bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic evidence for the link of misophonia with psychiatric disorders and personality
Authors: Smit Dirk J.A. , Bakker Melissa , Abdellaoui Abdel , Hoetink Alex E. , Vulink Nienke C.C. , Denys Damiaan 
Published: September 2022

AbstractPatients with misophonia experience strong negative emotional responses to human-produced sounds at a level disrupting normal social interaction. The exact nature of the disorder remains a matter of debate. Here, we investigated the genetic aetiology of misophonia in order to understand contributing factors and shed light on the nosology of the disorder. For misophonia, we used an unpublished genome-wide association study (GWAS) from 23andMe on a self-report item probing a common misophonic symptom: the occurrence of rage when others produce eating sounds.. We used gene-based and to functional annotation analyses to establish its neurobiological determinants. Next, we calculated genetic correlations (rG) of this misophonia GWAS with a wide range of traits and disorders from audiology (tinnitus, hearing performance and hearing trauma), psychiatry, neurology, and personality traits. Misophonia was significantly correlated with tinnitus, major depression disorder, post-traumatic stress disorder, and generalized anxiety disorder (0.12 < rG < 0.22). Stronger genetic correlations (0.21 < rG < 0.42) were observed for two clusters of personality traits: a neuroticism/guilt and an irritability/sensitivity cluster. Our results showed no genetic correlation with ADHD, OCD, and psychotic disorders. A negative correlation with autism spectrum disorder (ASD) was found, which may be surprising given the previously reported comorbidities and the sensory sensitivity reported in ASD. Clustering algorithms showed that misophonia consistently clustered with MDD, generalized anxiety, PTSD and related personality traits. We conclude that — based on genetics — misophonia most strongly clusters with psychiatric disorders and specific personality profile that matches those for anxiety and PTSD.
(Pro)Renin Receptor Antagonism Attenuates High-Fat-Diet–Induced Hepatic Steatosis in Non-Alcoholic Fatty Liver Disease
Authors: Gayban Ariana Julia B. , Souza Lucas , Cooper Silvana G. , Regalado Erick , Kleemann Robert , Earley Yumei Feng 
Published: September 2022

AbstractNon-alcoholic fatty liver disease (NAFLD) comprises a spectrum of liver damage directly related to diabetes, obesity, and metabolic syndrome. The (pro)renin receptor (PRR) has recently been demonstrated to play a role in glucose and lipid metabolism. Here, we hypothesized that inhibition of the PRR would prevent the development of diet-induced hepatic steatosis and fibrosis. To test our hypothesis, we fed wild-type mice on a C57Bl/6J background either a high-fat diet (HFD; 60% calories from fat) or normal fat diet (NFD; 10% calories from fat) with matching calories for 6 weeks. An 8-week methionine choline-deficient (MCD) diet was used to induce fibrosis in C57BL/6J mice. Two weeks following diet treatment, mice were implanted with a subcutaneous osmotic pump delivering either PRO20, a peptide PRR antagonist, or scrambled peptide (700 μg/kg/d) for 4 or 6 weeks. We found that a 6-week HFD significantly increased liver lipid accumulation, as detected by Oil Red O staining, and liver triglyceride content compared with NFD-fed mice. Importantly, PRO20 treatment significantly reduced hepatic lipid accumulation in HFD-fed mice without affecting body weight or glucose levels. Furthermore, PRR antagonism attenuated HFD-induced steatosis, particularly microvesicular steatosis. In the MCD diet model, the percentage of collagen area detected by Sirius Red staining was reduced in PRO20-treated compared with control mice. PRO20 treatment also significantly decreased levels of liver alanine aminotransferase (ALT), an indicator of liver damage, in MCD-fed mice compared with controls. Mechanistically, we found that PRR antagonism prevented HFD-induced increases in PPARγ and glycerol-3-phosphate acyltransferase 3 expression in the liver. Taken together, our findings establish the mechanism by which PRR regulates lipid metabolism in the liver and suggest the therapeutic potential of PRR antagonism for the treatment of liver steatosis and fibrosis development in NAFLD.
A novel biopolymer for mucosal adjuvant against respiratory pathogens
Authors: Hoover Ashley R. , More Sunil , Liu Kaili , West Connor L. , Valerio Trisha I. , Furrer Coline L. , Yu Ningli , Villalva Crystal , Kumar Amit , Alleruzzo Lu , Lam Samuel S. K. , Hode Tomas , Zhao Meng , Papin James F. , Chen Wei R. 
Published: September 2022

