bluuebunny/crossref_metadata_2025_split huggingface dataset:
Connectomic Organization of the Suprachiasmatic Nucleus
Authors: Liu Jing , Yu Jing , Shen Lijun , Chen Xi , Ma Lei , Zhai Hao , Li Linlin , Zhang Lina , Wang Lu , Yuan Jingbin , Chen Bohao , Hong Bei , Liu Jiazheng , Lv Yanan , Cai Yu , Zhang Yanchao , Chang Sheng , Guo Jinyue , Chen Haoran , Liu Mianzhi , Wang Zichen , Xin Tong , Zhou Fangxu , Zhao Xinghui , Zhang Dandan , Xie Qiwei , Ma Hongtu , Xu Ying , Cheng Heping , Han Hua 
Published: October 2024

AbstractThe suprachiasmatic nucleus (SCN), the mammalian master clock, is a special structure dedicated to the time computation. However, a connectomic understanding of the nucleus as a whole is lacking. Using serial section electron microscopy, we reconstructed multiscale and multimodal SCN communication networks. Intra-SCN synaptic network consists of 9,566 morphologically similar neurons and 4.3 million synapses, organized into multiscale circuitries that interact with SCN-traversing axon fascicles. Strikingly, SCN neurons engage in unique soma-soma ephaptic interaction, forming 2,038 electrotonic integrative units with the largest overlapping the light-responsive area (LRA). SCN’s paracrine modality contains 47,396 μm3dense core vesicles, with notable scarcity in the LRA, suggesting cross-modal coordination and functional integration. These distinct network features provide comprehensive insights into the system architecture of the mammalian circadian clock.
The Zoonotic Potential of Poultry-Associated Nitrofurantoin-ResistantEscherichia coli
Authors: Sealey Jordan E , Astley Beth , Avison Matthew B 
Published: October 2024

AbstractEscherichia coliis the most common cause of urinary tract infection (UTI) in humans. Nitrofurantoin is the most frequent UTI therapy in the United Kingdom. Here we identify poultry as a potential zoonotic reservoir of nitrofurantoin resistant (NFT-R) and pre-resistant (one mutation away from NFT-R)E. coli. We found NFT-RE. coliexcreted by dogs fed a raw meat diet, as well as NFT-R and pre-resistantE. colicontaminating chicken meat sold for human consumption and chicken-based raw dog food. By whole genome sequence analysis, with reference to additional data from public repositories, we identified NFT-R or pre-resistantE. coliclones. These were ST919/8874, ST665, ST6805, ST69, ST752 and ST7529, which were dominated by isolates from poultry sources in Europe, though the ST752 clone is globally disseminated. Five of these clones included isolates from human clinical samples, of which several were confirmed urinary isolates. Our findings have important implications for public health and domestic hygiene, particularly for people being treated for UTI. They also increase concerns about the roles of raw-fed dogs as vectors for the entry of resistantE. coliinto the home. It is likely that nitrofuran use in poultry production was the initial driver for the emergence of NFT-R on poultry farms. Therefore, whilst NFT-RE. colisample-level positivity in poultry meat was far lower than resistance to more recently used fluoroquinolones, NFT-R and pre-resistantE. coliappear to have persisted among poultry flocks despite 30 years of zero legal use in Europe.
Hijacking and Integration of Algal Plastids and Mitochondria in a Polar Planktonic Host
Authors: Rao Ananya Kedige , Yee Daniel , Chevalier Fabien , LeKieffre Charlotte , Pavie Marie , Olivetta Marine , Dudin Omaya , Gallet Benoit , Hehenberger Elisabeth , Seifi Mehdi , Jug Florian , Deschamps Joran , Wu Ting-Di , Gast Rebecca , Jouneau Pierre-Henri , Decelle Johan 
Published: October 2024

