bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of sexual and reproductive empowerment: a cross-national analysis in five Sub-Saharan African countries
Authors: Moreau Caroline , Karp Celia , Wood Shannon N. , Guiella Georges , Gichangi Peter , Makumbi Frederick , Mosso Rosine , Oumarou Sani , Zimmerman Linnea 
Published: August 2024

AbstractResearch has shown inconsistent associations between women’s empowerment and sexual and reproductive health (SRH) in sub-Saharan Africa (SSA), pointing to a lack of salient measures in this context. A novel measure provides an opportunity to explore different facets of SRH empowerment in SSA.MethodsWe used five national surveys among women 15-49 years conducted between 2019-2020 in Kenya (n=5,504), Uganda (n=2,273), Cote d’Ivoire (n=2,329), Burkina Faso (n=4,135), and Niger (n=2,228). Two measures of contraceptive and sexual empowerment were combined into a four-category SRH empowerment measure to identify the opportunity structures associated with SRH empowerment using multinomial logistic regression modeling.ResultsSRH empowerment was lowest in Niger and highest in Kenya. Between 15.0% and 21.7% of participants had more sexual but less contraceptive empowerment than their peers, while the opposite was true for 15.4% to 20.4% of participants. Education increased overall SRH empowerment or sexual empowerment alone in all sites and contraceptive empowerment alone in Kenya. Wealth increased overall SRH empowerment or sexual empowerment alone in three sites. Parity increased overall empowerment or contraceptive empowerment alone in all sites but decreased sexual empowerment alone in Uganda. Finally, healthcare provider contact increased overall and contraceptive empowerment in four sites while family planning media messages increased overall empowerment in two sites.ConclusionThis study confirms the multidimensional nature of SRH empowerment, which varies by country, domain, and by women’s parity and social capital. Longitudinal research is needed to comprehend how women gain or lose SRH empowerment and how empowerment predicts SRH outcomes.
Citizen science informs demand-driven breeding of opportunity crops
Authors: Voss Rachel C. , de Sousa Kauê , N’Danikou Sognigbé , Shango Abdul , Aglinglo Lys Amavi , Laporte Marie-Angélique , Legba Eric C. , Houdegbe Aristide Carlos , Diarra Danfing dit Youssouf , Dolo Aminata , Sidibe Amadou , Ouedraogo Colette , Coulibaly Harouna , Achigan-Dako Enoch G. , Kileo Aishi , Malulu Dickson , Matumbo Zamira , Dinssa Fekadu , van Heerwaarden Joost , van Etten Jacob , Riar Amritbir , van Zonneveld Maarten 
Published: August 2024

AbstractCONTEXTOpportunity crops, also known as neglected and underutilized species (NUS), offer benefits to diversify food systems with nutritious and climate-resilient foods. A major limitation to incorporate these crops in farming systems is the lack of improved varieties impedes farmers accessing quality planting material of these crops.OBJECTIVESThe study explored how citizen science methods can support demand-driven breeding and seed production of opportunity crops using leafy amaranth – a nutritious and hardy vegetable- as a case study. The study identified farmer preferences and market segments, with particular attention to gender and social differentiation.METHODSWe used the tricot approach to conduct participatory on-farm trials of 14 varieties with 2,063 farmers from Benin, Mali, and Tanzania. We then analyzed farmer trait and varietal preferences in aggregate and among segments of farmers, generated using cluster analysis.RESULTSFarmers’ overall preferences for amaranth varieties was driven principally by plant survival, yield, leaf size, taste, and marketability. Distinct farmer segments (older women generalists, young women specialists, older men generalists, and young men specialists) preferred different varieties depending on gender, business-orientation.DISCUSSION AND CONCLUSIONThe farmer segments identified here, along with their unique variety preferences provide valuable information for breeders and seed enterprises, and support demand-driven amaranth breeding and seed system development. We specifically noted the need for breeding programs to understand the preferences of young amaranth specialists, both men and women, and to explore organoleptic and market-related properties of amaranth.SIGNIFICANCEOur findings on differentiated producer preferences will support scaling seed supply of amaranth in Africa to diversify farming systems with a climate-resilient and nutritious crop. The methods used and lessons learned from our citizen science exercise can be applied to enhance breeding and seed supply of other opportunity crops that are underutilized in Africa or other continents.HighlightsFarmer citizen science methods reveal seed market insights for opportunity cropsAmaranth variety preferences vary widely across gender, age, and countriesYoung amaranth producers focus on market and sensory traits compared to old producersLarge-scale farmer feedback guides opportunity crop breeding for diverse segments
Beta-arrestin 1 mediated Src activation via Src SH3 domain revealed by cryo-electron microscopy
Authors: Pakharukova Natalia , Thomas Brittany N. , Bansia Harsh , Li Linus , Abzalimov Rinat R. , Kim Jihee , Kahsai Alem W. , Pani Biswaranjan , Bassford Dana K. , Liu Shibo , Zhang Xingdong , des Georges Amedee , Lefkowitz Robert J. 
Published: August 2024

