bluuebunny/crossref_metadata_2025 huggingface dataset:
Scale‐Dependent Contributors to River Profile Geometry
Authors: Wapenhans Isabel , Fernandes Victoria M. , O’Malley Conor , White Nicky , Roberts Gareth G.
Published: May 2021

A range of complex hydraulic and geomorphic processes shape terrestrial landscapes. It remains unclear how these processes act to generate observed drainage networks across scales of interest. To address this issue, we transform observed and synthetic longitudinal river profiles into the spectral domain with a view to interrogating the different scales at which fluvial landscapes are generated. North American river profiles are characterized by red noise (i.e., spectral power, ϕ ∝ k−2, where k is wave number) at wavelengths >100 km and pink noise (ϕ ∝ k−1) at shorter wavelengths. This observation suggests that river profile geometries are scale‐dependent and using small‐scale observations to develop a general understanding of large‐scale landscape evolution is not straightforward. At wavelengths >100 km, river profile geometries appear to be controlled by smoothly varying patterns of regional uplift and slope‐dependent incision. Landscape simulations, based upon stream power that are externally forced by regional uplift do not exhibit a spectral transition from red to pink noise because these simulations do not incorporate heterogeneous erodibility. Spectral analysis of erodibility extracted from patterns of lithologic variation along river profiles suggests that the missing spectral transition is accounted for by heterogeneous substrates, which are characterized by white or blue noise (ϕ ∝ k0 or k1). Our results have implications for the way by which rivers record large‐scale tectonic forcing while incising through complex lithologic patterns.
Disentangling the Impacts of Anthropogenic Aerosols on Terrestrial Carbon Cycle During 1850–2014
Authors: Zhang Yuan , Ciais Philippe , Boucher Olivier , Maignan Fabienne , Bastos Ana , Goll Daniel , Lurton Thibaut , Viovy Nicolas , Bellouin Nicolas , Li Laurent
Published: May 2021

Aerosols have a dimming and cooling effect and change hydrological regimes, thus affecting carbon fluxes, which are sensitive to climate. Aerosols also scatter sunlight, which increases the fraction of diffuse radiation, increasing photosynthesis. There remains no clear conclusion whether the impact of aerosols on land carbon fluxes is larger through diffuse radiation change than through changes in other climate variables. In this study, we quantified the overall physical impacts of anthropogenic aerosols on land C fluxes and explored the contribution from each factor using a set of factorial simulations driven by climate and aerosol data from the IPSL‐CM6A‐LR experiments during 1850–2014. A newly developed land surface model which distinguishes diffuse and direct radiation in canopy radiation transmission, ORCHIDEE_DF, was used. Specifically, a subgrid scheme was developed to distinguish the cloudy and clear sky conditions. We found that anthropogenic aerosol emissions since 1850 cumulatively enhanced the land C sink by 22.6 PgC. Seventy‐eight percent of this C sink enhancement is contributed by aerosol‐induced increase in the diffuse radiation fraction, much larger than the effect of the aerosol‐induced dimming. The cooling of anthropogenic aerosols has different impacts in different latitudes but overall increases the global land C sink. The dominant role of diffuse radiation changes found in this study implies that future aerosol emissions may have a much stronger impacts on the C cycle through changing radiation quality than through changing climate alone. Earth system models need to consider the diffuse radiation fertilization effect to better evaluate the impacts of climate change mitigation scenarios.
Associations of family income with cognition and brain structure in USA children: prevention implications
Authors: Tomasi Dardo , Volkow Nora D.
Published: May 2021