SUMMARYIn oceanic plankton, various host organisms are capable of engulfing and temporarily integrating microalgae (photosymbiosis) or just their photosynthetic plastids (kleptoplastidy) as a solar-powered energy source. These cellular interactions can be considered to be representative of evolutionary steps in plastid acquisition in eukaryotes, but the underlying cellular mechanisms and dynamics are not fully understood. Here, we studied a kleptoplastidic dinoflagellate (RSD: Ross Sea Dinoflagellate), which is known to steal plastids of the microalgaPhaeocystis antarctica. We tracked the morphology and activity of stolen plastids over several months by combining multimodal subcellular imaging and photophysiology. Upon integration inside a host vacuole, the volume of plastids and pyrenoids significantly increased and photosynthetic activity was boosted along with carbon fixation and transfer to the host. This may be supported by the retention of a 50-fold larger algal nucleus for ∼1 week. Once the algal nucleus was lost, there was a decrease in plastid volume and photosynthesis, but plastids were still beneficial for the host after > 2 months. Unlike other kleptoplastidic interactions, we showed that the algal mitochondrion was also stolen and retained for several months, transforming into an extensive network in close proximity with plastids. This highlights a new strategy in plankton along the continuum of plastid symbioses where both the energy-producing plastid and mitochondrion of a microalga are hijacked for several months by a host. This symbiosis that we found to be widely-distributed in polar regions suggests that plastid-mitochondrion interaction may have played a role in the evolution of plastid acquisition.
Genetic differentiation is constrained to chromosomal inversions and putative centromeres in locally adapted populations with higher gene flow
Authors: Akopyan Maria , Tigano Anna , Jacobs Arne , Wilder Aryn P. , Therkildsen Nina O. 
Published: October 2024

AbstractThe impact of genome structure on adaptation is a growing focus in evolutionary biology, revealing an important role for structural variation and recombination landscapes in shaping genetic diversity across genomes and among populations. This is particularly relevant when local adaptation occurs despite gene flow, where clustering of differentiated loci can maintain locally adapted variants by reducing recombination between them. However, the limited genomic resources for non-model species, including reference genomes and recombination maps, has constrained our understanding of these patterns. In this study, we leverage the Atlantic silverside—a non-model fish with extensive local adaptation across a steep latitudinal gradient—as an ideal system to explore how genome structure influences adaptation under varying levels of gene flow, using a newly available reference genome and multiple recombination maps. Analyzing 168 genomes from four populations, we found a continuum of genome-wide differentiation increasing from south to north, reflecting higher connectivity among southern populations and reduced gene flow at northern latitudes. With increasing gene flow, the number and clustering of FSToutlier loci also increased, with differentiated loci tightly clustered in large haploblocks harboring inversions and smaller peaks overlapping putative centromeres. Notably, sequence divergence was only evident in inversions, supporting their role in adaptive divergence with gene flow, whereas centromeres appeared differentiated because of low recombination and reduced diversity, with no indication of elevated sequence divergence. Our results support the hypothesis that clustered genomic architectures evolve with high gene flow and enhance our understanding of how inversions and centromeres are linked to different evolutionary processes.Significance StatementHow populations preserve favorable combinations of genes adapted to their local environment despite reproducing with populations adapted to different conditions is a longstanding question in evolutionary biology. By analyzing the genomes of 168 Atlantic silverside fish from four populations, we found that when populations adapted to different environments frequently interbreed, genetic differences concentrate in specific parts of the genome, particularly in chromosomal inversions—where segments of DNA are flipped. These inversions help preserve locally adapted gene combinations, enabling populations to maintain differences essential for survival in their habitats. This research enhances our understanding of genomic adaptation, a fundamental evolutionary question with increasing relevance as environmental changes pose new challenges globally.
Outpatient Portal Use and Blood Pressure Management during Pregnancy
Authors: Stamos Athena , Fareed Naleef 
Published: October 2024

AbstractWe investigated the association between systole and diastole, and outpatient portal use during pregnancy. We used electronic and administrative data from our academic medical center. We categorized patients into two groups: (<140 mm Hg; <90 mm Hg), and out-of-range (≥140 mm Hg, ≥ 90 mm Hg). Random effects linear regression models examined the association between mean trimester blood pressure (BP) levels and portal use, adjusting for covariates. As portal use increased, both systole and diastole levels decreased for the out-of-range group. These differences were statistically significant for patients who were initially out-of-range. For the in-range group, systole and diastole levels were stable as portal use increased. Results provide evidence to support a relationship between outpatient portal use and BP outcomes during pregnancy. More research is needed to expand on our findings, especially those focused on the implementation and design of outpatient portals for pregnancy.
Bifidobacterium animalis subsp. lactisBL-11 Promotes Height Growth in Children Aged 3-7 Years: A Self-controlled Cohort Study
Authors: Wang Qian , Yang Yanan , Xiao Yin , Liu Ziyi , Li Mingxi , Yu Yue , Wang Nannan , Li Junyan , Li Xiaohui , Xu Chuanhui , Liu Deyun , Wu Chongming 
Published: October 2024

