bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular architecture of black widow spider neurotoxins
Authors: Chen Minghao , Blum Daniel , Engelhard Lena , Raunser Stefan , Wagner Richard , Gatsogiannis Christos 
Published: November 2021

AbstractLatrotoxins (LaTXs) are presynaptic pore-forming neurotoxins found in the venom of Latrodectus spiders. The venom contains a toxic cocktail of seven LaTXs, with one of them targeting vertebrates (α-latrotoxin (α-LTX)), five specialized on insects (α, β, γ, δ, ε- latroinsectotoxins (LITs), and one on crustaceans (α-latrocrustatoxin (α-LCT)). LaTXs bind to specific receptors on the surface of neuronal cells, inducing the release of neurotransmitters either by directly stimulating exocytosis or by forming Ca2+-conductive tetrameric pores in the membrane. Despite extensive studies in the past decades, a high-resolution structure of a LaTX is not yet available and the precise mechanism of LaTX action remains unclear. Here, we report cryoEM structures of the α-LCT monomer and the δ-LIT dimer. The structures reveal that LaTXs are organized in four domains. A C-terminal domain of ankyrin-like repeats shields a central membrane insertion domain of six parallel α-helices. Both domains are flexibly linked via an N-terminal α-helical domain and a small β-sheet domain. A comparison between the structures suggests that oligomerization involves major conformational changes in LaTXs with longer C-terminal domains. Based on our data we propose a cyclic mechanism of oligomerization, taking place prior membrane insertion. Both recombinant α-LCT and δ-LIT form channels in artificial membrane bilayers, that are stabilized by Ca2+ ions and allow calcium flux at negative membrane potentials. Our comparative analysis between α-LCT and δ-LIT provides first crucial insights towards understanding the molecular mechanism of the LaTX family.
Angiogenin mediates paternal inflammation-induced metabolic disorders in offspring through sperm tsRNAs
Authors: Zhang Yanwen , Ren Li , Sun Xiaoxiao , Zhang Zhilong , Liu Jie , Xin Yining , Yu Jianmin , Jia Yimin , Sheng Jinghao , Hu Guo-fu , Zhao Ruqian , He Bin 
Published: November 2021

AbstractPaternal environmental inputs can influence various phenotypes in offspring, presenting tremendous implications for basic biology and public health and policy. However, which signals function as a nexus to transmit paternal environmental inputs to offspring remains unclear. Here we show that offspring of fathers with inflammation exhibit metabolic disorders including glucose intolerance and obesity. Deletion of a mouse tRNA RNase, Angiogenin (Ang), abolished paternal inflammation-induced metabolic disorders in offspring. Additionally,Angdeletion prevented the inflammation-induced alteration of 5′-tRNA-derived small RNAs (5′-tsRNAs) expression profile in sperm, which might be essential in composing a sperm RNA ‘coding signature’ that is needed for paternal epigenetic memory. Microinjection of sperm 30–40 nt RNA fractions (predominantly 5′-tsRNAs) from inflammatoryAng+/+males but notAng–/–males resulted in metabolic disorders in the resultant offspring. Moreover, zygotic injection with synthetic 5′-tsRNAs which increased in inflammatory mouse sperm and decreased byAngdeletion partially resembled paternal inflammation-induced metabolic disorders in offspring. Together, our findings demonstrate that Ang-mediated biogenesis of 5′-tsRNAs in sperm contributes to paternal inflammation-induced metabolic disorders in offspring.
Ensuring scientific reproducibility in bio-macromolecular modeling via extensive, automated benchmarks
Authors: Koehler Leman Julia , Lyskov Sergey , Lewis Steven M. , Adolf-Bryfogle Jared , Alford Rebecca F. , Barlow Kyle , Ben-Aharon Ziv , Farrell Daniel , Fell Jason , Hansen William A. , Harmalkar Ameya , Jeliazkov Jeliazko , Kuenze Georg , Krys Justyna D. , Ljubetič Ajasja , Loshbaugh Amanda L. , Maguire Jack , Moretti Rocco , Mulligan Vikram Khipple , Nance Morgan L. , Nguyen Phuong T. , Ó Conchúir Shane , Roy Burman Shourya S. , Samanta Rituparna , Smith Shannon T. , Teets Frank , Tiemann Johanna K. S. , Watkins Andrew , Woods Hope , Yachnin Brahm J. , Bahl Christopher D. , Bailey-Kellogg Chris , Baker David , Das Rhiju , DiMaio Frank , Khare Sagar D. , Kortemme Tanja , Labonte Jason W. , Lindorff-Larsen Kresten , Meiler Jens , Schief William , Schueler-Furman Ora , Siegel Justin B. , Stein Amelie , Yarov-Yarovoy Vladimir , Kuhlman Brian , Leaver-Fay Andrew , Gront Dominik , Gray Jeffrey J. , Bonneau Richard 
Published: November 2021

