bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infant inhibited temperament in primates predicts adult behavior, is heritable, and is associated with anxiety-relevant genetic variation
Authors: Fox Andrew S. , Harris Ronald A. , Rosso Laura Del , Raveendran Muthuswamy , Kamboj Shawn , Kinnally Erin L. , Capitanio John P. , Rogers Jeffrey 
Published: May 2021

AbstractAn anxious or inhibited temperament (IT) early in life is a major risk factor for the later development of stress-related psychopathology. Starting in infancy, nonhuman primates, like humans, begin to reveal their temperament when exposed to novel situations. Here, in Study 1 we demonstrate this infant IT predicts adult behavior. Specifically, in over 600 monkeys, we found that individuals scored as inhibited during infancy were more likely to refuse treats offered by potentially-threatening human experimenters as adults. In Study 2, using a sample of over 4000 monkeys from a large multi-generational family pedigree, we demonstrate that infant IT is partially heritable. The data revealed infant IT to reflect a co-inherited substrate that manifests across multiple latent variables. Finally, in Study 3 we performed whole-genome sequencing in 106 monkeys to identify IT-associated single-nucleotide variations (SNVs). Results demonstrated a genome-wide significant SNV nearCTNNA2, suggesting a molecular target worthy of additional investigation. Moreover, we observed lowerpvalues in genes implicated in human association studies of neuroticism and depression. Together, these data demonstrate the utility of our model of infant inhibited temperament in the rhesus monkey to facilitate discovery of genes that are relevant to the long-term inherited risk to develop anxiety and depressive disorders.
An analog of psychedelics restores functional neural circuits disrupted by unpredictable stress
Authors: Lu Ju , Tjia Michelle , Mullen Brian , Cao Bing , Lukasiewicz Kacper , Shah-Morales Sajita , Weiser Sydney , Cameron Lindsay P. , Olson David E. , Chen Lu , Zuo Yi 
Published: May 2021

AbstractPsychological stress affects a wide spectrum of brain functions and poses risks for many mental disorders. However, effective therapeutics to alleviate or revert its deleterious effects are lacking. A recently synthesized psychedelic analog tabernanthalog (TBG) has demonstrated anti-addictive and antidepressant potential. Whether TBG can rescue stress-induced affective, sensory, and cognitive deficits, and how it may achieve such effects by modulating neural circuits, remain unknown. Here we show that in mice exposed to unpredictable mild stress (UMS), administration of a single dose of TBG decreases their anxiety level and rescues deficits in sensory processing as well as in cognitive flexibility. Post-stress TBG treatment promotes the regrowth of excitatory neuron dendritic spines lost during UMS, decreases the baseline neuronal activity, and enhances whisking-modulation of neuronal activity in the somatosensory cortex. Moreover, calcium imaging in head-fixed mice performing a whisker-dependent texture discrimination task shows that novel textures elicit responses from a greater proportion of neurons in the somatosensory cortex than do familiar textures. Such differential response is diminished by UMS and is restored by TBG. Together, our study reveals the effects of UMS on cortical neuronal circuit activity patterns and demonstrate that TBG combats the detrimental effects of stress by modulating basal and stimulus-dependent neural activity in cortical networks.
Chemosynthetic and photosynthetic bacteria contribute differentially to primary production across a steep desert aridity gradient
Authors: Bay Sean K , Waite David W , Dong Xiyang , Gillor Osnat , Chown Steven L , Hugenholtz Philip , Greening Chris 
Published: May 2021

