bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gray matter abnormalities in Tourette Syndrome: a meta-analysis of voxel-based morphometry studies
Authors: Wan Xinyue , Zhang Simin , Wang Weina , Su Xiaorui , Li Jun , Yang Xibiao , Tan Qiaoyue , Yue Qiang , Gong Qiyong 
Published: May 2021

AbstractTourette syndrome (TS) is a neurobehavioral disorder for which the neurological mechanism has not been elucidated. Voxel-based morphometry (VBM) studies have revealed abnormalities in gray matter volume (GMV) in patients with TS; however, consistent results have not been obtained. The current study attempted to provide a voxel wise meta-analysis of gray matter changes using seed-based d mapping (SDM). We identified ten relevant studies that investigated gray matter alterations in TS patients and performed a meta-analysis using the SDM method to quantitatively estimate regional gray matter abnormalities. Next, we examined the relationships between GMV abnormalities and demographic and clinical characteristics. Our results demonstrated that TS patients had smaller GMV in the bilateral inferior frontal gyri and greater GMV in the cerebellum, right striatum (putamen), and bilateral thalami (pulvinar nucleus) than healthy controls. A meta-regression analysis did not identify correlations between GMV changes and demographic or clinical variables. This meta-analysis confirmed significant and consistent GMV changes in several brain regions of TS patients, primarily in the cortico-striato-thalamo-cortical network.
Heart rate variability in late pregnancy: exploration of distinctive patterns in relation to maternal mental health
Authors: Kimmel Mary C. , Fransson Emma , Cunningham Janet L. , Brann Emma , Grewen Karen , Boschiero Dario , Chrousos George P. , Meltzer-Brody Samantha , Skalkidou Alkistis 
Published: May 2021

AbstractExploration of photoplethysmography (PPG), a technique that can be translated to the clinic, has the potential to assess the autonomic nervous system (ANS) through heart rate variable (HRV) in pregnant individuals. This novel study explores the complexity of mental health of individuals in a clinical sample responding to a task in late pregnancy; finding those with several types of past or current anxiety disorders, greater trait anxiety, or greater exposure to childhood traumatic events had significantly different HRV findings from the others in the cohort. Lower high frequency (HF), a measure of parasympathetic activity, was found for women who met the criteria for the history of obsessive–compulsive disorder (OCD) (p = 0.004) compared with women who did not meet the criteria for OCD, and for women exposed to greater than five childhood traumatic events (p = 0.006) compared with those exposed to four or less childhood traumatic events. Conversely higher low frequency (LF), a measure thought to be impacted by sympathetic system effects, and the LF/HF ratio was found for those meeting criteria for a panic disorder (p = 0.006), meeting criteria for social phobia (p = 0.002), had elevated trait anxiety (p = 0.006), or exposure to greater than five childhood traumatic events (p = 0.004). This study indicates further research is needed to understand the role of PPG and in assessing ANS functioning in late pregnancy. Study of the impact of lower parasympathetic functioning and higher sympathetic functioning separately and in conjunction at baseline and in relation to tasks during late pregnancy has the potential to identify individuals that require more support and direct intervention.
Modeling regulatory network topology improves genome-wide analyses of complex human traits
Authors: Zhu Xiang , Duren Zhana , Wong Wing Hung 
Published: May 2021

AbstractGenome-wide association studies (GWAS) have cataloged many significant associations between genetic variants and complex traits. However, most of these findings have unclear biological significance, because they often have small effects and occur in non-coding regions. Integration of GWAS with gene regulatory networks addresses both issues by aggregating weak genetic signals within regulatory programs. Here we develop a Bayesian framework that integrates GWAS summary statistics with regulatory networks to infer genetic enrichments and associations simultaneously. Our method improves upon existing approaches by explicitly modeling network topology to assess enrichments, and by automatically leveraging enrichments to identify associations. Applying this method to 18 human traits and 38 regulatory networks shows that genetic signals of complex traits are often enriched in interconnections specific to trait-relevant cell types or tissues. Prioritizing variants within enriched networks identifies known and previously undescribed trait-associated genes revealing biological and therapeutic insights.
Epigenome-wide association meta-analysis of DNA methylation with coffee and tea consumption
Authors: Karabegović Irma , Portilla-Fernandez Eliana , Li Yang , Ma Jiantao , Maas Silvana C. E. , Sun Daokun , Hu Emily A. , Kühnel Brigitte , Zhang Yan , Ambatipudi Srikant , Fiorito Giovanni , Huang Jian , Castillo-Fernandez Juan E. , Wiggins Kerri L. , de Klein Niek , Grioni Sara , Swenson Brenton R. , Polidoro Silvia , Treur Jorien L. , Cuenin Cyrille , Tsai Pei-Chien , Costeira Ricardo , Chajes Veronique , Braun Kim , Verweij Niek , Kretschmer Anja , Franke Lude , van Meurs Joyce B. J. , Uitterlinden André G. , de Knegt Robert J. , Ikram M. Arfan , Dehghan Abbas , Peters Annette , Schöttker Ben , Gharib Sina A. , Sotoodehnia Nona , Bell Jordana T. , Elliott Paul , Vineis Paolo , Relton Caroline , Herceg Zdenko , Brenner Hermann , Waldenberger Melanie , Rebholz Casey M. , Voortman Trudy , Pan Qiuwei , Fornage Myriam , Levy Daniel , Kayser Manfred , Ghanbari Mohsen 
Published: May 2021

