bluuebunny/crossref_metadata_2025_split huggingface dataset:
Androgen receptor modulation of vocal circuitry in Alston’s singing mouse
Authors: Zheng Da-Jiang , Mardis Britt , Lam Denise , Islam Tarik , Tripp Joel , Phelps Steven 
Published: October 2024

AbstractAnimal courtship and aggressive displays are dramatic, often sexually dimorphic behaviors that require the coordinated modulation of diverse motivational and motor circuits. In Alston’s singing mice, a novel and elaborate advertisement vocalization is sexually dimorphic and steroid sensitive (Scotinomys teguina). Males sing more often than females, and on average male songs have more notes. Song is influenced by circulating androgens, but how such hormonal differences influence the diverse brain regions involved in vocal display is not understood. To characterize androgen-sensitive sites in the vocal motor pathway, we used two isoforms of pseudorabies virus (PRV) to double-label circuits ending in laryngeal and jaw muscles involved in vocalization, and co-labeled these neurons for androgen receptor (AR). Next we manipulated circulating androgens and observed the effects on AR distribution and male song. We find androgens drive coordinated changes in AR abundance across motor and motivational circuits, and both individual and group differences in song are associated with AR abundance. The results reveal how circulating androgens and the auto-regulation of androgen receptors can influence the diverse circuits necessary for elaborate advertisement displays.Significance statementCourtship and aggressive displays are among those most elaborate and dramatic of sexually dimorphic behaviors. We show that in Alston’s singing mouse, an androgen-sensitive network defined by retrograde tracing shapes vocal display effort. Our results reveal how the intensity of singing mouse vocalizations is influenced by androgen actions in the vocal motor pathway.
Chronic circadian disruption in adolescent mice impairs hippocampal memory disrupting gene expression oscillations
Authors: Gallego-Landin Ines , Berbegal-Sáez Paula , Valverde Olga 
Published: October 2024

AbstractChronodisruption, the misalignment of internal biological systems with external environmental changes, leads to adverse health effects. Particularly, Social Jet Lag (SJL) is defined as the discrepancy between social and biological time and it exemplifies this misalignment, affecting a large part of the young population and impacting cognitive function. Despite its prevalence, our understanding of how developmental chronodisruption ultimately translates into morbidity is limited. To address this, we implemented a chronic chronodisruption protocol in adolescent mice consisting of light/dark cycle manipulation. We employed a comprehensive battery of established behavioral tests alongside an in-depth analysis of the oscillatory expression of the molecular clock and other genes involved in relevant physiological function. Our results show that chronic circadian disruption during adolescence induces impairments in short-term, social, and spatial memory without prompting anxiety-like behavior. Additionally, we report altered gene expression patterns of circadian clock genesper1,per2,cry2andnpas2in the hypothalamus and the hippocampus. Lastly, we observed a disruption of hippocampal gene expression oscillations which may underlie the hippocampal memory impairments. Overall, this work underscores the critical role of adolescent circadian rhythms in maintaining cognitive function, the relevance of circadian control of hippocampal homeostasis, and the importance of further research into the mechanisms of chronodisruption, particularly during adolescence, to better understand its long-term implications for cognitive function and overall health.
Hippocampal place cell sequences are impaired in a rat model of Fragile X Syndrome
Authors: Donahue Margaret M. , Robson Emma , Colgin Laura Lee 
Published: October 2024

