bluuebunny/crossref_metadata_2025_split huggingface dataset:
Male reproductive phenotype and coercive mating performance in the guppyPoecilia reticulata
Authors: Glavaschi Alexandra , Morbiato Elisa , Pilastro Andrea 
Published: March 2024

AbstractIn species with fixed alternative male mating tactics, differences between male phenotypes associated with each tactic are well understood. By contrast, in species with fully interchangeable male mating strategies, associations between male phenotypes and fitness when adopting different tactics have received much less attention. One such species is the Trinidad guppyPoecilia reticulata,where males perform high rates of coercive mating attempts (gonopodial thrusts, GTs hereafter) but also switch between GTs and courtship with great flexibility. Male phenotypes favored by females have been described in detail and consist of complex, nonlinear combinations of traits. Coercive tactics also contribute towards male fitness, but no study to date has provided a multivariate description of guppy phenotypes able to obtain fertilizations via GTs, despite evidence suggesting they should be different from phenotypes successful in cooperative mating scenarios. Here we observe male mating behavior in freely interacting mixed-sex groups and compute a GT performance variable based on the closest distance the male approaches the female before abandoning the thrust. We use multivariate selection techniques to relate GT performance to traits and combinations of traits known to contribute towards male fitness. Guppy males that perform best in GTs are small, bold, with large areas of iridescent coloration and fast-swimming sperm, as well as intermediate orange coloration and sperm count. This phenotype only partly confirms our expectation, as it comprises traits advantageous in cooperative mating scenarios. Our study highlights the importance of using multivariate approaches when investigating sexual selection in the context of coercive mating strategies.
Human monocyte subtype expression of neuroinflammation and regeneration-related genes is linked to age and sex
Authors: Tampé Juliane F. , Monni Emanuela , Palma-Tortosa Sara , Brogårdh Emil , Böiers Charlotta , Lindgren Arne G. , Kokaia Zaal 
Published: March 2024

ABSTRACTStroke is a leading cause of disability and the third cause of death. The immune system plays an essential role in post-stroke recovery. After an ischemic stroke, monocytes infiltrate the injured brain tissue and can exacerbate or mitigate the damage. Ischemic stroke is more prevalent in the aged population, and the aging brain exhibits an altered immune response. There are also sex disparities in ischemic stroke incidence, outcomes, and recovery, and these differences may be hormone-driven and determined by genetic and epigenetic factors. Here, we studied whether human peripheral blood monocyte subtype (classical, intermediate, and non-classical) expression of neuronal inflammation- and regeneration-related genes depends on age and sex. A FACS analysis of blood samples from 44 volunteers (male and female, aged 28 to 98) showed that in contrast to other immune cells, the proportion of natural killer cells increased in females. The proportion of B-cells decreased in both sexes with age, and subtypes of monocytes were not linked to age or sex. Gene expression analysis by qPCR identified several genes differentially correlating with age and sex within different monocyte subtypes. Interestingly,ANXA1andCD36showed a consistent increase with aging in all monocytes, specifically in intermediate (CD36) and intermediate and non-classical (ANXA1) subtypes. Other genes (IL-1β, S100A8, TNFα, CD64, CD33, TGFβ1, TLR8, CD91) were differentially changed in monocyte subtypes with increased aging. Most age-dependent gene changes were differentially expressed in female monocytes. Our data shed light on the nuanced interplay of age and sex in shaping the expression of inflammation- and regeneration-related genes within distinct monocyte subtypes. Understanding these dynamics could pave the way for targeted interventions and personalized approaches in post-stroke care, particularly for the aging population and individuals of different sexes.
NOVEL SOLUTION BASED ON DETECTION OF MIRS-410-3P AND 141-5P FOR DIAGNOSTIC OF PROSTATE CANCER EVOLUTION
Authors: Carbache M.F , Nuñez E.R , Ouahid Y , Sainz E , Montoya J.J , Molera A , Soouto A , Vazquez D , Castan P , Carballido J 
Published: March 2024

