bluuebunny/crossref_metadata_2025_split huggingface dataset:
Community-Based Entomological Surveillance and Control of Vector-Borne Diseases: A Scoping Review
Authors: Eastman P. , Awolola T.S. , Yoshimizu M. , Govellla N. , Chaki P. , Zohdy S. 
Published: September 2024

AbstractCommunity-based surveillance and control methods (CBMs) present opportunities to decentralize surveillance and control efforts while simultaneously enhancing community education, leadership, and participation in the fight against vector-borne diseases (VBDs). A scoping review was conducted to describe how CBMs are being utilized currently to combat malaria, dengue fever, Chagas disease, tick-borne diseases (TBDs) and other mosquito-borne diseases (MBD) exclusive of dengue and malaria, and to overall highlight key approaches, lessons learned, potential challenges, and recommendations. A total of 304 potential publications were identified among which 82 met the inclusion criteria. This scoping review highlighted the following benefits to CBMs: cost savings, increased sustainability, increased community knowledge, human behavior changes, increased surveillance coverage, ease in deployment, and the creation of larger, more diverse entomological datasets. Potential challenges highlighted include: participant retention and motivation, participant recruitment and incentives, continued governmental support, data quality, and collaboration with local municipal authorities. CBMs are commonly and successfully used in vector surveillance and control systems, but the chosen vector management method varies by vector-borne disease and region of the world. Additional research is needed to support the implementation of CBMs including cost-effectiveness studies and those studies with negative outcomes. Taken together, this scoping review highlights key aspects, potential challenges, and benefits of CBMs, and outlines potential future directions for incorporating CBMs into VBD control and elimination programming, and potential for community based integrated vector management (IVM) approaches.
Mild activation of the mitochondrial unfolded protein response increases lifespan without increasing resistance to stress
Authors: Di Pede Alexa , Ko Bokang , AlOkda Abdelrahman , Tamez González Aura A. , Van Raamsdonk Jeremy M. 
Published: September 2024

AbstractThe mitochondrial unfolded protein response (mitoUPR) is a stress response pathway that responds to mitochondrial insults by altering gene expression to recover mitochondrial homeostasis. The mitoUPR is mediated by the stress-activated transcription factor ATFS-1. Constitutive activation of ATFS-1 increases resistance to exogenous stressors but paradoxically decreases lifespan. In this work, we determined the optimal levels of expression of activated ATFS-1 with respect to lifespan and resistance to stress by treating constitutively-activeatfs-1(et17)worms with different concentrations of RNA interference (RNAi) bacteria targetingatfs-1.We observed the maximum lifespan ofatfs-1(et17)worms at full-strengthatfs-1RNAi, which was significantly longer than wild-type lifespan. Under the conditions of maximum lifespan,atfs-1(et17)worms did not show enhanced resistance to stress, suggesting a trade-off between stress resistance and longevity. The maximum resistance to stress inatfs-1(et17)worms occurred on empty vector (0%atfs-1knockdown). Under these conditions,atfs-1(et17)worms are short-lived. This indicates that constitutive activation of ATFS-1 can increase lifespan or enhance resistance to stress but not both, at the same time. Finally, we determined the timing requirements for ATFS-1 to affect lifespan. We found that knocking downatfs-1expression only during development is sufficient to extendatfs-1(et17)lifespan, while adult-only knockdown has no effect. Overall, these results demonstrate that constitutively active ATFS-1 can extend lifespan when expressed at low levels and that this lifespan extension is not dependent on the ability of ATFS-1 to enhance resistance to stress.
Ripply3overdosage induces mid-face shortening throughTbx1downregulation in Down syndrome models
Authors: Ahumada Saavedra José Tomás , Chevalier Claire , Bloch Zupan Agnes , Herault Yann 
Published: September 2024