AbstractEach year vast international resources are wasted on irreproducible research. The scientific community has been slow to adopt standard software engineering practices, despite the increases in high-dimensional data, complexities of workflows, and computational environments. Here we show how scientific software applications can be created in a reproducible manner when simple design goals for reproducibility are met. We describe the implementation of a test server framework and 40 scientific benchmarks, covering numerous applications in Rosetta bio-macromolecular modeling. High performance computing cluster integration allows these benchmarks to run continuously and automatically. Detailed protocol captures are useful for developers and users of Rosetta and other macromolecular modeling tools. The framework and design concepts presented here are valuable for developers and users of any type of scientific software and for the scientific community to create reproducible methods. Specific examples highlight the utility of this framework, and the comprehensive documentation illustrates the ease of adding new tests in a matter of hours.
Location-specific co-benefits of carbon emissions reduction from coal-fired power plants in China
Authors: Wang Pu , Lin Cheng-Kuan , Wang Yi , Liu Dachuan , Song Dunjiang , Wu Tong 
Published: November 2021

AbstractClimate policies that achieve air quality co-benefits can better align developing countries’ national interests with global climate mitigation. Since the effects of air pollutants are highly dependent on source locations, spatially nuanced policies are crucial to maximizing the achievement of co-benefits. Using the coal power industry as a case study, this study presents an interdisciplinary approach to assessing facility level co-benefits at every specific source location in China. We find that co-benefits range from US$51-$278 per ton CO2 reduction nationwide and are highly heterogeneous spatially, with “hotspot” regions that should be the priority of emissions reduction policies, and that provinces should use different techno-economic strategies to reduce emissions. The location-specific co-benefit value plus a carbon price serves as a unified environmental indicator that enables policy makers to more accurately understand the social costs of electricity generation from coal burning and provides a scientific framework for geographically nuanced policymaking.
High-throughput mediation analysis of human proteome and metabolome identifies mediators of post-bariatric surgical diabetes control
Authors: Dreyfuss Jonathan M. , Yuchi Yixing , Dong Xuehong , Efthymiou Vissarion , Pan Hui , Simonson Donald C. , Vernon Ashley , Halperin Florencia , Aryal Pratik , Konkar Anish , Sebastian Yinong , Higgs Brandon W. , Grimsby Joseph , Rondinone Cristina M. , Kasif Simon , Kahn Barbara B. , Foster Kathleen , Seeley Randy , Goldfine Allison , Djordjilović Vera , Patti Mary Elizabeth 
Published: November 2021

AbstractTo improve the power of mediation in high-throughput studies, here we introduce High-throughput mediation analysis (Hitman), which accounts for direction of mediation and applies empirical Bayesian linear modeling. We apply Hitman in a retrospective, exploratory analysis of the SLIMM-T2D clinical trial in which participants with type 2 diabetes were randomized to Roux-en-Y gastric bypass (RYGB) or nonsurgical diabetes/weight management, and fasting plasma proteome and metabolome were assayed up to 3 years. RYGB caused greater improvement in HbA1c, which was mediated by growth hormone receptor (GHR). GHR’s mediation is more significant than clinical mediators, including BMI. GHR decreases at 3 months postoperatively alongside increased insulin-like growth factor binding proteins IGFBP1/BP2; plasma GH increased at 1 year. Experimental validation indicates (1) hepatic GHR expression decreases in post-bariatric rats; (2) GHR knockdown in primary hepatocytes decreases gluconeogenic gene expression and glucose production. Thus, RYGB may induce resistance to diabetogenic effects of GH signaling.Trial Registration: Clinicaltrials.gov NCT01073020.
Growth of lithium-indium dendrites in all-solid-state lithium-based batteries with sulfide electrolytes
Authors: Luo Shuting , Wang Zhenyu , Li Xuelei , Liu Xinyu , Wang Haidong , Ma Weigang , Zhang Lianqi , Zhu Lingyun , Zhang Xing 
Published: November 2021