AbstractBeta-arrestins (βarrs) are key regulators and transducers of G-protein coupled receptor signaling; however, little is known of how βarrs communicate with their downstream effectors. Here, we use cryo-electron microscopy to elucidate how βarr1 recruits and activates non-receptor tyrosine kinase Src. βarr1 binds Src SH3 domain via two distinct sites: a polyproline site in the N-domain and a non-proline site in the central crest region. At both sites βarr1 interacts with the aromatic surface of SH3 which is critical for Src autoinhibition, suggesting that βarr1 activates Src by SH3 domain displacement. Binding of SH3 to the central crest region induces structural rearrangements in the β-strand V, finger, and middle loops of βarr1 and interferes with βarr1 coupling to the receptor core potentially impacting receptor desensitization and downstream signaling.One-Sentence SummaryBeta-arrestin 1 uses two distinct sites to bind the SH3 domain of Src and drive relief of Src autoinhibition.
Contributions of genetic variation in astrocytes to cell and molecular mechanisms of risk and resilience to late onset Alzheimer’s disease
Authors: Lee Hyo , Pearse Richard V. , Lish Alexandra M. , Pan Cheryl , Augur Zachary M. , Terzioglu Gizem , Gaur Pallavi , Liao Meichen , Fujita Masashi , Tio Earvin S. , Duong Duc M. , Felsky Daniel , Seyfried Nicholas T. , Menon Vilas , Bennett David A. , De Jager Philip L. , Young-Pearse Tracy L. 
Published: August 2024

AbstractReactive astrocytes are associated with Alzheimer’s disease (AD), and several AD genetic risk variants are associated with genes highly expressed in astrocytes. However, the contribution of genetic risk within astrocytes to cellular processes relevant to the pathogenesis of AD remains ill-defined. Here we present a resource for studying AD genetic risk in astrocytes using a large collection of induced pluripotent stem cell (iPSC) lines from deeply phenotyped individuals with a range of neuropathological and cognitive outcomes. IPSC lines from forty-four individuals were differentiated into astrocytes followed by unbiased molecular profiling using RNA sequencing and tandem mass tag-mass spectrometry. We demonstrate the utility of this resource in examining gene- and pathway-level associations with clinical and neuropathological traits, as well as in analyzing genetic risk and resilience factors through parallel analyses of iPSC-astrocytes and brain tissue from the same individuals. Our analyses reveal that genes and pathways altered in iPSC-derived astrocytes from AD individuals are concordantly dysregulated in AD brain tissue. This includes increased prefoldin proteins, extracellular matrix factors, COPI-mediated trafficking components and reduced proteins involved in cellular respiration and fatty acid oxidation. Additionally, iPSC-derived astrocytes from individuals resilient to high AD neuropathology show elevated basal levels of interferon response proteins and increased secretion of interferon gamma. Correspondingly, higher polygenic risk scores for AD are associated with lower levels of interferon response proteins. This study establishes an experimental system that integrates genetic information with a heterogeneous set of iPSCs to identify genetic contributions to molecular pathways affecting AD risk and resilience.
HMCES corrupts replication fork stability during base excision repair in homologous recombination deficient cells
Authors: Peña-Gómez María José , Rodríguez-Martin Yaiza , Oliva Marta del Rio , Masson Jean Yves , Reyes José Carlos , Rosado Iván V. 
Published: August 2024