AbstractFragile X Syndrome (FXS) is a neurodevelopmental disorder that can cause impairments in spatial cognition and memory. The hippocampus is thought to support spatial cognition through the activity of place cells, neurons with spatial receptive fields. Coordinated firing of place cell populations is organized by different oscillatory patterns in the hippocampus during specific behavioral states. Theta rhythms organize place cell populations during awake exploration. Sharp wave-ripples organize place cell population reactivation during waking rest. Here, we examined the coordination of CA1 place cell populations during active behavior and subsequent rest in a rat model of FXS (Fmr1knockout rats). While the organization of individual place cells by the theta rhythm was normal, the coordinated activation of sequences of place cells during individual theta cycles was impaired inFmr1knockout rats. Further, the subsequent replay of place cell sequences was impaired during waking rest following active exploration. Together, these results expand our understanding of how genetic modifications that model those observed in FXS affect hippocampal physiology and suggest a potential mechanism underlying impaired spatial cognition in FXS.Significance StatementFragile X Syndrome (FXS) is a neurodevelopmental disorder that can cause impaired memory and atypical spatial behaviors such as “elopement” (i.e., wandering off and becoming lost). Activity in the CA1 subregion of the hippocampus supports spatial memory and spatial cognition, making it an important candidate to study in the context of FXS; however, how neuronal population activity in CA1 is affected by FXS is poorly understood. In this study, we found that the coordination of populations of CA1 neurons during active behavior and waking rest was impaired in a rat model of FXS. These results reveal hippocampal physiological deficits that may contribute to cognitive impairments in FXS.
Limited Impact of Schistosome Infection onBiomphalaria glabrataSnail Microbiomes
Authors: Nordmeyer Stephanie C. , Anderson Timothy J.C. , Chevalier Frédéric D. , Le Clec’h Winka 
Published: October 2024

AbstractBackgroundThe microbiome of disease vectors can be a key determinant of their ability to transmit parasites. Conversely, parasite infection may modify vector microbiomes. We are exploring the interactions between theBiomphalaria glabratasnail microbiome and the blood flukeSchistosoma mansoni, responsible for an estimated 200,000 human deaths each year. Snail hosts vary in their susceptibility to schistosome parasites, and the underlying mechanisms driving this variation are not fully understood. We have previously shown that the snail hemolymph (i.e., blood) and organs harbor a diverse microbiome. Here we investigate the impact of schistosome infection on snail microbiomes, hypothesizing that invading schistosomes can alter the snail microbiomes in both composition and abundance over the course of infection, as developing schistosome parasites are in close contact with the host tissues.ResultWe generated cohorts of uninfected andS. mansoniinfected snails. We collected snail hemolymph and hepatopancreas (i.e., liver) at 8 timepoints during the pre-patent and patent periods of schistosome infection. We quantified bacterial density using qPCR and profiled the microbiome composition of all samples by sequencing the V4 region of the 16S rRNA. Schistosome infection had surprisingly no effect on bacterial density and limited effect on the microbiome composition, affecting mainly the hemolymph during the pre-patent period (at day 7 and 21). Organ and hemolymph microbiomes were relatively stable overtime for both infected and uninfected snail cohorts. Thesample type(hemolymph, hepatopancreas) was the major driver of the differences observed in microbiome composition.ConclusionsThe limited impact of schistosome infection on the host snail microbiomes might be explained by the long-term interaction of the two partners and the fact that parasite fitness is closely dependent on host fitness. Further investigations into the interactions between snails, their microbiomes, and schistosome parasites are essential for developing strategies to disrupt the parasite lifecycle and, consequently, schistosomiasis transmission.
High-resolution mapping of Sigma Factor DNA Binding Sequences using Artificial Promoters, RNA Aptamers and Deep Sequencing
Authors: Khan Essa Ahsan , Rückert-Reed Christian , Dahiya Gurvinder Singh , Tietze Lisa , Fages-Lartaud Maxime , Busche Tobias , Kalinowski Jörn , Shingler Victoria , Lale Rahmi 
Published: October 2024

ABSTRACTThe variable sigma (σ) subunit of the bacterial RNA polymerase holoenzyme determines promoter specificity and facilitate open complex formation during transcription initiation. Understanding σ-factor binding sequences is therefore crucial for deciphering bacterial gene regulation. Here, we present a data-driven high-throughput approach that utilizes an extensive library of 1.54 million DNA templates providing artificial promoters and 5′UTR sequences for σ-factor DNA binding motif discovery. This method combines the generation of extensive DNA libraries,in vitrotranscription, RNA aptamer selection, and deep DNA and RNA sequencing. It allows direct assessment of promoter activity, identification of transcription start sites, and quantification of promoter strength based on mRNA production levels. We applied this approach to map σ54DNA binding sequences inPseudomonas putida. Deep sequencing of the enriched RNA pool revealed 64,966 distinct σ54binding motifs, significantly expanding the known repertoire. This data-driven approach surpasses traditional methods by directly evaluating promoter function and avoiding selection bias based solely on binding affinity. This comprehensive dataset enhances our understanding of σ-factor binding sequences and their regulatory roles, opening avenues for new research in biology and biotechnology.
A PDZ-kinase allosteric relay mediates Par complex regulator exchange
Authors: Vargas Elizabeth , Penkert Rhiannon R. , Prehoda Kenneth E. 
Published: October 2024

