bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered circadian behavior and light sensing in mouse models of Alzheimer’s disease
Authors: Weigel Thaddeus K. , Guo Cherry L. , Güler Ali D. , Ferris Heather A. 
Published: May 2023

AbstractCircadian symptoms have long been observed in Alzheimer’s disease (AD) and often appear before cognitive symptoms, but the mechanisms underlying circadian alterations in AD are poorly understood. We studied circadian re-entrainment in AD model mice using a “jet lag” paradigm, observing their behavior on a running wheel after a six hour advance in the light:dark cycle. Female 3xTg mice, which carry mutations producing progressive amyloid beta and tau pathology, re-entrained following jet lag more rapidly than age-matched wild type controls at both 8 and 13 months of age. This re-entrainment phenotype has not been previously reported in a murine AD model. Because microglia are activated in AD and in AD models, and inflammation can affect circadian rhythms, we hypothesized that microglia contribute to this re-entrainment phenotype. To test this, we used the colony stimulating factor 1 receptor (CSF1R) inhibitor PLX3397, which rapidly depletes microglia from the brain. Microglia depletion did not alter re-entrainment in either wild type or 3xTg mice, demonstrating that microglia activation is not acutely responsible for the re-entrainment phenotype. To test whether mutant tau pathology is necessary for this behavioral phenotype, we repeated the jet lag behavioral test with the 5xFAD mouse model, which develops amyloid plaques, but not neurofibrillary tangles. As with 3xTg mice, 7-month-old female 5xFAD mice re-entrained more rapidly than controls, demonstrating that mutant tau is not necessary for the re-entrainment phenotype. Because AD pathology affects the retina, we tested whether differences in light sensing may contribute to altered entrainment behavior. 3xTg mice demonstrated heightened negative masking, an SCN-independent circadian behavior measuring responses to different levels of light, and re-entrained dramatically faster than WT mice in a jet lag experiment performed in dim light. 3xTg mice show a heightened sensitivity to light as a circadian cue that may contribute to accelerated photic re-entrainment. Together, these experiments demonstrate novel circadian behavioral phenotypes with heightened responses to photic cues in AD model mice which are not dependent on tauopathy or microglia.
Stiffness Sensing by Smooth Muscle Cells: Continuum Mechanics Modeling of the Acto-Myosin Role
Authors: Karkhaneh Yousefi Ali Akbar , Petit Claudie , Hassine Amira Ben , Avril Stéphane 
Published: May 2023

AbstractAortic Smooth Muscle Cells (SMCs) play a vital role in maintaining homeostasis in the aorta by sensing and responding to mechanical stimuli. However, the mechanisms that underlie the ability of SMCs to sense and respond to stiffness change in their environment are still partially unclear. In this study, we focus on the role of acto-myosin contractility in stiffness sensing and introduce a novel continuum mechanics approach based on the principles of thermal strains. Each stress fiber satisfies a universal stress-strain relationship driven by a Young’s modulus, a contraction coefficient scaling the fictitious thermal strain, a maximum contraction stress and a softening parameter describing the sliding effects between actin and myosin filaments. To account for the inherent variability of cellular responses, large populations of SMCs are modeled with the finite-element method, each cell having a random number and a random arrangement of stress fibers. Moreover, the level of myosin activation in each stress fiber satisfies a Weibull probability density function. Model predictions are compared to traction force measurements on different SMC lineages. It is demonstrated that the model not only predicts well the effects of substrate stiffness on cellular traction, but it can also successfully approximate the statistical variations of cellular tractions induced by intercellular variability. Finally, stresses in the nuclear envelope and in the nucleus are computed with the model, showing that the variations of cytoskeletal forces induced by substrate stiffness directly induce deformations of the nucleus which can potentially alter gene expression. The predictability of the model combined to its relative simplicity are promising assets for further investigation of stiffness sensing in 3D environments. Eventually, this could contribute to decipher the effects of mechanosensitivity impairment, which are known to be at the root of aortic aneurysms.
Wild birds’ plight and role in the current bird flu panzootic
Authors: Klaassen Marcel , Wille Michelle 
Published: May 2023