Poverty, as assessed by several socioeconomic (SES) factors, has been linked to worse cognitive performance and reduced cortical brain volumes in children. However, the relative contributions of the various SES factors on brain development and the mediating effects between cognition and brain morphometry have not been investigated. Here we used cross-sectional data from the ABCD Study to evaluate associations among various SES and demographic factors, brain morphometrics, and cognition and their reproducibility in two independent subsamples of 3892 children. Among the SES factors, family income (FI) best explained individual differences in cognitive test scores (stronger for crystallized than for fluid cognition), cortical volume (CV), and thickness (CT). Other SES factors that showed significant associations with cognition and brain morphometrics included parental education and neighborhood deprivation, but when controlling for FI, their effect sizes were negligible and their regional brain patterns were not reproducible. Mediation analyses showed that cognitive scores, which we used as surrogate markers of the children’s level of cognitive stimulation, partially mediated the association of FI and CT, whereas the mediations of brain morphometrics on the association of FI and cognition were not significant. These results suggest that lack of supportive/educational stimulation in children from low-income families might drive the reduced CV and CT. Thus, strategies to enhance parental supportive stimulation and the quality of education for children in low-income families could help counteract the negative effects of poverty on children’s brain development.
Adult hippocampal neurogenesis shapes adaptation and improves stress response: a mechanistic and integrative perspective
Authors: Surget A. , Belzung C.
Published: May 2021

Adult hippocampal neurogenesis (AHN) represents a remarkable form of neuroplasticity that has increasingly been linked to the stress response in recent years. However, the hippocampus does not itself support the expression of the different dimensions of the stress response. Moreover, the main hippocampal functions are essentially preserved under AHN depletion and adult-born immature neurons (abGNs) have no extrahippocampal projections, which questions the mechanisms by which abGNs influence functions supported by brain areas far from the hippocampus. Within this framework, we propose that through its computational influences AHN is pivotal in shaping adaption to environmental demands, underlying its role in stress response. The hippocampus with its high input convergence and output divergence represents a computational hub, ideally positioned in the brain (1) to detect cues and contexts linked to past, current and predicted stressful experiences, and (2) to supervise the expression of the stress response at the cognitive, affective, behavioral, and physiological levels. AHN appears to bias hippocampal computations toward enhanced conjunctive encoding and pattern separation, promoting contextual discrimination and cognitive flexibility, reducing proactive interference and generalization of stressful experiences to safe contexts. These effects result in gating downstream brain areas with more accurate and contextualized information, enabling the different dimensions of the stress response to be more appropriately set with specific contexts. Here, we first provide an integrative perspective of the functional involvement of AHN in the hippocampus and a phenomenological overview of the stress response. We then examine the mechanistic underpinning of the role of AHN in the stress response and describe its potential implications in the different dimensions accompanying this response.
Evolutionary origin and ecological implication of a unique nif island in free-living Bradyrhizobium lineages
Authors: Tao Jinjin , Wang Sishuo , Liao Tianhua , Luo Haiwei
Published: May 2021

The alphaproteobacterial genus Bradyrhizobium has been best known as N2-fixing members that nodulate legumes, supported by the nif and nod gene clusters. Recent environmental surveys show that Bradyrhizobium represents one of the most abundant free-living bacterial lineages in the world’s soils. However, our understanding of Bradyrhizobium comes largely from symbiotic members, biasing the current knowledge of their ecology and evolution. Here, we report the genomes of 88 Bradyrhizobium strains derived from diverse soil samples, including both nif-carrying and non-nif-carrying free-living (nod free) members. Phylogenomic analyses of these and 252 publicly available Bradyrhizobium genomes indicate that nif-carrying free-living members independently evolved from symbiotic ancestors (carrying both nif and nod) multiple times. Intriguingly, the nif phylogeny shows that the vast majority of nif-carrying free-living members comprise an independent cluster, indicating that horizontal gene transfer promotes nif expansion among the free-living Bradyrhizobium. Comparative genomics analysis identifies that the nif genes found in free-living Bradyrhizobium are located on a unique genomic island of ~50 kb equipped with genes potentially involved in coping with oxygen tension. We further analyze amplicon sequencing data to show that Bradyrhizobium members presumably carrying this nif island are widespread in a variety of environments. Given the dominance of Bradyrhizobium in world’s soils, our findings have implications for global nitrogen cycles and agricultural research.
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

Tourette 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

Exploration 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

Genome-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

Coffee 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

Tin 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

Polycomb 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

The 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

Amorphous 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

The 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

A 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

Twenty-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

Photochemical 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

Engineered 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

Atmospheric 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

Although 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.
Rapid mechanochemical synthesis of polyanionic cathode with improved electrochemical performance for Na-ion batteries
Authors: Shen Xing , Zhou Quan , Han Miao , Qi Xingguo , Li Bo , Zhang Qiangqiang , Zhao Junmei , Yang Chao , Liu Huizhou , Hu Yong-Sheng
Published: May 2021