ABSTRACTThe most frequent and unique features of Down syndrome (DS) are learning disability and ucraniofacial (CF) dysmorphism. The DS-specific CF features are an overall reduction in head dimensions (microcephaly), relatively wide neurocranium (brachycephaly), reduced mediolaterally orbital region, reduced bizygomatic breadth, small maxilla, small mandible, and increased individual variability. Until now, the cellular and molecular mechanisms underlying the specific craniofacial phenotype have remained poorly understood. Investigating a new panel of DS mouse models with different segmental duplications on mouse chromosome 16 in the region homologous to human chromosome 21, we identified new regions and the role of two candidate gene for DS-specific CF phenotypes. First, we confirmed the role ofDyrk1ain the neurocranium brachycephaly. Then, we identified the role of the transcription factorRipply3overdosage in midface shortening through the downregulation ofTbx1, another transcription factor involved in the CF midface phenotype encountered in DiGeorge syndrome. This last effect occurs during branchial arches development through a reduction in cell proliferation. Our findings define a new dosage-sensitive gene responsible for the DS craniofacial features and propose new models for rescuing all aspects of DS CF phenotypes. This data may also provide insights into specific brain and cardiovascular phenotypes observed in DiGeorge and DS models, opening avenues for potential targeted treatment to soften craniofacial dysmorphism in Down syndrome.
Practical media formulations for rapid growth ofLactobacillus inersand other vaginal bacteria
Authors: Serrador Daniella , Campbell Jhenielle R. , Cheung Dorothy , Shefraw Gelila , Kaul Rupert , Navarre William W. 
Published: September 2024

AbstractVaginal microbiome composition is closely tied to host health. A microbiome dominated by specific anaerobes (e.g.,Gardnerella vaginalis) is termed bacterial vaginosis (BV) and is associated with negative health outcomes, while colonization byLactobacillusspecies is thought to protect against BV. However, the role of the speciesLactobacillus inersin vaginal health is controversial, with evidence that some strains may not protect against BV while others do. To better characterizeL. inersstrains, their interactions with vaginal bacteria and human cells need to be investigatedin vitro, but this has been impeded by the lack of liquid media for rapidL. inersgrowth. We have developed three liquid media formulations forL. inersgrowth: Serrador’s Lactobacilli-adapted Iscove’s Medium (SLIM) which leads to robustL. inersgrowth, a vaginally adapted version of SLIM (SLIM-V) and a chemically defined medium (SLIM-CD). SLIM and SLIM-V lead to dramatically improvedL. inersgrowth compared to previously published formulations and support growth of other vaginal bacteria, includingL. crispatus, L. jensenii, L. gasseriandG. vaginalis. SLIM-CD leads to slower growth but could prove useful for characterizingL. inersnutrient requirements or metabolite production. A modified version of SLIM-V supports growth of human cervical epithelial cells and provides a base for future co-culture work. Here, we present the formulations of SLIM, SLIM-V and SLIM-CD, and compare the growth of bacterial strains and human cells in the media.
A brain-body feedback loop driving HPA-axis dysfunction in breast cancer
Authors: Gomez Adrian , Wu Yue , Zhang Chao , Boyd Leah , Wee Tse-Luen , Gewolb Joseph , Amor Corina , Cheadle Lucas , Borniger Jeremy C. 
Published: September 2024

AbstractBreast cancer patients often exhibit disrupted circadian rhythms in circulating glucocorticoids (GCs), such as cortisol. This disruption correlates with reduced quality of life and higher cancer mortality1–3. The exact cause of this phenomenon — whether due to treatments, stress, age, co-morbidities, lifestyle factors, or the cancer itself remains unclear. Here, we demonstrate that primary breast cancer alone blunts host GC rhythms by disinhibiting neurons in the hypothalamus, and that circadian phase-specific neuromodulation of these neurons can attenuate tumor growth by enhancing anti-tumor immunity. We find that mice with mammary tumors exhibit blunted GC rhythms before tumors are palpable, alongside increased activity in paraventricular hypothalamic neurons expressing corticotropin-releasing hormone (i.e., PVNCRHneurons). Tumor-bearing mice have fewer inhibitory synapses contacting PVNCRHneurons and reduced miniature inhibitory post-synaptic current (mIPSC) frequency, leading to net excitation. Tumor-bearing mice experience impaired negative feedback on GC production, but adrenal and pituitary gland functions are largely unaffected, indicating that alterations in PVNCRHneuronal activity are likely a primary cause of hypothalamic-pituitary-adrenal (HPA) axis dysfunction in breast cancer. Using chemogenetics (hM3Dq) to stimulate PVNCRHneurons at different circadian phases, we show that stimulation just before the light-to-dark transition restores normal GC rhythms and reduces tumor progression. These mice have significantly more effector T cells (CD8+) within the tumor than non-stimulated controls, and the anti-tumor effect of PVNCRHneuronal stimulation is absent in mice lacking CD8+ T cells. Our findings demonstrate that breast cancer distally regulates neurons in the hypothalamus that control output of the HPA axis and provide evidence that therapeutic targeting of these neurons could mitigate tumor progression.
CD11B+CD36+cells are bone anabolic macrophages that limit age-associated bone loss
Authors: Koroth Jinsha , Karkache Ismael Y. , Vu Elizabeth K. , Mansky Kim C. , Bradley Elizabeth W. 
Published: September 2024

