bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of BA.2.86 to JN.1 reveals functional changes in non-structural viral proteins are required for fitness of SARS-CoV-2
Authors: Tsujino Shuhei , Tsuda Masumi , Nao Naganori , Okumura Kaho , Wang Lei , Oda Yoshitaka , Mimura Yume , Li Jingshu , Hashimoto Rina , Matsumura Yasufumi , Suzuki Rigel , Suzuki Saori , Yoshimatsu Kumiko , Nagao Miki ,   The Genotype to Phenotype Japan (G2P-Japan) Consortium, Ito Jumpei , Takayama Kazuo , Sato Kei , Matsuno Keita , Tamura Tomokazu , Tanaka Shinya , Fukuhara Takasuke 
Published: February 2025

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19), is still circulating among humans, leading to the continuous evolution. SARS-CoV-2 Omicron JN.1 evolved from a distinct SARS-CoV-2 lineage, BA.2.86, spread rapidly worldwide. It is unclear why BA.2.86 did not become dominant and was quickly replaced by JN.1, which possesses one amino acid substitution in the spike protein (S:L455S) and two in the non-spike proteins NSP6 and ORF7b (NSP6:R252K and ORF7b:F19L) compared to BA.2.86. Here, we utilized recombinant viruses to elucidate the impact of these mutations on the virological characteristics of JN.1. We found that the mutation in the spike attenuated viral replication, but the non-spike mutations enhanced replication, suggesting the mutations in the non-spike proteins compensate for the one in the spike to improve viral fitness, as the mutations in the spike contribute to further immune evasion. Our findings suggest that functional changes in both the spike and non-spike proteins are necessary in the evolution of SARS-CoV-2 to enable evasion of adaptive immunity within the human population while sustaining replication.IMPORTANCEBecause the spike protein is strongly associated with certain virological properties of SARS-CoV-2, such as immune evasion and infectivity, most previous studies on SARS-CoV-2 variants have focused on spike protein mutations. However, the non-spike proteins also contribute to infectivity, as observed throughout the evolution of Omicron subvariants. In this study, we demonstrate a “trade-off” strategy in SARS-CoV-2 Omicron JN.1 in which the reduced infectivity caused by spike mutation is compensated by non-spike mutations. Our results provide insight into the evolutionary scenario of the emerging virus in the human population.
Development of a novel hybrid alphavirus-Nipah virus pseudovirion for rapid quantification of neutralization antibodies
Authors: Hetrick Brian , Nakka Sravya Sowdamini , Yu Dongyang , Swineford Sarah , Storm Nadia , Griffiths Anthony , Wu Yuntao 
Published: February 2025

SUMMARYNipah virus (NiV) is an emergent paramyxovirus that causes serious disease in humans and animals. Accurate quantification of neutralizing antibodies (nAB) against NiV is essential for vaccine development. The current standard, the plaque reduction neutralization test (PRNT), requires authentic infectious NiV and BSL-4 containment, taking 4-7 days to complete. In this study, we developed a hybrid alphavirus-Nipah virus pseudovirion (Ha-NiV) composed of a non-replicating Nipah virus virus-like particle (VLP) that encapsulates an RNA genome from a fast-expressing SFV (Semliki Forest Virus) alphaviral vector. Ha-NiV can infect NiV target cells but is replication incompetent, enabling rapid quantification of nAB (6-18 hours) in BSL-2 conditions. We validated Ha-NiV using sera from Nipah virus-infected African green monkeys and established a good correlation (R2= 0.86) with PRNT, demonstrating comparable specificity and sensitivity. These results demonstrate that the Ha-NiV assay can serve as a novel platform for convenient and rapid quantification of nAB in BSL-2 settings.
Prevalence and consequences ofAPCmosaicism in patients with colorectal adenomas
Authors: Terlouw Diantha , Suerink Manon , Buitelaar Yentl , van Leerdam Monique E , Hes Frederik J , van Egmond Demi , Ruano Dina , Wagner Anja , Groenendijk Floris H , Meijssen Isabelle C , Overwater Eline , Bajwa-ten Broeke Sanne W , Mensenkamp Arjen R , Nagtegaal Iris D , Tops Carli M , Langers Alexandra M J , van Wezel Tom , Morreau Hans , Nielsen Maartje 
Published: February 2025

