bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesolimbic local field potentials are modulated by motor control
Authors: Mann Leah G , Qian Helen , Hughes Natasha Cindy , Zhao Zixiang , Singh Balbir , Wang Zhengyang , Johnson Graham W. , Fulton Jenna N. , Yan Bailu , Kang Hakmook , Li Rui , Dawant Benoit M. , Englot Dario J. , Constantinidis Christos , Roberson Shawniqua Williams , Claassen Daniel O. , Bick Sarah K. 
Published: July 2024

AbstractBackground and ObjectivesWhile historically cortico-basal ganglia-thalamocortical loops were believed to process limbic and sensorimotor data in parallel, there is now evidence to suggest that the two information streams can be processed in a single open loop. However, the limbic-motor interface remains insufficiently characterized. We sought to further investigate how extrastriatal regions may regulate motor output by examining electrophysiological activity in these areas during a response inhibition paradigm.MethodsWe recorded local field potentials (LFPs) from epilepsy patients implanted with intracranial depth electrodes for seizure localization purposes. Participants performed the stop-signal task, during which they made speeded choice reactions to “go” stimuli and occasionally inhibited their reactions in the incident of a “stop” signal. To compare power during movement and the absence of movement, we applied a Wilcoxon signed-rank test. Additionally, we performed a linear mixed-effects model to relate power in limbic regions to power in the motor cortex. Finally, we implemented exploratory analyses to identify power differences for correct go versus correct stop trials and for correct stop versus incorrect stop trials using cluster-based permutation testing.Results14 patients participated. A comparison between movement and baseline fixation revealed that motor response is associated with reduced beta (15-35 Hz) power in the amygdala, hippocampus, and motor cortex and reduced gamma (35-100 Hz) power in the amygdala and hippocampus. Moreover, average beta and gamma power in the amygdala and hippocampus during motor execution were positively associated with average beta and gamma power in the motor cortex. Additionally, we identified significant differences between correct go and stop trials in delta (1-4 Hz) power for all three regions and in theta (4-8 Hz) power for the amygdala and motor cortex. Likewise, we identified significant differences between correct and incorrect stop trials in delta power for the hippocampus and motor cortex, in theta power for the motor cortex, in alpha (8-15 Hz) and beta power for the amygdala and motor cortex, and in gamma power for all three areas.DiscussionThese correlations between neural oscillations in the hippocampus and amygdala and movement strengthen the notion of mesolimbic modulation of motor activity.
Detecting Delta and Omicron co-infection cases in the Philippines from SARS-CoV-2 genomic surveillance
Authors: Realingo Adeliza Mae L. , Polotan Francisco Gerardo M. , Abulencia Miguel Francisco B. , Pantoni Roslind Anne R. , Capin Jessel Babe G. , Sotelo Gerald Ivan , Corpuz Maria Carmen A. , Yabut Neil Tristan M. , Rojas Saul M. , Nicolasora Amalea Dulcene , Tujan Ma. Angelica , Tomas Karen Iana , Dolor Ardiane Ysabelle , Celis Czarina Christelle Alyannah , Ortia Stephen Paul , Melo Ezekiel , Reyes Chelsea Mae , Flores Elijah Miguel P. , Alpino Anne Pauline A. , Penales Aldwin Kim A. , Medina Kathlene Mae C. , Manalo Joanna Ina , Dizon Timothy John R. , Hampson Katie , Kasaragod Sandeep , Hughes Joseph , Brunker Kirstyn 
Published: July 2024