AbstractMucosal vaccinations for respiratory pathogens provide effective protection as they stimulate localized cellular and humoral immunities at the site of infection. Currently, the major limitation of intranasal vaccination is using effective adjuvants capable of withstanding the harsh environment imposed by the mucosa. Herein, we describe the efficacy of using a novel biopolymer, N-dihydrogalactochitosan (GC), as a nasal mucosal vaccine adjuvant against respiratory infections. Specifically, using COVID as an example, we mixed GC with recombinant SARS-CoV-2 trimeric spike (S) and nucleocapsid (NC) proteins to intranasally vaccinate K18-hACE2 transgenic mice, in comparison with Addavax (AV), an MF-59 equivalent. In contrast to AV, intranasal application of GC induces a robust, systemic antigen-specific antibody response and increases the number of T cells in the cervical lymph nodes. Moreover, GC+S+NC-vaccinated animals were largely resistant to the lethal SARS-CoV-2 challenge and experienced drastically reduced morbidity and mortality, with animal weights and behavior returning to normal 22 days post-infection. In contrast, animals intranasally vaccinated with AV+S+NC experienced severe weight loss, mortality, and respiratory distress, with none surviving beyond 6 days post-infection. Our findings demonstrate that GC can serve as a potent mucosal vaccine adjuvant against SARS-CoV-2 and potentially other respiratory viruses.
Aerosolized Desert Dusts Collected Near a Drying Lake and Pulmonary Inflammation in Mice: Implications for Environmental Exposures and Asthma
Authors: Biddle Trevor A. , Yisrael Keziyah , Drover Ryan , Li Qi , Maltz Mia R. , Topacio Talyssa M. , Yu Jasmine , Del Castillo Diana , Gonzales Daniel , Freund Hannah M. , Swenson Mark P. , Shapiro Malia L. , Botthoff Jon K. , Aronson Emma , Cocker David R. , Lo David D. 
Published: September 2022

AbstractBackgroundA high incidence of asthma is prevalent among residents near the Salton Sea, a large inland terminal lake in southern California. This arid region has high levels of ambient particulate matter (PM); yet while high PM levels are often associated with asthma in many environments, it is possible that the rapidly retreating lake may contribute components with a specific role in promoting asthma symptoms.ObjectivesOur hypothesis is that asthma may be higher in residents closest to the Salton Sea due to chronic exposures to playa dust. Playa emissions may be concentrating dissolved material from the lake, with microbial components capable of inducing pulmonary innate immune responses. Such inflammatory responses may contribute to the development of asthma-like symptoms in residents. To test this hypothesis, we used a mouse model of aerosol exposures to assess the effects of playa dust.MethodsFrom dust collected around the Salton Sea region, aqueous extracts were used to generate aerosols, which were injected into an environmental chamber for mouse exposure studies. We compared the effects of exposure to Salton Sea aerosols, as well as to known immunostimulatory reference materials. Acute 48-hour and chronic 7-day exposures were compared, with lungs analyzed for inflammatory cell recruitment and gene expression.ResultsDust from sites nearest to the Salton Sea triggered lung neutrophil inflammation that was stronger at 48-hours but reduced at 7-days. This acute inflammatory profile and kinetics resembled the response to innate immune ligands LTA and LPS while distinct from the classic allergic response to Alternaria.ConclusionLung inflammatory responses to Salton Sea dusts are similar to acute innate immune responses, raising the possibility that microbial components are entrained in the dust, promoting inflammation. This effect highlights the health risks at drying terminal lakes from inflammatory components in dust emissions from exposed lakebed.
Seasonality of pollinators in Mediterranean montane habitats: cool-blooded bees for early-blooming plants
Authors: Herrera Carlos M. , Núñez Alejandro , Aguado Luis O. , Alonso Conchita 
Published: September 2022