AbstractApurinic/apyrimidinic (AP) sites and single-strand breaks (SSB) arising from base excision repair (BER) during misincorporation of damaged nucleobases may hinder replication fork stability in homologous recombination-deficient (HRD) cells. At templated AP-sites, HMCES DNA-protein crosslinks (DPC) regulate replication fork speed while avoiding APE1-mediated cytotoxic double-strand breaks (DSB). Whereas the role of HMCES at template DNA strand is well studied, its consequences on nascent DNA are less understood. Here, we provide evidence that HMCES play detrimental roles during removal of 5- hydroxymethyl-2’-deoxycytidine (5hmdC)-derived 5-hydroxymethyl-2’-deoxyuridine (5hmdU) by BER at replication forks. HRD cells display heightened HMCES chromatin levels, which increase upon 5hmdC exposure, suggesting that HMCES binds both spontaneous and 5hmdC-induced AP-sites. HMCES depletion largely suppresses 5hmdC- mediatedFancd2-/-replication fork defects, chromosomal aberrations and cell lethality, suggesting that HMCES is responsible for the replication fork impairment and lethality observed in HRD cells. Therefore, HMCES-DPCs are a novel source of BER-initiated PRIMPOL-mediated ssDNA gaps, implying endogenous DPCs as a source of DNA damage in HRD tumours.TeaserCovalent binding of HMCES to nascent DNA blocks replication progression and kills homologous recombination deficient cancer cells
Modelling Protein-Glycan Interactions with HADDOCK
Authors: Ranaudo Anna , Giulini Marco , Ayuso Angela Pelissou , Bonvin Alexandre M. J. J. 
Published: August 2024

AbstractThe term glycan refers to a broad category of molecules composed of monosaccharides units linked to each other in a variety of ways, whose structural diversity is related to different functions in living organisms. Among others, glycans are recognized by proteins with the aim of carrying information and for signalling purposes. Determining the three-dimensional structures of protein-protein-glycan complexes is essential both for the understanding of the mechanisms glycans are involved in, and for applications such as drug design. In this context, molecular docking approaches are of undoubted importance as complementary approaches to experiments. In this study, we show how HADDOCK can be efficiently used for the prediction of protein-glycan complexes. Using a benchmark of 89 complexes, starting from their bound or unbound forms, and assuming some knowledge of the binding site on the protein, our protocol reaches a 70% and 40% top 5 success rate on bound and unbound datasets, respectively. We show that the main limiting factor is related to the complexity of the glycan to be modelled and the associated conformational flexibility.
Sex-chromosome-dependent aging in female heterogametic methylomes
Authors: Tangili Marianthi , Sudyka Joanna , Furni Fabricio , Palsbøll Per J. , Verhulst Simon 
Published: August 2024

AbstractDNA methylation-based indices predict mortality and provide insights into aging mechanisms. Even though sex chromosomes are thought to play an important role in sex-specific aging, they have been largely ignored in epigenetic aging studies. We identified age-related CpG (AR-CpG) sites in the full methylomes of two avian species (zebra finch and jackdaw), including for the first time the avian sex chromosomes (Z and the female-specific, haploid W). In both species, we find a high concentration of AR-CpG sites on the W chromosome, with DNA methylation levels predominantly decreasing with age. Our results highlight distinct age-related changes in sex chromosome DNA methylation compared to the rest of the genome, suggesting that this feature of sex chromosomes may contribute to sex-dependent aging.
PRMT7 mediated PTEN activation promotes bone formation in female mice
Authors: Zhang Yingfei , Qing Jia , Li Yang , Gao Xin , Lu Dazhuang , Wang Yiyang , Gu Lanxin , Zhang Hui , Li Zechuan , Wang Xu , Zhou Yongsheng , Zhang Ping 
Published: August 2024

AbstractAlthough the epigenetic mechanisms underlying bone formation are recognized, their specific roles and regulatory pathways remain largely unexplored. In this study, we unveil PRMT7 as a novel epigenetic modulator of MSCs’ osteogenic commitment. The conditional knockout ofPrmt7in mice reveals significantly impaired osteogenesis and bone regeneration exclusively in females, affecting both long bones and craniofacial structures, with no discernible impact in males. Our findings demonstrate that PRMT7 orchestrates osteogenic differentiation through a methyltransferase-dependent manner. Mechanistically, PRMT7 modulates MSCs’ osteogenic differentiation through the activation of PTEN. Specifically, PRMT7 augmentsPTENtranscription by increasing H3R2me1 levels at thePTENpromoter. Furthermore, PRMT7 interacts with the PTEN protein, and its deficiency leads to the ubiquitination and subsequent degradation of nuclear PTEN, revealing an unprecedented pathway. Crucially, PTEN overexpression ameliorates the osteogenic deficits observed inPrmt7-deficient mice. Our research positions PRMT7 as a potential therapeutic target to enhance bone formation and offers novel molecular insights into the PRMT7-PTEN regulatory axis, underscoring its significance in bone biology and regenerative medicine.Subject CategoriesDevelopmental Biology, Musculoskeletal System, Epigenetics, Post-translational Modifications
Model-driven engineering ofYarrowia lipolyticafor improved microbial oil production
Authors: Duman-Özdamar Zeynep Efsun , Julsing Mattijs K. , Martins dos Santos Vitor A.P. , Hugenholtz Jeroen , Suarez-Diez Maria 
Published: August 2024