ABSTRACTCo-infection with multiple SARS-CoV-2 variants, though rare, may have clinical and public health implications, including facilitating variant recombination. Early detection of co-infections is therefore crucial. In this study, we report two probable cases of co-infection identified during routine genomic surveillance. Initially suspected as cross-contamination due to the presence of private mutations and nucleotide mixtures flagged by Nextclade and bammix, the samples were re-extracted and resequenced after workspace decontamination, yet the anomalies persisted. To investigate further, we developed a bioinformatics pipeline incorporating tools such as Pangolin, Nextclade, and bammix, which consistently revealed lineage inconsistencies and nucleotide mixtures in both samples. Lineage abundance results from Freyja supported the presence of multiple variants within each sample, while VirStrain confirmed the inconsistent lineage assignment. We also visualised the alternative allele fractions for each lineage-defining mutation and amplicon, which revealed evidence of two variants — Delta and Omicron — co-existing within a single amplicon, indicative of co-infection. Amplicon sorting effectively separated the reads corresponding to the two variants, and the resulting consensus sequences aligned with their respective lineage assignments. These findings suggest that the first sample, PH-RITM-1395, involved a Delta-Omicron co-infection, while the second sample, PH-RITM-4146, was a recombinant case. To further support the second sample’s recombinant nature, we employed sc2rf, which identified breakpoints consistent with Delta-Omicron recombination. Retrospective analysis of 1,078 samples from July 2021 to July 2022, encompassing the period of co-circulation of different variants in the Philippines, flagged four additional co-infection cases, including Delta-Omicron and Beta-Omicron suggesting a lower bound co-infection rate of 0.27%, and 0.19%, respectively. Our findings underscore the critical importance of real-time genomic surveillance and advanced bioinformatics pipelines in detecting SARS-CoV-2 co-infections and variant recombination. Such insights are vital to anticipating shifts in viral evolution, offering insights for public health preparedness.
Inherited infertility - mapping loci associated with impaired female reproduction
Authors: Ruotsalainen Sanni , Karjalainen Juha , Kurki Mitja , Lahtela Elisa , Pirinen Matti , Riikonen Juha , Ritari Jarmo , Tammi Silja , Partanen Jukka , Laivuori Hannele ,   FinnGen, Palotie Aarno , Heyne Henrike , Daly Mark , Widen Elisabeth 
Published: July 2024

ABSTRACTFemale infertility is a common and complex health problem affecting millions of women worldwide. While multiple factors can contribute to this condition, the underlying cause remains elusive in up to 15-30% of cases. In our large genome-wide association study (GWAS) of 22,849 women with infertility and 198,989 controls from the Finnish population cohort FinnGen, we unveil a unique landscape of genetic factors associated with the disease. Our recessive analysis identified a low-frequency stop-gained mutation inTBPL2(p.Arg331Ter; minor allele frequency (MAF) = 1.2%) with an impact comparable to highly penetrant monogenic mutations (OR = 650, p = 4.1 ×10-25). While previous studies have linked the homologous gene to anovulation and sterility in knockout mice, the severe consequence of the p.Arg331Ter mutation was evidenced by homozygous carriers having significantly fewer offspring (average of 0.16) compared to women belonging to the other genotype groups (average of 1.75 offspring, p = 1.4×10-15). Notably, all homozygous women who had given birth had received infertility therapy. Moreover, our age-stratified analyses identified three additional genome-wide significant loci. Two loci were associated with early-onset disease (infertility diagnosed before age 30), located nearCHEK2and within the major histocompatibility complex (MHC)-region. The third locus, associated with late-onset disease, had its lead SNP located in an intron of a lncRNA gene. Taken together, our data highlight the significance of rare recessive alleles in shaping female infertility risk. The results further provide evidence supporting specific age-dependent mechanisms underlying this complex disorder.
Aging promotes lung cancer metastasis through epigenetic ATF4 induction
Authors: Patel Angana A.H. , Dzanan Jozefina , Ali Kevin X. , Eklund Ella A. , Alvarez Samantha W. , Altinönder Ilayda , Raj Dorota , El Zowalaty Ahmed Ezat , Sayin Sama I. , Dankis Martin , Schwarz Maria , Jonasson Emma , Gal Kristell Le , Albatrok Heba , Bagge Roger Olofsson , Härtlova Anetta , Ståhlberg Anders , Hallqvist Andreas , Wiel Clotilde , Sayin Volkan I. 
Published: July 2024