AbstractUnderstanding the factors that drive community-wide assembly of plant-pollinator systems along environmental gradients has considerable evolutionary, ecological and applied significance. Variation in thermal environments combined with intrinsic differences among pollinators in thermal biology (tolerance limits, thermal optima, thermoregulatory ability) have been proposed as drivers of community-wide pollinator gradients, but this suggestion remains largely speculative. We test the hypothesis that seasonality in bee pollinator composition in montane habitats of southeastern Spain, which largely reflects the prevalence during the early flowering season of mining bees (Andrena), is a consequence of the latter’s thermal biology. Quantitative information on seasonality ofAndrenabees in the whole plant community (275 plant species) was combined with field and laboratory data on key aspects of the thermal biology of 30 species ofAndrena(endothermic ability, warming constant, relationships of body temperature with ambient and operative temperatures).Andrenabees were a conspicuous, albeit strongly seasonal component of the pollinator assemblage of the regional plant community, visiting flowers of 153 different plant species (57% of total). Proportion ofAndrenarelative to all bees reached a maximum among plant species which flowered in late winter and early spring, and declined precipitously from May onwards.Andrenawere recorded only during the cooler segment of the annual range of air temperatures experienced at flowers by the whole bee assemblage. These patterns can be explained by features ofAndrena’s thermal biology: null or negligible endothermy; ability to forage at much lower body temperature than endothermic bees (difference ~10°C); low upper tolerable limit of body temperature, beyond which thermal stress presumably precluded foraging at the warmest period of year; weak thermoregulatory capacity; and high warming constant enhancing ectothermic warming. Our results demonstrate the importance of lineage-specific pollinator traits as drivers of seasonality in community-wide pollinator composition; show that exploitation of cooler microclimates by bees does not require endothermy; falsify the frequent assumption that endothermy and thermoregulation apply to all bees; and suggest that medium- and large-sized ectothermic bees with low upper thermal limits and weak thermoregulatory ability can actually be more adversely affected by climate warming than large endothermic species.
Engineering High-Quality Cartilage Microtissues using Hydrocortisone Functionalised Microwells
Authors: Burdis Ross , Kronemberger Gabriela Soares , Kelly Daniel J. 
Published: September 2022

AbstractEngineering clinically-relevant musculoskeletal tissues at a human scale is a considerable challenge. Developmentally-inspired scaffold-free approaches for engineering cartilage tissues have shown great promise in recent years, enabling the generation of highly biomimetic tissues. Despite the relative success of these approaches, the absence of a supporting scaffold or hydrogel creates challenges in the development of large scale tissues. Combining numerous scaled-down tissue units (herein termed microtissues) into a larger macrotissue represents a promising strategy to address this challenge. The overall success of such approaches, however, relies on the development of strategies to support the robust and consistent chondrogenic differentiation of clinically relevant cell sources such as mesenchymal stem/stromal cells (MSCs) within microwell arrays to biofabricate numerous microtissues rich in cartilage-specific extracellular matrix components. In this paper, we first describe a simple method to manufacture cartilage microtissues at various scales using novel microwell array stamps. This system allows the rapid and reliable generation of cartilage microtissues, and can be used as a platform to study microtissue phenotype and development. Based on the unexpected discovery that Endothelial Growth Medium (EGM) enhanced MSC aggregation and chondrogenic capacity within the microwell arrays, this work also sought to identify soluble factors within the media capable of supporting robust differentiation using heterogeneous MSC populations. Hydrocortisone was found to be the key factor within EGM that enhanced the chondrogenic capacity of MSCs within these microwell arrays. This strategy represents a promising means of generating large numbers of high-quality, scaffold-free cartilage microtissues for diverse biofabrication applications.
Population Normalization in SARS-CoV-2 Wastewater-Based Epidemiology: Implications from Statewide Wastewater Monitoring in Missouri
Authors: Li Chenhui , Bayati Mohamed , Hsu Shu-Yu , Hsieh Hsin-Yeh , Lindsi Wilfing , Belenchia Anthony , Zemmer Sally A. , Klutts Jessica , Samuelson Mary , Reynolds Melissa , Semkiw Elizabeth , Johnson Hwei-Yiing , Foley Trevor , Wieberg Chris G. , Wenzel Jeff , Lyddon Terri D. , LePique Mary , Rushford Clayton , Salcedo Braxton , Young Kara , Graham Madalyn , Suarez Reinier , Ford Anarose , Antkiewicz Dagmara S. , Janssen Kayley H. , Shafer Martin M. , Johnson Marc C. , Lin Chung-Ho 
Published: September 2022

