bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organization of the corticotropin-releasing hormone and corticotropin-releasing hormone-binding protein systems in the central nervous system of the sea lamprey Petromyzon marinus
Authors: Sobrido-Cameán Daniel , González-Llera Laura , Anadón Ramón , Barreiro-Iglesias Antón 
Published: May 2022

AbstractThe expression of the corticotropin-releasing hormone (PmCRH) and the CRH-binding protein (PmCRHBP) mRNAs was studied by in situ hybridization in the brain of prolarvae, larvae and adults of the sea lamprey Petromyzon marinus. We also generated an antibody against the PmCRH mature peptide to study the distribution of PmCRH-immunoreactive cells and fibers. PmCRH immunohistochemistry was combined with anti-tyrosine hydroxylase immunohistochemistry, PmCRHBP in situ hybridization or neurobiotin transport from the spinal cord. The most numerous PmCRH-expressing cells were observed in the magnocellular preoptic nucleus-paraventricular nucleus and in the superior and medial rhombencephalic reticular formation. PmCRH expression was more extended in adults than in larvae, and some cell populations were mainly (olfactory bulb) or only (striatum, ventral hypothalamus, prethalamus) observed in adults. The preopto-paraventricular fibers form conspicuous tracts coursing towards the neurohypophysis, but many immunoreactive fibers were also observed coursing in many other brain regions. Brain descending fibers in the spinal cord come from cells located in the isthmus and in the medial rhombencephalic reticular nucleus. The distribution of PmCRHBP-expressing neurons was different from that of PmCRH cells, with cells mainly present in the septum, striatum, preoptic region, tuberal hypothalamus, pretectum, pineal complex, isthmus, reticular formation, and spinal cord. Again, expression in adults was more extended than in larvae. PmCRH- and PmCRHBP-expressing cells are different, excluding colocalization of these substances in the same neuron. Present findings reveal a complex CRH/CRHBP system in the brain of the oldest extant vertebrate group, the agnathans, which shows similarities but important divergences with that of mammals.
Mapping the risks of China’s global coastal development to marine socio-ecological systems
Authors: Simmons B. Alexander , Butt Nathalie , O’Hara Casey C. , Ray Rebecca , Ma Yaxiong , Gallagher Kevin P. 
Published: May 2022

AbstractRapid coastal development continues to jeopardize the integrity of marine socio-ecological systems. China is now the largest bilateral creditor in the world, committing nearly half a trillion US dollars to overseas development finance since 2008. Meanwhile, there are growing concerns over the impacts of this boom in Chinese development finance on marine systems. Here, we quantify the risks of coastal development projects financed by China to marine biodiversity and coastal Indigenous communities. Ports present the greatest impact risks to marine systems, in terms of both magnitude and area at risk, with power plants, roads, and other facilities presenting relatively high localized risks. Risks are most prominent in Africa and the Caribbean, with coastal Indigenous communities in Western and Central Africa particularly vulnerable to the potential negative impacts of development. All projects present some risk to threatened marine species and potential critical habitats, but few present high risks to nearby marine protected areas. Most projects present additional risks to ecosystems that are already under increasing human pressures, but some are likely to introduce new risks to relatively intact ecosystems. “Bluing” future coastal development projects in China’s overseas development finance portfolio will require more social and environmental safeguards, higher standards for host-country impact assessments, and greater integration of land-sea risk mitigation and management approaches.
ALDH2 DEFICIENCY INCREASES SUSCEPTIBILITY TO BINGE ALCOHOL-INDUCED GUT LEAKINESS, ENDOTOXEMIA, AND ACUTE LIVER INJURY IN MICE THROUGH THE GUT-LIVER AXIS
Authors: Rungratanawanich Wiramon , Wang Xin , Kawamoto Toshihiro , Chidambaram Saravana Babu , Song Byoung-Joon 
Published: May 2022