AbstractBackgroundShort status of children has captured extensive attention since it reflects the health status of children and affects physical and psychological health throughout children’s life. Compelling evidences have revealed that gut microbiota participates in the skeletal development directly or indirectly. Currently, the calcium agent and growth hormone-like drugs have provided potential opportunities to promote growth and development among children, yet limited trials existed with probiotic intake as a primary strategy.ObjectivesPresent cohort study was designed to evaluate the height-promoting effect of gut probioticBifidobacterium animalis subsp. lactisBL-11 among 3-7 years old children. Registered underClinicalTrials.govIdentifier no. ChiCTR2400089723.MethodsThis study was conducted with Chinese children aged 3 to 7 years (n = 124) who fall between the 3rd and 25th percentiles (P3-P25) for height, and whose annual growth rate in height is less than 5 cm. TheBifidobacterium animalis subsp. lactisBL-11 oiling agent were taken every day with total live bacteria ≥ 30 billion. The height of each participant was measured and recorded before and after three-monthsBifidobacterium animalis subsp. lactisBL-11 intervention.ResultsBifidobacterium animalis subsp. lactisBL-11 could strikingly promote the height growth of children, and shift the height percentile rage from P3-P10 to P10-P25. Importantly, this promoting effect has no specificity between age and sex. Comparatively, children with shorter height (P3-P10) were more sensitive toBifidobacterium animalis subsp. lactisBL-11.ConclusionsAdministration ofBifidobacterium animalis subsp. lactisBL-11 as early as possible is in favor of the child’s growth and development, which provided a strategy for pediatricians to address some plights that how to promote children’s growth effectively and safely.
Insights into the Structural Regulation of Polo-Like Kinase Activity using AlphaFold
Authors: Wyatt Michael D. , McInnes Campbell 
Published: October 2024

ABSTRACTThe Polo Like Kinases including the major family member, PLK1 are key regulatory enzymes controlling the cell cycle and mitosis. PLK1 is associated with poor survival rates in cancer and has been extensively investigated as an oncology drug target. Each member of the Polo like kinase family (PLKs 1-5) have two subdomains with independent functions and include the well conserved N-terminal kinase domain (KD) and the C-terminal polobox domain (PBD). The PBD is involved in the recognition of substrates primed by other kinases and in the PLK1 context is responsible for subcellular localization to specific sites in the nucleus including centrosomes and kinetochores. While the phosphosubstrate recognition site in PLKs 1-3 is highly conserved, its role in PLKs 2 and 3 is not well characterized and phosphopeptides that inhibit PLK1 have dramatically lower affinity for PLKs 2 and 3. An additional role of the PBD is its ability through domain-domain interactions with the KD to regulate PLK1 activity by an autoinhibited state of PLK1, conceptually similar to that which occurs through other kinases. Other mechanisms regulating PLK activity include the interchange between monomeric and dimeric forms, which inhibit or activate PLK1 during the cell cycle. Furthermore, PLK1 may exist as heterodimers with PLK2 and/or PLK3 and thus play context dependent roles. Here, through the use of the AlphaFold (AF) algorithm, structural insights into regulation of activity of the PLK1 and other family members have been obtained. These include dramatically different tertiary arrangement of the individual domains in each individual PLK. Analysis of the domain-domain interactions, interdomain and intradomain loops in each PLK sheds light onto plausible mechanisms by which the activity of each PLK is regulated and provides insights into the selectivity of phosphopeptides. The results also suggest a mechanism for the heterodimerization of PLK1 and PLK2 which has been observed in the literature.
Fatty acid desaturases link cell metabolism pathways to promote proliferation of Epstein-Barr virus-infected B cells
Authors: Bonglack Emmanuela N. , Hill Kaeden K. , Barry Ashley P. , Bartlett Alexandria , Castellano-Escuder Pol , Hirschey Matthew D. , Luftig Micah A. 
Published: October 2024