AbstractCoffee and tea are extensively consumed beverages worldwide which have received considerable attention regarding health. Intake of these beverages is consistently linked to, among others, reduced risk of diabetes and liver diseases; however, the mechanisms of action remain elusive. Epigenetics is suggested as a mechanism mediating the effects of dietary and lifestyle factors on disease onset. Here we report the results from epigenome-wide association studies (EWAS) on coffee and tea consumption in 15,789 participants of European and African-American ancestries from 15 cohorts. EWAS meta-analysis of coffee consumption reveals 11 CpGs surpassing the epigenome-wide significance threshold (P-value <1.1×10−7), which annotated to theAHRR,F2RL3,FLJ43663,HDAC4,GFI1andPHGDHgenes. Among them, cg14476101 is significantly associated with expression of thePHGDHand risk of fatty liver disease. Knockdown ofPHGDHexpression in liver cells shows a correlation with expression levels of genes associated with circulating lipids, suggesting a role ofPHGDHin hepatic-lipid metabolism. EWAS meta-analysis on tea consumption reveals no significant association, only two CpGs annotated toCACNA1AandPRDM16genes show suggestive association (P-value <5.0×10−6). These findings indicate that coffee-associated changes in DNA methylation levels may explain the mechanism of action of coffee consumption in conferring risk of diseases.
Degradation mechanism of hybrid tin-based perovskite solar cells and the critical role of tin (IV) iodide
Authors: Lanzetta Luis , Webb Thomas , Zibouche Nourdine , Liang Xinxing , Ding Dong , Min Ganghong , Westbrook Robert J. E. , Gaggio Benedetta , Macdonald Thomas J. , Islam M. Saiful , Haque Saif A. 
Published: May 2021

AbstractTin perovskites have emerged as promising alternatives to toxic lead perovskites in next-generation photovoltaics, but their poor environmental stability remains an obstacle towards more competitive performances. Therefore, a full understanding of their decomposition processes is needed to address these stability issues. Herein, we elucidate the degradation mechanism of 2D/3D tin perovskite films based on (PEA)0.2(FA)0.8SnI3(where PEA is phenylethylammonium and FA is formamidinium). We show that SnI4, a product of the oxygen-induced degradation of tin perovskite, quickly evolves into iodine via the combined action of moisture and oxygen. We identify iodine as a highly aggressive species that can further oxidise the perovskite to more SnI4, establishing a cyclic degradation mechanism. Perovskite stability is then observed to strongly depend on the hole transport layer chosen as the substrate, which is exploited to tackle film degradation. These key insights will enable the future design and optimisation of stable tin-based perovskite optoelectronics.
PHC1 maintains pluripotency by organizing genome-wide chromatin interactions of the Nanog locus
Authors: Chen Li , Tong Qiaoqiao , Chen Xiaowen , Jiang Penglei , Yu Hua , Zhao Qianbing , Sun Lingang , Liu Chao , Gu Bin , Zheng Yuping , Fei Lijiang , Jiang Xiao , Li Wenjuan , Volpe Giacomo , Abdul Mazid MD. , Guo Guoji , Zhang Jin , Qian Pengxu , Sun Qiming , Neculai Dante , Esteban Miguel A. , Li Chen , Wen Feiqiu , Ji Junfeng 
Published: May 2021