AbstractMitochondrial aldehyde dehydrogenase 2 (ALDH2) is the major enzyme responsible for metabolizing toxic acetaldehyde to acetate and acts as a protective or defensive protein against various disease states associated with alcohol used disorder (AUD), including alcoholic liver disease (ALD), and elevated oxidative stress. We hypothesized thatAldh2-knockout (KO) mice are susceptible to binge alcohol-mediated liver injury than wild-type (WT) mice through increased gut leakiness and endotoxemia. Therefore, this study aimed to investigate the protective role of ALDH2 in binge alcohol-induced gut permeability, endotoxemia, and acute inflammatory liver injury by exposingAldh2-KO or WT mice to a single oral dose of binge alcohol 3.5, 4.0, or 5.0 g/kg. Our findings showed for the first time that ALDH2 deficiency inAldh2-KO mice increases their sensitivity to alcohol-induced oxidative and nitrative stress, enterocyte apoptosis, and nitration of gut tight junction (TJ) and adherent junction (AJ) proteins, leading to their degradation. These resulted in gut leakiness and endotoxemia inAldh2-KO mice after exposure to a single dose of ethanol even at 3.5 g/kg, while no changes were observed in the corresponding WT mice. The elevated serum endotoxin (lipopolysaccharide, LPS) and/or bacterial translocation contributed to systemic inflammation, hepatocyte apoptosis, and subsequently acute liver injury, indicating the disruption in the gut-liver axis. Furthermore, treatment with Daidzin, an ALDH2 inhibitor, exacerbated ethanol-induced cell permeability and reduced TJ/AJ proteins in T84 human colonic cells. These changes were reversed by Alda-1, an ALDH2 activator, indicating a crucial role of ALDH2 in protecting against alcohol-induced epithelial barrier dysfunction. All these findings suggest thatALDH2deficiency or gene mutation in humans is a risk factor to alcohol-mediated gut and liver injury, and ALDH2 could be an important therapeutic target against alcohol-associated tissue/organ damage.HighlightsBinge alcohol increases oxidative and nitrative stress in the intestine and liver.Binge alcohol causes gut leakiness, endotoxemia, and acute liver injury.Leaky gut is caused by elevated degradation of nitrated intestinal TJ/AJ proteins.Aldh2-KO mice are susceptible to binge-alcohol-induced leaky gut and liver injury.ALDH2 inhibition increases alcohol-induced T84 colonic epithelial cell permeability.
Regulation of metabolic health by dietary histidine in mice
Authors: Flores Victoria , Spicer Alexandra B. , Sonsalla Michelle , Richardson Nicole E. , Yu Deyang , Sheridan Grace E. , Trautman Michaela E. , Babygirija Reji , Cheng Eunhae P. , Rojas Jennifer M. , Yang Shany E. , Wakai Matthew H. , Hubbell Ryan , Kasza Ildiko , Tomasiewicz Jay L. , Green Cara L. , Dantoin Claudia , Alexander Caroline M. , Baur Joseph A. , Malecki Kristen C. , Lamming Dudley W. 
Published: May 2022

AbstractLow protein (LP) diets are associated with a decreased risk of diabetes in humans, and a low protein diet promotes leanness and glycemic control in both rodents and humans. While the effects of a LP diet on glycemic control are mediated by reduced dietary levels of the branched- chain amino acids (BCAAs), we have observed that reducing dietary levels of the other six essential amino acids leads to changes in body composition. Here, we find that dietary histidine plays a key role in the response to a LP diet in male C57BL/6J mice. Specifically reducing dietary levels of histidine by 67% reduces weight gain of young, lean male mice, reducing both adipose and lean mass gain, without altering glucose metabolism. Specifically reducing dietary histidine rapidly reverses diet-induced obesity and hepatic steatosis in diet-induced obese male mice, increasing insulin sensitivity; this normalization of metabolic health was associated not with caloric restriction or increased activity, but with increased energy expenditure. We find that the effects of histidine restriction surprisingly does not require the energy balance hormone Fgf21. Histidine restriction started in mid-life promoted leanness and glucose tolerance in aged males but not females, but did not affect frailty or lifespan in either sex. Finally, we demonstrate that variation in dietary histidine levels helps to explain body mass index differences in humans. Overall, our findings demonstrate that dietary histidine is a key regulator of weight and body composition in male mice and in humans, and suggest that reducing dietary levels of histidine may be a highly translatable option for the treatment of obesity.Key PointsProtein restriction (PR) promotes metabolic health in rodents and humans and extends rodent lifespan.Restriction of specific individual essential amino acids can recapitulate the benefits of PR.Reduced histidine promotes leanness and increased energy expenditure in mice.Reduced histidine does not extend the lifespan of mice when begun in mid-life.Dietary levels of histidine are positively associated with BMI in humans.
Immune Checkpoint Activity Regulates Polycystic Kidney Disease Progression
Authors: Kleczko Emily K. , Nguyen Dustin T. , Marsh Kenneth H. , Bauer Colin D. , Li Amy S. , Furgeson Seth B. , Gitomer Berenice Y. , Chonchol Michel B. , Clambey Eric T. , Zimmerman Kurt A. , Nemenoff Raphael A. , Hopp Katharina 
Published: May 2022