Na-ion batteries have been considered promising candidates for stationary energy storage. However, their wide application is hindered by issues such as high cost and insufficient electrochemical performance, particularly for cathode materials. Here, we report a solvent-free mechanochemical protocol for the in-situ fabrication of sodium vanadium fluorophosphates. Benefiting from the nano-crystallization features and extra Na-storage sites achieved in the synthesis process, the as-prepared carbon-coated Na3(VOPO4)2F nanocomposite exhibits capacity of 142 mAh g−1 at 0.1C, higher than its theoretical capacity (130 mAh g−1). Moreover, a scaled synthesis with 2 kg of product was conducted and 26650-prototype cells were demonstrated to proof the electrochemical performance. We expect our findings to mark an important step in the industrial application of sodium vanadium fluorophosphates for Na-ion batteries.
NMDAR-dependent long-term depression is associated with increased short term plasticity through autophagy mediated loss of PSD-95
Authors: Compans Benjamin , Camus Come , Kallergi Emmanouela , Sposini Silvia , Martineau Magalie , Butler Corey , Kechkar Adel , Klaassen Remco V. , Retailleau Natacha , Sejnowski Terrence J. , Smit August B. , Sibarita Jean-Baptiste , Bartol Thomas M. , Perrais David , Nikoletopoulou Vassiliki , Choquet Daniel , Hosy Eric
Published: May 2021

Long-term depression (LTD) of synaptic strength can take multiple forms and contribute to circuit remodeling, memory encoding or erasure. The generic term LTD encompasses various induction pathways, including activation of NMDA, mGlu or P2X receptors. However, the associated specific molecular mechanisms and effects on synaptic physiology are still unclear. We here compare how NMDAR- or P2XR-dependent LTD affect synaptic nanoscale organization and function in rodents. While both LTDs are associated with a loss and reorganization of synaptic AMPARs, only NMDAR-dependent LTD induction triggers a profound reorganization of PSD-95. This modification, which requires the autophagy machinery to remove the T19-phosphorylated form of PSD-95 from synapses, leads to an increase in AMPAR surface mobility. We demonstrate that these post-synaptic changes that occur specifically during NMDAR-dependent LTD result in an increased short-term plasticity improving neuronal responsiveness of depressed synapses. Our results establish that P2XR- and NMDAR-mediated LTD are associated to functionally distinct forms of LTD.
Tissue context determines the penetrance of regulatory DNA variation
Authors: Halow Jessica M. , Byron Rachel , Hogan Megan S. , Ordoñez Raquel , Groudine Mark , Bender M. A. , Stamatoyannopoulos John A. , Maurano Matthew T.
Published: May 2021

Functional assessment of disease-associated sequence variation at non-coding regulatory elements is complicated by their high degree of context sensitivity to both the local chromatin and nuclear environments. Allelic profiling of DNA accessibility across individuals has shown that only a select minority of sequence variation affects transcription factor (TF) occupancy, yet low sequence diversity in human populations means that no experimental assessment is available for the majority of disease-associated variants. Here we describe high-resolution in vivo maps of allelic DNA accessibility in liver, kidney, lung and B cells from 5 increasingly diverged strains of F1 hybrid mice. The high density of heterozygous sites in these hybrids enables precise quantification of effect size and cell-type specificity for hundreds of thousands of variants throughout the mouse genome. We show that chromatin-altering variants delineate characteristic sensitivity profiles for hundreds of TF motifs. We develop a compendium of TF-specific sensitivity profiles accounting for genomic context effects. Finally, we link maps of allelic accessibility to allelic transcript levels in the same samples. This work provides a foundation for quantitative prediction of cell-type specific effects of non-coding variation on TF activity, which will facilitate both fine-mapping and systems-level analyses of common disease-associated variation in human genomes.
Exploring ligand binding pathways on proteins using hypersound-accelerated molecular dynamics
Authors: Araki Mitsugu , Matsumoto Shigeyuki , Bekker Gert-Jan , Isaka Yuta , Sagae Yukari , Kamiya Narutoshi , Okuno Yasushi
Published: May 2021