AbstractAll-solid-state lithium-based batteries with inorganic solid electrolytes are considered a viable option for electrochemical energy storage applications. However, the application of lithium metal is hindered by issues associated with the growth of mossy and dendritic Li morphologies upon prolonged cell cycling and undesired reactions at the electrode/solid electrolyte interface. In this context, alloy materials such as lithium-indium (Li-In) alloys are widely used at the laboratory scale because of their (electro)chemical stability, although no in-depth investigations on their morphological stability have been reported yet. In this work, we report the growth of Li-In dendritic structures when the alloy material is used in combination with a Li6PS5Cl solid electrolyte and Li(Ni0.6Co0.2Mn0.2)O2 positive electrode active material and cycled at high currents (e.g., 3.8 mA cm−2) and high cathode loading (e.g., 4 mAh cm−2). Via ex situ measurements and simulations, we demonstrate that the irregular growth of Li-In dendrites leads to cell short circuits after room-temperature long-term cycling. Furthermore, the difference between Li and Li-In dendrites is investigated and discussed to demonstrate the distinct type of dendrite morphology.
Heterochromatin is a quantitative trait associated with spontaneous epiallele formation
Authors: Zhang Yinwen , Jang Hosung , Xiao Rui , Kakoulidou Ioanna , Piecyk Robert S. , Johannes Frank , Schmitz Robert J. 
Published: November 2021

AbstractEpialleles are meiotically heritable variations in expression states that are independent from changes in DNA sequence. Although they are common in plant genomes, their molecular origins are unknown. Here we show, using mutant and experimental populations, that epialleles in Arabidopsis thaliana that result from ectopic hypermethylation are due to feedback regulation of pathways that primarily function to maintain DNA methylation at heterochromatin. Perturbations to maintenance of heterochromatin methylation leads to feedback regulation of DNA methylation in genes. Using single base resolution methylomes from epigenetic recombinant inbred lines (epiRIL), we show that epiallelic variation is abundant in euchromatin, yet, associates with QTL primarily in heterochromatin regions. Mapping three-dimensional chromatin contacts shows that genes that are hotspots for ectopic hypermethylation have increases in contact frequencies with regions possessing H3K9me2. Altogether, these data show that feedback regulation of pathways that have evolved to maintain heterochromatin silencing leads to the origins of spontaneous hypermethylated epialleles.
Mammographic texture features associated with contralateral breast cancer in the WECARE Study
Authors: Watt Gordon P. , Knight Julia A. , Lin Christine , Lynch Charles F. , Malone Kathleen E. , John Esther M. , Bernstein Leslie , Brooks Jennifer D. , Reiner Anne S. , Liang Xiaolin , Woods Meghan , Nguyen Tuong L. , Hopper John L. , Pike Malcolm C. , Bernstein Jonine L. 
Published: November 2021

AbstractTo evaluate whether mammographic texture features were associated with second primary contralateral breast cancer (CBC) risk, we created a “texture risk score” using pre-treatment mammograms in a case–control study of 212 women with CBC and 223 controls with unilateral breast cancer. The texture risk score was associated with CBC (odds per adjusted standard deviation = 1.25, 95% CI 1.01–1.56) after adjustment for mammographic percent density and confounders. These results support the potential of texture features for CBC risk assessment of breast cancer survivors.
Trajectories of performance change indicate multiple dissociable links between working memory and fluid intelligence
Authors: Cochrane Aaron , Green C. Shawn 
Published: November 2021

AbstractMany areas of psychology assume that performance on tasks of interest is stable through time. Here, using time-sensitive modeling of working memory task performance, we show not only was this assumption incorrect, but that certain components of the performance trajectory (e.g., final task performance; rate of change) were independently predictive of fluid intelligence. This fact has clear implications for theoretical frameworks linking working memory and fluid intelligence, and beyond.
OME-NGFF: a next-generation file format for expanding bioimaging data-access strategies
Authors: Moore Josh , Allan Chris , Besson Sébastien , Burel Jean-Marie , Diel Erin , Gault David , Kozlowski Kevin , Lindner Dominik , Linkert Melissa , Manz Trevor , Moore Will , Pape Constantin , Tischer Christian , Swedlow Jason R. 
Published: November 2021