ABSTRACTDisruptions in the bone remodeling cycle that occur with increasing age lead to degeneration of the skeleton and increased risk of fragility fractures. Our understanding of how bone remodeling within cortical bone is controlled and altered with age in males and females is limited. Here, we generated bone marrow chimeric mice to understand the impacts of age and sex on bone remodeling. We demonstrate that transplantation of aged male or female bone marrow into young, lethally irradiated male hosts unexpectedly enhances cortical bone mass without impacting cancellous bone. Our single cell RNA-sequencing data show that mice reconstituted with aged bone marrow exhibited subsets of cells marked by CD11B/CD36 expression that demonstrate enhanced production of anabolic cytokines as compared to young counterparts, and that these myeloid subsets exist under conditions of normal physiology in aged mice. Importantly, CD11B+CD36+cells do not differentiate into osteoclasts in vitro, and CD36 does not mark TRAP+ cells in vivo. Instead, CD36+cells localize to resorption sites, including within cortical bone defects, suggesting their involvement in cortical bone remodeling and healing. CD11B+CD36+cells also express elevated levels of bone anabolic WNT ligands, especially Wnt6. In functional assays, we demonstrate that soluble factors produced by CD11B+CD36+cells enhance osteoblast progenitor commitment, mineralization, and activation of WNT signaling in vitro. Moreover, CD11B/CD36 exquisitely mark a subset of anabolic myeloid cells within human bone marrow. In conclusion, our studies identified a novel population of aged macrophages that limit cortical bone loss.
tRNA lysidinylation is essential for the minimal translation system found in the apicoplast ofPlasmodium falciparum
Authors: Elahi Rubayet , Prigge Sean T. 
Published: September 2024

AbstractFor decades, researchers have sought to define minimal genomes to elucidate the fundamental principles of life and advance biotechnology. tRNAs, essential components of this machinery, decode mRNA codons into amino acids. The apicoplast of malaria parasites encodes 25 tRNA isotypes in its organellar genome - the lowest number found in known translation systems. Efficient translation in such minimal systems depends heavily on post-transcriptional tRNA modifications, especially at the wobble anticodon position. Lysidine modification at the wobble position (C34) of tRNACAUdistinguishes between methionine (AUG) and isoleucine (AUA) codons, altering the amino acid delivered by this tRNA and ensuring accurate protein synthesis. Lysidine is formed by the enzyme tRNA isoleucine lysidine synthetase (TilS) and is nearly ubiquitous in bacteria and essential for cellular viability. We identified a TilS ortholog (PfTilS) located in the apicoplast ofPlasmodium falciparumparasites. By complementingPfTilS with a bacterial ortholog, we demonstrated that the lysidinylation activity ofPfTilS is critical for parasite survival and apicoplast maintenance, likely due to its impact on apicoplast protein translation. Our findings represent the first characterization of TilS in an endosymbiotic organelle, advancing eukaryotic organelle research and our understanding of minimal translational machinery. Due to the absence of lysidine modifications in humans, this research also exposes a potential vulnerability in malaria parasites that could be targeted by antimalarial strategies.SignificanceIn recent decades, synthetic biologists have sought the minimal cellular components required for life, focusing on simpler systems for easier modeling. The apicoplast organelle of malaria parasites, with only 25 tRNA isotypes, contains the smallest known complete tRNA set, even smaller than in synthetic organisms. This makes it an ideal model for studying minimal translational machinery, where tRNAs depend on post-transcriptional modifications for efficient protein translation. A key modification, lysidine, is crucial for decoding isoleucine and methionine. This study describes a tRNA-isoleucine lysidine synthetase (TilS) enzyme, essential for apicoplast protein translation. These findings have implications for understanding eukaryotic organelles and minimal translation machinery. Additionally, the absence of lysidine in humans suggests a potential target for antimalarial strategies.
Operant alcohol self-administration targets GluA2-containing AMPA receptor expression and synaptic activity in the nucleus accumbens in a manner that drives the positive reinforcing properties of the drug
Authors: Faccidomo Sara , Saunders Briana L , May Ashley M. , Eastman Vallari R. , Kim Michelle , Taylor Seth M. , Hoffman Jessica L. , McElligott Zoé A , Hodge Clyde W 
Published: September 2024