SummaryExtensive usage of plant-based oils, especially palm oil, has led to environmental and social issues, such as deforestation and loss of biodiversity, thus sustainable alternatives are required. Microbial oils, especially fromYarrowia lipolytica, offer a promising solution due to their similar composition to palm oil, low carbon footprint, and ability to utilize low-cost substrates. In this study, we employed the Design-Build-Test-Learn (DBTL) approach to enhance lipid production inY. lipolytica. We systematically evaluated predictions from the genome-scale metabolic model to identify and overcome bottlenecks in lipid biosynthesis. We tested the effect of predicted medium supplements and genetic intervention targets, including the overexpression of ATP-citrate lyase (ACL), acetyl-CoA carboxylase (ACC), threonine synthase (TS), diacylglycerol acyltransferase(DGA1), the deletion of citrate exporter gene (CEX1) and disruption of β-oxidation pathway (MFE1). CombiningTSandDGA1overexpression in theΔmfe_Δcexbackground achieved a remarkable 200% increase in lipid content (56 % w/w) and a 230% increase in lipid yield on glycerol. These findings underscore the potential ofY. lipolyticaas an efficient microbial cell factory for fatty acid production. Our study advances the understanding of lipid metabolism inY. lipolyticaand demonstrates a viable approach for developing sustainable and economically feasible alternatives to palm oil.Graphical AbstractWe followed the Design-Build-Test-Learn approach to identify and overcome bottlenecks in lipid biosynthesis inY. lipolytica. DBTL intertwined the predictions from the metabolic model with addressed bottlenecks, investigated the effect of genetic interventions and medium supplements on lipid content, and ultimately defined an efficient strain design strategy.
Comparative lifespan and healthspan of nonhuman primate species common to biomedical research
Authors: Huber Hillary F , Ainsworth Hannah C , Quillen Ellen E , Salmon Adam , Ross Corinna , Azhar Adinda D , Bales Karen , Basso Michele A , Coleman Kristine , Colman Ricki , Darusman Huda S , Hopkins William , Hotchkiss Charlotte E , Jorgensen Matthew J , Kavanagh Kylie , Li Cun , Mattison Julie A , Nathanielsz Peter W , Saputro Suryo , Scorpio Diana G , Sosa Paul-Michael , Vallender Eric J , Wang Yaomin , Zeiss Caroline J , Shively Carol A , Cox Laura A 
Published: August 2024

AbstractThere is a critical need to generate age- and sex-specific survival curves to characterize chronological aging consistently across nonhuman primates (NHP) used in biomedical research. Sex-specific Kaplan-Meier survival curves were computed in 12 translational aging models: baboon, bonnet macaque, chimpanzee, common marmoset, coppery titi monkey, cotton-top tamarin, cynomolgus macaque, Japanese macaque, pigtail macaque, rhesus macaque, squirrel monkey, and vervet/African green. After employing strict inclusion criteria, primary results are based on 12,269 NHP that survived to adulthood and died of natural/health-related causes. A secondary analysis was completed for 32,616 NHP that died of any cause. Results show a pattern of reduced male survival among catarrhines (African and Asian primates), especially macaques, but not platyrrhines (Central and South American primates). For many species, median lifespans were lower than previously reported. An important consideration is that these analyses may offer a better reflection of healthspan than lifespan since research NHP are typically euthanized for humane welfare reasons before their natural end of life. This resource represents the most comprehensive characterization of sex-specific lifespan and age-at-death distributions for 12 biomedically relevant species, to date. These results clarify relationships among NHP ages and provide a valuable resource for the aging research community, improving human-NHP age equivalencies, informing investigators of expected survival rates, providing a metric for comparisons in future studies, and contributing to understanding of factors driving lifespan differences within and among species.
Autophagy-mediated CTR1 turnover orchestrates the reciprocal interaction between autophagy and ethylene signaling
Authors: Park Hye Lin , Zhang Weiwei , Chien Yuan-Chi , Park Chanung , Yoon Gyeong Mee 
Published: August 2024