AbstractThe Par complex polarizes the plasma membrane of diverse animal cells using the catalytic activity of atypical Protein Kinase C (aPKC) to pattern substrates. Two upstream regulators of the Par complex, Cdc42 and Par-3, bind separately to the complex to influence its activity in different ways. Each regulator binds a distinct member of the complex, Cdc42 to Par-6 and Par-3 to aPKC, making it unclear how they influence one another’s binding. Here we report the discovery that Par-3 binding to aPKC is regulated by aPKC autoinhibition and link this regulation to Cdc42 and Par-3 exchange. The Par-6 PDZ domain activates aPKC binding to Par-3 via a novel interaction with the aPKC kinase domain. Cdc42 and Par-3 have opposite effects on the Par-6 PDZ–aPKC kinase interaction: while the Par-6 kinase domain interaction competes with Cdc42 binding to the complex, Par-3 binding is enhanced by the interaction. The differential effect of Par-3 and Cdc42 on the Par-6 PDZ interaction with the aPKC kinase domain forms an allosteric relay that connects their binding sites and is responsible for the negative cooperativity that underlies Par complex polarization and activity.
Cryo-electron microscopy reveals a single domain antibody with a unique binding epitope on fibroblast activation protein alpha
Authors: Xu Zhen , Sinha Akesh , Pandya Darpan N. , Schnicker Nicholas J. , Wadas Thaddeus J. 
Published: October 2024

AbstractFibroblast activation protein alpha (FAP) is a serine protease that is expressed at basal levels in benign tissues but is overexpressed in a variety of pathologies, including cancer. Despite this unique expression profile, designing effective diagnostic and therapeutic agents that effectively target this biomarker remain elusive. Here we report the structural characterization of the interaction between a novel single domain antibody (sdAbs), I3, and FAP using cryo-electron microscopy. The reconstructions were determined to a resolution of 2.7 Å and contained two distinct populations; one I3 bound and two I3 molecules bound to the FAP dimer. In both cases, the sdAbs bound a unique epitope that was distinct from the active site of the enzyme. Furthermore, this report describes the rational mutation of specific residues within the complementarity determining region 3 (CDR3) loop to enhance affinity and selectivity of the I3 molecule for FAP. This report represents the first sdAb-FAP structure to be described in the literature.
Tet Transgene Activation is Disrupted in Lipogenic Triple Negative Breast Cancer Cells
Authors: Townsel Ashley , Wu Yifei , Jaffe Maya , Shields Cara , Haynes Karmella A. 
Published: October 2024

ABSTRACTAn important challenge for mammalian cell engineering is the unexpected response of transgenes to native transcriptional regulation pathways. One transgene can show different levels of expression at different genomic sites, in different cell types, and under different growth conditions. Collisions between transcription and DNA replication, heterochromatin encroachment, and viral defense have been linked to transgene silencing. In this study we identify fatty acid metabolism as another mediator of transgene behavior. Adipocyte secretome-induced lipogenesis in epithelial breast cancer cells was accompanied by the loss of expression from a Tet-TA regulatedpCMV-AmCyan fluorescent protein (CFP) transgene. Transcription profiling verified the activation of lipid droplet biosynthesis genes, and revealed repression of loci at every chromosome, consistent with the idea that lipogenesis affects the availability of substrates and cofactors for global chromatin remodeling. Pre-induction ofpCMVprevented full transgene silencing during lipogenesis. Our results provide new insights into the influence of the lipogenic epigenetic state on transgene behavior.
Isolation and Identification of P(3HB)-Degrading Bacteria from Malaysian Environment
Authors: Zahra Umber , Amirul A.A , Nawaz Ali , Mukhtar Hamid 
Published: October 2024