AbstractLung cancer is primarily a disease of the elderly. Despite shared molecular changes between aging and cancer1– such as permissive chromatin states and deregulated protein homeostasis – studies on physiologically aged models of human lung cancer are lacking. Here, we show that aging alters the progression of KRAS-driven non-small cell lung cancer (NSCLC), promoting metastasis while suppressing primary lung tumor growth. Clinically, a multicenter analysis of all consecutively diagnosed NSCLC cases in Western Sweden over a 3-year period confirmed increased metastasis and smaller primary tumor size with age in KRAS-driven NSCLC. In addition, primary lung tumor cultures derived from older mice demonstrated an increased metastatic phenotype. Unbiased transcriptomic and epigenomic analyses identified ATF4, a major arm of the unfolded protein response (UPR), as a driver of aging-induced lung cancer metastasis. Furthermore, we found that the age-associated increase in ATF4 fuels metastatic dissemination through metabolic rewiring, including increased glutaminolysis. Finally, we report that pharmacological inhibition of glutaminase effectively suppressed aging-induced metastasis. Our findings suggest a novel adjuvant therapy for human lung cancer by targeting aging-induced metabolic plasticity, highlighting the need to consider the biology of aging in the development of cancer therapy.
Dicarbonyl stress enhances tumor intravasation
Authors: Kumar Nilesh , Samanta Bidita , Jyothsna KM , Raghunathan Varun , Sen Prosenjit , Bhat Ramray 
Published: July 2024

AbstractMetastasis of cancer is a multi-step process that involves the migration of transformed cells from their native organ into a vascular channel, followed by their dissemination to prospective sites of colonization. The entry of tumor cells into blood or lymph, known as intravasation involves their breaching the stromal and endothelial extracellular matrix (ECM) and the endothelial barriers. How the kinetics of these cell-ECM interactions are confounded by chronic inflammatory stresses seen in comorbid risk factors of cancer such as diabetes and aging remain ill-investigated. Here, we construct and deploy a histopathology-motivated, imaging-tractable, microfluidic multi-organ-on-chip platform, that seamlessly integrates two tissue environments: that of a breast tumor and a vascular channel, to study the problem. The former comprises invasive triple-negative MDA-MB-231 breast cancer cells embedded within a three-dimensional fibrillar Collagen I milieu. The latter consists of a monolayer of TeloHAEC, immortalized human aortic endothelial cells arranged on laminin-rich basement membrane ECM, both of which concentrically line a hollow channel, wherein unidirectional fluid flows are implemented. The chip showcases the complexity of intravasation, wherein tumor cells and endothelia cooperate to form anastomotic structures. The formation of such structures is regulated by fluid flow in the vascular channel and is associated with cancer cell migration and entry into the vascular channel. Disseminated cancer cells are observed to enter, get adhered within, and flow through the vascular channel. Exposure to methylglyoxal (MG), a mediator of dicarbonyl stress associated with diabetic circulatory milieu, leads to greater cancer cell intravasation and flow through the vascular channel. This could be driven not just by MG-induced endothelial senescence and shedding, but also by the effect of MG on the chip ECM: we demonstrate it can degrade basement membrane and pathologically crosslink Collagen I, diminishing their cell adhesiveness. Our results thus show how dicarbonyl stress may attenuate homoeostatic barriers to cancer intravasation, exacerbating metastasis.
Basal Cambrian soft-bodied segmented bilaterians preserved as microbial pseudomorphs
Authors: Yang Xiaoguang , Wang Deng , Zhang Zhiliang , Wang Xing , Sun Jie , Hao Wenjing , Liu Yiqun , Uesugi Kentaro , Komiya Tsuyoshi , Han Jian 
Published: July 2024

AbstractBefore Cambrian Stage 3, unambiguous body fossils of segmented bilaterians were rare, severely hampering our understanding of the early history of such important animals. Here we report a variety of microfossils with quintessential features such as paired appendages, dorsoventral and anteroposterior differentiations from the basal Cambrian Fortunian of South China, representing the earliest known three-dimensional body fossils of segmented bilaterians. These fossils were all microbial pseudomorphs built up by secondarily phosphatized bacteria aggregations, testifying microbial pseudomorph could serve as a novel and important pathway to preserve tiny, fragile bilaterian progenitors. This finding unveils a diversified segmented bilaterian world at the very beginning of Cambrian and would arouse a more comprehensive perspective on the early evolution of bilaterian body plans.
Intravital imaging reveals glucose-dependent cilia movement in pancreatic isletsin vivo
Authors: Melnyk Olha , Guo Jeff Kaihao , Li Zipeng Alex , Hughes Jing W. , Linnemann Amelia K. 
Published: July 2024

