bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylation in AgRP neurons regulates voluntary exercise behavior in mice
Authors: MacKay Harry , Scott C. Anthony , Duryea Jack D. , Baker Maria S. , Laritsky Eleonora , Elson Amanda E. , Garland Theodore , Fiorotto Marta L. , Chen Rui , Li Yumei , Coarfa Cristian , Simerly Richard B. , Waterland Robert A. 
Published: December 2019

AbstractDNA methylation regulates cell type-specific gene expression. Here, in a transgenic mouse model, we show that deletion of the gene encoding DNA methyltransferase Dnmt3a in hypothalamic AgRP neurons causes a sedentary phenotype characterized by reduced voluntary exercise and increased adiposity. Whole-genome bisulfite sequencing (WGBS) and transcriptional profiling in neuronal nuclei from the arcuate nucleus of the hypothalamus (ARH) reveal differentially methylated genomic regions and reduced expression of AgRP neuron-associated genes in knockout mice. We use read-level analysis of WGBS data to infer putative ARH neural cell types affected by the knockout, and to localize promoter hypomethylation and increased expression of the growth factor Bmp7 to AgRP neurons, suggesting a role for aberrant TGF-β signaling in the development of this phenotype. Together, these data demonstrate that DNA methylation in AgRP neurons is required for their normal epigenetic development and neuron-specific gene expression profiles, and regulates voluntary exercise behavior.
Unveiling how intramolecular stacking modes of covalently linked dimers dictate photoswitching properties
Authors: Lu Ru-Qiang , Yan Xiao-Yun , Zhu Lei , Yang Lin-Lin , Qu Hang , Wang Xin-Chang , Luo Ming , Wang Yu , Chen Rui , Wang Xiao-Ye , Lan Yu , Pei Jian , Weng Wengui , Xia Haiping , Cao Xiao-Yu 
Published: December 2019

AbstractCovalently linked π-stacked dimers represent the most significant platform for elucidating the relationship between molecular alignments and their properties. Here, we present the one-pot synthesis of two intramolecularly π-stacked dimers and disclose how intramolecular stacking modes dictate photoswitching properties. The dimer, which features cofacially stacked chromophores and geometrically favours intramolecular photochemical [2 + 2] cycloadditions, displays a nearly irreversible photoswitching behaviour. By contrast, the dimer, bearing crosswise stacked chromophores, is geometrically unfavourable for the cycloaddition and exhibits a highly reversible photoswitching process, in which the homolysis and reformation of carbon−carbon single bonds are involved. Moreover, the chiral carbon centres of both dimers endow these photoswitches with chirality and the separated enantiomers exhibit tuneable chiroptical properties by photoswitching. This work reveals that intramolecular stacking modes significantly influence the photochemical properties of π-stacked dimers and offers a design strategy toward chiral photoswitchable materials.
Single phase charge ordered stoichiometric CaFe3O5 with commensurate and incommensurate trimeron ordering
Authors: Cassidy Simon J. , Orlandi Fabio , Manuel Pascal , Clarke Simon J. 
Published: December 2019

AbstractMixed-valent transition metal compounds display complex structural, electronic and magnetic properties which can often be exquisitely tuned. Here the charge-ordered state of stoichiometric CaFe3O5 is probed using neutron powder diffraction, Monte Carlo simulation and symmetry analysis. Magnetic ordering is dominated by the formation of ferromagnetic Fe3+–Fe2+–Fe3+ trimers which are evident above the magnetic ordering transition. Between TN = 289 K and 281 K an incommensurate magnetically ordered phase develops due to magnetic frustration, but a spin Jahn-Teller distortion lifts the frustration and enables the magnetic ordering to lock in to a charge-ordered commensurate state at lower temperatures. Stoichiometric CaFe3O5 exhibits single phase behaviour throughout and avoids the phase separation into two distinct crystallographic phases with different magnetic structures and Fe valence distributions reported recently, which likely occurs due to partial Fe2+ for Ca2+ substitution. This underlines the sensitivity of the magnetism and chemistry of these mixed-valent systems to composition.
LRIG1 is a pleiotropic androgen receptor-regulated feedback tumor suppressor in prostate cancer
Authors: Li Qiuhui , Liu Bigang , Chao Hsueh-Ping , Ji Yibing , Lu Yue , Mehmood Rashid , Jeter Collene , Chen Taiping , Moore John R. , Li Wenqian , Liu Can , Rycaj Kiera , Tracz Amanda , Kirk Jason , Calhoun-Davis Tammy , Xiong Jie , Deng Qu , Huang Jiaoti , Foster Barbara A. , Gokhale Abhiram , Chen Xin , Tang Dean G. 
Published: December 2019