ABSTRACTThe aim of this study was to identify Poly(3-hydroxybutyrate) [P(3HB)] degrading bacterial strains in Penang Malaysia. Samples were collected from various locations in Penang. Five isolates (SMA-1, SMB-2, SMC-3, SMD-4, and SME-5) with highest P(3HB) degradation indices were isolated through meticulous screening. These gram-negative bacilli were characterized first morphologically and then through scanning electron microscopy. Growth profiles of the isolates revealed that at 24 hrs, SME-5 showed the highest growth rate. Maximum depolymerase enzyme activity for all five isolates was observed after 72 hrs. 16S rDNA sequencing identified all isolates asComamonas testosteroni. This study provides insights into the growth characteristics and extracellular depolymerase activity of P(3HB)-degrading bacteria isolated from the Malaysian environment. It highlights the potential ofComamonas testosteronistrains as P(3HB) bioplastic degraders in diverse habitats.
Drp1-mediated mitochondrial fission protects macrophages from mtDNA/ZBP1-mediated sterile inflammation and inhibits post-infarct cardiac remodeling
Authors: Kondo Yuki , Koga Jun-ichiro , Orkhonselenge Nasanbadrakh , Wang Lixiang , Hasuzawa Nao , Katsuki Shunsuke , Matoba Tetsuya , Nishimura Yosuke , Nomura Masatoshi , Kataoka Masaharu 
Published: October 2024

AbstractBackgroundIschemic heart disease is a leading cause of death worldwide, and heart failure after myocardial infarction (MI) is a growing issue in this aging society. Macrophages play central roles in left ventricular (LV) remodeling after MI. Mitochondria consistently change their morphology, including fission and fusion, but the role of these mitochondrial morphological changes, especially in macrophages, is unknown. This study aims to illuminate the effects and mechanisms of Dynamin-related protein 1 (Drp1), a molecule mediating mitochondrial fission, in macrophages for cardiac remodeling after MI.MethodsThis study utilized genetically altered mice lacking Drp1 in monocytes/macrophages (Drp1-KO) to elucidate the specific role of macrophage Drp1 in post-infarct LV remodeling.ResultsDeletion of Drp1 in macrophages exacerbated LV remodeling, including reduced ejection fraction and increased LV diameters, which resulted in decreased survival after MI. Histological analysis indicated increased fibrosis and sustained macrophage accumulation in Drp1-KO mice. Blockade of Drp1 in macrophages decreased mitochondrial fission and impaired mitophagy, leading to the subsequent release of mitochondrial DNA (mtDNA) to the cytosol and induction of inflammatory cytokines. This induction was abrogated by an autophagy inducer, Tat-beclin1, or siRNA-mediated knockdown of Z-DNA Binding Protein 1 (ZBP1). Deletion of ZBP1 in bone marrow-derived cells abrogated LV remodeling induced by Drp1 inhibitor, Mdivi-1.ConclusionMacrophage Drp1 plays a critical role in the pathobiology of LV remodeling after MI, especially mitochondria quality control mechanisms. Macrophage Drp1 could be a novel therapeutic molecule to mitigate the progression of LV remodeling and consequent heart failure after MI.
ASSISTED REPRODUCTIVE TECHNOLOGIES (ART) EQUITY, JUSTICE AND AUTONOMY IN GHANA
Authors: Moses Kodzo Damalie Francis Jojo , Senaya Charles Mawunyo , Damalie Elikplim Adzo , Dankluvi Herbert Ekoe , Osaah Millicent , Yeboah Beatrice , Annan John Jude , Djoleto Ellis Fleischer , Adageba Rudolf Kantum , Odoi Alexander Tawiah 
Published: October 2024

