bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of Oocyte Meiotic Maturation: Unraveling the Interplay between PKA Inhibition and Cdk1 Activation
Authors: Santoni Martina , Sekhsoukh Nabil , Castella Sandrine , Le Tran , Miot Marika , Daldello Enrico Maria 
Published: September 2023

ABSTRACTOocyte meiosis is arrested at the first prophase stage, until hormonal stimulation triggers progression into the meiotic divisions. This process, called meiotic maturation, depends on extensive post-transcriptional events. In all vertebrates, two bottleneck events orchestrate meiosis resumption: first, the inhibition of PKA and, second, the activation of Cdk1, the master regulator of eukaryotic cell division. However, the molecular events occurring between these two steps are almost unknown. To address this issue, we took advantage of a Cdk1 inhibitor to identify the early events that depend on PKA downregulation and occur independently of Cdk1 activity. Unexpectedly, we show that accumulation of Cyclin B1 and Mos, the kinase responsible for MAPK activation in oocytes, are regulated in an opposing manner by a two-step mechanism. PKA downregulation induces first the accumulation of Cyclin B1 without any increase of its translation, independently of Cdk1 activation. Subsequently, the rate of Cyclin B1 translation increases in response to Cdk1 activation. In contrast, Mos translation begins downstream PKA inhibition, but the protein does not accumulate until Cdk1 is activated. These intertwined regulations create the positive feedback loops required for the full activation of Cdk1. Additionally, we show that two consecutive waves of translation occur during the G2-M transition, the first induced by PKA inhibition and the second by Cdk1 activation. Finally, we demonstrate that Arpp19, the only known early substrate of PKA inXenopusoocytes, is not involved in the control of these early events. This study reveals that PKA downregulation promotes multiple molecular pathways that converge on the activation of Cdk1 to induce the G2/M transition in vertebrate oocytes.
Differential susceptibility of human microglia HMC3 cells and brain microvascular endothelial HBEC-5i cells to Mayaro and Una virus infection
Authors: Campos Dalkiria , Sugasti-Salazar Madelaine , Galán-Jurado Paola Elaine , Valdés-Torres Patricia , Zegarra Dalel , González-Santamaría José 
Published: September 2023

ABSTRACTMayaro (MAYV) and Una (UNAV) are emerging alphaviruses circulating in the Americas. Earlier reports have revealed that MAYV infects different human cell lines, including synovial and dermal fibroblasts, chondrocytes, osteoblasts, astrocytes and pericytes, as well as neural progenitor cells. In this study we evaluated the susceptibility of immortalized human microglia HMC3 cells and brain microvascular endothelial HBEC-5i cells to MAYV and UNAV infection. Cytopathic effects, cell viability, viral progeny yields, and the presence of E1 and nsP1 proteins in HMC3 and HBEC-5i cells infected with several MAYV or UNAV strains were assessed using an inverted microscope, MTT assay, plaque-forming assays, and immunofluorescence or Western blot, respectively. Finally, the expression of immune response genes was analyzed using qRT-PCR. MAYV and UNAV demonstrated strong cytopathic effects and significantly reduced cell viability in HMC3 cells. Moreover, the HMC3 cells were efficiently infected regardless of the virus strains tested, and E1 and nsP1 viral proteins were detected. In contrast, only MAYV appeared to infect HBEC-5i cells, and minimal effects on cell morphology or viability were observed. Furthermore, the MAYV titer and viral protein levels were substantially lower in the infected HBEC-5i cells when compared to those of the infected microglia cells. Finally, unlike UNAV, MAYV elicited a strong expression of specific interferon-stimulated genes in microglia cells, along with pro-inflammatory cytokines implicated in the immune response. Collectively, these findings demonstrate that MAYV and UNAV are capable of infecting relevant human brain cells.
Ancient DNA supports that the evolution of Skin Tone in East Asians intensified after their split with Native Americans
Authors: Ferrando-Bernal Manuel 
Published: September 2023