AbstractPolycomb group (PcG) proteins maintain cell identity by repressing gene expression during development. Surprisingly, emerging studies have recently reported that a number of PcG proteins directly activate gene expression during cell fate determination process. However, the mechanisms by which they direct gene activation in pluripotency remain poorly understood. Here, we show that Phc1, a subunit of canonical polycomb repressive complex 1 (cPRC1), can exert its function in pluripotency maintenance via a PRC1-independent activation of Nanog. Ablation of Phc1 reduces the expression of Nanog and overexpression of Nanog partially rescues impaired pluripotency caused by Phc1 depletion. We find that Phc1 interacts with Nanog and activates Nanog transcription by stabilizing the genome-wide chromatin interactions of the Nanog locus. This adds to the already known canonical function of PRC1 in pluripotency maintenance via a PRC1-dependent repression of differentiation genes. Overall, our study reveals a function of Phc1 to activate Nanog transcription through regulating chromatin architecture and proposes a paradigm for PcG proteins to maintain pluripotency.
Edge channels of broken-symmetry quantum Hall states in graphene visualized by atomic force microscopy
Authors: Kim Sungmin , Schwenk Johannes , Walkup Daniel , Zeng Yihang , Ghahari Fereshte , Le Son T. , Slot Marlou R. , Berwanger Julian , Blankenship Steven R. , Watanabe Kenji , Taniguchi Takashi , Giessibl Franz J. , Zhitenev Nikolai B. , Dean Cory R. , Stroscio Joseph A. 
Published: May 2021

AbstractThe quantum Hall (QH) effect, a topologically non-trivial quantum phase, expanded the concept of topological order in physics bringing into focus the intimate relation between the “bulk” topology and the edge states. The QH effect in graphene is distinguished by its four-fold degenerate zero energy Landau level (zLL), where the symmetry is broken by electron interactions on top of lattice-scale potentials. However, the broken-symmetry edge states have eluded spatial measurements. In this article, we spatially map the quantum Hall broken-symmetry edge states comprising the graphene zLL at integer filling factors of $${{\nu }}={{0}},\pm {{1}}$$
ν
=
0
,
±
1
across the quantum Hall edge boundary using high-resolution atomic force microscopy (AFM) and show a gapped ground state proceeding from the bulk through to the QH edge boundary. Measurements of the chemical potential resolve the energies of the four-fold degenerate zLL as a function of magnetic field and show the interplay of the moiré superlattice potential of the graphene/boron nitride system and spin/valley symmetry-breaking effects in large magnetic fields.
Tuning network topology and vibrational mode localization to achieve ultralow thermal conductivity in amorphous chalcogenides
Authors: Aryana Kiumars , Stewart Derek A. , Gaskins John T. , Nag Joyeeta , Read John C. , Olson David H. , Grobis Michael K. , Hopkins Patrick E. 
Published: May 2021

AbstractAmorphous chalcogenide alloys are key materials for data storage and energy scavenging applications due to their large non-linearities in optical and electrical properties as well as low vibrational thermal conductivities. Here, we report on a mechanism to suppress the thermal transport in a representative amorphous chalcogenide system, silicon telluride (SiTe), by nearly an order of magnitude via systematically tailoring the cross-linking network among the atoms. As such, we experimentally demonstrate that in fully dense amorphous SiTe the thermal conductivity can be reduced to as low as 0.10 ± 0.01 W m−1 K−1 for high tellurium content with a density nearly twice that of amorphous silicon. Using ab-initio simulations integrated with lattice dynamics, we attribute the ultralow thermal conductivity of SiTe to the suppressed contribution of extended modes of vibration, namely propagons and diffusons. This leads to a large shift in the mobility edge - a factor of five - towards lower frequency and localization of nearly 42% of the modes. This localization is the result of reductions in coordination number and a transition from over-constrained to under-constrained atomic network.
bric à brac controls sex pheromone choice by male European corn borer moths
Authors: Unbehend Melanie , Kozak Genevieve M. , Koutroumpa Fotini , Coates Brad S. , Dekker Teun , Groot Astrid T. , Heckel David G. , Dopman Erik B. 
Published: May 2021