AbstractLRIG1 has been reported to be a tumor suppressor in gastrointestinal tract and epidermis. However, little is known about the expression, regulation and biological functions of LRIG1 in prostate cancer (PCa). We find that LRIG1 is overexpressed in PCa, but its expression correlates with better patient survival. Functional studies reveal strong tumor-suppressive functions of LRIG1 in both AR+ and AR− xenograft models, and transgenic expression of LRIG1 inhibits tumor development in Hi-Myc and TRAMP models. LRIG1 also inhibits castration-resistant PCa and exhibits therapeutic efficacy in pre-established tumors. We further show that 1) AR directly transactivates LRIG1 through binding to several AR-binding sites in LRIG1 locus, and 2) LRIG1 dampens ERBB expression in a cell type-dependent manner and inhibits ERBB2-driven tumor growth. Collectively, our study indicates that LRIG1 represents a pleiotropic AR-regulated feedback tumor suppressor that functions to restrict oncogenic signaling from AR, Myc, ERBBs, and, likely, other oncogenic drivers.
A High Throughput Isolation Method for Phosphate-Accumulating Organisms
Authors: Anand Ajeeta , Aoyagi Hideki 
Published: December 2019

AbstractHyperphosphatemia is a secondary issue associated with chronic kidney disorder. Use of phosphate binders and dialysis are the treatments for hyperphosphatemia, albeit with harmful side effects and high cost, respectively. A safer and healthier approach is attempted to administer phosphate-accumulating organisms (PAOs) from probiotics to prevent hyperphosphatemia. However, screening and isolation of PAOs are limited by inefficient enrichment of relevant metabolism and contamination. Therefore, we devised a novel strategy to isolate elite PAOs from Lactobacillus casei JCM 1134 and Bifidobacterium adolescentis JCM 1275 (previously reported PAOs). PAOs were first enriched for phosphate uptake and incubated in low-pH phosphate-free media to dormant non-PAOs, and then purified using Percoll density gradient centrifugation. Subsequently, elite PAOs were isolated from centrifuged pellet on a toluidine blue O-supplemented agar-based media. Using this technique, elite PAOs could not only be isolated, but also semi-quantitatively scored for their phosphate accumulation capabilities. Additionally, these scores correlated well with their accumulated phosphate values. The elite PAOs isolated from L. casei and B. adolescentis showed 0.81 and 0.70 [mg-phosphate/mg-dry cell], respectively (23- and 4.34-fold increase, respectively). Thus, our method can be used to successfully isolate elite PAOs, which might be of use to prevent hyperphosphatemia at early stages.
Study on Chemical Modifications of Glutathione by Cold Atmospheric Pressure Plasma (Cap) Operated in Air in the Presence of Fe(II) and Fe(III) Complexes
Authors: Śmiłowicz Dariusz , Kogelheide Friederike , Stapelmann Katharina , Awakowicz Peter , Metzler-Nolte Nils 
Published: December 2019

AbstractCold atmospheric pressure plasma is an attractive new research area in clinical trials to treat skin diseases. However, the principles of plasma modification of biomolecules in aqueous solutions remain elusive. It is intriguing how reactive oxygen and nitrogen species (RONS) produced by plasma interact on a molecular level in a biological environment. Previously, we identified the chemical effects of dielectric barrier discharges (DBD) on the glutathione (GSH) and glutathione disulphide (GSSG) molecules as the most important redox pair in organisms responsible for detoxification of intracellular reactive species. However, in the human body there are also present redox-active metals such as iron, which is the most abundant transition metal in healthy humans. In the present study, the time-dependent chemical modifications on GSH and GSSG in the presence of iron(II) and iron(III) complexes caused by a dielectric barrier discharge (DBD) under ambient conditions were investigated by IR spectroscopy, mass spectrometry and High Performance Liquid Chromatography (HPLC). HPLC chromatograms revealed one clean peak after treatment of both GSH and GSSH with the dielectric barrier discharge (DBD) plasma, which corresponded to glutathione sulfonic acid GSO3H. The ESI-MS measurements confirmed the presence of glutathione sulfonic acid. In our experiments, involving either iron(II) or iron(III) complexes, glutathione sulfonic acid GSO3H appeared as the main oxidation product. This is in sharp contrast to GSH/GSSG treatment with DBD plasma in the absence of metal ions, which gave a wild mixture of products. Also interesting, no nitrosylation of GSH/GSSG was oberved in the presence of iron complexes, which seems to indicate a preferential oxygen activation chemistry by this transition metal ion.
Genomewide Gene-by-Sex Interaction Scans Identify ADGRV1 for Sex Differences in Opioid Dependent African Americans
Authors: Yang Bao-Zhu , Zhou Hang , Cheng Zhongshan , Kranzler Henry R. , Gelernter Joel 
Published: December 2019