AbstractSkin tone has been deeply studied in European populations both using modern and ancient DNA. However, other populations are underrepresented in such studies. One such population is East Asians, for which, interestingly, it has been claimed to evolve light skin tones in parallel to Europeans. Moreover, it is not clear whether this happened before or after their split from Native Americans. Over the last few years, several studies have sequenced hundreds of ancient genomes belonging to East Asians ancient populations. Additionally, some variants have been associated with light skin in East Asians. To shed some light, I applied a Polygenic Risk Score for some of the variants associated with light skin, in 237 modern Native Americans and East Asian individuals and in more than 700 East Asians ancient samples. The results suggest that this phenotype may have started to evolve in the ancestors of East Asians and Native Americans but intensified after their split.
Propagation of human respiratory syncytial virus in cells derived from the black flying fox (Pteropus alecto)
Authors: Tan Timothy , Tan Boon Huan , Sugrue Richard 
Published: September 2023

AbstractThe propagation of human respiratory syncytial virus (hRSV) was evaluated in thePteropus alectokidney (PaKi) cell line. At 20 hrs post-infection, immunoblotting of hRSV-infected PaKi cell lysates with anti-G, anti-N, anti-P and anti-M2-1 indicated expression of the respective virus proteins of the correct size. The hRSV-infected PaKi cell were also stained using anti-F, anti-G, anti-N, anti-P and anti-M2-1 and imaged using immunofluorescence microscopy, which confirmed high levels of virus infection, and the presence of numerous virus filaments and virus-induced inclusion bodies. PaKi cell monolayers also supported multiple cycle infection when hRSV was used to infect PaKi cells using a low multiplicity of infection. These data indicate that prior adaptation of hRSV was not required for its propagation in the PaKi cell line, and suggests that PaKi cell line is a suitable cell model system with which to examine virus-host interactions involving RSV infection in fruit bats.
Genetic basis of variation in thermal developmental plasticity forDrosophila melanogasterbody pigmentation
Authors: Lafuente E , Duneau D , Beldade P 
Published: September 2023

ABSTRACTSeasonal differences in insect pigmentation are attributed to the influence of ambient temperature on pigmentation development. This thermal plasticity is adaptive and heritable, thereby capable of evolving. However, the specific genes contributing to the variation in plasticity that can drive its evolution remain largely unknown. To address this, we analyzed pigmentation and pigmentation plasticity inDrosophila melanogaster. We measured two components of pigmentation in the thorax and abdomen: overall darkness and the proportion of length covered by darker pattern elements (a trident in the thorax and bands in the abdomen) in females from two developmental temperatures (17°C or 28°C) and 191 genotypes. Using a GWAS approach to identify the genetic basis of variation in pigmentation and its response to temperature, we identified numerous dispersed QTLs, including some mapping to melanogenesis genes (yellow,ebony, andtan). Remarkably, we observed limited overlap between QTLs for variation within specific temperatures and those influencing thermal plasticity, as well as minimal overlap between plasticity QTLs across pigmentation components and across body parts. For most traits, consistent with selection favoring the retention of plasticity, we found that lower plasticity alleles were often at lower frequencies. The functional analysis of selected candidate QTLs and pigmentation genes largely confirmed their contributions to variation in pigmentation and/or pigmentation plasticity. Overall, our study reveals the existence and underlying basis of extensive and trait-specific genetic variation for pigmentation and pigmentation plasticity, offering a rich reservoir of raw material for natural selection to shape the independent evolution of these traits.
Molecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post-radiotherapy, and those withde novometastatic disease
Authors: Charlton P , O’Reilly D , Philippou Y , Rao SR , Lamb AD , Mills IG , Higgins G , Hamdy FC , Verrill C , Buffa FM , Bryant RJ 
Published: September 2023

