings define a new pathway ensuring microtubule-dependent chromosome capture and demonstrate that spindle checkpoint proteins safeguard the fidelity of chromosome segregation both by actively promoting chromosome alignment and delaying cell cycle progression until this has occurred.
A speed limit on serial strain replacement from original antigenic sin
Authors: McGough Lauren , Cobey Sarah 
Published: January 2024

AbstractMany pathogens evolve to escape immunity, yet it remains difficult to predict whether immune pressure will lead to diversification, serial replacement of one variant by another, or more complex patterns. Pathogen strain dynamics are mediated by cross-protective immunity, whereby exposure to one strain partially protects against infection by antigenically diverged strains. There is growing evidence that this protection is influenced by early exposures, a phenomenon referred to as original antigenic sin (OAS) or imprinting. In this paper, we derive new constraints on the emergence of the pattern of successive strain replacements demonstrated by influenza, SARS-CoV-2, seasonal coronaviruses, and other pathogens. We find that OAS implies that the limited diversity found with successive strain replacement can only be maintained ifR0is less than a threshold set by the characteristic antigenic distances for cross-protection and for the creation of new immune memory. This bound implies a “speed limit” on the evolution of new strains and a minimum variance of the distribution of infecting strains in antigenic space at any time. To carry out this analysis, we develop a theoretical model of pathogen evolution in antigenic space that implements OAS by decoupling the antigenic distances required for protection from infection and strain-specific memory creation. Our results demonstrate that OAS can play an integral role in the emergence of strain structure from host immune dynamics, preventing highly transmissible pathogens from maintaining serial strain replacement without diversification.
Preclinical Development of a Stabilized RH5 Virus-Like Particle Vaccine that Induces Improved Anti-Malarial Antibodies
Authors: King Lloyd D. W. , Pulido David , Barrett Jordan R. , Davies Hannah , Quinkert Doris , Lias Amelia M. , Silk Sarah E. , Pattinson David J. , Diouf Ababacar , Williams Barnabas G. , McHugh Kirsty , Rodrigues Ana , Rigby Cassandra A. , Strazza Veronica , Suurbaar Jonathan , Rees-Spear Chloe , Dabbs Rebecca A. , Ishizuka Andrew S. , Zhou Yu , Gupta Gaurav , Jin Jing , Li Yuanyuan , Carnrot Cecilia , Minassian Angela M. , Campeotto Ivan , Fleishman Sarel J. , Noe Amy R. , MacGill Randall S. , King C. Richter , Birkett Ashley J. , Soisson Lorraine A. , Long Carole A. , Miura Kazutoyo , Ashfield Rebecca , Skinner Katherine , Howarth Mark , Biswas Sumi , Draper Simon J. 
Published: January 2024

AbstractThe development of a highly effective vaccine against the pathogenic blood-stage infection of human malaria will require a delivery platform that can induce an antibody response of both maximal quantity and functional quality. One strategy to achieve this includes presenting antigens to the immune system on virus-like particles (VLPs). Here we sought to improve the design and delivery of the blood-stagePlasmodium falciparumreticulocyte-binding protein homolog 5 (RH5) antigen, which is currently in a Phase 2 clinical trial as a full-length soluble protein-in-adjuvant vaccine candidate called RH5.1/Matrix-M™. We identify disordered regions of the full-length RH5 molecule induce non-growth inhibitory antibodies in human vaccinees, and a re-engineered and stabilized immunogen that includes just the alpha-helical core of RH5 induces a qualitatively superior growth-inhibitory antibody response in rats vaccinated with this protein formulated in Matrix-M™ adjuvant. In parallel, bioconjugation of this new immunogen, termed “RH5.2”, to hepatitis B surface antigen VLPs using the “plug-and-display” SpyTag-SpyCatcher platform technology also enabled superior quantitative antibody immunogenicity over soluble antigen/adjuvant in vaccinated mice and rats. These studies identify a new blood-stage malaria vaccine candidate that may improve upon the current leading soluble protein vaccine candidate RH5.1/Matrix-M™. The RH5.2-VLP/Matrix-M™ vaccine candidate is now under evaluation in Phase 1a/b clinical trials.
Genome binding properties of Zic transcription factors underlie their changing functions during neuronal maturation
Authors: Minto Melyssa , Sotelo-Fonseca Jesús Emiliano , Ramesh Vijyendra , West Anne E. 
Published: January 2024