AbstractThe sex pheromone system of ~160,000 moth species acts as a powerful form of assortative mating whereby females attract conspecific males with a species-specific blend of volatile compounds. Understanding how female pheromone production and male preference coevolve to produce this diversity requires knowledge of the genes underlying change in both traits. In the European corn borer moth, pheromone blend variation is controlled by two alleles of an autosomal fatty-acyl reductase gene expressed in the female pheromone gland (pgFAR). Here we show that asymmetric male preference is controlled by cis-acting variation in a sex-linked transcription factor expressed in the developing male antenna, bric à brac (bab). A genome-wide association study of preference using pheromone-trapped males implicates variation in the 293 kb bab intron 1, rather than the coding sequence. Linkage disequilibrium between bab intron 1 and pgFAR further validates bab as the preference locus, and demonstrates that the two genes interact to contribute to assortative mating. Thus, lack of physical linkage is not a constraint for coevolutionary divergence of female pheromone production and male behavioral response genes, in contrast to what is often predicted by evolutionary theory.
In situ correlation between metastable phase-transformation mechanism and kinetics in a metallic glass
Authors: Orava Jiri , Balachandran Shanoob , Han Xiaoliang , Shuleshova Olga , Nurouzi Ebrahim , Soldatov Ivan , Oswald Steffen , Gutowski Olof , Ivashko Oleh , Dippel Ann-Christin , Zimmermann Martin v. , Ivanov Yurii P. , Greer A. Lindsay , Raabe Dierk , Herbig Michael , Kaban Ivan 
Published: May 2021

AbstractA combination of complementary high-energy X-ray diffraction, containerless solidification during electromagnetic levitation and transmission electron microscopy is used to map in situ the phase evolution in a prototype Cu-Zr-Al glass during flash-annealing imposed at a rate ranging from 102 to 103 K s−1 and during cooling from the liquid state. Such a combination of experimental techniques provides hitherto inaccessible insight into the phase-transformation mechanism and its kinetics with high temporal resolution over the entire temperature range of the existence of the supercooled liquid. On flash-annealing, most of the formed phases represent transient (metastable) states – they crystallographically conform to their equilibrium phases but the compositions, revealed by atom probe tomography, are different. It is only the B2 CuZr phase which is represented by its equilibrium composition, and its growth is facilitated by a kinetic mechanism of Al partitioning; Al-rich precipitates of less than 10 nm in a diameter are revealed. In this work, the kinetic and chemical conditions of the high propensity of the glass for the B2 phase formation are formulated, and the multi-technique approach can be applied to map phase transformations in other metallic-glass-forming systems.
Using mobile phone data to reveal risk flow networks underlying the HIV epidemic in Namibia
Authors: Valdano Eugenio , Okano Justin T. , Colizza Vittoria , Mitonga Honore K. , Blower Sally 
Published: May 2021

AbstractTwenty-six million people are living with HIV in sub-Saharan Africa; epidemics are widely dispersed, due to high levels of mobility. However, global elimination strategies do not consider mobility. We use Call Detail Records from 9 billion calls/texts to model mobility in Namibia; we quantify the epidemic-level impact by using a mathematical framework based on spatial networks. We find complex networks of risk flows dispersed risk countrywide: increasing the risk of acquiring HIV in some areas, decreasing it in others. Overall, 40% of risk was mobility-driven. Networks contained multiple risk hubs. All constituencies (administrative units) imported and exported risk, to varying degrees. A few exported very high levels of risk: their residents infected many residents of other constituencies. Notably, prevalence in the constituency exporting the most risk was below average. Large-scale networks of mobility-driven risk flows underlie generalized HIV epidemics in sub-Saharan Africa. In order to eliminate HIV, it is likely to become increasingly important to implement innovative control strategies that focus on disrupting risk flows.
Excitonic structure and charge separation in the heliobacterial reaction center probed by multispectral multidimensional spectroscopy
Authors: Song Yin , Sechrist Riley , Nguyen Hoang H. , Johnson William , Abramavicius Darius , Redding Kevin E. , Ogilvie Jennifer P. 
Published: May 2021

AbstractPhotochemical reaction centers are the engines that drive photosynthesis. The reaction center from heliobacteria (HbRC) has been proposed to most closely resemble the common ancestor of photosynthetic reaction centers, motivating a detailed understanding of its structure-function relationship. The recent elucidation of the HbRC crystal structure motivates advanced spectroscopic studies of its excitonic structure and charge separation mechanism. We perform multispectral two-dimensional electronic spectroscopy of the HbRC and corresponding numerical simulations, resolving the electronic structure and testing and refining recent excitonic models. Through extensive examination of the kinetic data by lifetime density analysis and global target analysis, we reveal that charge separation proceeds via a single pathway in which the distinct A0 chlorophyll a pigment is the primary electron acceptor. In addition, we find strong delocalization of the charge separation intermediate. Our findings have general implications for the understanding of photosynthetic charge separation mechanisms, and how they might be tuned to achieve different functional goals.
Characterization of an engineered live bacterial therapeutic for the treatment of phenylketonuria in a human gut-on-a-chip
Authors: Nelson M. Tyler , Charbonneau Mark R. , Coia Heidi G. , Castillo Mary J. , Holt Corey , Greenwood Eric S. , Robinson Peter J. , Merrill Elaine A. , Lubkowicz David , Mauzy Camilla A. 
Published: May 2021