AbstractPurposeIt is important to identify molecular features that improve prostate cancer (PCa) risk stratification before radical treatment with curative intent. Molecular analysis of historical diagnostic formalin-fixed paraffin-embedded (FFPE) prostate biopsies from cohorts with post-radiotherapy (RT) long-term clinical follow-up has been limited. Utilizing parallel sequencing modalities, we performed a proof-of-principle sequencing analysis of historical diagnostic FFPE prostate biopsies. We compared patients with i) stable PCa post-primary or salvage RT (sPCa), ii) progressing PCa post-RT (pPCa), and iii)de novometastatic PCa (mPCa).Experimental DesignA cohort of 19 patients with diagnostic prostate biopsies (n=6 sPCa, n=5 pPCa, n=8 mPCa) and mean 4 years 10 months follow-up (diagnosed 2009-2016) underwent nucleic acid extraction from demarcated malignancy. Samples underwent 3’RNA sequencing (3’RNAseq) (n=19), nanoString analysis (n=12) and Illumina 850k methylation (n=8) sequencing. Bioinformatic analysis was performed to coherently identify differentially expressed genes (DEGs) and methylated genomic regions (MGRs).Results18 of 19 samples provided useable 3’RNAseq data. Principal Component Analysis (PCA) demonstrated similar expression profiles between pPCa and mPCa cases, versus sPCa. Coherently differentially methylated probes between these groups identified ∼600 differentially MGRs. The top 50 genes with increased expression in pPCa patients were associated with reduced progression-free survival post-RT (p<0.0001) in an external cohort.Conclusions3’RNAseq, nanoString and 850K-methylation analyses are each achievable from historical FFPE diagnostic pre-treatment prostate biopsies, unlocking the potential to utilize large cohorts of historic clinical samples. Profiling similarities between individuals with pPCa and mPCa suggests biological similarities and historical radiological staging limitations, which warrant further investigation.
High resolution longitudinal molecular and morphological tracking of planktonic threats to salmon aquaculture: new candidates and old players
Authors: Algueró-Muñiz María , Spatharis Sofie , Dwyer Toni , de Noia Michele , Chaib Bachar , Robertson Brendan , Johnstone Calum , Welsh Jennifer , Macphee Annabell , Mazurkiewicz Marta , Bickerdike Ralph , Migaud Hervé , McGhee Clara , Præbel Kim , Llewellyn Martin 
Published: September 2023

AbstractMarine-phase salmonid aquaculture is a major component of the coastal economies of Northern Europe, North America and Chile and is under threat from numerous challenges to gill health, many of which originate from the phyto- and zooplankton. Associated losses are growing as a proportion of production year on year. A first step towards mitigating losses is to characterize the biological drivers of poor gill health. Numerous planktonic species have been implicated, including toxic and siliceous microalgae, hydrozoans and scyphozoans; however, rigorous longitudinal surveys of planktonic diversity and gill health have been lacking. In the current study, we present and assess an ‘exhaustive’ identification approach combining both morphological and molecular methods (environmental DNA metabarcoding) approaches in combination with robust statistical models to identify the planktonic drivers of complex gill disease (CGD) and fish mortality. We undertook longitudinal molecular and microscopic evaluation at two marine aquaculture facilities on the west coast of Scotland using daily data collected during the 2021 growing season (March-October). Examining these two different sites, one sheltered and one exposed to the open sea, we identified new, important, and unexpected planktonic drivers (e.g. doliolids and appendicularians) of CGD and mortality and confirmed the significance of some established threats (e.g. hydrozoans and diatoms). We also explored delayed or ‘lagged’ effects of planktonic abundances on gill health and undertook a comparison of environmental DNA metabarcoding and microscopy in their ability to identify and quantify planktonic species. Our data highlight the diversity of planktonic threats to salmonid aquaculture as well as the importance of using both molecular and morphological approaches to detect those. Despite our study relying on two farm sites only, our results evidence the role of the different planktonic players on salmon gill disease; there is now an urgent need to expand systematic longitudinal molecular and morphological approach across multiple sites and over multiple years. The resultant catalogue of main biological drivers will enable early warning systems, new treatments and, ultimately, a sustainable platform for future salmonid aquaculture in the marine environment.
Characterising the metabolic rewiring of extremely slow growingKomagataella phaffii
Authors: Coltman Benjamin Luke , Rebnegger Corinna , Gasser Brigitte , Zanghellini Jürgen 
Published: September 2023