AbstractBackgroundThe Zic family of transcription factors (TFs) promote both proliferation and maturation of cerebellar granule neurons (CGNs), raising the question of how a single, constitutively expressed TF family can support distinct developmental processes. Here we use an integrative experimental and bioinformatic approach to discover the regulatory relationship between Zic TF binding and changing programs of gene transcription during CGN differentiation.ResultsWe first established a bioinformatic pipeline to integrate Zic ChIP-seq data from the developing mouse cerebellum with other genomic datasets from the same tissue. In newborn CGNs, Zic TF binding predominates at active enhancers that are co-bound by developmentally-regulated TFs including Atoh1, whereas in mature CGNs, Zic TF binding consolidates toward promoters where it co-localizes with activity-regulated TFs. We then performed CUT&RUN-seq in differentiating CGNs to define both the time course of developmental shifts in Zic TF binding and their relationship to gene expression. Mapping Zic TF binding sites to genes using chromatin looping, we identified the set of Zic target genes that have altered expression in RNA-seq from Zic1 or Zic2 knockdown CGNs.ConclusionOur data show that Zic TFs are required for both induction and repression of distinct, developmentally regulated target genes through a mechanism that is largely independent of changes in Zic TF binding. We suggest that the differential collaboration of Zic TFs with other TF families underlies the shift in their biological functions across CGN development.
Constraint on boric acid resistance and tolerance evolvability inCandida albicans
Authors: Syvolos Yana , Salama Ola E. , Gerstein Aleeza C. 
Published: January 2024

AbstractBoric acid is a broad-spectrum antimicrobial used to treat vulvovaginal candidiasis when patients relapse on the primary azole drug fluconazole.Candida albicansis the most common cause of vulvovaginal candidiasis, colloquially referred to as a "vaginal yeast infection". Little is known about the propensity ofC. albicansto develop BA resistance or tolerance (the ability of a subpopulation to grow slowly in high levels of drug). We evolved 96 replicates from eight diverseC. albicansstrains to increasing BA concentrations to test the evolvability of BA resistance and tolerance. Replicate growth was individually assessed daily, with replicates passaged when they had reached an optical density consistent with exponential growth. Many replicates went extinct quickly. Although some replicates could grow in much higher levels of BA than the ancestral strains, evolved populations isolated from the highest terminal BA levels (after 11 weeks of passages) surprisingly showed only modest growth improvements and only at low levels of BA. No large increases in resistance or tolerance were observed in the evolved replicates. Overall, our findings illustrate that there may be evolutionary constraints limiting the emergence of BA resistance and tolerance, which could explain why it remains an effective treatment for recurrent yeast infections.
Disease-associated astrocyte epigenetic memory promotes CNS pathology
Authors: Lee Hong-Gyun , Rone Joseph M. , Li Zhaorong , Akl Camilo Faust , Shin Seung Won , Lee Joon-Hyuk , Flausino Lucas E. , Pernin Florian , Chao Chun-Cheih , Kleemann Kilian L. , Srun Lena , Illouz Tomer , Giovannoni Federico , Charabati Marc , Sanmarco Liliana M. , Kenison Jessica E. , Piester Gavin , Zandee Stephanie E. J. , Antel Jack , Rothhammer Veit , Wheeler Michael A. , Prat Alexandre , Clark Iain C. , Quintana Francisco J. 
Published: January 2024