AbstractThe current avian influenza panzootic is unprecedented and catastrophic for birds. With a focus on the implications of this panzootic for poultry, there is limited attention on wild birds. We highlight shortcomings and geographic biases in reporting leading to a severe underappreciation of wildlife mortality. We estimate the scale of mortality amongst wild birds is in the millions rather than tens-of-thousands reported, through comparison of notification data to accounts literature. The outbreaks amongst wild birds are causing population and species level concerns which may drive extinctions and jeopardise decades of conservation efforts.
Brain activity of professional investors signals future stock performance
Authors: van Brussel Leonard D. , Boksem Maarten A.S. , Dietvorst Roeland C. , Smidts Ale 
Published: May 2023

AbstractA major aspiration of investors is to better forecast stock performance. Interestingly, emerging ‘neuroforecasting’ research suggests that brain activity associated with anticipatory reward relates to market behavior and population-wide preferences, including stock price dynamics. In this study we extend these findings to professional investors processing comprehensive real-world information on stock investment options while making predictions of long-term stock performance. Using functional magnetic resonance imaging (fMRI), we sampled investors’ neural responses to investment cases and assessed whether these responses relate to future performance on the stock market. We find that our sample of investors could not successfully predict future market performance of the investment cases, confirming that stated preferences do not predict the market. Stock metrics of the investment cases were not predictive of future stock performance either. However, as investors processed case information, nucleus accumbens (NAcc) activity was higher for investment cases that ended up overperforming in the market. These findings remained robust, even when controlling for stock metrics and investors’ predictions made in the scanner. Cross-validated prediction analysis indicated that NAcc activity could significantly predict future stock performance out-of-sample above chance. Our findings resonate with recent neuroforecasting studies and suggest that brain activity of professional investors may help in forecasting future stock performance.Significance StatementThe investors’ dream of forecasting the stock market is typically considered to be just that: An unrealistic aspiration. However, we find that forecasting stock performance may in fact not be completely unattainable. Results of our neuroimaging experiment reveal that professional investors fail to accurately predict long-term stock performance. However, while processing complex information pertaining to investment cases, brain activity in a region associated with reward anticipation was increased for stocks that would end up overperforming in the future market. Remarkably, this effect held after controlling for the stock information presented in the investment cases. Our findings add to recent work in ‘neuroforecasting’, demonstrating that market behavior can be forecasted by brain activity of a small sample, here of professional investors.
MSH2 stimulates interfering and inhibits non-interfering crossovers in response to genetic polymorphism
Authors: Dluzewska Julia , Dziegielewski Wojciech , Szymanska-Lejman Maja , Gazecka Monika , Henderson Ian R. , Higgins James D. , Ziolkowski Piotr A. 
Published: May 2023

AbstractIn Arabidopsis, local sequence polymorphism between homologs can stimulate double-strand break (DSB) repair via crossover formation in a MSH2-dependent manner. To understand how MSH2 regulates crossovers formed by the independent interfering and non-interfering pathways, we combine mutants that elevate non-interfering crossovers withmsh2. We demonstrate that MSH2 blocks non-interfering crossovers at polymorphic loci, which is the opposite effect to interfering crossovers. We also observe MSH2-independent crossover inhibition at highly polymorphic sites. We measure recombination along the chromosome arms, in lines differing in the heterozygosity pattern, and observe a dramatic crossover increase at the boundaries between heterozygous and homozygous regions, which is MSH2-dependent. Together, we show that MSH2 is a master regulator of meiotic DSB repair, with antagonistic effects on interfering and non-interfering crossovers, that shapes the crossover landscape in relation to interhomolog polymorphism.
Ribosomal protein L24 modulates mammalian microRNA processing and transfer RNA fragment production
Authors: Tzur Yonat , Dubnov Serafima , Madrer Nimrod , Bar Adi , Nadorp Bettina , Mishra Nibha , Heppenstall Paul , Bennett Estelle R , Greenberg David S , Winek Katarzyna , Soreq Hermona 
Published: May 2023