AbstractRetentostat cultivations have enabled investigations into substrate-limited near-zero growth for a number of microbes. Quantitative physiology at these near-zero growth conditions has been widely discussed, yet characterisation of the fluxome is relatively under-reported. We investigated the rewiring of metabolism in the transition of a recombinant protein producing strain ofKomagataella phaffiito glucose-limited near-zero growth rates. We used cultivation data from a 200-fold range of growth rates and comprehensive biomass composition data to integrate growth rate dependent biomass equations, generated using a number of different approaches, into aK. phaffiigenome scale metabolic model. Here we show that a non-growth associated maintenance value of 0.65 mmolATPgCDW−1h−1and a growth-associated maintenance value oflead to accurate growth-rate predictions. In-line with its role as energy source, metabolism is rewired to increase the yield of ATP per glucose. This includes a reduction of flux through the pentose phosphate pathway, and a greater utilisation of glycolysis and the TCA cycle. Interestingly, we observed activity of an external, non-proton translocating NADH dehydrogenase in addition to the malate-aspartate shuttle. Regardless of the method used for the generation of biomass equations, a similar, yet different, growth rate dependent rewiring was predicted. As expected, these differences between the different methods were clearer at higher growth rates, where the biomass equation provides a much greater constraint than at slower growth rates. When placed on an increasingly limited glucose diet, the metabolism ofK. phaffiiadapts, enabling it to continue to drive critical processes sustaining its high viability at near-zero growth rates.
Phylogeny structures species’ interactions in experimental ecological communities
Authors: Lemos-Costa Paula , Miller Zachary R. , Allesina Stefano 
Published: September 2023

AbstractThe advent of molecular phylogenetics provided a new perspective on the structure and function of ecological communities. In particular, the hypothesis that traits responsible for species’ interactions are largely determined by shared evolutionary history has suggested the possibility of connecting the phylogeny of ecological communities to their functioning. However, statistical tests of this link have yielded mixed results. Here we propose a novel framework to test whether phylogeny influences the patterns of coexistence and abundance of species assemblages, and apply it to analyze data from large biodiversity-ecosystem functioning experiments. In our approach, phylogenetic trees are used to parameterize species’ interactions, which in turn determine the abundance of species in a specified assemblage. We use a maximum likelihood-based approach to score models parameterized with a given phylogenetic tree. To test whether evolutionary history structures interactions, we fit and score ensembles of randomized trees, allowing us to determine if phylogenetic information helps to predict species’ abundances. Moreover, we can determine the contribution of each branch of the tree to the likelihood, revealing particular clades in which interaction strengths are closely tied to phylogeny. We find strong evidence of phylogenetic signal across a range of published experiments and a variety of models. The flexibility of our framework permits incorporation of ecological information beyond phylogeny, such as functional groups or traits, and provides a principled way to test hypotheses about which factors shape the structure and function of ecological communities.
Reservoir ecosystems support large pools of fish biomass
Authors: Parisek Christine A. , De Castro Francine A. , Colby Jordan D. , Leidy George R. , Sadro Steve , Rypel Andrew L. 
Published: September 2023

AbstractHumans increasingly dominate Earth’s natural freshwater ecosystems, and many freshwater fisheries resources are imperiled and at-risk of collapse. Yet despite this, the productive capacity of intensively modified freshwater ecosystems is rarely studied. We digitized, and provide open access to, a legacy database containing empirical fish biomass from 1,127 surveys on 301 USA reservoirs. In parallel, we developed a slate of reservoir classification schemas that were deployed to better understand distributions of biomass and secondary production. By fusing these data products, we generated a predictive capacity for understanding the scope of fisheries biomass and secondary production across all USA reservoirs. We estimate total potential fish total standing stock in USA reservoirs is 3.4 billion (B) kg, and annual secondary production is 4.5 B kg y-1. In southern USA alone, total standing stock and secondary production are 1.9 B kg and 2.5 B kg y-1, respectively. We also observe non-linear trends in reservoir fish production and biomass over time, indicating that these ecosystems are quite dynamic. Results demonstrate that reservoirs represent globally relevant pools of freshwater fisheries, in part due to their immense spatial and limnetic footprint. This study further shows that reservoir ecosystems play major roles in food security, and fisheries conservation, even though they are frequently overlooked by freshwater scientists. We encourage additional effort be expended to effectively manage reservoir environments for the good of humanity, biodiversity, and fishery conservation.Significance StatementGlobally, many freshwater fishes and fisheries resources are imperiled and at-risk of collapse. However, previous research overwhelmingly focuses on freshwater fisheries in natural rivers and lakes. This study provides evidence that novel and reconciled ecosystems, such as reservoirs, hold massive pools of freshwater fisheries biomass and may have higher ecological value than previously thought. While dams are patently ecological catastrophes, ecosystem services including secondary fish production provided by reservoirs are nonetheless substantial. Indeed, in many locations (e.g., arid regions), reservoirs are the only remaining fisheries resource. We suggest considerable conservation management is warranted for reservoir fisheries worldwide.Data DepositionCode is available on GitHub (https://github.com/caparisek/res_biomass_USA; DOI 10.5281/zenodo.8316696). All data and reservoir classifications are available on Zenodo (DOI 10.5281/zenodo.8317007). Furthermore, data will also be deposited in the Environmental Data Initiative repository upon acceptance of this manuscript.
WITHDRAWN: Comparison of the effects of methylene blue with adrenaline and Marcaine with adrenaline on pain control after hemorrhoidectomy
Authors: Azhough Ramin , Dashti Mohammad Reza , Taher Sahar , Jalali Pooya 
Published: September 2023