AbstractSex differences in opioid dependence (OD) are genetically influenced. We conducted genomewide gene-by-sex interaction scans for the DSM-IV diagnosis of OD in 8,387 African-American (AA) or European-American subjects (43.6% women; 4,715 OD subjects). Among AAs, 9 SNPs were genome-wide significant at ADGRV1 (adhesion G-protein-coupled receptor V1, lead-SNP rs2366929*(C/T), p = 1.5 × 10−9) for sex-different risk of OD, with the rs2366929*C-allele increasing OD risk only for men. The top co-expressions in brain were between ADGRV1 and GRIK2 in substantia nigra and medullary inferior olivary nucleus, and between ADGRV1 and EFHC2 in frontal cortex and putamen. Significant sex-differential ADGRV1 expression from GTEx was detected in breast (Bonferroni-corrected-p < 0.002) and in heart (p < 0.0125), with nominal significance identified in brain, thyroid, lung, and stomach (p < 0.05). ADGRV1 co-expression and disease-enrichment analysis identifying the top 10 diseases showed strikingly sexually dimorphic risks. The enrichment and transcriptome analyses provided convergent support that ADGRV1 exerts a sex-different effect on OD risk. This is the first study to identify genetic variants contributing to sex differences in OD. It shows that ADGRV1 contributes to OD risk only in AA men, a finding that warrants further study.
Mitochondrial Dysfunction and Changes in High-Energy Compounds in Different Cellular Models Associated to Hypoxia: Implication to Schizophrenia
Authors: e Silva Luiz Felipe Souza , Brito Mariana Dutra , Yuzawa Jéssica Mayumi Camargo , Rosenstock Tatiana Rosado 
Published: December 2019

AbstractSchizophrenia (SZ) is a multifactorial mental disorder, which has been associated with a number of environmental factors, such as hypoxia. Considering that numerous neural mechanisms depends on energetic supply (ATP synthesis), the maintenance of mitochondrial metabolism is essential to keep cellular balance and survival. Therefore, in the present work, we evaluated functional parameters related to mitochondrial function, namely calcium levels, mitochondrial membrane potential, redox homeostasis, high-energy compounds levels and oxygen consumption, in astrocytes from control (Wistar) and Spontaneously Hypertensive Rats (SHR) animals exposed both to chemical and gaseous hypoxia. We show that astrocytes after hypoxia presented depolarized mitochondria, disturbances in Ca2+ handling, destabilization in redox system and alterations in ATP, ADP, Pyruvate and Lactate levels, in addition to modification in NAD+/NADH ratio, and Nfe2l2 and Nrf1 expression. Interestingly, intrauterine hypoxia also induced augmentation in mitochondrial biogenesis and content. Altogether, our data suggest that hypoxia can induce mitochondrial deregulation and a decrease in energy metabolism in the most prevalent cell type in the brain, astrocytes. Since SHR are also considered an animal model of SZ, our results can likewise be related to their phenotypic alterations and, therefore, our work also allow an increase in the knowledge of this burdensome disorder.
Fluctuating thermal environments of shallow-water rocky reefs in the Gulf of California, Mexico
Authors: Galland Grantly R. , Hastings Philip A. , Leichter James J. 
Published: December 2019