ABSTRACTAbstract FigureThe primary objective of this study was to identify a universal wastewater biomarker for population normalization for SARS-CoV-2 wastewater-based epidemiology (WBE). A total of 2,624 wastewater samples (41 weeks) were collected weekly during May 2021-April 2022 from 64 wastewater facilities across Missouri, U.S. Three wastewater biomarkers, caffeine and its metabolite, paraxanthine, and pepper mild mottle virus (PMMoV), were compared for the population normalization effectiveness for wastewater SARS-CoV-2 surveillance. Paraxanthine had the lowest temporal variation and strongest relationship between population compared to caffeine and PMMoV. This result was confirmed by data from ten different Wisconsin’s WWTPs with gradients in population sizes, indicating paraxanthine is a promising biomarker of the real-time population across a large geographical region. The estimated real-time population was directly compared against the population patterns with human movement mobility data. Of the three biomarkers, population normalization by paraxanthine significantly strengthened the relationship between wastewater SARS-CoV-2 viral load and COVID-19 incidence rate the most (40 out of 61 sewersheds). Caffeine could be a promising population biomarker for regions where no significant exogenous caffeine sources (e.g., discharges from food industries) exist. In contrast, PMMoV showed the highest variability over time, and therefore reduced the strength of the relationship between sewage SARS-CoV-2 viral load and the COVID-19 incidence rate, as compared to wastewater data without population normalization and the population normalized by either recent Census population or the population estimated based on the number of residential connections and average household size for that municipality from the Census. Overall, the findings of this long-term surveillance study concluded that the paraxanthine has the best performance as a biomarker for population normalization for SARS-CoV-2 wastewater-based epidemiology.
Cell cycle progression defects and impaired DNA damage signaling drive enlarged cells into senescence
Authors: Manohar Sandhya , Estrada Marianna E. , Uliana Federico , Neurohr Gabriel E. 
Published: September 2022

AbstractCellular senescence plays an important role in development, ageing, and cancer biology. Senescence is associated with increased cell size, but how this contributes to permanent cell cycle exit is poorly understood. Using reversible G1 cell cycle arrests combined with growth rate modulation, we examined the effects of excess cell size on cell cycle progression in human cells. We show that enlarged cells paradoxically have high levels of G1/S regulators relative to cells that were maintained at physiological size but also induce p21, which restrains cell cycle entry and protects against cell division failure. Furthermore, we find that enlarged cells bear an increased propensity for DNA breakage and concomitant DNA damage repair defects that are established during G1. Based on these observations, we propose that impaired DNA damage repair pathways prime enlarged cells for persistent replication-acquired damage, ultimately leading to catastrophic cell cycle failure and permanent cell cycle exit.
Prefrontal network engagement by deep brain stimulation in limbic hubs
Authors: Allawala Anusha , Bijanki Kelly R , Oswalt Denise , Mathura Raissa K , Adkinson Joshua , Pirtle Victoria , Shofty Ben , Robinson Meghan , Harrison Matthew T , Mathew Sanjay J , Goodman Wayne K , Pouratian Nader , Sheth Sameer A , Borton David A 
Published: September 2022

AbstractBackgroundPrefrontal circuits in the human brain play an important role in cognitive and affective processing. Neuromodulation therapies delivered to certain key hubs within these circuits are being used with increasing frequency to treat a host of neuropsychiatric disorders. However, the detailed neurophysiological effects of stimulation to these hubs are largely unknown.MethodsHere, we performed intracranial recordings across prefrontal networks while delivering electrical stimulation to two well-established white matter hubs involved in cognitive regulation and depression: the subcallosal cingulate (SCC) and ventral capsule/ventral striatum (VC/VS).ResultsWe demonstrate a shared frontotemporal circuit consisting of the ventromedial PFC, amygdala, and lateral orbitofrontal cortex where gamma oscillations are differentially modulated by stimulation target. Additionally, we found subject-specific responses to stimulation in the dorsal anterior cingulate cortex and demonstrate the capacity for further tuning of neural activity using current-steered stimulation.ConclusionsOur findings indicate a potential neurophysiological mechanism for the dissociable therapeutic effects seen across the SCC and VC/VS DBS targets for psychiatric neuromodulation and our results lay the groundwork for personalized, network-guided neurostimulation therapy.
Variation in morphology among populations of threespine stickleback (Gasterosteus aculeatus) from western Newfoundland, Canada
Authors: Scott RJ , Haines GE , Biedak NR , Baker JA 
Published: September 2022