Abstract
Desert soils harbour diverse communities of aerobic bacteria despite lacking substantial organic carbon inputs from vegetation. A major question is therefore how these communities maintain their biodiversity and biomass in these resource-limiting ecosystems. Here, we investigated desert topsoils and biological soil crusts collected along an aridity gradient traversing four climatic regions (sub-humid, semi-arid, arid, and hyper-arid). Metagenomic analysis indicated these communities vary in their capacity to use sunlight, organic compounds, and inorganic compounds as energy sources. Thermoleophilia, Actinobacteria, and Acidimicrobiia were the most abundant and prevalent bacterial classes across the aridity gradient in both topsoils and biocrusts. Contrary to the classical view that these taxa are obligate organoheterotrophs, genome-resolved analysis suggested they are metabolically flexible, with the capacity to also use atmospheric H2 to support aerobic respiration and often carbon fixation. In contrast, Cyanobacteria were patchily distributed and only abundant in certain biocrusts. Activity measurements profiled how aerobic H2 oxidation, chemosynthetic CO2 fixation, and photosynthesis varied with aridity. Cell-specific rates of atmospheric H2 consumption increased 143-fold along the aridity gradient, correlating with increased abundance of high-affinity hydrogenases. Photosynthetic and chemosynthetic primary production co-occurred throughout the gradient, with photosynthesis dominant in biocrusts and chemosynthesis dominant in arid and hyper-arid soils. Altogether, these findings suggest that the major bacterial lineages inhabiting hot deserts use different strategies for energy and carbon acquisition depending on resource availability. Moreover, they highlight the previously overlooked roles of Actinobacteriota as abundant primary producers and trace gases as critical energy sources supporting productivity and resilience of desert ecosystems.
OPRD1 SNPs associated with opioid addiction are cis-eQTLs for the phosphatase and actin regulator 4 gene, PHACTR4, a mediator of cytoskeletal dynamics
Authors: Levran Orna , Randesi Matthew , Adelson Miriam , Kreek Mary Jeanne 
Published: May 2021

AbstractSeveral OPRD1 intronic variants were associated with opioid addiction (OD) in a population-specific manner. This follow-up study aims to further characterize the OPRD1 haplotype pattern of the risk variants in different populations and apply in silico analysis to identify potential causal variants. A population-specific haplotype pattern was revealed based on six OPRD1 eQTL SNPs and five common haplotypes were identified in a sample of European ancestry (CEU). A European-specific haplotype (‘Hap 3’) that includes SNPs previously associated with OD and is tagged by SNP rs2236861 is more common in subjects with OD. It is quite common (10%) in CEU but is absent in the African sample (YRI) and extends upstream of OPRD1. SNP rs2236857 is most probably a non-causal variant in LD with the causal SNP/s in a population-specific manner. The study provides an explanation for the lack of association in African Americans, despite its high frequency in this population. OD samples homozygous for ‘Hap 3’ were reanalyzed using a denser coverage of the region and revealed at least 25 potentially regulatory SNPs in high LD. Notably, GTEx data indicate that some of the SNPs are eQTLs for the upstream phosphatase and actin regulator 4 (PHACTR4), in the cortex, and others are eQTLs for OPRD1 and the upstream lncRNA ENSG00000270605, in the cerebellum. The study highlights the limitation of single SNP analysis and the sensitivity of association studies of OPRD1 to a genetic background. It proposes a long-range functional connection between OPRD1 and PHACTR4. PHACTR4, a mediator of cytoskeletal dynamics, may contribute to drug addiction by modulating synaptic plasticity.
Essential genes from genome-wide screenings as a resource for neuropsychiatric disorders gene discovery
Authors: Zhang Wei , Quevedo Joao , Fries Gabriel R. 
Published: May 2021

AbstractGenome-wide screenings of “essential genes”, i.e., genes required for an organism or cell survival, have been traditionally conducted in vitro in cancer cell lines, limiting the translation of results to other tissues and non-cancerous cells. Recently, an in vivo screening was conducted in adult mouse striatum tissue, providing the first genome-wide dataset of essential genes in neuronal cells. Here, we aim to investigate the role of essential genes in brain development and disease risk with a comprehensive set of bioinformatics tools, including integration with transcriptomic data from developing human brain, publicly available data from genome-wide association studies, de novo mutation datasets for different neuropsychiatric disorders, and case–control transcriptomic data from postmortem brain tissues. For the first time, we found that the expression of neuronal essential genes (NEGs) increases before birth during the early development of human brain and maintains a relatively high expression after birth. On the contrary, common essential genes from cancer cell line screenings (ACEGs) tend to be expressed at high levels during development but quickly drop after birth. Both gene sets were enriched in neurodevelopmental disorders, but only NEGs were robustly associated with neuropsychiatric disorders risk genes. Finally, NEGs were more likely to show differential expression in the brains of neuropsychiatric disorders patients than ACEGs. Overall, genome-wide central nervous system screening of essential genes can provide new insights into neuropsychiatric diseases.
The KDM4B–CCAR1–MED1 axis is a critical regulator of osteoclast differentiation and bone homeostasis
Authors: Yi Sun-Ju , Jang You-Jee , Kim Hye-Jung , Lee Kyubin , Lee Hyerim , Kim Yeojin , Kim Junil , Hwang Seon Young , Song Jin Sook , Okada Hitoshi , Park Jae-Il , Kang Kyuho , Kim Kyunghwan 
Published: May 2021