ABSTRACTInnate and adaptive immune cells modulate Autosomal Dominant Polycystic Kidney Disease (ADPKD) severity, a common kidney disease with inadequate treatment options. ADPKD shares parallels with cancer where immune checkpoint inhibitors have been shown to reactivate CD8+ T cells and slow tumor growth. We have shown that, in PKD, CD8+ T cell loss worsens disease. This study used orthologous early-onset and adult-onset ADPKD models (Pkd1 p.R3277C) to evaluate the role of immune checkpoints in PKD. Flow cytometry of kidney cells showed increased levels of PD-1 on CD8+ T cells and PD-L1 on macrophages and epithelial cells in Pkd1RC/RC mice versus wildtypes, paralleling disease severity. PD-L1 was also upregulated in ADPKD human cells and patient kidney tissue versus controls. Genetic PD-L1 loss or treatment with an anti-PD-1 antibody did not impact PKD severity in early-onset or adult-onset ADPKD models. However, treatment with anti-PD-1 plus anti-CTLA-4, blocking two immune checkpoints, improved PKD outcomes in adult-onset ADPKD mice; neither monotherapy altered PKD. Combination therapy resulted in increased kidney CD8+ T cell numbers/activation and decreased kidney regulatory T cell numbers. Together, our data suggests that immune checkpoint activation is an important feature of and potential novel therapeutic target in ADPKD.
Legacy of past exposure to hypoxia and warming regulates ecosystem service provided by oysters
Authors: Donelan Sarah C. , Ogburn Matthew B. , Breitburg Denise 
Published: May 2022

AbstractClimate change is having substantial impacts on organism fitness and ability to deliver critical ecosystem services, but these effects are often examined only in response to current environments. Past exposure to stress can also affect individuals via carryover effects, and whether these effects scale from individuals to influence ecosystem function and services is unclear. We explored carryover effects of two coastal climate change stressors – hypoxia and warming – on oyster (Crassostrea virginica) growth and nitrogen bioassimilation, an important ecosystem service. Oysters were exposed to a factorial combination of two temperature and two diel-cycling dissolved oxygen treatments at three-months-old and again one year later. Carryover effects of hypoxia and warming influenced oyster growth and nitrogen storage, with early life stress generally reducing nitrogen storage and relative tissue growth, particularly in warm environments. When extrapolated to the reef scale, carryover effects reduced estimated nitrogen storage by a restored oyster reef by as much as 41%, a substantial decline in a critical ecosystem service. Even brief exposure to climate change stressors early in life has persistent, negative effects on an ecosystem service one year later. Carryover effects on individuals impact processes at the ecological scale and must be considered in assessments of and management plans for species and ecosystems threatened by anthropogenic change.Significance StatementAnthropogenic change threatens organisms’ ability to provide ecosystem services through effects on individual phenotypes. Past experiences with anthropogenic stress can have delayed, persistent impacts on organisms via carryover effects, but how carryover effects scale to influence ecosystem function and services is not yet established. In marine systems, foundation species such as oysters mitigate effects of eutrophication by storing nutrients like nitrogen in their tissue and shell. We show that past exposure to two interacting climate change stressors (hypoxia and warming) reduces nitrogen stored by oysters by as much as 41% one year after initial exposure. Our results reveal carryover effects as a novel pathway through which climate change affects ecosystem processes that should be incorporated into conservation and management plans.
Rapid biomechanical imaging at low irradiation level via dual line-scanning Brillouin microscopy
Authors: Zhang Jitao , Nikolic Milos , Tanner Kandice , Scarcelli Giuliano 
Published: May 2022