AbstractTo date, prostate cancer (PCa) is both the most common tumour diagnosed in males and the second most common cause of cancer-related mortality(1,). Prevention programs and screening protocols have proven useful to detect the disease at population level, but they lack sensitivity and specificity in comparison to the molecular tests routinely available for screening of other types of cancer, leading to unnecessary biopsies and overtreatment in many cases. In this context, a new set of small RNA biomarkers are surfacing with promising results to predict tumour progression, risk reclassification and treatment response(2)such as miR-410-3p -3p and miR-141-5p. Former studies where these biomarkers were examined in prostate cancer tissues and cell lines by qRT-PCR have shown that high expression of miR-410-3p -3p correlates to both a) accurate diagnosis in certain groups where the PSA levels do not match results from biopsy, surgery and/or digital rectal examination and b) poor prognosis of prostate cancer patients(3). Likewise, miR-141-5p shows a parallel behaviour suggesting a potential combo for fine molecular analysis of the ratios. In this sense, recent studies have demonstrated that miR-410-3p -3p exert oncogenic functions through downregulating PTEN, proving that miR-410-3p -3p inhibits prostate cancer progression via downregulating PTEN/AKT/mTOR signalling pathway. Curiously enough, different behaviour has been reported for the biomarker in both, peripheral blood from patients and cancer-cell line(s)(34.5.6)models further pointing at the advantages of a dual gauging made possible by parallel semi-quantitation of miR-141-5p. In this sense, miR-141-5p has been clearly identified as to be upregulated in large cohorts (n over 500) of prostate cancer patients confirming overexpression in multivariate analysis in tumour epithelium and tumour stroma. This overexpression taken into the context of a peripheral blood reduction of miR-410-3p appears to be associated with increased risk of biochemical cancer recurrence in an independent study over 500 patients(7). Here we present the design, molecular set up and preclinical assessment of a novel system that uses the discarded volume from PSA blood tests to predict prostate cancer progression and biochemical cancer recurrence via detection of the biomarkers. The method described could potentially eliminate the need of invasive means such as biopsy, surgery and digital rectal examination.
Piloting wastewater-based surveillance of norovirus in England
Authors: Walker David I. , Witt Jessica , Rostant Wayne , Burton Robert , Davison Vicki , Ditchburn Jackie , Evens Nicholas , Godwin Reg , Heywood Jane , Lowther James , Peters Nancy , Porter Jonathan , Posen Paulette , Wickens Tyler , Wade Matthew J. 
Published: March 2024

AbstractWastewater-based epidemiology (WBE) gained widespread use as a tool for supporting clinical disease surveillance during the COVID-19 pandemic. There is now significant interest in the continued development of WBE for other pathogens of clinical significance. In this study, approximately 3,200 samples of wastewater from across England, previously collected for quantification of SARS-CoV-2, were re-analysed for the quantification of norovirus genogroup I (GI) and II (GII). Overall, GI and GII were detected in 93% and 98% of samples respectively, and at least one of the genogroups was detected in 99% of samples. GI was found at significantly lower concentrations than GII, but the proportion of each genogroup varied over time, with GI becoming more prevalent than GII in some areas towards the end of the study period (May 2021 – March 2022). Using relative strength indices (RSI), it was possible to study the trends of each genogroup, and total norovirus over time. Increases in norovirus levels appeared to coincide with the removal of COVID-19 related lockdown restrictions within England. Local Moran’s I analyses indicated several localised outbreaks of both GI and GII across England, notably the possible GI outbreak in the north of England in early 2022. Comparisons of national average norovirus concentrations in wastewater against concomitant norovirus reported case numbers showed a significant linear relationship. This highlights the potential for wastewater-based monitoring of norovirus as a valuable approach to support surveillance of norovirus in communities.
Copy number variants underlie the major selective sweeps in insecticide resistance genes inAnopheles arabiensisfrom Tanzania
Authors: Lucas Eric R. , Nagi Sanjay C. , Kabula Bilali , Batengana Bernard , Kisinza William , Egyir-Yawson Alexander , Essandoh John , Dadzie Sam , Chabi Joseph , Van’t Hof Arjen E. , Rippon Emily J. , Pipini Dimitra , Harding Nicholas J. , Dyer Naomi A. , Clarkson Chris S. , Miles Alistair , Weetman David , Donnelly Martin J. 
Published: March 2024