AbstractAs part of a broad-scale study of the biogeography of rocky reefs in the Gulf of California, Mexico (GOC), we collected a continuous 1-yr temperature time series at ~5 m water depth at 16 sites spanning 5° of latitude and ~700 km along the western boundary of the basin. Throughout the region, thermal conditions were most variable in summer with fluctuations concentrated at diurnal and semi-diurnal frequencies, likely associated with solar and wind forcing and vertical water column oscillations forced by internal waves. Temperatures in winter were less variable than in summer, and minimum temperatures also differed among sites. Thermal variability integrated across the diurnal and semi-diurnal frequency bands was greatest near the Midriff Islands in the northern GOC and decreased toward the southern sites. Diurnal variability was greater than semi-diurnal variability at 13 of the 16 sites. A statistic-of-extremes analysis indicated shortest return times for cooling events in summer, and reef organisms at many of the sites may experience anomalous 2 to 5 °C cooling events multiple times per month. The significant extent of local temperature variability may play important roles in limiting species occurrences among sites across this biogeographic region.
Glacial lakes exacerbate Himalayan glacier mass loss
Authors: King Owen , Bhattacharya Atanu , Bhambri Rakesh , Bolch Tobias 
Published: December 2019

AbstractHeterogeneous glacier mass loss has occurred across High Mountain Asia on a multi-decadal timescale. Contrasting climatic settings influence glacier behaviour at the regional scale, but high intra-regional variability in mass loss rates points to factors capable of amplifying glacier recession in addition to climatic change along the Himalaya. Here we examine the influence of surface debris cover and glacial lakes on glacier mass loss across the Himalaya since the 1970s. We find no substantial difference in the mass loss of debris-covered and clean-ice glaciers over our study period, but substantially more negative (−0.13 to −0.29 m w.e.a−1) mass balances for lake-terminating glaciers, in comparison to land-terminating glaciers, with the largest differences occurring after 2000. Despite representing a minor portion of the total glacier population (~10%), the recession of lake-terminating glaciers accounted for up to 32% of mass loss in different sub-regions. The continued expansion of established glacial lakes, and the preconditioning of land-terminating glaciers for new lake development increases the likelihood of enhanced ice mass loss from the region in coming decades; a scenario not currently considered in regional ice mass loss projections.
Geography is essential for reproductive isolation between florally diversified morning glory species from Amazon canga savannahs
Authors: Babiychuk Elena , Teixeira Juliana Galaschi , Tyski Lourival , Guimaraes José Tasso Felix , Romeiro Luiza Araújo , da Silva Edilson Freitas , dos Santos Jorge Filipe , Vasconcelos Santelmo , da Silva Delmo Fonseca , Castilho Alexandre , Siqueira José Oswaldo , Fonseca Vera Lucia Imperatriz , Kushnir Sergei 
Published: December 2019

AbstractThe variety, relative importance and eco-evolutionary stability of reproductive barriers are critical to understanding the processes of speciation and species persistence. Here we evaluated the strength of the biotic prezygotic and postzygotic isolation barriers between closely related morning glory species from Amazon canga savannahs. The flower geometry and flower visitor assemblage analyses supported pollination by the bees in lavender-flowered Ipomoea marabaensis and recruitment of hummingbirds as pollinators in red-flowered Ipomoea cavalcantei. Nevertheless, native bee species and alien honeybees foraged on flowers of both species. Real-time interspecific hybridization underscored functionality of the overlap in flower visitor assemblages, questioning the strength of prezygotic isolation underpinned by diversification in flower colour and geometry. Interspecific hybrids were fertile and produced offspring in nature. No significant asymmetry in interspecific hybridization and hybrid incompatibilities among offspring were found, indicating weak postmating and postzygotic isolation. The results suggested that despite floral diversification, the insular-type geographic isolation remains a major barrier to gene flow. Findings set a framework for the future analysis of contemporary evolution of plant-pollinator networks at the population, community, and ecosystem levels in tropical ecosystems that are known to be distinct from the more familiar temperate climate models.
An electronic medical records-based approach to identify idiosyncratic drug-induced liver injury in children
Authors: Sandritter Tracy L. , Goldman Jennifer L. , Habiger Clayton J. , Daniel James F. , Lowry Jennifer , Fischer Ryan T. 
Published: December 2019