AbstractBackground and aimsA substantial proportion of patients with adenomatous polyposis have no germline pathogenic variant inAPC. The aim of this study was to determine the prevalence ofAPCmosaicism in these patients with unexplained polyposis and to draft guidelines forAPCmosaicism testing and surveillance.MethodsAPCmosaicism was analyzed by targeted Next-Generation sequencing in 542 patients with a broad spectrum of polyposis phenotypes.ResultsThe rate ofAPCmosaicism was 9.4%. This rate was 14.3% (46/322) in patients who meet the scope of national hereditary polyposis testing guidelines (≥10 adenomas before the age of 60 or with ≥20 adenomas before the age of 70). In patients who do not meet the scope of national guidelines, the detection rate was 2.3% (5/219). In patients with ≥20 adenomas before the age of 60, or ≥30 adenomas before the age of 70 the detection rate was ≥10%. Of 34 mosaic patients who underwent an esophagogastroduodenoscopy, 26% were diagnosed with gastroduodenal polyps. In one patient, the mosaic variant was detected in semen, but none of the children tested in this cohort inherited the mosaic variant.ConclusionWe recommendAPCmosaicism testing at least in patients negative for germline pathogenic variants with (1) ≥20 adenomas before the age of 60 or (2) ≥30 adenomas before the age of 70. Regular colonoscopy and at least one gastroduodenoscopy should be offered toAPCmosaics, with frequency of follow-up based on findings. Offering germline testing for offspring should be considered.
Interrelations Between Dopaminergic-, GABAergic- and Glutamatergic Neurotransmitters in Antipsychotic-Naïve Psychosis Patients and the Association to Initial Treatment Response
Authors: Bojesen Kirsten Borup , Ambrosen Karen S. , Sigvard Anne Korning , Nielsen Mette Ødegaard , Gjedde Albert , Kumakura Yoshitaka , Jensen Lars Thorbjørn , Fuglø Dan , Ebdrup Bjørn H. , Rostrup Egill , Glenthøj Birte Yding 
Published: February 2025

AbstractPreclinical evidence points to disturbances in neural networks in psychosis involving interrelations between dopaminergic-, GABAergic- and glutamatergic neurotransmitter systems. In support, we have previously shown that aberrant interrelations between these neurotransmitters, in contrast to individual transmitter systems, can separate antipsychotic-naïve first-episode psychotic patients (AN-FEP) from healthy controls (HC). Here, we characterized neurotransmitter interrelations, examined their association with treatment response, and explored the effect of treatment on the interrelations.Sixty participants (29 AN-FEP and 31 HC) underwent dynamic [18F]-DOPA PET with arterial blood sampling using a four-parameter model to measure dopamine synthesis (DS) (k3) in nucleus accumbens (NAcc) and magnetic resonance spectroscopy (MRS) to estimate levels of glutamate (Glu) in anterior cingulate cortex (ACC) and thalamus, and gamma-aminobutyric-acid (GABA) in ACC. A subgroup of the patients was re-scanned after six weeks antipsychotic monotherapy with aripiprazole. Psychopathology was assessed at both visits. Multiple linear regression models and linear mixed models were used to analyze data.We found a negative association between k3(dependent variable) and GABA in HC (β=-0.15, p=0.03) and a positive association in patients (β=0.15, p=0.04). The aberrant relationship between k3and GABA was driven by the group-GABA interaction (p=0.002) and related to treatment response (p=0.02). No significant group interactions were found for the interrelations between k3and Glu, but a positive association was found between k3and Glu in thalamus (p=0.04) in both groups and the association decreased after treatment in AN-FEP (p=0.01).The data show that DS in NAcc and GABA levels in ACC are inversely interrelated in AN-FEP, and that the degree of abnormality predicts treatment effect. Moreover, antipsychotic treatment alters the relationship between dopaminergic activity in NAcc and Glu levels in thalamus. The findings suggest that combined instead of single neurotransmitter disturbances should be considered when novel therapeutics are developed for schizophrenia.
Transposons and accessory genes drive adaptation in a clonally evolving fungal pathogen
Authors: Díaz Cristina López , Ayhan Dilay Hazal , Rodríguez López Ana , Gil Lucía Gómez , Ma Li-Jun , Di Pietro Antonio 
Published: February 2025