AbstractTo keep ahead of the evolution of resistance to insecticides in mosquitoes, national malaria control programmes must make use of a range of insecticides, both old and new, while monitoring resistance mechanisms. Knowledge of the mechanisms of resistance remains limited inAnopheles arabiensis, which in many parts of Africa is of increasing importance because it is apparently less susceptible to many indoor control interventions. Furthermore, comparatively little is known in general about resistance to non-pyrethroid insecticides such as pirimiphos-methyl (PM), which are crucial for effective control in the context of resistance to pyrethroids. We performed a genome-wide association study to determine the molecular mechanisms of resistance to deltamethrin (commonly used in bednets) and PM, inAn. arabiensisfrom two regions in Tanzania. Genomic regions of positive selection in these populations were largely driven by copy number variants (CNVs) in gene families involved in resistance to these two insecticides. We found evidence of a new gene cluster involved in resistance to PM, identifying a strong selective sweep tied to a CNV in theCoeae2g-Coeae6gcluster of carboxylesterase genes. Using complementary data fromAn. coluzziiin Ghana, we show that copy number at this locus is significantly associated with PM resistance. Similarly, for deltamethrin, resistance was strongly associated with a novel CNV allele in theCyp6aa/Cyp6pcluster. Against this background of metabolic resistance, target site resistance was very rare or absent for both insecticides. Mutations in the pyrethroid target siteVgscwere at very low frequency in Tanzania, yet combining these samples with threeAn. arabiensisindividuals from West Africa revealed a startling diversity of evolutionary origins of target site resistance, with up to 5 independent origins ofVgsc-995 mutations found within just 8 haplotypes. Thus, despite having been first recorded over 10 years ago,Vgscresistance mutations in TanzanianAn. arabiensishave remained at stable low frequencies. Overall, our results provide a new copy number marker for monitoring resistance to PM in malaria mosquitoes, and reveal the complex picture of resistance patterns inAn. arabiensis.
Genome-Wide Identification of G-Quadruplex forming regions in Arabidopsis: Unraveling the Role of Pif like Helicase (AtPLH1) in Gene Regulation and Stress Response
Authors: Singh Surabhi , Singh Shubhangi , Gupta Khushboo , Sharma Himanshi , Bady Shivsam , Sondhi Manushka , Garg Rohini 
Published: March 2024

AbstractG-quadruplexes (GQSes) are highly stable DNA secondary structures, which exist as knots in the genome during different cellular processes like replication, transcription and translation. Although several studies have shown the role of GQS-helicases regulating several cellular processes in yeast and human, their detailed characterization in plants is still lacking. In this study, we identified GQS-enriched regions by DNA affinity purification followed by sequencing from Arabidopsis Pif-like helicase 1 (Atplh1) mutant. Differentially enriched peaks (DEPs) in the mutant showed preferential distribution in the exonic and promoter regions. The genes involved in various processes like transcriptional regulation, UDP- glucosylation, response to abiotic stress, ethylene biosynthesis and response to carbohydrate stimulus, were found to be differentially regulated between control and mutant plants. The differentially expressed genes (DEGs) showed enrichment of binding sites of ERF, WRKY, BBM and BIM transcription factors. Further, the DEGs harboring DEPs were found associated with response to wounding and salt stress, response to unfolded protein, heat stress response and UDP-glycosyl transferase activity. In addition, the mutants exhibited lesser growth inhibition under cold stress. Overall, our study identified genome-wide GQSes inArabidopsisand altered gene expression regulated by AtPLH1.
Identification of novel myelodysplastic syndromes prognostic subgroups by integration of inflammation, cell-type composition, and immune signatures in the bone marrow
Authors: Gerlevik Sila , Seymen Nogayhan , Hama Shan , Mumtaz Warisha , Thompson I. Richard , Jalili Seyed R. , Kaya Deniz E. , Iacoangeli Alfredo , Pellagatti Andrea , Boultwood Jacqueline , Napolitani Giorgio , Mufti Ghulam J. , Karimi Mohammad M. 
Published: March 2024