ABSTRACTRationale:The positive reinforcing effects of alcohol (ethanol) drive its repetitive use and contribute to alcohol use disorder (AUD). Ethanol alters the expression of glutamate AMPA receptor (AMPAR) subunits in reward-related brain regions, but the extent to which this effect regulates ethanol’s reinforcing properties is unclear.Objective:This study investigates whether ethanol self-administration changes AMPAR subunit expression and synaptic activity in the nucleus accumbens core (AcbC) to regulate ethanol’s reinforcing effects in male C57BL/6J mice.Results:Sucrose-sweetened ethanol self-administration (0.81 g/kg/day) increased AMPAR GluA2 protein expression in the AcbC, without effect on GluA1, compared to sucrose-only controls. Infusion of myristoylated Pep2m in the AcbC, which blocks GluA2 binding to N-ethylmaleimide-sensitive fusion protein (NSF) and reduces GluA2-containing AMPAR activity, reduced ethanol-reinforced responding without affecting sucrose-only self-administration or motor activity. Antagonizing GluA2-lacking AMPARs, through AcbC infusion of NASPM, had no effect on ethanol self-administration. AcbC neurons receiving projections from the basolateral amygdala (BLA) showed increased sEPSC area under the curve (a measurement of charge transfer) and slower decay kinetics in ethanol self-administering mice as compared to sucrose. Optogenetic activation of these neurons revealed an ethanol-enhanced AMPA/NMDA ratio and significantly reduced paired-pulse ratio, suggesting elevated GluA2 contributions specifically within the BLA→AcbC pathway.Conclusions:Ethanol use upregulates GluA2 protein expression in the AcbC and AMPAR synaptic activity in AcbC neurons receiving BLA projections and enhances synaptic plasticity directly within the BLA→AcbC circuit. GluA2-containing AMPAR activity in the AcbC regulates the positive reinforcing effects of ethanol through an NSF-dependent mechanism, highlighting a potential therapeutic target in AUD.
Age-related decline of PKA-RIIβ level in SNc dopaminergic neurons underlies PD pathogenesis
Authors: Zhao Yun , Wang Bingwei , Zhao Miao , Liu Jiarui , Hou Yujia , Wei Shizhang , Xiong Changxian , Li Daotong , Zheng Ruimao 
Published: September 2024

AbstractThe cyclic-AMP dependent protein kinase A (Protein kinase A, PKA) regulates dopaminergic function in the substantia nigra pars compacta (SNc). However, whether PKA is involved in the pathogenesis of Parkinson’s disease (PD) is unknown. Here, by collecting and analyzing the current worldwide SNc transcriptomic datasets of PD patients, we found a decline of PKA-RIIβ subunit level in the SNc of PD patients. The decreased PKA-RIIβ subunit level was positively correlated with decreased dopamine synthesis and increased oxidative stress in the SNc of PD patients. PKA-RIIβ subunit is expressed in the striatum and the SNc. PKA-RIIβ gene knockout mice (RIIβ-KO) showed a age-related parkinsonism at 12 months of age. Using Cre-LoxP system, we observed that RIIβ re-expression in the SNc dopaminergic neurons rescued parkinsonism of RΙΙβ-KO mice. RIIβ re-expression in striatal neurons did not affect parkinsonism of RΙΙβ-KO mice. The spontaneous parkinsonism could be developed in 12-month-old SNc dopaminergic neuron-specific RIIβ-deficient mice. Single-nucleus RNA sequencing revealed decreased PKA activity, reduced dopamine synthesis and raised oxidative stress in the SNc dopaminergic neurons of RIIβ-KO mice. Adeno-associated virus (AAV)-mediated gene therapy targeting PKA-RΙΙβ in the SNc dopaminergic neurons rescued parkinsonism in PD mouse model. Taken together, these findings indicate that PKA-RIIβ may be a key factor of human genetic etiologies of PD. The therapy targeting PKA-RIIβ in the SNc dopaminergic neurons may be promising for PD treatment.
Mayo Normative Studies: regression-based normative data for remote self-administration of the Stricker Learning Span, Symbols Test and Mayo Test Drive Screening Battery Composite and validation in individuals with Mild Cognitive Impairment and dementia
Authors: Stricker Nikki H. , Frank Ryan D. , Boots Elizabeth A. , Fan Winnie Z. , Christianson Teresa J. , Kremers Walter K. , Stricker John L. , Machulda Mary M. , Fields Julie A. , Lucas John A. , Hassenstab Jason , Aduen Paula A. , Day Gregory S. , Graff-Radford Neill R. , Jack Clifford R. , Graff-Radford Jonathan , Petersen Ronald C. 
Published: September 2024