AbstractFreshwater populations of threespine stickleback (Gasterosteus aculeatus) have diverged from their marine ancestor and show extensive variation among populations throughout most of their range. However, phenotypes of freshwater populations from the east coast of North America does not appear to demonstrate extensive variability observed throughout the rest of the species’ range. The relative young age of east coast North American populations may explain the apparent lack of freshwater variability. On the other hand, populations in this part of the species’ range have not received the level of attention as have populations throughout the rest of its range and the low level of variability observed may simply reflect lack of data for this region. We examined morphological traits (including linear measurements of body armor and body shape) of stickleback from 52 locations representing marine and freshwater populations along the west coast of Newfoundland, Canada. We found that variability in morphological traits among freshwater populations was much more extensive than previously assumed and similar to patterns observed throughout the rest of the species’ range.
The evolution of host resistance to a virus is determined by resources, historical contingency, and time scale
Authors: Visher Elisa , Mahjoub Hannah , Soufi Khadija , Pascual Nilbert , Hoang Vivian , Bartlett Lewis J. , Roberts Katherine , Meaden Sean , Boots Mike 
Published: September 2022

AbstractHosts can often evolve resistance to parasites (and other stressors), but such resistance is generally thought to be constrained by trade-offs with other traits. These trade-offs determine the host’s optimal resistance strategy and whether resistance cycles, diversifies, and/or is maintained in the absence of parasite. However, trade-offs are often inconsistently measured across experiments and can depend on environmental conditions. Here, we extend a selection experiment evolving resistance to viral infection under variable resource quality in thePlodia interpunctellamodel system to explore the evolutionary conditions leading to an incongruent earlier measurement of costless resistance. We find that environmental resource quality, historical contingency, and the time scale of selection all affect trade-offs in our long-term selection experiment. Specifically, populations selected for resistance with the dual stressor of low resource quality are slowed, but not prevented, from evolving resistance. Second, variation in starting populations or early sampled adaptations led to contingency towards context-dependent resistance. Finally, some costs to resistance observed at early time points were compensated over longer evolutionary time scales. Our work therefore informs perspectives for the predictability of adaptation and how variation in specific evolutionary conditions can alter the evolutionary trajectories of a population towards costly or costless resistance strategies.
When good species have porous boundaries: weak reproductive isolation and extensive gene flow between Mimulus glaucescens and M. guttatus in northern California
Authors: Ivey C. T. , Habecker N. M. , Bergmann J. P. , Ewald J. , Coughlan J. M. 
Published: September 2022

AbstractBarriers to reproduction are often how progress in speciation is measured. Nonetheless, a key unresolved question is the extent to which reproductive barriers diminish gene flow in incipient species in nature. The Sierra Nevada foothill endemic Mimulus glaucescens and the widespread M. guttatus are considered to be distinct species based on contrasting vegetative traits, but barriers to reproduction are not readily apparent, although these species are not known to hybridize in nature. To explore boundaries between taxa, we examined 15 potential reproductive barriers between species in a Northern California area of broad sympatry. Most barriers, with the exception of ecogeographic isolation, were weak, and total isolation for each species was estimated to be incomplete. Population genomic analyses of range-wide and broadly sympatric accessions revealed that gene flow between these taxa is common across the range, and rampant within areas of sympatry. Thus, despite fairly strong ecological differentiation - which may be involved in maintenance of vegetative differences - ecological isolation is a weak barrier to gene flow in this system. This work underscores the value of combining classical measures of reproductive isolation with estimates of natural gene flow for studies of speciation in natural communities.