ABSTRACTRestrictive legislation, which is the main barrier to some assisted reproductive technology (ART) services in many countries, is non-existent in Ghana. However, ART services are concentrated in the capital cities of only four out of the sixteen regions, serving predominantly middle- and upper-class individuals. There is limited evidence about the factors preventing broader access to ART services in Ghana, and this study aims to document these barriers. A cross-sectional survey was conducted in July 2024 across all 22 fertility centers in Ghana, using two structured questionnaires administered via Google App to 61 ART personnel and 104 treatment defaulters. Results showed that mentorship from senior colleagues (65.57%) was the most common way for ART professionals to acquire skills. Almost all (91.80%) professionals offered a full range of ART procedures, but 86.89% advocated for regulated practice. They identified high treatment costs (70.49%) and lack of awareness (16.39%) as the most significant barriers. Among treatment defaulters, 88.47% had sought ART services based on word-of-mouth recommendations, compared to only 4.8% influenced by traditional or social media. More than half (50.96%) of the women were in their thirties, and 48.08% required in vitro fertilization (IVF). While 58.65% sought treatment within five years of infertility, 70.2% discontinued due to high costs, and 35.57% due to partner non-availability. Despite the absence of restrictive policies for ART services in Ghana, Prohibitive costs, partner non-availability, and lack of awareness limit access. However, ART professionals expressed the need for regulated practices.
Strategies to Reduce Hyperglycemia-Related Anxiety in Elite Athletes with Type 1 Diabetes: A Qualitative Analysis
Authors: Katz Alexandra , Shulkin Aidan , Fortier Marc-André , Yardley Jane E. , Kichler Jessica , Housni Asmaa , Talbo Meryem K. , Rabasa-Lhoret Rémi , Brazeau Anne-Sophie 
Published: October 2024

AbstractObjectiveManaging blood glucose levels is challenging for elite athletes with type 1 diabetes (T1D) as competition can cause unpredictable fluctuations. Hyperglycemia-related anxiety (HRA) likely affects performance and diabetes management, but research is limited. This study investigates current strategies employed to mitigate HRA during competition and the development of alternative approaches.Research Design and MethodsElite athletes with TID, aged>14 who self-reported HRA during competition were recruited. Elite athletes were defined as individuals exercising >10 hours per week whose athletic performance has achieved the highest competition level. 60 to 90-minute virtual semi-structured interviews were analyzed using an Interpretative Phenomenological Analysis.ResultsTen elite athletes with T1D (average age 25 ± 3 years; T1D duration 12 ± 8 years; # of competitions per year 27 ± 19; training time per week 12 ± 6 hours) reported the strategies they currently use to mitigate HRA. These strategies include managing insulin and nutrition intake, embracing social support networks, using technology, practicing relaxation techniques, establishing routines, performing pre-competition aerobic exercise, and maintaining adequate sleep hygiene. Several additional approaches that could be implemented were identified including establishing targeted support networks, developing peer-reviewed resources on HRA, ensuring support teams have sufficient tools, and improving existing technology.ConclusionsElite athletes with T1D use physiological and psychological strategies to mitigate HRA during competition. This finding highlights the need for increased support and education for these athletes, and advancements in technology. Targeted strategies and personalized approaches are also needed to optimize performance and diabetes management in this population.
Variations in the temperature dependence of photosynthesis among nine common tree species planted in Singapore
Authors: Rachel Teo Li Ming , Yu Liyao , Luo Xiangzhong 
Published: October 2024

AbstractTree planting is regarded as one of the most cost-effective ways to mitigate climate change impacts. As a part of the global tree planting movement, the tropical city-state of Singapore initiated a project to plant one million trees in 10 years. However, the environmental impacts (e.g., carbon sequestration, urban cooling) of this reforestation effort are challenging to assess as historically we lack understanding of key plant traits (i.e. photosynthetic capacity, or Vcmax) for species in tropical Asia. Here, we conducted a comprehensive survey of key photosynthetic traits of the nine most popular tree species planted in Singapore and their short-term temperature dependence. We found a three-fold inter-species variation in their photosynthetic capacities (e.g., Vcmaxranges from 20 to 60 μmol m−2s−1) as well as a large discrepancy in their temperature dependence. The photosynthesis of some species (e.g., Tembusu) is more sensitive to rising temperature than others (e.g., Mangroves) while a commonly-used photosynthesis model consistently overestimates photosynthesis but underestimates many species’ temperature sensitivities. The species with smaller temperature sensitivity of photosynthesis is likely related to their stronger ability to adjust leaf temperature via transpiration. Our study provides critical information on the temperature-dependence of photosynthesis of tree species in tropical Asia, which can be used to guide reforestation in Singapore and broadly in Southeast Asia.