AbstractThe evolutionary mechanism(s) underlying the expression of novel microRNAs (miRs) are still elusive. To explore this issue, we studied the expression of intronic primate-specific hsa-miR-608, located in the Semaphorin 4G (SEMA4G) gene. Engineered ‘humanized’ mice carrying human miR-608 flanked by 250 bp in the murine Sema4g gene expressed miR-608 in several tissues. Moreover, miR-608 flanked by shortened fragments of its human genome region elevated miR-608 levels by 100-fold in murine and human-originated cells, identifying the 150 nucleotides 5’ to pre-miR-608 as an active promoter. Surprisingly, pulldown of this 5’ sequence revealed tight interaction with ribosomal protein L24 (RPL24), which inhibited miR-608 expression. Furthermore, RPL24 depletion altered the levels of 22 miRs, and we discovered that direct interaction of RPL24 with DDX5, a component of the large microprocessor complex, inhibits pri-miR processing. Moreover, RPL24 depletion resulted in Angiogenin (ANG)-mediated production of 5’-half tRFs in human cells, and altered plant tRF profiles. Expanding previous reports that RPL24 regulates miR processing in Arabidopsis thaliana, we implicate RPL24 in an evolutionarily-conserved regulation of miR processing and tRF production.Abstract Figure
Lactate transporter MCT1 in hepatic stellate cells promotes fibrotic collagen expression in nonalcoholic steatohepatitis
Authors: Min Kyounghee , Yenilmez Batuhan , Kelly Mark , Echeverria Dimas , Elleby Michael , Lifshitz Lawrence M. , Raymond Naideline , Tsagkaraki Emmanouela , Harney Shauna M. , DiMarzio Chloe , Wang Hui , McHugh Nicholas , Bramato Brianna , Morrision Brett , Rothstein Jeffery D. , Khvorova Anastasia , Czech Michael P. 
Published: May 2023

AbstractCirculating lactate is a fuel source for liver metabolism but may exacerbate metabolic diseases such as nonalcoholic steatohepatitis (NASH). Indeed, haploinsufficiency of lactate transporter monocarboxylate transporter 1 (MCT1) in mice reportedly promotes resistance to hepatic steatosis and inflammation. Here, we used adeno-associated virus (AAV) vectors to deliver thyroxin binding globulin (TBG)-Cre or lecithin-retinol acyltransferase (Lrat)-Cre to MCT1fl/flmice on a choline deficient, high fat NASH diet to deplete hepatocyte or stellate cell MCT1, respectively. Stellate cell MCT1KO (AAV-Lrat-Cre) attenuated liver type 1 collagen protein expression and caused a downward trend in trichrome staining. MCT1 depletion in cultured human LX2 stellate cells also diminished collagen 1 protein expression. Tetra-ethylenglycol-cholesterol (Chol)-conjugated siRNAs, which enter all hepatic cell types, and hepatocyte-selective tri-N-acetyl galactosamine (GN)-conjugated siRNAs were then used to evaluate MCT1 function in a genetically obese NASH mouse model. MCT1 silencing by Chol-siRNA decreased liver collagen 1 levels, while hepatocyte-selective MCT1 depletion by AAV-TBG-Cre or by GN-siRNA unexpectedly increased collagen 1 and total fibrosis without effect on triglyceride accumulation. These findings demonstrate that stellate cell lactate transporter MCT1 significantly contributes to liver fibrosis through increased collagen 1 protein expressionin vitroandin vivo, while hepatocyte MCT1 appears not to be an attractive therapeutic target for NASH.
Cities as parasitic amplifiers? Malaria prevalence and diversity in great tits along an urbanization gradient
Authors: Caizergues Aude E. , Robira Benjamin , Perrier Charles , Jeanneau Mélanie , Berthomieu Arnaud , Perret Samuel , Gandon Sylvain , Charmantier Anne 
Published: May 2023