ABSTRACTEpstein-Barr virus (EBV) is a gamma herpesvirus that infects up to 95% of the human population by adulthood, typically remaining latent in the host memory B cell pool. In immunocompromised individuals, EBV can drive the transformation and rapid proliferation of infected B cells, ultimately resulting in neoplasia. The same transformation process can be inducedin vitro, with EBV-infected peripheral blood mononuclear cells (PBMCs) forming immortalized lymphoblastoid cell lines (LCLs) within weeks. In this study, we found that the fatty acid desaturases stearoyl-CoA desaturase 1 (SCD1) and fatty acid desaturase 2 (FADS2) are upregulated by EBV, and crucial for EBV-induced B cell proliferation. Additionally, we found that pharmacological and genetic inhibition of both SCD1 and FADS2 results in a significantly greater reduction in proliferation and cell cycle arrest, compared to perturbing either enzyme individually. Additionally, we found that inhibiting either SCD1 or FADS2 alone hypersensitizes LCLs to palmitate-induced apoptosis, recapitulating studies in other tissue types. Further lipidomic and metabolic analysis of dual SCD1/FADS2-inhibited LCLs revealed an increase in free unsaturated fatty acids, a reduction of oxidative phosphorylation, and a reduction of glycolysis, thereby linking the activity of SCD1 and FADS2 to overall growth-promoting metabolism. Lastly, we show that SCD1 and FADS2 are important in the growth of clinically derived EBV+ immunoblastic lymphoma cells. Collectively, these data demonstrate a previously uncharacterized role of lipid desaturation in EBV+ transformed B cell proliferation, revealing a metabolic pathway that can be targeted in future anti-lymphoma therapies.
Investigating the barley methylome, its variation and association with genomic, transcriptomic, and phenotypic variation
Authors: Kühl Marius , Wu Po-Ya , Shrestha Asis , Engelhorn Julia , Hartwig Thomas , Stich Benjamin 
Published: October 2024

ABSTRACTEpigenetic variation contributes to explaining the missing heritability of complex traits. In order to understand the genome-wide methylation variation in spring barley, our objectives were to gain fundamental insight into the barley methylome through whole genome bisulfite sequencing, characterizing methylation variation among 23 parental inbreds of a community resource for genetic mapping of phenotypic traits, and assessing the association of differentially methylated regions (DMRs) with single nucleotide polymorphisms (SNPs) and gene expression variation. Compared to other angiosperms, barley was found to have a highly methylated genome with an average genome wide methylation level of 88.6%, 58.1%, and 1.4% in the CpG, CHG, and CHH sequence context, respectively. We identified just below 500 000 differentially methylated regions (DMRs) among the inbreds. About 64%, 64%, and 83% of the DMRs were not associated with genomic variation in the CpG, CHG, and CHH context, respectively. The methylation level of around 6% of all DMRs was significantly associated with gene expression, where the directionality of the correlation was depended on the relative location of the DMR to the respective gene with a recognizable pattern. Notably, this pattern was much more specific and spatially confined than the association of methylation with gene expression across genes in a singular inbred line. We exemplified this association between DNA methylation and gene expression on the known flowering promoting geneVRN-H1and identified a highly methylated epiallele associated with earlier flowering time. Finally, methylation was shown to improve the prediction abilities of genomic prediction models for a variety of traits over models using solely SNPs and gene expression as predictors. These observations highlight the independence of DNA methylation to sequence variation and their difference in information content. Our discoveries suggest that epigenetic variation provides a layer of information likely not predictable by other means and is therefore a valuable addition to genomic prediction models.
Scrutinized lipid utilization disrupts Amphotericin-B responsiveness in clinical isolates ofLeishmania donovani
Authors: Pradhan Supratim , Dhar Dhruba , Manna Debolina , Chakraborty Shubhangi , Bhattacharyya Arkapriya , Chauhan Khushi , Mukherjee Rimi , Sen Abhik , Pandey Krishna , Das Soumen , Mukherjee Budhaditya 
Published: October 2024