AbstractBone undergoes a constant and continuous remodeling process that is tightly regulated by the coordinated and sequential actions of bone-resorbing osteoclasts and bone-forming osteoblasts. Recent studies have shown that histone demethylases are implicated in osteoblastogenesis; however, little is known about the role of histone demethylases in osteoclast formation. Here, we identified KDM4B as an epigenetic regulator of osteoclast differentiation. Knockdown of KDM4B significantly blocked the formation of tartrate-resistant acid phosphatase-positive multinucleated cells. Mice with myeloid-specific conditional knockout of KDM4B showed an osteopetrotic phenotype due to osteoclast deficiency. Biochemical analysis revealed that KDM4B physically and functionally associates with CCAR1 and MED1 in a complex. Using genome-wide chromatin immunoprecipitation (ChIP)-sequencing, we revealed that the KDM4B–CCAR1–MED1 complex is localized to the promoters of several osteoclast-related genes upon receptor activator of NF-κB ligand stimulation. We demonstrated that the KDM4B–CCAR1–MED1 signaling axis induces changes in chromatin structure (euchromatinization) near the promoters of osteoclast-related genes through H3K9 demethylation, leading to NF-κB p65 recruitment via a direct interaction between KDM4B and p65. Finally, small molecule inhibition of KDM4B activity impeded bone loss in an ovariectomized mouse model. Taken together, our findings establish KDM4B as a critical regulator of osteoclastogenesis, providing a potential therapeutic target for osteoporosis.
Ligand-dependent kinase activity of MERTK drives efferocytosis in human iPSC-derived macrophages
Authors: Wanke Florian , Gutbier Simon , Rümmelin Anna , Steinberg Malte , Hughes Lindsey D. , Koenen Mascha , Komuczki Juliana , Regan-Komito Daniel , Wagage Sagie , Hesselmann Julia , Thoma Ralf , Brugger Doris , Christopeit Tony , Wang Hayian , Point Floriane , Hallet Remy , Ghosh Sourav , Rothlin Carla V. , Patsch Christoph , Geering Barbara 
Published: May 2021

AbstractRemoval of apoptotic cells by phagocytes (also called efferocytosis) is a crucial process for tissue homeostasis. Professional phagocytes express a plethora of surface receptors enabling them to sense and engulf apoptotic cells, thus avoiding persistence of dead cells and cellular debris and their consequent effects. Dysregulation of efferocytosis is thought to lead to secondary necrosis and associated inflammation and immune activation. Efferocytosis in primarily murine macrophages and dendritic cells has been shown to require TAM RTKs, with MERTK and AXL being critical for clearance of apoptotic cells. The functional role of human orthologs, especially the exact contribution of each individual receptor is less well studied. Here we show that human macrophages differentiated in vitro from iPSC-derived precursor cells express both AXL and MERTK and engulf apoptotic cells. TAM RTK agonism by the natural ligand growth-arrest specific 6 (GAS6) significantly enhanced such efferocytosis. Using a newly-developed mouse model of kinase-dead MERTK, we demonstrate that MERTK kinase activity is essential for efferocytosis in peritoneal macrophages in vivo. Moreover, human iPSC-derived macrophages treated in vitro with blocking antibodies or small molecule inhibitors recapitulated this observation. Hence, our results highlight a conserved MERTK function between mice and humans, and the critical role of its kinase activity in homeostatic efferocytosis.
SARS-CoV-2 nucleocapsid protein impairs stress granule formation to promote viral replication
Authors: Zheng Zhou-Qin , Wang Su-Yun , Xu Zhi-Sheng , Fu Yu-Zhi , Wang Yan-Yi 
Published: May 2021