AbstractMutational profiles of Myelodysplastic syndromes (MDS) have established that a relatively small number of genetic aberrations, including SF3B1 and SRSF2 spliceosome mutations, lead to specific phenotypes and prognostic subgrouping. We performed a Multi-Omics Factor Analysis (MOFA) on two published MDS cohorts of bone marrow mononuclear cells (BMMNCs) and CD34+ cells with three data modalities (clinical, genotype, and transcriptomics). Seven different views, including immune profile, inflammation/aging, Retrotransposon (RTE) expression, and cell-type composition, were derived from these modalities to identify the latent factors with significant impact on MDS prognosis. SF3B1 was the only mutation among 13 mutations in the BMMNC cohort, indicating a significant association with high inflammation. This trend was also observed to a lesser extent in the CD34+ cohort. Interestingly, the MOFA factor representing the inflammation shows a good prognosis for MDS patients with high inflammation. In contrast, SRSF2 mutant cases show a granulocyte-monocyte progenitor (GMP) pattern and high levels of senescence, immunosenescence, and malignant myeloid cells, consistent with their poor prognosis. Furthermore, MOFA identified RTE expression as a risk factor for MDS. This work elucidates the efficacy of our integrative approach to assess the MDS risk that goes beyond all the scoring systems described thus far for MDS.
eATP/P2X7R axis drives nanoparticle induced neutrophil recruitment in the pulmonary microcirculation
Authors: Li Chenxi , Liu Qiongliang , Han Lianyong , Immler Roland , Rathkolb Birgit , Secklehner Judith , Hrabe de Angelis Martin , Yildirim Ali Önder , Nicke Annette , Carlin Leo M. , Sperandio Markus , Stoeger Tobias , Rehberg Markus 
Published: March 2024

AbstractExposure to nanoparticles (NPs) is frequently associated with adverse cardiovascular effects. In contrast, NPs in nanomedicine hold great promise for precise lung-specific drug delivery, especially considering the extensive pulmonary capillary network that facilitates interactions with bloodstream-suspended particles. Therefore, exact knowledge about interactions and effects of engineered NPs with the pulmonary microcirculation are instrumental for future application of this technology in patients. To unravel the real-time dynamics of intravenously delivered NPs and their effects in the pulmonary microvasculature, we employed intravital microscopy of the mouse lung. PEG amine-modified quantum dots (aQDs) with a low potential for biomolecule and cell interactions and carboxyl-modified quantum dots (cQDs) with a high interaction potential were used, representing two different NP subtypes.Only aQDs triggered rapid neutrophil recruitment in microvessels and their subsequent recruitment to the alveolar space. Application of specific inhibitors revealed that the aQDs induced neutrophil recruitment was linked to cellular degranulation, TNF-α, and DAMP release into the circulation, particularly extracellular ATP (eATP). Stimulation of the ATP-gated P2X7R induced the expression of E-selectin on microvascular endothelium with the subsequent E-selectin depended neutrophilic immune response. Leukocyte integrins (LFA-1 and MAC-1) mediated adhesion and reduction in neutrophil crawling velocity on the vascular surface.In summary, this study unravels the complex cascade of neutrophil recruitment during NP-induced sterile inflammation. Thereby we demonstrate novel adverse effects for NPs in the pulmonary microcirculation and provide critical insights for optimizing NP-based drug delivery and therapeutic intervention strategies, to ensure their efficacy and safety in clinical applications.Graphical Abstract
Benchmarking clustering, alignment, and integration methods for spatial transcriptomics
Authors: Hu Yunfei , Li Yikang , Xie Manfei , Rao Mingxing , Shen Wenjun , Luo Can , Qin Haoran , Baek Jihoon , Zhou Xin Maizie 
Published: March 2024

AbstractSpatial transcriptomics (ST) is advancing our understanding of complex tissues and organisms. However, building a robust clustering algorithm to define spatially coherent regions in a single tissue slice, and aligning or integrating multiple tissue slices originating from diverse sources for essential downstream analyses remain challenging. Numerous clustering, alignment, and integration methods have been specifically designed for ST data by leveraging its spatial information. The absence of benchmark studies complicates the selection of methods and future method development. Here we systematically benchmark a variety of state-of-the-art algorithms with a wide range of real and simulated datasets of varying sizes, technologies, species, and complexity. Different experimental metrics and analyses, like adjusted rand index (ARI), uniform manifold approximation and projection (UMAP) visualization, layer-wise and spot-to-spot alignment accuracy, spatial coherence score (SCS), and 3D reconstruction, are meticulously designed to assess method performance as well as data quality. We analyze the strengths and weaknesses of each method using diverse quantitative and qualitative metrics. This analysis leads to a comprehensive recommendation that covers multiple aspects for users. The code used for evaluation is available on GitHub. Additionally, we provide jupyter notebook tutorials and documentation to facilitate the reproduction of all benchmarking results and to support the study of new methods and new datasets (https://benchmarkst-reproducibility.readthedocs.io/en/latest/).
Traveling waves link human visual and frontal cortex during working memory-guided behavior
Authors: Luo Canhuang , Ester Edward F. 
Published: March 2024