Capturing the dynamic processes of biomolecular systems in atomistic detail remains difficult despite recent experimental advances. Although molecular dynamics (MD) techniques enable atomic-level observations, simulations of “slow” biomolecular processes (with timescales longer than submilliseconds) are challenging because of current computer speed limitations. Therefore, we developed a method to accelerate MD simulations by high-frequency ultrasound perturbation. The binding events between the protein CDK2 and its small-molecule inhibitors were nearly undetectable in 100-ns conventional MD, but the method successfully accelerated their slow binding rates by up to 10–20 times. Hypersound-accelerated MD simulations revealed a variety of microscopic kinetic features of the inhibitors on the protein surface, such as the existence of different binding pathways to the active site. Moreover, the simulations allowed the estimation of the corresponding kinetic parameters and exploring other druggable pockets. This method can thus provide deeper insight into the microscopic interactions controlling biomolecular processes.
Niche partitioning shaped herbivore macroevolution through the early Mesozoic
Authors: Singh Suresh A. , Elsler Armin , Stubbs Thomas L. , Bond Russell , Rayfield Emily J. , Benton Michael J.
Published: May 2021

The Triassic (252–201 Ma) marks a major punctuation in Earth history, when ecosystems rebuilt themselves following the devastating Permian-Triassic mass extinction. Herbivory evolved independently several times as ecosystems comprising diverse assemblages of therapsids, parareptiles and archosauromorphs rose and fell, leading to a world dominated by dinosaurs. It was assumed that dinosaurs prevailed either through long-term competitive replacement of the incumbent clades or rapidly and opportunistically following one or more extinction events. Here we use functional morphology and ecology to explore herbivore morphospace through the Triassic and Early Jurassic. We identify five main herbivore guilds (ingestion generalists, prehension specialists, durophagous specialists, shearing pulpers, and heavy oral processors), and find that herbivore clades generally avoided competition by almost exclusively occupying different guilds. Major ecosystem remodelling was triggered multiple times by external environmental challenges, and previously dominant herbivores were marginalised by newly emerging forms. Dinosaur dominance was a mix of opportunity following disaster, combined with competitive advantage in their new world.
All-day fresh water harvesting by microstructured hydrogel membranes
Authors: Shi Ye , Ilic Ognjen , Atwater Harry A. , Greer Julia R.
Published: May 2021

Solar steam water purification and fog collection are two independent processes that could enable abundant fresh water generation. We developed a hydrogel membrane that contains hierarchical three-dimensional microstructures with high surface area that combines both functions and serves as an all-day fresh water harvester. At night, the hydrogel membrane efficiently captures fog droplets and directionally transports them to a storage vessel. During the daytime, it acts as an interfacial solar steam generator and achieves a high evaporation rate of 3.64 kg m−2 h−1 under 1 sun enabled by improved thermal/vapor flow management. With a homemade rooftop water harvesting system, this hydrogel membrane can produce fresh water with a daily yield of ~34 L m−2 in an outdoor test, which demonstrates its potential for global water scarcity relief.
Biofilm viability checker: An open-source tool for automated biofilm viability analysis from confocal microscopy images
Authors: Mountcastle Sophie E. , Vyas Nina , Villapun Victor M. , Cox Sophie C. , Jabbari Sara , Sammons Rachel L. , Shelton Richard M. , Walmsley A. Damien , Kuehne Sarah A.
Published: May 2021