SUMMARYPancreatic islet cells harbor primary cilia, small sensory organelles that detect environmental changes to regulate hormone secretion and intercellular communication. While the sensory and signaling capacity of primary cilia are well-appreciated, it is less recognized that these organelles also possess active motility, including in dense multicellular tissues such as the pancreatic islet. In this manuscript, we use transgenic cilia reporter mice and an intravital imaging approach to quantitate primary cilia dynamics as it occurs in live mouse pancreatic islets. We validate this imaging workflow as suitable for studying islet cilia motion in real timein vivoand demonstrate that glucose stimulation corresponds to a change in cilia motility, which may be a physiologic measure of nutrient-dependent fluxes in islet cell function.
A long-lived pool of PINK1 imparts a molecular memory of depolarisation-induced activity
Authors: Pollock Liam , Georgiou Ioanna Ch. , Rusilowicz-Jones Emma V. , Clague Michael J. , Urbé Sylvie 
Published: July 2024

SummaryThe Parkinson’s disease linked kinase, PINK1, is a short lived protein that undergoes cleavage upon mitochondrial import leading to its release to the cytosol and proteasomal degradation. Under mitochondria depolarising conditions, it accumulates on mitochondria where it becomes activated, phosphorylating both ubiquitin and the ubiquitin E3 ligase Parkin, at Ser65. Here we have used a ubiquitylation inhibitor TAK-243 to accumulate cleaved PINK1 (cPINK1) in a cell line that lacks Parkin. We show that cPINK1 phosphorylates free ubiquitin and can be released to the cytosol in an active form. We show that in RPE1 cells under mitochondria depolarising conditions (i) the majority of PINK1 cleavage proceeds unimpeded and (ii) accrued PINK1 cannot be accounted for by protein stabilisation alone. Accordingly, we suggest that translation of PINK1 mRNA must be mobilised under mitochondrial depolarisation. We have further discovered a pre-conditioning phenomenon, whereby an initial depolarising treatment leaves a residual pool of active PINK1, which remains competent for seeding the activation of nascent cPINK1, despite a 16 hour recuperation period.
Evaluation of the efficacy of the protopine total alkaloids ofMacleaya cordata(Willd.) R. Br. in controllingE. coliinfection in broiler chickens
Authors: Dong Zhen , Xu Yufeng , Liu Zhiqin , Zeng Jianguo 
Published: July 2024

AbstractObjectiveThis study was carried out to investigate the preliminary evaluation of the effectiveness of protopine total alkaloids of Macleaya cordata (Willd.) R. Br. (MPTA) extract in the control of artificially infected avian pathogenic E. coli in the peritoneal cavity of chickens.MethodsIn this test, Lingnan yellow hybrid chickens (male, 10 days old) were attacked with E. coli O78 and then treated orally with different concentrations (25 - 1600 mg/kg) of MPTA Pulvis (MPTA-P) and 0.5% Siweichuanxinlian Powder (SWCXL-P).ResultsThe results showed that different concentrations of MPTA-P and SWCXL-P were effective in reducing the mortality of E. coli and promoting the recovery of the affected organs, with the best intervention being the supplementation of 400-1600 mg/kg of MPTA-P for 7 consecutive days. It has been concluded that the addition of 400 mg/kg MPTA-P for 7 days reduces the severity and mortality and accelerates the recovery process of E. coli disease in chickens and has a protective effect against organ lesions caused by E. coli infection.LimitationsThe study lacked comparisons of carrier populations and characterization of inflammatory markers.ConclusionsMPTA may be a potential alternative drug for the prevention or treatment of avian E. coli disease.
A DIY guide for image-based spatial transcriptomic: TLS as a case example
Authors: Defard Thomas , Desrentes Auxence , Fouillade Charles , Mueller Florian 
Published: July 2024