AbstractGenomes of clonally reproducing fungal pathogens are often compartmentalized into conserved core and lineage-specific accessory regions (ARs), enriched in transposable elements (TEs). ARs and TEs are thought to promote pathogen adaptation, but direct experimental evidence is sparse. Using an evolve and re-sequence approach, we found that serial passaging of the cross-kingdom fungal pathogenFusarium oxysporumthrough tomato plants or axenic media rapidly increased fitness under the selection condition. TE insertions were the predominant type of mutations in the evolved lines, with a single non-autonomous hAT-type TE accounting for 63% of total events detected. TEs inserted preferentially at sites of histone H3 lysine 27 trimethylation, a hallmark of ARs. Recurrent evolutionary trajectories during plate adaptation led to increased proliferation concomitant with reduced virulence. Unexpectedly, adaptive mutations in accessory genes strongly impacted core functions such as growth, development, quorum sensing or virulence. Thus, TEs and ARs drive rapid adaptation in this important fungal pathogen.
Disrupted transcriptional networks regulated byCHD1Lduring neurodevelopment underlie the mirrored neuroanatomical and growth phenotypes of the 1q21.1 copy number variant
Authors: Lemée Marianne Victoria , Loviglio Maria Nicla , Ye Tao , Tilly Peggy , Keime Céline , Weber Chantal , Petrova Anastasiya , Klein Pernelle , Morlet Bastien , Wendling Olivia , Jacobs Hugues , Tharreau Mylène , Geneviève David , Godin Juliette D , Romier Christophe , Duteil Delphine , Golzio Christelle 
Published: February 2025

ABSTRACTDistal 1q21.1 deletions and duplications are associated with variable phenotypes including autism, head circumference and height defects. To elucidate which gene(s) are responsible for the 1q21.1 duplication/deletion-associated phenotypes, we performed gene manipulation in zebrafish and mice. We modeled 1q21.1 duplication by overexpressing the eight human protein-coding genes in zebrafish. We found that overexpression ofCHD1Lonly led to macrocephaly and increased larval body length, whereas chd1l deletion caused opposite phenotypes. These mirrored phenotypes were also observed in mouse embryos. Transcriptomic, cistromic, and chromatin accessibility analyses ofCHD1Lknock-out hiPSC-derived neuronal progenitor cells revealed that CHD1L regulates the expression levels and chromatin accessibility of genes involved in neuronal differentiation and synaptogenesis, including autism genes. Moreover, we found thatCHD1Lfavors telencephalon development during forebrain regionalization by facilitating chromatin accessibility to pioneer transcription factors including SOX2 and OTX2 while simultaneously compacting chromatin through its interaction with the repressor NuRD complex. Last, atypical 1q21.1 CNV encompassingCHD1Land pathogenic missense and truncatingCHD1Lvariants were found in individuals with autism. Overall, our data reveal a novel role for CHD1L as a master regulator of cell fate and its dosage imbalance contributes to the neuroanatomical and growth phenotypes associated with the 1q21.1 distal CNV.GRAPHICAL ABSTRACT
Chromosome segregation dynamics during the cell cycle ofStaphylococcus aureus
Authors: Izquierdo-Martinez Adrian , Schäper Simon , Brito António D. , Liao Qin , Tesseur Coralie , Sorg Moritz , Botinas Daniela S. , Wang Xindan , Pinho Mariana G. 
Published: February 2025

AbstractResearch on chromosome organization and cell cycle progression in spherical bacteria, particularlyStaphylococcus aureus, remains limited and fragmented. In this study, we established a working model to investigate chromosome dynamics inS. aureususing a Fluorescent Repressor-Operator System (FROS), which enabled precise localization of specific chromosomal loci. This approach revealed that theS. aureuscell cycle and chromosome replication cycle are not coupled, with cells exhibiting two segregated origins of replication at the start of the cell cycle. The chromosome has a specific origin-terminus-origin conformation, with origins localizing near the membrane, towards the tip of each hemisphere, or the “cell poles”. We further used this system to assess the role of various proteins with a role inS. aureuschromosome biology, focusing on the ParB-parSand SMC-ScpAB systems. Our results demonstrate that ParB binds fiveparSchromosomal sequences and the resulting complexes influence chromosome conformation, but play a minor role in chromosome compaction and segregation. In contrast, the SMC-ScpAB complex plays a key role inS. aureuschromosome biology, contributing to chromosome compaction, segregation and spatial organization. Additionally, we systematically assessed and compared the impact of proteins linking chromosome segregation to cell division—Noc, FtsK, SpoIIIE and XerC—on origin and terminus number and positioning. This work provides a comprehensive study of the factors governing chromosome dynamics and organization inS. aureus, contributing to our knowledge on chromosome biology of spherical bacteria.
Multi-alignment framework - consider and detect genomic and transcriptomic sequence alignment variability by comparing different techniques
Authors: Zhao Xinwei , Korsching Eberhard 
Published: February 2025