AbstractThe rapid pace of innovation in biological imaging and the diversity of its applications have prevented the establishment of a community-agreed standardized data format. We propose that complementing established open formats such as OME-TIFF and HDF5 with a next-generation file format such as Zarr will satisfy the majority of use cases in bioimaging. Critically, a common metadata format used in all these vessels can deliver truly findable, accessible, interoperable and reusable bioimaging data.
Response-locked classification image analysis of perceptual decision making in contrast detection
Authors: Maruyama Hironori , Ueno Natsuki , Motoyoshi Isamu 
Published: November 2021

AbstractIn many situations, humans make decisions based on serially sampled information through the observation of visual stimuli. To quantify the critical information used by the observer in such dynamic decision making, we here applied a classification image (CI) analysis locked to the observer's reaction time (RT) in a simple detection task for a luminance target that gradually appeared in dynamic noise. We found that the response-locked CI shows a spatiotemporally biphasic weighting profile that peaked about 300 ms before the response, but this profile substantially varied depending on RT; positive weights dominated at short RTs and negative weights at long RTs. We show that these diverse results are explained by a simple perceptual decision mechanism that accumulates the output of the perceptual process as modelled by a spatiotemporal contrast detector. We discuss possible applications and the limitations of the response-locked CI analysis.
Selective activation of central thalamic fiber pathway facilitates behavioral performance in healthy non-human primates
Authors: Janson A. P. , Baker J. L. , Sani I. , Purpura K. P. , Schiff N. D. , Butson C. R. 
Published: November 2021

AbstractCentral thalamic deep brain stimulation (CT-DBS) is an investigational therapy to treat enduring cognitive dysfunctions in structurally brain injured (SBI) patients. However, the mechanisms of CT-DBS that promote restoration of cognitive functions are unknown, and the heterogeneous etiology and recovery profiles of SBI patients contribute to variable outcomes when using conventional DBS strategies,which may result in off-target effects due to activation of multiple pathways. To disambiguate the effects of stimulation of two adjacent thalamic pathways, we modeled and experimentally compared conventional and novel ‘field-shaping’ methods of CT-DBS within the central thalamus of healthy non-human primates (NHP) as they performed visuomotor tasks. We show that selective activation of the medial dorsal thalamic tegmental tract (DTTm), but not of the adjacent centromedian-parafascicularis (CM-Pf) pathway, results in robust behavioral facilitation. Our predictive modeling approach in healthy NHPs directly informs ongoing and future clinical investigations of conventional and novel methods of CT-DBS for treating cognitive dysfunctions in SBI patients, for whom no therapy currently exists.
Multicast tree construction algorithm for dynamic traffic on software defined networks
Authors: Bijur Gururaj , Ramakrishna M. , Kotegar Karunakar A. 
Published: November 2021

AbstractDynamic traffic of multicast communication in the Software Defined Network environment focused less though it is more natural and practical. In multicast communication, the traffic is dynamic due to the dynamic group memberships (i.e., participants join and leave the group anytime), which are not explored much in the previous research works. The multicast in dynamic traffic requires a method to handle dynamic group membership and minimum tree alteration for every join and leave of participants from the multicast group. This paper proposes a multicast tree construction algorithm, which considers receiving devices and network capability as base parameters to construct the multicast path. The proposed routing method uses Dijkstra’s Shortest Path algorithm for initial tree formation, identifies a multicast path, and processes the Shortest Path Tree to reduce the overall hop count and path cost. The multicast tree generated by the proposed enables the dynamic join and leaves of participating devices with reduced tree alteration using more common paths to reach the devices. The implementation and results show that the proposed method works efficiently in resource utilization with a reduced hop count and quality for multicast communication in static and dynamic scenarios. Also, the results demonstrate that the proposed method generates a stable common path for multicast communication.
Methylated (−)-epigallocatechin 3-O-gallate potentiates the effect of split vaccine accompanied with upregulation of Toll-like receptor 5
Authors: Kumazoe Motofumi , Takamatsu Kanako , Horie Fuyumi , Yoshitomi Ren , Hamagami Hiroki , Tanaka Hiroshi , Fujimura Yoshinori , Tachibana Hirofumi 
Published: November 2021