AbstractSpatial RNA profiling methods provide insight to the cellular heterogeneity and spatial architecture of complex, multi-cellular systems. Combining molecular and spatial information provides important clues to study tissue architecture in development and disease. Here, we present a comprehensive do-it-yourself guide to perform such experiments at reduced costs leveraging open-source approaches. This guide spans the entire life cycle of a project, from its initial definition to experimental choices, wet lab approaches, instrumentation and analysis. As a concrete example, we focus on Tertiary lymphoid structures (TLS), which we use to develop typical questions that can be addressed by these approaches.
De novoacquisition of antibiotic resistance in six species of bacteria
Authors: Wang Xinyu , de Koster Alphonse , Koenders Belinda B. , Jonker Martijs , Brul Stanley , ter Kuile Benno H. 
Published: July 2024

ABSTRACTBacteria can become resistant to antibiotics in two ways, by acquiring resistance genes through horizontal gene transfer and byde novodevelopment of resistance upon exposure to non-lethal concentrations. The importance of the second process,de novobuild-up, has not been investigated systematically over a range of species and may be underestimated as a result. To investigate the DNA mutation patterns accompanying thede novoantibiotic resistance acquisition process, six bacterial species encountered in the food chain were exposed to step-wise increasing sublethal concentrations of six antibiotics to develop high levels of resistance. Phenotypic and mutational landscapes were constructed based on whole genome sequencing (WGS) sequencing at two time points of the evolutionary trajectory. In this study, we found: 1) all of the six strains can develop high levels of resistance against most antibiotics. 2) increased resistance is accompanied by different mutations for each bacterium-antibiotic combination. 3) the number of mutations varies widely, withY. enterocoliticahaving by far the most. 4) in the case of fluoroquinolone resistance, a mutational pattern ofgyrAcombined withparCis conserved in five of six species. 5) mutations in genes coding for efflux pumps are widely encountered in gram-negative species. The overall conclusion is that very similar phenotypic outcomes are instigated by very different genetic changes.IMPORTANCEThe significance of this study lies in the comparison of how six species of distinct genomic background under uniform conditions develop high levels of antibiotic resistance against six antibiotics. The mutational patterns in these six species of bacteria identify common target mutations and reveal how they acquire mutations from various pathways to survive and grow when exposed to sub-lethal levels of antibiotics. In addition to providing insights in microbial genetics, outcome of this study will assist policymakers when formulating practical strategies to prevent development of antimicrobial resistance in human and veterinary health care.
The archaeal classNitrososphaeriais a key player of the reproductive microbiome in sponges during gametogenesis
Authors: Turon Marta , Koutsouveli Vasiliki , Conejero María , Taboada Sergi , Verdes Aida , Lorente-Sorolla José María , Díez-Vives Cristina , Riesgo Ana 
Published: July 2024

ABSTRACTSponge-associated microbes play fundamental roles in regulating their hosts’ physiology, yet their contribution to sexual reproduction has been largely overlooked. Most studies have concentrated on the proportion of the microbiome transmitted from parents to offspring, providing little evidence of the putative microbial functions during gametogenesis in sponges. Here, we use 16S rRNA gene analysis to assess whether the microbial composition of five gonochoristic sponge species differs between reproductive and non-reproductive individuals and correlate these changes with their gametogenic stages. In sponges with mature oocytes, reproductive status did not influence either beta or alpha microbial diversity. Interestingly, in two of the studied species,Geodia macandrewiiandPetrosia ficiformis,which presented oocytes at the previtellogenic stage, significant microbial composition changes were detected between reproductive and non-reproductive individuals. These disparities were primarily driven by differentially abundant taxa affiliated with theNitrososphaeriaarchaeal class in both species. We speculate that the previtellogenic stages are more energetically demanding, leading to microbial changes due to the phagocytosis of microbes to meet nutritional demands during this period. Supporting our hypothesis, we observed significant transcriptomic differences inG. macandrewii, mainly associated with the immune system, indicating potential changes in the sponge’s recognition system. Overall, we provide the first insights into the possible roles of sponge microbiomes during reproductive periods, potentially uncovering critical interactions that support reproductive success.