AbstractDNA and RNA nucleotide sequences are an ubiquitous element of all biological cells and are serving on one hand as a comprehensive library of capabilities for the cells and on the other as an impressive regulatory system to control cellular function.The presented multi-alignment framework (MAF) should give researchers a simple sequence alignment platform as a functional template, flexible enough to adjust all steps but also comprehensive enough to join many different tools and custom parameter combinations if in-depth analysis is necessary or advised in e.g. low read rate situations. So this tool should fill the gap between the minimalistic solutions in service facilities and the less flexible all in one software tools like e.g. Galaxy. The platform enables researcher to apply multiple aligner and further processing tools in flexible combinations to analyze the subtle to remarkable differences between different alignment programs and algorithms applied to the same data basis. This flexibility is supporting sophisticated research concepts and enables to uncover robust and relevant biological results.
Continuousin situsynthesis of a complete set of tRNAs sustains steady-state translation in a recombinant cell-free system
Authors: Li Fanjun , Baranwal Amogh Kumar , Maerkl Sebastian J. 
Published: February 2025

AbstractConstruction of a self-regenerating biochemical system is critical for building a synthetic cell. An essential step in building a self-regenerative system is producing a complete set of tRNAs for translation, which remains a significant challenge. We reconstituted a complete set of 21in vitrotranscribed (IVT) tRNAs by improving the transcription yield of four tRNAs and optimized their abundance to improve protein yield. Next, we showed that protein expression in the PURE transcription-translation system can be achieved byin situtranscribing tRNAs from 21 linear tRNA templates or a single plasmid encoding all 21 tRNAs. To enable synthesis of mature tRNAs from a circular template, we employed either a nicked plasmid template orT. maritimatRNase Z to post-transcriptionally process the precursor tRNAs. We ultimately achieved continuousin situsynthesis of a complete set of tRNAs capable of supporting sustained, steady-state protein expression in PURE reactions running on microfluidic chemostats. Our findings advance the development of an autopoietic biochemical system.
Potential mode of action of multispecies inoculums on wheat growth under water stress
Authors: Agoussar Asmaâ , Tremblay Julien , Yergeau Étienne 
Published: February 2025

AbstractManipulating microbial communities could increase crop resistance to environmental stressors such as drought. It is, however, not clear what would be the best approach to do so and what microbial traits are important. Here, we first compare multispecies inoculums created using different approaches. The only inoculum that increased wheat fresh biomass under drought was the one created from 25 isolates that had showed a capacity to grow under high osmolarity. We then looked at two potential mechanisms of action of this inoculum: 1) direct action, by sequencing and screening the genomes of the inoculated bacteria, 2) indirect action, by sequencing the 16S rRNA gene and ITS region of rhizosphere, root and leaves microbial communities. The microbes in the inoculum harbored many traits related to plant growth promoting, competition and water stress resistance. The inoculation also resulted in significant shifts in the microbial communities associated with wheat, including some microorganisms previously reported to improve plant drought resistance. We conclude that the inoculum studied here increased wheat growth because it potentially acted on two fronts: directly, through the traits it was selected for, and indirectly, through inducing shifts in the resident plant microbial communities.
Effective connectivity between the medial temporal lobes and early visual cortex modulated by unrestricted viewing predicts memory retrieval and gaze reinstatement
Authors: Ladyka-Wojcik N. , Liu Z.-X. , Ryan J.D. 
Published: February 2025

AbstractMemory and gaze behavior are intricately linked, guiding one another to extract information and create mental representations of our environment for subsequent retrieval. Recent findings from functional neuroimaging and computational modeling suggest that reciprocal interactions between the extended hippocampal system and visuo-oculomotor regions are functionally relevant for building these mental representations during visual exploration. Yet, evidence for the directionality of information flow during encoding within this reciprocal architecture in humans is limited. In the current study, we used dynamic causal modeling (DCM) to give a non-invasive account for the directional influences between these systems when new memories are created. Here, we provide novel evidence demonstrating how unrestricted, naturalistic visual exploration induces changes in this connectivity. Subsequent memory retrieval performance was also predicted by the pattern of connectivity modulated by unrestricted visual exploration, identifying the mechanism underlying a rich history of previous work linking increased gaze behavior during encoding to later memory. Together, these findings suggest that gaze behavior shapes the ways in which brain dynamics within and between the hippocampal system and early visual cortex unfold during encoding in humans. Importantly, these directional interactions support the building of coherent, lasting mental representations.
A Syntenic Pangenome forGardnerellaReveals Taxonomic Boundaries and Stratification of Metabolic and Virulence Potential across Species
Authors: Bouzek Heather , Srinivasan Sujatha , Jones Dakota S. , McMahon Elsa F. , Strenk Susan M. , Fiedler Tina L. , Fredricks David N. , Johnston Christopher D. 
Published: February 2025