SummaryCortical traveling waves, or global patterns of activity that extend over several centimeters of the cortical surface, are a key mechanism for guiding the spatial propagation of neural activity and computational processes across the brain. Recent studies have implicated cortical traveling waves in successful short- and long-term memory encoding, storage, and retrieval. However, human memory systems are fundamentally-action oriented: eventually, the contents of memory must be utilized to produce appropriate behaviors. Cortical traveling waves could contribute to the production and control of memory-guided behaviors by flexibly routing information between brain areas responsible for storing memory content and brain areas responsible for planning and executing actions. Here, using short-term memory as a test case, we report evidence supporting this possibility. By applying image-based analyses to published human EEG studies, we show that the initiation of a memory-guided behavior is accompanied by a low-frequency (2-6 Hz) feedforward (occipital to frontal) traveling wave that predicts intra- and inter-individual differences in response onset, while the termination of a memory-guided behavior is followed by a higher frequency (14-32 Hz) feedback (frontal-to-occipital) traveling wave. Control analyses established that neither waveform could be explained by nuisance factors (e.g., propagation of visually-evoked potentials, eye movements, or passive volume conduction). Moreover, both waveforms required an overt behavior: when participants selected task-relevant memory content and prepared but did not yet execute an action based on this content, neither waveform was observed. Our findings suggest a role for traveling waves in the generation and control of memory-guided behaviors by flexibly organizing the timing and direction of interactions between brain regions involved in memory storage and action.
The occurrence ofAerococcus urinaeequiand non-aureus Staphylococci in raw milk negatively correlates withEscherichia coliclinical mastitis
Authors: Jung Dongyun , Park Soyoun , Kurban Daryna , Dufour Simon , Ronholm Jennifer 
Published: March 2024

AbstractEscherichia coliis a common environmental pathogen associated with clinical mastitis (CM) in dairy cattle. There is an interest in optimizing the udder microbiome to increase the resistance of dairy cattle toE. coliCM; however, the details of which members of the healthy udder microbiota may play a role in antagonizingE. coliare unknown. In this study, we characterized the bacterial community composition in raw milk collected from quarters of lactating Holstein dairy cows that developedE. coliCM during lactation, including milk from both healthy and diseased quarters (n=1,172). The milk microbiome from infected quarters was compared before, during, and after CM. A combination of 16S rRNA gene amplicon and shotgun metagenomic sequencing were used generate datasets with a high level of both depth and breadth. The microbial diversity present in raw milk significantly decreased in quarters experiencingE. coliCM, indicating thatE. colidisplaces other members of the microbiome. However, the diversity recovered very rapidly after infection. Two genera:Staphylococcus, Aerococcus,and the familyOscillospiraceaewere significantly more abundant in healthy quarters with low inflammation. Species of these genera:Staphylococcus auricularis, Staphylococcus haemolyticus,andAerocussus urinaeequiwere identified by shotgun metagenomics. Thus, these species are of interest for optimizing the microbiome to discourageE. colicolonization without triggering inflammation.ImportanceIn this study we show thatE. colioutcompetes and displaces several members of the udder microbiome during CM, but that microbial diversity recovers post-infection. In milk from quarters which remained healthy, the community composition was often highly dominated byS. auricularis, S. haemolyticus, A. urinaeequi,andS. marcescenswithout corresponding increases in somatic cell count (SCC). Community dominance by these organisms, without inflammation, could indicate that these species could be potential prophylactics that could contribute to colonization resistance for the pathogen and prevent future instances ofE. coliCM.