ABSTRACTUrbanization is a worldwide phenomenon that modifies the environment. By affecting the reservoirs of pathogens and the body and immune conditions of hosts, urbanization alters the epidemiological dynamics and diversity of diseases. Cities could act as areas of pathogen dilution or amplification, depending on whether urban features have positive or negative effects on vectors and hosts. In this study, we focused on a host species and investigated the prevalence and diversity of avian malaria parasites (Plasmodium/Haemoproteussp. andLeucocytozoonsp.) in great tits (Parus major) living across an urbanization gradient. In general, we observed high prevalence in adult birds (from 95% to 100%), yet lower prevalence in fledglings (from 0% to 38%). We found a slight tendency for increased Plasmodium sp. prevalence with increasing urbanization in adults. Urban nestlings had higherPlasmodiumsp. infection rates than non-urban nestlings. We found evidence of higher diversity of parasites in the most natural urban park; however, parasite diversity was similar across other urbanization levels (e.g. from a little artificialized park to a highly anthropized industrial area). Parasite lineages were not habitat specific. Only onePlasmodiumsp. lineage (YWT4) was associated with urban areas and some rare lineages (e.g., AFR065) were present only in a zoo area, perhaps because of the presence of African birds. This study suggests that urbanization can lead to a parasite amplification effect and can favor different avian malaria lineages.
Identifying size-dependent toxin sorting in bacterial outer membrane vesicles
Authors: Singh Aarshi N. , Nice Justin B , Brown Angela C. , Wittenberg Nathan J. 
Published: May 2023

AbstractGram-negative bacteria produce outer membrane vesicles (OMVs) that play a critical role in cell-cell communication and virulence. Despite being isolated from a single population of bacteria, OMVs can exhibit heterogeneous size and toxin content, which can be obscured by assays that measure ensemble properties. To address this issue, we utilize fluorescence imaging of individual OMVs to reveal size-dependent toxin sorting. Our results showed that the oral bacteriumAggregatibacter actinomycetemcomitans (A.a.)produces OMVs with a bimodal size distribution, where larger OMVs were much more likely to possess leukotoxin (LtxA). Among the smallest OMVs (< 100 nm diameter), the fraction that are toxin positive ranges from 0-30%, while the largest OMVs (> 200 nm diameter) are between 70-100% toxin positive. Our single OMV imaging method provides a non-invasive way to observe OMV surface heterogeneity at the nanoscale level and determine size-based heterogeneities without the need for OMV fraction separation.
DrosophilaFMRP recruits the miRISC to target mRNAs to repress translation
Authors: Kaul Navneeta , Pradhan Sarala J. , Boin Nathan G. , Mason Madeleine M. , Rosales Julian , Starke Emily L. , Wilkinson Emily C. , Chapman Erich G. , Barbee Scott A. 
Published: May 2023

ABSTRACTFragile X syndrome (FXS) is the most common inherited form of intellectual disability and is caused by mutations in the gene encoding for the Fragile X messenger ribonucleoprotein (FMRP). FMRP is an evolutionarily conserved and neuronally enriched RNA binding protein (RBP) with functions in the control of processes including RNA editing, RNA transport, and protein translation. Specific target RNAs play critical roles in neurodevelopment including the regulation of neurite morphogenesis, synaptic plasticity, and cognitive function. The different biological functions of FMRP are modulated by its cooperative interaction with distinct sets of neuronal RNA and protein binding partners. Here, we focus on interactions between FMRP and components of the microRNA (miRNA) pathway. Using theDrosophilamodel system, we show that dFMRP can repress the translation of a reporter mRNA via a deadenylation-independent mechanism. This repression requires the activity of both AGO1 and GW182, conserved components of the miRNA-containing RISC (miRISC). Interestingly, we find that dFMRP can bind directly to a short stem loop structure in the reporter and that dFMRP binding is a prerequisite for repression by miR-958. Finally, we show thatdFmr1interacts genetically withGW182to control neurite morphogenesis. Collectively, these data suggest the dFMRP can directly recruit the miRISC to nearby miRNA binding sites and then repress translation via the activity of the miRISC effector, GW182.
Drosophilacells that express octopamine receptors can either inhibit or promote oviposition
Authors: Rohrbach Ethan W. , Knapp Elizabeth M. , Deshpande Sonali A. , Krantz David E. 
Published: May 2023