AbstractBrillouin microscopy is a promising all-optical technique for biomechanics but is limited by slow acquisition speed and/or large irradiation doses. Here, we introduce multiplexed Brillouin microscopy that overcomes both these limits by over one order of magnitude with selective illumination and single-shot analysis of hundreds of points along the incident beam axis. We demonstrate the enabling capabilities of this method probing rapid response to perturbations and long-term mechanical evolution of tumor spheroids.
Reverse engineering environmental metatranscriptomes clarifies best practices for eukaryotic assembly
Authors: Krinos Arianna I. , Cohen Natalie R. , Follows Michael J. , Alexander Harriet 
Published: May 2022

AbstractDiverse communities of microbial eukaryotes in the global ocean provide a variety of essential ecosystem services, from primary production and carbon flow through trophic transfer to cooperation via symbioses. Increasingly, these communities are being understood through the lens of omics tools, which enable high-throughput processing of communities of multiple species. Metatranscriptomics in particular offers an understanding of real-time gene expression in microbial eukaryotic communities, providing a window into community metabolic activity. However, these approaches are rarely validated. A systematic validation of metatranscriptome assembly and annotation methods is necessary to appropriately assess (1) the fidelity of our community composition measurements and (2) the confidence of novel taxonomic and functional content discovered with metatranscriptomics. Here, we presenteukrhythmic, an automated and customizable multi-assembler workflow for eukaryotic metatranscriptome assembly, annotation, and analysis, and validate the ability of the pipeline to recapitulate simulated eukaryotic community-level expression data treated as a gold standard. Finally, we apply this pipeline to two previously published metatranscriptomic datasets, showing both recapitulation of previous results as well as enhanced taxonomic and functional gene discovery.
SOCS3 limits endotoxin-induced endothelial dysfunction by blocking a required autocrine interleukin 6 signal in human umbilical vein endothelial cells
Authors: Martino Nina , Ramos Ramon Bossardi , Chuy Dareen , Tomaszek Lindsay , Adam Alejandro P 
Published: May 2022

AbstractIncreased circulating levels of soluble interleukin (IL)-6 receptor α (sIL-6Rα) are commonly observed during inflammatory responses, allowing for IL-6 signaling to occur in cells that express the ubiquitous receptor subunit gp130 but not IL-6Rα, such as endothelial cells. Activation of Toll-like receptor (TLR)-4 or the tumor necrosis factor (TNF) receptor leads to NF-κB-dependent increases in endothelial IL-6 expression. Thus, we hypothesize that danger signals may induce autocrine IL-6 signaling within the endothelium via sIL-6Rα-mediated trans-signaling. In support of this hypothesis, we recently demonstrated that conditional deletion in the endothelium of the IL-6 signaling inhibitor SOCS3 leads to rapid mortality in mice challenged with the TLR-4 agonist endotoxin through increases in vascular leakage, thrombosis, leukocyte adhesion, and a type I-like interferon response. Here, we sought to directly test a role for sIL-6Rα in LPS-treated human umbilical vein endothelial cells. We show that cotreatment with sIL-6Rα dramatically increases the loss of barrier function and the expression of COX2 and tissue factor mRNA levels induced by LPS. This co-treatment led to a strong activation of STAT1 and STAT3 while not affecting LPS-induced activation of p38 and NF-κB signaling. Similar results were obtained when sIL-6Rα was added to a TNF challenge. JAK inhibition by pretreatment with ruxolitinib or by SOCS3 overexpression blunted LPS and sIL-6R synergistic effects, while SOCS3 knockdown further increased the response. Together, these findings demonstrate that IL-6 signaling downstream of NF-kB activation leads to a strong endothelial activation and may explain the acute endotheliopathy observed during critical illness.
Unravelling the mechanisms of adaptation to high pressure in proteins
Authors: Caliò Antonino , Koza Michael Marek , Fontanay Stephane , Oger Philippe , Peters Judith 
Published: May 2022