SummaryAstrocytes play important roles in the central nervous system (CNS) physiology and pathology. Indeed, astrocyte subsets defined by specific transcriptional activation states contribute to the pathology of neurologic diseases, including multiple sclerosis (MS) and its pre-clinical model experimental autoimmune encephalomyelitis (EAE)1–8. However, little is known about the stability of these disease-associated astrocyte subsets, their regulation, and whether they integrate past stimulation events to respond to subsequent challenges. Here, we describe the identification of an epigenetically controlled memory astrocyte subset which exhibits exacerbated pro-inflammatory responses upon re-challenge. Specifically, using a combination of single-cell RNA sequencing (scRNA-seq), assay for transposase-accessible chromatin with sequencing (ATAC–seq), chromatin immunoprecipitation with sequencing (ChIP–seq), focused interrogation of cells by nucleic acid detection and sequencing (FIND-seq), and cell-specificin vivoCRISPR/Cas9-based genetic perturbation studies we established that astrocyte memory is controlled by the metabolic enzyme ATP citrate lyase (ACLY), which produces acetyl coenzyme A (acetyl-CoA) used by the histone acetyltransferase p300 to control chromatin accessibility. ACLY+p300+memory astrocytes are increased in acute and chronic EAE models; the genetic targeting of ACLY+p300+astrocytes using CRISPR/Cas9 ameliorated EAE. We also detected responses consistent with a pro-inflammatory memory phenotype in human astrocytesin vitro; scRNA-seq and immunohistochemistry studies detected increased ACLY+p300+astrocytes in chronic MS lesions. In summary, these studies define an epigenetically controlled memory astrocyte subset that promotes CNS pathology in EAE and, potentially, MS. These findings may guide novel therapeutic approaches for MS and other neurologic diseases.
Predicting RNA Sequence-Structure Likelihood via Structure-Aware Deep Learning
Authors: Zhou You , Pedrielli Giulia , Zhang Fei , Wu Teresa 
Published: January 2024

AbstractMotivationThe active functionalities of RNA are recognized to heavily dependent on the structure and sequence. Therefore, A model that can accurately evaluate a design by giving RNA sequence-structure pairs would be a valuable tool for many researchers. Machine learning methods have been explored to develop such tools, showing promising results. However, two key issues remain. Firstly, the performance of machine learning models is affected by the features used to characterize RNA. Currently, there is no consensus on which features are the most effective for characterizing RNA sequence-structure pairs. Secondly, most existing machine learning methods extract features describing entire RNA molecule. We argue that it is essential to define additional features that characterize nucleotides and specific sections of RNA structure to enhance the overall efficacy of the RNA design process.ResultsWe develop two deep learning models for evaluating RNA sequence-structure pairs. The first model, NU-ResNet, uses a convolutional neural network architecture that solves the aforementioned problems by explicitly encoding RNA sequence-structure information into a 3D matrix. Building upon NU-ResNet, our second deep learning model, NUMO-ResNet, incorporates additional information derived from the characterizations of RNA, specifically the 2D folding motifs. In this work, we introduce an automated method to extract these motifs based on fundamental secondary structure descriptions. To assess the robustness of our models, we conduct 10-fold cross validation. Furthermore, we evaluate the performance of both models on two independent testing datasets. Our proposed models demonstrate excellent performance across both datasets and surpass the performance of the ENTRNA approach.Availability and ImplementationThe corresponding source code and data for this research is available athttps://github.com/yzhou617/NU-ResNet_and_NUMO-ResNet.ContactGiulia.Pedrielli@asu.eduSupplementary informationSupplementary data are available at Bioinformatics online.
Molecular Characterization ofTephromela atraandTephromela grumosafrom Bozdag Mountain Based on ITS1 rDNA Sequences Analysis
Authors: Alzebair Awad , Yilmaz Cankiliç Meral , Candan Mehmet , Avan İlker 
Published: January 2024

ABSTRACTThe lichensTephromela atraandTephromela grumosawere studied in detail using various techniques, including morphological identification, biochemical taxonomy (chemotaxonomy), anatomical, and molecular characterization. The molecular characterization ofTephromela atraandTephromela grumosa(Pers.) Hafelner & Cl. Roux was analyzed using internal transcribed spacer rDNA (ITS1) genes and the sequences obtained were compared with the ITS sequences of the otherTephromelaspecies in GenBank (NCBI). The sequences were analyzed against reference sequences from the GenBank databases using the programs; BLAST, ClustalW, and MEGA11. The phylogenetic relationship was evaluated. The results show that some samples ofTephromela atraobtained in this study are closer to the same species isolated from Greece, while other samples are closer to other samples isolated from Italy and Austria. Moreover, theTephromela grumosaisolated from Eskisehir Bozdag Mountain form a separate branch closer to theTephromela grumosasamples isolated from Italy. Our study shows that lichens are an important source of biodiversity in Türkiye, which has a high species richness in Anatolia.