AbstractDrug-induced liver injury (DILI) is the leading cause of liver failure in the United States and the most common cause of drug recall. As opposed to the recognized direct toxicity of super-therapeutic acetaminophen or chemotherapeutic agents in children, limited data exists for pediatric populations on the incidence of idiosyncratic DILI (iDILI) that may develop independently of drug dose or duration of administration. To improve the detection of adverse drug reactions at our hospital, we utilized electronic medical records-based automated trigger tools to alert providers of potential iDILI. Clinical criteria concerning for iDILI were defined as serum ALT > 5x or serum bilirubin > 1.5x upper limit of normal in the setting of medication exposure. Over a two year period, 12 patients were identified as having possible or probable iDILI. Out of the identified patients, three were males, and the mean age was 10.8 years. Implicated agents included eight antibiotics, two anti-epileptics, one anti-psychotic, and one anti-inflammatory medication. Roussel-Uclaf Causality Assessment Methods identified one “possible” case, 11 “probable” cases, and one “highly probable” case of iDILI. Improved awareness and more vigilant programming can generate better data on iDILI and improve our understanding of the condition and its incidence in children.
Mechanics of very slow human walking
Authors: Wu Amy R. , Simpson Cole S. , van Asseldonk Edwin H. F. , van der Kooij Herman , Ijspeert Auke J. 
Published: December 2019

AbstractHuman walking speeds can be influenced by multiple factors, from energetic considerations to the time to reach a destination. Neurological deficits or lower-limb injuries can lead to slower walking speeds, and the recovery of able-bodied gait speed and behavior from impaired gait is considered an important rehabilitation goal. Because gait studies are typically performed at faster speeds, little normative data exists for very slow speeds (less than 0.6 ms$${}^{-1}$$−1). The purpose of our study was to investigate healthy gait mechanics at extremely slow walking speeds. We recorded kinematic and kinetic data from eight adult subjects walking at four slow speeds from 0.1 ms$${}^{-1}$$−1 to 0.6 ms$${}^{-1}$$−1 and at their self-selected speed. We found that known relations for spatiotemporal and work measures are still valid at very slow speeds. Trends derived from slow speeds largely provided reasonable estimates of gait measures at self-selected speeds. Our study helps enable valuable comparisons between able-bodied and impaired gait, including which pathological behaviors can be attributed to slow speeds and which to gait deficits. We also provide a slow walking dataset, which may serve as normative data for clinical evaluations and gait rehabilitative devices.
Early life nutrition influences susceptibility to chronic inflammatory colitis in later life
Authors: Ley Delphine , Desseyn Jean-Luc , Gouyer Valérie , Plet Ségolène , Tims Sebastian , Renes Ingrid , Mischke Mona , Gottrand Frédéric 
Published: December 2019

AbstractThe first thousand days of life are a critical time of development in humans during which the risk profile for diseases in later life can be modified. Nevertheless, long-term consequences of early environment on susceptibility to intestinal diseases have not yet been assessed. Using a mouse model of postnatal growth restriction (PNGR), we showed that early life nutrition influences intestinal maturation and gut health in later life. PNGR induced an alteration of the intestinal barrier in pups at weaning, resulting in increased intestinal permeability, and affected gut bacterial colonization. Specifically, pups with PNGR harbored a decreased bacterial diversity, higher Enterococcus spp., Staphylococcus spp., and Escherichia-Shigella spp., and lower Odoribacter spp. and several members of the Lachnospiraceae family. The lack of an efficient intestinal barrier in early life and the dysbiosis induced by PNGR were associated with a higher susceptibility to chronic colitis in adulthood.
Light therapy with boxes or glasses to counteract effects of acute sleep deprivation
Authors: Comtet Henri , Geoffroy Pierre A. , Kobayashi Frisk Mio , Hubbard Jeffrey , Robin-Choteau Ludivine , Calvel Laurent , Hugueny Laurence , Viola Antoine U. , Bourgin Patrice 
Published: December 2019

AbstractSleep deprivation, in the context of shift work, is an increasing major public health issue. We aimed to determine whether early light administration can counteract sleep deprivation effects, and to compare LED-glasses with a traditional light therapy box. This cross-over design study included 18 individuals exposed to light therapy for 30 minutes at 5 am after one night of complete sleep deprivation, to mimic the night shift condition. Individuals were randomly exposed to 10,000 Lux light box, 2,000 Lux LED blue-enriched glasses, and control (ambient dim-light at 8 lux). Alertness, cognition and mood were assessed throughout the night and following morning. Five women and 13 men (mean 24.78 year old) presented with a progressive and increasing alteration of alertness, cognition, and mood during each sleep deprivation. A rebound was observed at 8 am resulting from the circadian drive overriding cumulative sleep homeostatic effects. Morning light significantly improved sleepiness and sustained attention from 5 to 7 am. These effects were comparable between devices and significantly different from control. Both devices were overall well and similarly tolerated. Early morning light therapy in the condition of sleep loss may have broad practical applications to improve sleepiness, sustained attention and subsequent risk of accidents.