AbstractEngineered bacteria (synthetic biotics) represent a new class of therapeutics that leverage the tools of synthetic biology. Translational testing strategies are required to predict synthetic biotic function in the human body. Gut-on-a-chip microfluidics technology presents an opportunity to characterize strain function within a simulated human gastrointestinal tract. Here, we apply a human gut-chip model and a synthetic biotic designed for the treatment of phenylketonuria to demonstrate dose-dependent production of a strain-specific biomarker, to describe human tissue responses to the engineered strain, and to show reduced blood phenylalanine accumulation after administration of the engineered strain. Lastly, we show how in vitro gut-chip models can be used to construct mechanistic models of strain activity and recapitulate the behavior of the engineered strain in a non-human primate model. These data demonstrate that gut-chip models, together with mechanistic models, provide a framework to predict the function of candidate strains in vivo.
Oxygen suppression of macroscopic multicellularity
Authors: Bozdag G. Ozan , Libby Eric , Pineau Rozenn , Reinhard Christopher T. , Ratcliff William C. 
Published: May 2021

AbstractAtmospheric oxygen is thought to have played a vital role in the evolution of large, complex multicellular organisms. Challenging the prevailing theory, we show that the transition from an anaerobic to an aerobic world can strongly suppress the evolution of macroscopic multicellularity. Here we select for increased size in multicellular ‘snowflake’ yeast across a range of metabolically-available O2 levels. While yeast under anaerobic and high-O2 conditions evolved to be considerably larger, intermediate O2 constrained the evolution of large size. Through sequencing and synthetic strain construction, we confirm that this is due to O2-mediated divergent selection acting on organism size. We show via mathematical modeling that our results stem from nearly universal evolutionary and biophysical trade-offs, and thus should apply broadly. These results highlight the fact that oxygen is a double-edged sword: while it provides significant metabolic advantages, selection for efficient use of this resource may paradoxically suppress the evolution of macroscopic multicellular organisms.
Crystal structure of SARS-CoV-2 Orf9b in complex with human TOM70 suggests unusual virus-host interactions
Authors: Gao Xiaopan , Zhu Kaixiang , Qin Bo , Olieric Vincent , Wang Meitian , Cui Sheng 
Published: May 2021

AbstractAlthough the accessory proteins are considered non-essential for coronavirus replication, accumulating evidences demonstrate they are critical to virus-host interaction and pathogenesis. Orf9b is a unique accessory protein of SARS-CoV-2 and SARS-CoV. It is implicated in immune evasion by targeting mitochondria, where it associates with the versatile adapter TOM70. Here, we determined the crystal structure of SARS-CoV-2 orf9b in complex with the cytosolic segment of human TOM70 to 2.2 Å. A central portion of orf9b occupies the deep pocket in the TOM70 C-terminal domain (CTD) and adopts a helical conformation strikingly different from the β-sheet-rich structure of the orf9b homodimer. Interactions between orf9b and TOM70 CTD are primarily hydrophobic and distinct from the electrostatic interaction between the heat shock protein 90 (Hsp90) EEVD motif and the TOM70 N-terminal domain (NTD). Using isothermal titration calorimetry (ITC), we demonstrated that the orf9b dimer does not bind TOM70, but a synthetic peptide harboring a segment of orf9b (denoted C-peptide) binds TOM70 with nanomolar KD. While the interaction between C-peptide and TOM70 CTD is an endothermic process, the interaction between Hsp90 EEVD and TOM70 NTD is exothermic, which underscores the distinct binding mechanisms at NTD and CTD pockets. Strikingly, the binding affinity of Hsp90 EEVD motif to TOM70 NTD is reduced by ~29-fold when orf9b occupies the pocket of TOM70 CTD, supporting the hypothesis that orf9b allosterically inhibits the Hsp90/TOM70 interaction. Our findings shed light on the mechanism underlying SARS-CoV-2 orf9b mediated suppression of interferon responses.