AbstractThe newly emerging coronavirus SARS-CoV-2 causes severe lung disease and substantial mortality. How the virus evades host defense for efficient replication is not fully understood. In this report, we found that the SARS-CoV-2 nucleocapsid protein (NP) impaired stress granule (SG) formation induced by viral RNA. SARS-CoV-2 NP associated with the protein kinase PKR after dsRNA stimulation. SARS-CoV-2 NP did not affect dsRNA-induced PKR oligomerization, but impaired dsRNA-induced PKR phosphorylation (a hallmark of its activation) as well as SG formation. SARS-CoV-2 NP also targeted the SG-nucleating protein G3BP1 and impaired G3BP1-mediated SG formation. Deficiency of PKR or G3BP1 impaired dsRNA-triggered SG formation and increased SARS-CoV-2 replication. The NP of SARS-CoV also targeted both PKR and G3BP1 to impair dsRNA-induced SG formation, whereas the NP of MERS-CoV targeted PKR, but not G3BP1 for the impairment. Our findings suggest that SARS-CoV-2 NP promotes viral replication by impairing formation of antiviral SGs, and reveal a conserved mechanism on evasion of host antiviral responses by highly pathogenic human betacoronaviruses.
Disproportionate exposure to urban heat island intensity across major US cities
Authors: Hsu Angel , Sheriff Glenn , Chakraborty Tirthankar , Manya Diego 
Published: May 2021

AbstractUrban heat stress poses a major risk to public health. Case studies of individual cities suggest that heat exposure, like other environmental stressors, may be unequally distributed across income groups. There is little evidence, however, as to whether such disparities are pervasive. We combine surface urban heat island (SUHI) data, a proxy for isolating the urban contribution to additional heat exposure in built environments, with census tract-level demographic data to answer these questions for summer days, when heat exposure is likely to be at a maximum. We find that the average person of color lives in a census tract with higher SUHI intensity than non-Hispanic whites in all but 6 of the 175 largest urbanized areas in the continental United States. A similar pattern emerges for people living in households below the poverty line relative to those at more than two times the poverty line.
Ultrastrong magnon–magnon coupling dominated by antiresonant interactions
Authors: Makihara Takuma , Hayashida Kenji , Noe II G. Timothy , Li Xinwei , Marquez Peraca Nicolas , Ma Xiaoxuan , Jin Zuanming , Ren Wei , Ma Guohong , Katayama Ikufumi , Takeda Jun , Nojiri Hiroyuki , Turchinovich Dmitry , Cao Shixun , Bamba Motoaki , Kono Junichiro 
Published: May 2021

AbstractExotic quantum vacuum phenomena are predicted in cavity quantum electrodynamics systems with ultrastrong light-matter interactions. Their ground states are predicted to be vacuum squeezed states with suppressed quantum fluctuations owing to antiresonant terms in the Hamiltonian. However, such predictions have not been realized because antiresonant interactions are typically negligible compared to resonant interactions in light-matter systems. Here we report an unusual, ultrastrongly coupled matter-matter system of magnons that is analytically described by a unique Hamiltonian in which the relative importance of resonant and antiresonant interactions can be easily tuned and the latter can be made vastly dominant. We found a regime where vacuum Bloch-Siegert shifts, the hallmark of antiresonant interactions, greatly exceed analogous frequency shifts from resonant interactions. Further, we theoretically explored the system’s ground state and calculated up to 5.9 dB of quantum fluctuation suppression. These observations demonstrate that magnonic systems provide an ideal platform for exploring exotic quantum vacuum phenomena predicted in ultrastrongly coupled light-matter systems.
Evidence from oyster suggests an ancient role for Pdx in regulating insulin gene expression in animals
Authors: Xu Fei , Marlétaz Ferdinand , Gavriouchkina Daria , Liu Xiao , Sauka-Spengler Tatjana , Zhang Guofan , Holland Peter W. H. 
Published: May 2021

AbstractHox and ParaHox genes encode transcription factors with similar expression patterns in divergent animals. ThePdx(Xlox) homeobox gene, for example, is expressed in a sharp spatial domain in the endodermal cell layer of the gut in chordates, echinoderms, annelids and molluscs. The significance of comparable gene expression patterns is unclear because it is not known if downstream transcriptional targets are also conserved. Here, we report evidence indicating that a classic transcriptional target of Pdx1 in vertebrates, theinsulingene, is a likely direct target of Pdx in Pacific oyster adults. We show that oneinsulin-related gene,cgILP, is co-expressed withcgPdxin oyster digestive tissue. Transcriptomic comparison suggests that this tissue plays a similar role to the vertebrate pancreas. Using ATAC-seq and ChIP, we identify an upstream regulatory element of the cgILPgene which shows binding interaction with cgPdx protein in oyster hepatopancreas and demonstrate, using a cell culture assay, that the oyster Pdx can act as a transcriptional activator through this site, possibly in synergy with NeuroD. These data argue that a classic homeodomain-target gene interaction dates back to the origin of Bilateria.
The neutral rate of whole-genome duplication varies among yeast species and their hybrids
Authors: Marsit S. , Hénault M. , Charron G. , Fijarczyk A. , Landry C. R. 
Published: May 2021