Quantifying biofilm formation on surfaces is challenging because traditional microbiological methods, such as total colony-forming units (CFUs), often rely on manual counting. These are laborious, resource intensive techniques, more susceptible to human error. Confocal laser scanning microscopy (CLSM) is a high-resolution technique that allows 3D visualisation of biofilm architecture. In combination with a live/dead stain, it can be used to quantify biofilm viability on both transparent and opaque surfaces. However, there is little consensus on the appropriate methodology to apply in confocal micrograph processing. In this study, we report the development of an image analysis approach to repeatably quantify biofilm viability and surface coverage. We also demonstrate its use for a range of bacterial species and translational applications. This protocol has been created with ease of use and accessibility in mind, to enable researchers who do not specialise in computational techniques to be confident in applying these methods to analyse biofilm micrographs. Furthermore, the simplicity of the method enables the user to adapt it for their bespoke needs. Validation experiments demonstrate the automated analysis is robust and accurate across a range of bacterial species and an improvement on traditional microbiological analysis. Furthermore, application to translational case studies show the automated method is a reliable measurement of biomass and cell viability. This approach will ensure image analysis is an accessible option for those in the microbiology and biomaterials field, improve current detection approaches and ultimately support the development of novel strategies for preventing biofilm formation by ensuring comparability across studies.
Public attitudes toward COVID-19 vaccination: The role of vaccine attributes, incentives, and misinformation
Authors: Kreps Sarah , Dasgupta Nabarun , Brownstein John S. , Hswen Yulin , Kriner Douglas L.
Published: May 2021

While efficacious vaccines have been developed to inoculate against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; also known as COVID-19), public vaccine hesitancy could still undermine efforts to combat the pandemic. Employing a survey of 1096 adult Americans recruited via the Lucid platform, we examined the relationships between vaccine attributes, proposed policy interventions such as financial incentives, and misinformation on public vaccination preferences. Higher degrees of vaccine efficacy significantly increased individuals’ willingness to receive a COVID-19 vaccine, while a high incidence of minor side effects, a co-pay, and Emergency Use Authorization to fast-track the vaccine decreased willingness. The vaccine manufacturer had no influence on public willingness to vaccinate. We also found no evidence that belief in misinformation about COVID-19 treatments was positively associated with vaccine hesitancy. The findings have implications for public health strategies intending to increase levels of community vaccination.
Micro-CT data of early physiological cancellous bone formation in the lumbar spine of female C57BL/6 mice
Authors: Zenzes Michael , Zaslansky Paul
Published: May 2021

Micro-CT provides critical data for musculoskeletal research, yielding three-dimensional datasets containing distributions of mineral density. Using high-resolution scans, we quantified changes in the fine architecture of bone in the spine of young mice. This data is made available as a reference to physiological cancellous bone growth. The scans (n = 19) depict the extensive structural changes typical for female C57BL/6 mice pups, aged 1-, 3-, 7-, 10- and 14-days post-partum, as they attain the mature geometry. We reveal the micro-morphology down to individual trabeculae in the spine that follow phases of mineral-tissue rearrangement in the growing lumbar vertebra on a micrometer length scale. Phantom data is provided to facilitate mineral density calibration. Conventional histomorphometry matched with our micro-CT data on selected samples confirms the validity and accuracy of our 3D scans. The data may thus serve as a reference for modeling normal bone growth and can be used to benchmark other experiments assessing the effects of biomaterials, tissue growth, healing, and regeneration.
Accuracy of digital model generated from CT data with metal artifact reduction algorithm
Authors: Lee Chena , Lee Ari , Choi Yoon Joo , Jeon Kug Jin , Kim Young Hyun , Han Sang-Sun
Published: May 2021

This study investigated whether metal artifact reduction (MAR) applied computed tomography (CT) scans could be used to generate precise digital models and explored possible correlations between the amount of metal artifact and model accuracy. Thirty maxillofacial CT scans were randomly selected and a MAR algorithm was applied. By subtracting the original and MAR-applied CT images, the amount of metal artifact was quantified. Digital models were generated from the original and the MAR-applied CT data. Paired digital models were superimposed and shape deviation in planar surface was measured at 10 points in 4 planes. Statistical analyses were performed to compare deviations and to assess correlations between the amount of artifact and deviation. The MAR algorithm reduced metal artifact in all cases. The overall mean deviation of the MAR-applied models was 0.0868 mm, with no significant difference according to the reference plane. The amount of artifact did not significantly influence the accuracy of the digital models. MAR-applied CT is a convenient source for digital modeling with clinically acceptable accuracy. The MAR algorithm can be used regardless of the amount of metal artifact, which are generated by dental prostheses, for the quick and convenient manipulation of dental digital models.