AbstractSplit-virus vaccine serves as a major countermeasure against influenza virus, but its effectiveness and protective action are not complete. We previously demonstrated the effect of Benifuuki, a green tea cultivar in Japan, on enhancing the split-virus vaccine–elicited immune response. However, little is known about the detail mechanisms. Here, we show that EGCG3”Me intake significantly potentiated the vaccine-elicited hemagglutination inhibition titer increase. Flow cytometry analysis revealed the increased Toll-like receptor 5 (TLR5) expression after EGCG3”Me treatment in lamina propria dendritic cells (LPDCs) and macrophages, which play crucial roles in the humoral immune system. TLR5 expression correlated with the level of interleukin-6 (IL-6)/C–C chemokine type receptor 5, which are important mediators of the humoral immunity. Taken together, In vivo and ex vivo studies showed that EGCG3”Me potentiated the split-virus vaccine–elicited immune response accompanied with the upregulation of TLR5 in intestine and splenocyte macrophages.
Electrochemical oxidation of ferricyanide
Authors: Cheah Mun Hon , Chernev Petko 
Published: November 2021

AbstractWe report the electrochemical oxidation of ferricyanide, [FeIII(CN)6]3− and characterised the oxidation product by in-situ FTIR and XAS spectroelectrochemistry methods. Oxidation of [FeIII(CN)6]3− is proposed to proceed via a tentative Fe(IV) intermediate that undergoes reduction elimination to give cis-[FeIII(CN)4(CH3CN)2]1− as stable product in acetonitrile. Speciation of the oxidation product by DFT calculations is underpinned by good agreement to experimental data.
Individualized cyclic mechanical loading improves callus properties during the remodelling phase of fracture healing in mice as assessed from time-lapsed in vivo imaging
Authors: Wehrle Esther , Paul Graeme R. , Tourolle né Betts Duncan C. , Kuhn Gisela A. , Müller Ralph 
Published: November 2021

AbstractFracture healing is regulated by mechanical loading. Understanding the underlying mechanisms during the different healing phases is required for targeted mechanical intervention therapies. Here, the influence of individualized cyclic mechanical loading on the remodelling phase of fracture healing was assessed in a non-critical-sized mouse femur defect model. After bridging of the defect, a loading group (n = 10) received individualized cyclic mechanical loading (8–16 N, 10 Hz, 5 min, 3 × /week) based on computed strain distribution in the mineralized callus using animal-specific real-time micro-finite element analysis with 2D/3D visualizations and strain histograms. Controls (n = 10) received 0 N treatment at the same post-operative time-points. By registration of consecutive scans, structural and dynamic callus morphometric parameters were followed in three callus sub-volumes and the adjacent cortex showing that the remodelling phase of fracture healing is highly responsive to cyclic mechanical loading with changes in dynamic parameters leading to significantly larger formation of mineralized callus and higher degree of mineralization. Loading-mediated maintenance of callus remodelling was associated with distinct effects on Wnt-signalling-associated molecular targets Sclerostin and RANKL in callus sub-regions and the adjacent cortex (n = 1/group). Given these distinct local protein expression patterns induced by cyclic mechanical loading during callus remodelling, the femur defect loading model with individualized load application seems suitable to further understand the local spatio-temporal mechano-molecular regulation of the different fracture healing phases.
Vulnerability of cities to toxic airborne releases is written in their topology
Authors: Fellini Sofia , Salizzoni Pietro , Ridolfi Luca 
Published: November 2021

AbstractThe incidental or malicious release of toxic gases in the atmosphere is one of the most critical scenarios for cities. The impact of these releases varies with the ventilation potential of the urban environment. To disentangle this crucial aspect, vulnerability to airborne releases is here traced back to essential properties of the urban fabric. To this aim, pollutant dispersion is disassembled in its fundamental bricks and the main drivers of the process are captured. The analysis is based on four cities with emblematic architectures: Paris, Firenze, Lyon and New York. Results show that vulnerability is driven by the topology of the city and by its interaction with the approaching wind. In this sense, fragility to toxic releases is written in the layout of the urban fabric and results from its historical evolution. This study paves the way to the assessment of air pollution-related issues from a morphological point of view.