AbstractObjectiveFew normative data for unsupervised, remotely-administered computerized cognitive measures are available. We examined variables to include in normative models for Mayo Test Drive (a multi-device remote cognitive assessment platform) measures, developed normative data, and validated the norms.Method1240 Cognitively Unimpaired (CU) adults ages 32-100-years (96% white) from the Mayo Clinic Study of Aging and Mayo Alzheimer’s Disease Research Center with Clinical Dementia Rating® of 0 were included. We converted raw scores to normalized scaled scores and derived regression-based normative data adjusting for age, age2, sex and education (base model); alternative norms are also provided (age+age2+sex; age+age2). We assessed additional terms using ana prioricut-off of 1% variance improvement above the base model. We examined low test performance rates (<-1 standard deviation) in independent validation samples (n=167 CU, n=64 mild cognitive impairment (MCI), n=14 dementia). Rates were significantly different when 95% confidence intervals (CI) did not include the expected 14.7% base rate.ResultsNo model terms met thea prioricut-off beyond the base model, including device type, response input source (e.g., mouse, etc.) or session interference. Norms showed expected low performance rates in CU and greater rates of low performance in MCI and dementia in independent validation samples.ConclusionTypical normative models appear appropriate for remote self-administered MTD measures and are sensitive to cognitive impairment. Device type and response input source did not explain enough variance for inclusion in normative models but are important for individual-level interpretation. Future work will increase inclusion of individuals from under-represented groups.
Human genetic evidence to inform clinical development of interleukin-6 signaling inhibition for abdominal aortic aneurysm
Authors: Burgess Stephen , Cronjé Héléne T. , deGoma Emil , Chyung Yung , Gill Dipender 
Published: September 2024

AbstractBackgroundAbdominal aortic aneurysm (AAA) represents a significant cause of mortality, yet no medical therapies have proven efficacious. The aim of the current study was to leverage human genetic evidence to inform clinical development of interleukin-6 (IL6) signaling inhibition for treatment of AAA.MethodsWe focused on rs2228145, a missense variant in theIL6Rgene region whose associations are expressed per additional copy of the C allele, corresponding to the genetically-predicted effect of IL6 signaling inhibition. We consider genetic associations with AAA risk in the AAAgen consortium (39,221 cases, 1,086,107 controls) and UK Biobank (2215 cases, 365,428 controls). To validate against known effects of IL6 signaling inhibition, we present associations with rheumatoid arthritis, polymyalgia rheumatica, and severe COVID-19. To explore mechanism specificity, we present associations with thoracic aortic aneurysm, intracranial aneurysm, and coronary artery disease. We further evaluated associations with measures of the abdominal aorta in UK Biobank, and explored genetic associations in clinically-relevant subgroups of the population.ResultsWe observed strong genetic associations with AAA risk in the AAAgen consortium and in UK Biobank: odds ratio (OR) 0.91 (95% confidence interval [CI]: 0.90 to 0.92, p = 4×10-30) and OR 0.90 (95% CI: 0.84, 0.96, p=0.0007), respectively. The association with AAA risk in UK Biobank was linear in the number of minor alleles: OR 0.91 (95% CI: 0.83, 1.00) in heterozygotes and OR 0.80 (95% CI: 0.71, 0.92) in minor homozygotes. The association was similar for fatal AAA, but with greater uncertainty due to the lower number of events. The association with AAA was of greater magnitude than associations with coronary artery disease and even rheumatologic disorders for which IL6 inhibitors have been approved. No strong associations were observed with thoracic aortic aneurysm, intracranial aneurysm, or abdominal aorta diameter in the general population without AAA. Associations attenuated towards the null in populations with concomitant inflammatory or connective tissue disease.ConclusionsThis drug target Mendelian randomization study supports that IL6 signaling inhibition will be efficacious for treating AAA, but not other types of aneurysmal disease. These findings serve to help inform clinical development of IL6 signaling inhibition for AAA treatment.