AbstractHybridization and polyploidization are powerful mechanisms of speciation. Hybrid speciation often coincides with whole-genome duplication (WGD) in eukaryotes. This suggests that WGD may allow hybrids to thrive by increasing fitness, restoring fertility and/or increasing access to adaptive mutations. Alternatively, it has been suggested that hybridization itself may trigger WGD. Testing these models requires quantifying the rate of WGD in hybrids without the confounding effect of natural selection. Here we show, by measuring the spontaneous rate of WGD of more than 1300 yeast crosses evolved under relaxed selection, that some genotypes or combinations of genotypes are more prone to WGD, including some hybrids between closely related species. We also find that higher WGD rate correlates with higher genomic instability and that WGD increases fertility and genetic variability. These results provide evidence that hybridization itself can promote WGD, which in turn facilitates the evolution of hybrids.
Arbuscular mycorrhizal trees influence the latitudinal beta-diversity gradient of tree communities in forests worldwide
Authors: Zhong Yonglin , Chu Chengjin , Myers Jonathan A. , Gilbert Gregory S. , Lutz James A. , Stillhard Jonas , Zhu Kai , Thompson Jill , Baltzer Jennifer L. , He Fangliang , LaManna Joseph A. , Davies Stuart J. , Aderson-Teixeira Kristina J. , Burslem David F.R.P. , Alonso Alfonso , Chao Kuo-Jung , Wang Xugao , Gao Lianming , Orwig David A. , Yin Xue , Sui Xinghua , Su Zhiyao , Abiem Iveren , Bissiengou Pulchérie , Bourg Norm , Butt Nathalie , Cao Min , Chang-Yang Chia-Hao , Chao Wei-Chun , Chapman Hazel , Chen Yu-Yun , Coomes David A. , Cordell Susan , de Oliveira Alexandre A. , Du Hu , Fang Suqin , Giardina Christian P. , Hao Zhanqing , Hector Andrew , Hubbell Stephen P. , Janík David , Jansen Patrick A. , Jiang Mingxi , Jin Guangze , Kenfack David , Král Kamil , Larson Andrew J. , Li Buhang , Li Xiankun , Li Yide , Lian Juyu , Lin Luxiang , Liu Feng , Liu Yankun , Liu Yu , Luan Fuchen , Luo Yahuang , Ma Keping , Malhi Yadvinder , McMahon Sean M. , McShea William , Memiaghe Hervé , Mi Xiangcheng , Morecroft Mike , Novotny Vojtech , O’Brien Michael J. , Ouden Jan den , Parker Geoffrey G. , Qiao Xiujuan , Ren Haibao , Reynolds Glen , Samonil Pavel , Sang Weiguo , Shen Guochun , Shen Zhiqiang , Song Guo-Zhang Michael , Sun I-Fang , Tang Hui , Tian Songyan , Uowolo Amanda L. , Uriarte María , Wang Bin , Wang Xihua , Wang Youshi , Weiblen George D. , Wu Zhihong , Xi Nianxun , Xiang Wusheng , Xu Han , Xu Kun , Ye Wanhui , Yu Mingjian , Zeng Fuping , Zhang Minhua , Zhang Yingming , Zhu Li , Zimmerman Jess K. 
Published: May 2021

AbstractArbuscular mycorrhizal (AM) and ectomycorrhizal (EcM) associations are critical for host-tree performance. However, how mycorrhizal associations correlate with the latitudinal tree beta-diversity remains untested. Using a global dataset of 45 forest plots representing 2,804,270 trees across 3840 species, we test how AM and EcM trees contribute to total beta-diversity and its components (turnover and nestedness) of all trees. We find AM rather than EcM trees predominantly contribute to decreasing total beta-diversity and turnover and increasing nestedness with increasing latitude, probably because wide distributions of EcM trees do not generate strong compositional differences among localities. Environmental variables, especially temperature and precipitation, are strongly correlated with beta-diversity patterns for both AM trees and all trees rather than EcM trees. Results support our hypotheses that latitudinal beta-diversity patterns and environmental effects on these patterns are highly dependent on mycorrhizal types. Our findings highlight the importance of AM-dominated forests for conserving global forest biodiversity.