ABSTRACTAdrenergic signaling is known to play a critical role in regulating female reproductive processes in both mammals and insects. InDrosophila, the ortholog of noradrenaline, octopamine (Oa), is required for ovulation as well as several other female reproductive processes. Loss of function studies using mutant alleles of receptors, transporters, and biosynthetic enzymes for Oa have led to a model in which disruption of octopaminergic pathways reduces egg laying. However, neither the complete expression pattern in the reproductive tract nor the role of most octopamine receptors in oviposition is known. We show that all six known Oa receptors are expressed in peripheral neurons at multiple sites within in the female fly reproductive tract as well as in non-neuronal cells within the sperm storage organs. The complex pattern of Oa receptor expression in the reproductive tract suggests the potential for influencing multiple regulatory pathways, including those known to inhibit egg-laying in unmated flies. Indeed, activation of some neurons that express Oa receptors inhibits oviposition, and neurons that express different subtypes of Oa receptor can affect different stages of egg laying. Stimulation of some Oa receptor expressing neurons (OaRNs) also induces contractions in lateral oviduct muscle and activation of non-neuronal cells in the sperm storage organs by Oa generates OAMB-dependent intracellular calcium release. Our results are consistent with a model in which adrenergic pathways play a variety of complex roles in the fly reproductive tract that includes both the stimulation and inhibition of oviposition.
Kappa Opioid Receptor Antagonism Restores Phosphorylation, Trafficking and Behavior induced by a Disease Associated Dopamine Transporter Variant
Authors: Mayer Felix P. , Stewart Adele , Varman Durairaj Ragu , Moritz Amy E. , Foster James D. , Owens Anthony W. , Areal Lorena B. , Gowrishankar Raajaram , Velez Michelle , Wickham Kyria , Phelps Hannah , Katamish Rania , Rabil Maximilian , Jayanthi Lankupalle D. , Vaughan Roxanne A. , Daws Lynette C. , Blakely Randy D. , Ramamoorthy Sammanda 
Published: May 2023

AbstractAberrant dopamine (DA) signaling is implicated in schizophrenia, bipolar disorder (BPD), autism spectrum disorder (ASD), substance use disorder, and attention-deficit/hyperactivity disorder (ADHD). Treatment of these disorders remains inadequate, as exemplified by the therapeutic use of d-amphetamine and methylphenidate for the treatment of ADHD, agents with high abuse liability. In search for an improved and non-addictive therapeutic approach for the treatment of DA-linked disorders, we utilized a preclinical mouse model expressing the human DA transporter (DAT) coding variant DAT Val559, previously identified in individuals with ADHD, ASD, or BPD. DAT Val559, like several other disease-associated variants of DAT, exhibits anomalous DA efflux (ADE) that can be blocked by d-amphetamine and methylphenidate. Kappa opioid receptors (KORs) are expressed by DA neurons and modulate DA release and clearance, suggesting that targeting KORs might also provide an alternative approach to normalizing DA-signaling disrupted by perturbed DAT function. Here we demonstrate that KOR stimulation leads to enhanced surface trafficking and phosphorylation of Thr53 in wildtype DAT, effects achieved constitutively by the Val559 mutant. Moreover, these effects can be rescued by KOR antagonism of DAT Val559 inex vivopreparations. Importantly, KOR antagonism also correctedin vivoDA release as well as sex-dependent behavioral abnormalities observed in DAT Val559 mice. Given their low abuse liability, our studies with a construct valid model of human DA associated disorders reinforce considerations of KOR antagonism as a pharmacological strategy to treat DA associated brain disorders.
The impacts of economic growth, corruption, energy consumption and trade openness upon CO2 emissions: West African countries case
Authors: Abid Lobna , Kacem Sana , Saadaoui Haifa 
Published: May 2023

PurposeThis research paper aims to handle the effects of economic growth, corruption, energy consumption as well as trade openness on CO2 emissions for a sample of West African countries during the period 1980 and 2018.Design/methodology/approachThe current work uses the pooled mean group (PMG)-autoregressive distributed lag (ARDL) panel model to estimate the dynamics among the different variables used in the short and long terms.FindingsThe findings demonstrate that all variables have long-term effects. These results suggest that gross domestic product (GDP) per capita exhibits a positive and prominent effect on CO2 emissions. Corruption displays a negative and outstanding effect on long-term CO2 emissions. In contrast, energy consumption in West African countries and trade openness create environmental degradation. Contrarily to long-term results, short-term results demonstrate that economic growth, corruption and trade openness do not influence the environmental quality.Originality/valueEmpirical findings provide useful information to explore deeper and better the link between the used variables. They stand for a theoretical basis as well as an enlightening guideline for policymakers to set strategies founded on the analyzed links.