AbstractThe management ofLeishmania donovani (LD), responsible for fatal visceral leishmaniasis (VL), faces increasing challenges due to rising drug-unresponsiveness, leading to increasing treatment failures. While hypolipidemia characterizes VL, LD, a cholesterol auxotroph, relies on host lipid scavenging for its intracellular survival. The aggressive pathology, in terms of increased organ parasite load, observed in hosts infected with antimony-unresponsive-LD (LD-R) as compared to their sensitive counterparts (LD-S), highlights LD-R’s heightened reliance on host lipids. Here we report that LD-R-infection promotes fluid-phase endocytosis in the host, selectively accumulating neutral lipids while excluding oxidized-LDL. LD-R enhances the fusion of endocytosed LDL- vesicles with its phagolysosomal membrane and inhibits cholesterol mobilization from these vesicles by suppressing NPC-1. This provides LD-R amastigotes with excess lipids, supporting their rapid proliferation and membrane synthesis. This excess LDL-influx leads to an eventual accumulation of neutral lipid droplets around LD-R amastigotes, thereby increasing their unresponsiveness towards Amphotericin-B, a second-line amphiphilic antileishmanial. Notably, VL patients showing relapse with Amphotericin-B treatment exhibited significantly lower serum LDL and cholesterol than cured cases. Treatment with Aspirin, a lipid droplet blocker, reduced lipid droplets around LD-R amastigotes, restoring Amphotericin-B responsiveness.
This is SPRTA: assessing phylogenetic confidence at pandemic scales
Authors: De Maio Nicola , Ly-Trong Nhan , Minh Bui Quang , Goldman Nick 
Published: October 2024

AbstractPhylogenetics plays a central role in evolutionary biology and genomic epidemiology. Assessing phylogenetic confidence and reliability is therefore crucial and methods to do this, such as Felsenstein’s bootstrap, are among the most used in modern science. However, methods based on Felsenstein’s bootstrap suffer from excessive computational demand, and are unsuitable for large datasets. Furthermore, most of these methods emerge from a cladistic framework which makes their results hard to interpret in the context of genomic epidemiology.We propose SPRTA (“ SPR-based Tree Assessment”), an efficient and interpretable approach to assess confidence in phylogenetic trees. SPRTA shifts the paradigm of phylogenetic support measurement from evaluating the confidence in clades (groupings of taxa) to genome evolution histories, for example assessing if a lineage evolved from another considered lineage or not. This focus on evolutionary histories is particularly valuable in genomic epidemiology, where typically the evolutionary and transmission history of a pathogen are of interest, not clade content.We illustrate the use of SPRTA by investigating a global SARS-CoV-2 phylogenetic tree relating>2M genomes, highlighting plausible alternative evolutionary origins of many SARS-CoV-2 variants. We have implemented SPRTA within the free and open source maximum likelihood phylogenetic software MAPLE, available fromhttps://github.com/NicolaDM/MAPLE.
Crystallographic and NMR studies of Streptococcus pneumonia LCP protein PsrSpindicate the importance of dynamics in four long loops for ligand specificity
Authors: Sandalova Tatyana , Sala Benedetta Maria , Moche Martin , Ljunggren Hans-Gustaf , Alici Evren , Henriques-Normark Birgitta , Agback Tatiana , Lesovoy Dmitry , Agback Peter , Achour Adnane 
Published: October 2024

AbstractThe crystal structure of the extracellular region of the second pneumococcal LCP, a polyisoprenyl-teichoic acid-peptidoglycan teichoic acid transferase PsrSp, was determined and refined to 2.15Å resolution. Despite the low sequence homology with other LCP proteins, the PsrSpmaintains the fold of the LCP domain and the positions of the 15 residues suggested to participate in the transferase function are conserved. The empty tunnel found in the PsrSpbetween the central β-sheet and three α-helices is wide enough to accommodate polyisoprenyl-teichoic acid. Comparison of the crystallographic temperature factors of LCP from distinct bacteria demonstrated that the four long loops located close to the teichoic acid and peptidoglycan binding sites have different relative mobility. To compare the dynamics of the PsrSpin crystalline state and in solution, NMR spectra were recorded, and 88% of the residues were assigned in the1H-15N TROSY HSQC spectra. Comparison of the secondary structure of the crystal structure of PsrSpwith NMR data demonstrated a perfect concordance between the results using these two methods. Moreover, the relative mobility of the essential loops estimated from the crystallographic B-factor is in good agreement with order parameter S2, predicted from chemical shift. We hypothesize that the dynamics of these loops are important for the substrate promiscuity of LCP proteins.