AbstractLife is thought to have appeared in the depth of the sea, under high hydrostatic pressure. Nowadays, it is known that the deep biosphere hosts a myriad of life forms thriving under high pressure conditions. However, the evolutionary mechanisms leading to their adaptation are still not known. Here we show the molecular bases of these mechanisms through a neutron scattering study of two orthologous proteins. We observed that pressure adaptation involves the decoupling of protein-water dynamics and the elimination of cavities in the protein core. This is achieved by an enrichment of acidic residues on the protein surface and by the use of bulkier hydrophobic residues in the core. These findings will be the starting point in the search of a complete genomic model explaining high pressure adaptation.
Linkage mapping reveals loci that underlie differences in C. elegans growth
Authors: Nyaanga Joy , Andersen Erik C. 
Published: May 2022

AbstractGrowth rate and body size are complex traits that contribute to the fitness of organisms. The identification of loci that underlie differences in these traits provides insights into the genetic contributions to development. Leveraging Caenorhabditis elegans as a tractable metazoan model for quantitative genetics, we can identify genomic regions that underlie differences in growth. We measured post-embryonic growth of the laboratory-adapted wild-type strain (N2) and a wild strain from Hawaii (CB4856), and found differences in body size. Using linkage mapping, we identified three distinct quantitative trait loci (QTL) on chromosomes IV, V, and X that are associated with variation in body size. We further examined these size-associated QTL using chromosome substitution strains and near-isogenic lines, and validated the chromosome X QTL. Additionally, we generated a list of candidate genes for the chromosome X QTL. These genes could potentially contribute to differences in animal growth and should be evaluated in subsequent studies. Our work reveals the genetic architecture underlying animal growth variation and highlights the genetic complexity of body size in C. elegans natural populations.
Targeted genomic sequencing with probe capture for discovery and surveillance of coronaviruses in bats
Authors: Kuchinski Kevin S. , Loos Kara D. , Suchan Danae M. , Russell Jennifer N. , Sies Ashton N. , Kumakamba Charles , Muyembe Francisca , Kingebeni Placide Mbala , Lukusa Ipos Ngay , N’Kawa Frida , Losoma Joseph Atibu , Makuwa Maria , Gillis Amethyst , LeBreton Matthew , Ayukekbong James A. , Monagin Corina , Joly Damien O. , Saylors Karen , Wolfe Nathan D. , Rubin Edward M. , Tamfum Jean J. Muyembe , Prystajecky Natalie A. , McIver David J. , Lange Christian E. , Cameron Andrew D.S. 
Published: May 2022

ABSTRACTPublic health emergencies like SARS, MERS, and COVID-19 have prioritized surveillance of zoonotic coronaviruses, resulting in extensive genomic characterization of coronavirus diversity in bats. Sequencing viral genomes directly from animal specimens remains a laboratory challenge, however, and most bat coronaviruses have been characterized solely by PCR amplification of small regions from the best-conserved gene. This has resulted in limited phylogenetic resolution and left viral genetic factors relevant to threat assessment undescribed.In this study, we evaluated whether a technique called hybridization probe capture can achieve more extensive genome recovery from surveillance specimens. Using a custom panel of 20,000 probes, we captured and sequenced coronavirus genomic material in 21 swab specimens collected from bats in the Democratic Republic of the Congo. For 15 of these specimens, probe capture recovered more genome sequence than had been previously generated with standard amplicon sequencing protocols, providing a median 6.1-fold improvement (ranging up to 69.1-fold). Probe capture data also identified five novel alpha- and betacoronaviruses in these specimens, and their full genomes were recovered with additional deep sequencing. Based on these experiences, we discuss how probe capture could be effectively operationalized alongside other sequencing technologies for high-throughput, genomics-based discovery and surveillance of bat coronaviruses.