Withdrawal StatementThe authors have withdrawn their manuscript owing to Improve the article. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Prospective exploration of a prognostic biomarker of nivolumab for head and neck cancer patients (BIONEXT)
Authors: Sato Kuniaki , Toh Satoshi , Murakami Taku , Nakano Takafumi , Hongo Takahiro , Matsuo Mioko , Hashimoto Kazuki , Sugasawa Masashi , Yamasaki Keisuke , Ueki Yushi , Nakashima Torahiko , Uryu Hideoki , Ono Takeharu , Umeno Hirohito , Ueda Tsutomu , Kano Satoshi , Tsukahara Kiyoaki , Watanabe Akihito , Ota Ichiro , Monden Nobuya , Iwae Shigemichi , Maruo Takashi , Asada Yukinori , Hanai Nobuhiro , Sano Daisuke , Ozawa Hiroyuki , Asakage Takahiro , Fukusumi Takahito , Masuda Muneyuki 
Published: September 2023

AbstractBACKGROUNDNivolumab paved a new way in the treatment of patients with recurrent or metastatic (RM) head and neck squamous cell carcinoma (RM-HNSCC). However, the limited rates of long-term survivors (< 20%) demand a robust prognostic biomarker. This nationwide multi-centric prospective study aimed to identify a plasma exosome (PEX) mRNA signature, which serves as a companion diagnostic of nivolumab and provides a biological clue to develop effective therapies for a majority of non-survivors.METHODSPre-treatment plasmas (N= 104) of RM-HNSCC patients were subjected to comprehensive PEX mRNA analyses for prognostic marker discovery and validation. In parallel, paired treatment-naïve tumor and plasma samples (N= 20) were assayed to elucidate biological implications of the PEX mRNA signature.RESULTSA combination of 6 candidate PEX mRNAs plus neutrophil-to-lymphocyte ratio precisely distinguished non-survivors from >2-year survivors (2-year OS; 0% vs 57.7%;P= 0.000124) with a high hazard ratio of 2.878 (95% CI 1.639-5.055;P= 0.0002348). In paired samples, PEXHLA-EmRNA (a non-survivor-predicting marker) was positively corelated with overexpression of HLA-E protein (P= 0.0191) and the dense population of tumor-infiltrating NK cells (P= 0.024) in the corresponding tumor, suggesting the HLA-E-NKG2A immune checkpoint may inhibit the antitumor effect of PD-1blockade in patients with high PEXHLA-EmRNA.CONCLUSIONThe PEX mRNA signature could be useful as a companion diagnostic of nivolumab. The combination of an anti-NKG2A antibody (i.e., monalizumab) and nivolumab may serve as a treatment option for non-survivors predicted by a RT-qPCR-based pre-treatment measurement of PEX mRNAs.TRIAL REGISTRATIONThis study is registered to the UMIN Clinical Trial Registry: UMIN000037029.FUNDINGThis study is partly funded by JSPS KAKENHI (Grant number JP 21436707 to MM) and Sota memorial fund to MM. PEXmRNA analyses were conducted by Showa Denko America Materials. CReS Kyushu organized sample collection and transfer, and conducted clinical data management with funding provided by Ono and Bristol-Myers Squibb.Graphical abstract