AbstractBacterial vaginosis (BV) is a prevalent condition associated with an imbalance in the vaginal microbiota, often involving species ofGardnerella. The taxonomic complexity and inconsistent nomenclature ofGardnerellahave impeded progress in understanding the role of specific species in health and disease. In this study, we conducted a comprehensive genomic and pangenomic analysis to resolve taxonomic ambiguities and elucidate metabolic and virulence potential acrossGardnerellaspecies. We obtained complete, closed genomes for 42Gardnerellaisolates from women with BV and curated publicly available genome sequences (n = 291). Average nucleotide identity (ANI) analysis, digital DNA-DNA hybridization (dDDH), and thecpn60gene sequences identified nine species and eleven subspecies withinGardnerella, for which we refined species and subspecies boundaries and proposed updated nomenclature. Pangenome analysis revealed species-specific gene clusters linked to metabolic pathways, virulence factors, and niche adaptations, distinguishing species specialized for mucin degradation in the vaginal environment from those potentially adapted to urinary tract colonization. Notably, we identified lineage-specific evolutionary divergence in gene clusters associated with biofilm formation, carbohydrate metabolism, and antimicrobial resistance. We further discovered the first cryptic plasmids naturally present within theGardnerellagenus. Our findings provide a unified framework forGardnerellataxonomy and nomenclature, and enhance our understanding of species-specific functional capabilities, with implications forGardnerellaresearch, diagnostics, and targeted therapeutics in BV.
ACE2 utilization of HKU25 clade MERS-related coronaviruses with broad geographic distribution
Authors: Liu Chen , Park Young-Jun , Ma Cheng-Bao , Stuart Cameron , Gen Risako , Sun Yu-Cheng , Yang Xiao , Lin Mei-Yi , Xiong Qing , Si Jun-Yu , Liu Peng , Veesler David , Yan Huan 
Published: February 2025

AbstractDipeptidyl peptidase-4 (DPP4) is a well-established receptor for several MERS-related coronaviruses (MERSr-CoVs) isolated from humans, camels, pangolins, and bats (1–6). However, the receptor usage of many genetically diverse bat MERSr-CoVs with broad geographical distributions remains poorly understood. Recent studies have identified angiotensin-converting enzyme 2 (ACE2) as an entry receptor for multiple merbecovirus clades. Here, using viral antigen and pseudovirus-based functional assays, we demonstrate that several bat merbecoviruses from the HKU25 clade previously thought to utilize DPP4 (7), employ ACE2 as their functional receptor. Cryo-electron microscopy analysis revealed that HsItaly2011 and VsCoV-a7 recognize ACE2 with a binding mode sharing similarity with that of HKU5 but involving remodeled interfaces and distinct ortholog selectivity, suggesting a common evolutionary origin of ACE2 utilization for these two clades of viruses. EjCoV-3, a strain closely related to the DPP4-using MERSr-CoV BtCoV-422, exhibited relatively broad ACE2 ortholog tropism and could utilize human ACE2 albeit suboptimally. Despite differences in entry mechanisms and spike proteolytic activation compared to MERS-CoV, these viruses remain sensitive to several broadly neutralizing antibodies and entry inhibitors. These findings redefine our understanding of the evolution of receptor usage among MERSr-CoVs and highlight the versatility of ACE2 as a functional receptor for diverse coronaviruses.SignificanceRecent studies unexpectedly revealed that several merbecoviruses convergently evolved ACE2 receptor usage with distinct binding modes across three continents, challenging the dogma that DPP4 is their primary receptor. Here, we demonstrate that HKU25 clade MERS-related coronaviruses broadly distributed across Eurasia utilize ACE2 as host receptor through a binding mode shared with HKU5, challenging prior findings. These findings reveal a prevalence of ACE2 usage in diverse MERS-related coronaviruses in bats and show that EjCoV-3 is preadapted to use human ACE2, suggesting a potential for spillover. Our data provide a blueprint of host receptor barrier determinants which will facilitate global surveillance and development of countermeasures against these poorly characterized merbecoviruses.