ABSTRACTThe phytohormone ethylene and autophagy are crucial for plant adaptation to various environmental stresses, yet the integration of these signaling networks into stress responses is not fully understood. Here, we report that ethylene signaling and autophagy reciprocally regulate each other through Constitutive Triple Response 1 (CTR1), a negative regulator of ethylene signaling. Autophagy facilitates the turnover of the CTR1 protein, which interacts with the key autophagy-related protein ATG8 as autophagic cargo. Impaired autophagy attenuates ethylene responses. Conversely, ethylene-insensitive mutants exhibit enhanced autophagic flux, while a constitutive ethylene response mutant is hypersensitive to carbon starvation stress, which induces autophagy. This suggests that ethylene suppresses autophagy during carbon limitation. We further elucidated that ethylene receptors with a receiver domain play a primary role in modulating autophagy, while receptor kinase activity is not essential. Our findings uncover that the autophagic control of CTR1 degradation allows reciprocal cross-regulation between autophagy and ethylene transduction cascades, optimizing stress responses and resilience.
Interferon-induced activation state of circulating dendritic cells and monocytes triggered by yellow fever vaccination correlates with early protective antibody responses
Authors: Winheim Elena , Santos-Peral Antonio , Ehm Tamara , Rinke Linus , Riemer Sandra , Zaucha Magdalena , Goresch Sebastian , Lehmann Lisa , Eisenächer Katharina , Pritsch Michael , Barba-Spaeth Giovanna , Straub Tobias , Rothenfusser Simon , Krug Anne B. 
Published: August 2024

AbstractYellow fever vaccination provides long-lasting protection and is a unique model for studying the immune response to an acute RNA virus infection in humans. To elucidate the early innate immune events preceding the rapid generation of protective immunity, we performed transcriptome analysis of human blood dendritic cell (DC) and monocyte subpopulations before and 3, 7, 14 and 28 days after vaccination. We detected temporary upregulation of IFN-stimulated genes (ISG) in all DC and monocyte subsets on day 3 and 7 after vaccination as well as cell type specific responses and temporal dynamics. Single cell RNA sequencing revealed rapid appearance of activated DC and monocyte clusters dominated by ISGs, inflammatory chemokines and genes involved in antigen processing and presentation. This was confirmed by flow cytometric analysis in a large cohort of vaccinees. We identified SIGLEC1/CD169 upregulation as a sensitive indicator of the transient IFN-induced activation state elicited in DCs and monocytes by YF17D vaccination correlating with early protective IgM antibody responses.
MDR1 DNA glycosylase regulates the expression of genomically imprinted genes and helitrons
Authors: Higgins Kaitlin M , Gent Jonathan , Anderson Sarah N 
Published: August 2024

AbstractTargeted demethylation by DNA glycosylases (DNGs) results in differential methylation between parental alleles in the endosperm, which drives imprinted expression. Here, we performed RNA sequencing on endosperm derived from DNG mutantmdr1and wild-type endosperm. Consistent with the role of DNA methylation in gene silencing, we find 96 gene and 86 TE differentially expressed (DE) transcripts that lost expression in the hypermethylatedmdr1mutant. Compared with other endosperm transcripts, themdr1targets are enriched for TEs (particularly Helitrons), and DE genes are depleted for both core genes and GO term assignments, suggesting that the majority of DE transcripts are TEs and pseudo-genes. By comparing DE genes to imprinting calls from prior studies, we find that the majority of DE genes have maternally biased expression, and approximately half of all maternally expressed genes (MEGs) are DE in this study. In contrast, no paternally expressed genes (PEGs) are DE. DNG-dependent imprinted genes are distinguished by maternal demethylation and expression primarily in the endosperm, so we also performed EM-seq on hybrids to identify maternal demethylation and utilized a W22 gene expression atlas to identify genes expressed primarily in the endosperm. Overall, approximately ⅔ of all MEGs show evidence of regulation by DNA glycosylases. Taken together, this study solidifies the role of MDR1 in the regulation of maternally expressed, imprinted genes and TEs and identifies subsets of genes with DNG-independent imprinting regulation.Significance StatementThis work investigates the transcriptome changes resulting from the loss of function of DNA glycosylase MDR1, revealing that, in wild-type endosperm, targets of MDR1 are expressed predominantly from the maternal allele and this expression is suppressed in mutants. Furthermore, by combining expression data, DNA methylation data, and developmental expression data, we are able to categorize all maternally expressed, imprinted genes based on DNA glycosylase dependent or independent regulatory methods.