bluuebunny/crossref_metadata_2025_split huggingface dataset:
A standardized gnotobiotic mouse model harboring a minimal 15-member mouse gut microbiota recapitulates SOPF/SPF phenotypes
Authors: Darnaud Marion , De Vadder Filipe , Bogeat Pascaline , Boucinha Lilia , Bulteau Anne-Laure , Bunescu Andrei , Couturier Céline , Delgado Ana , Dugua Hélène , Elie Céline , Mathieu Alban , Novotná Tereza , Ouattara Djomangan Adama , Planel Séverine , Saliou Adrien , Šrůtková Dagmar , Yansouni Jennifer , Stecher Bärbel , Schwarzer Martin , Leulier François , Tamellini Andrea 
Published: November 2021

AbstractMus musculusis the classic mammalian model for biomedical research. Despite global efforts to standardize breeding and experimental procedures, the undefined composition and interindividual diversity of the microbiota of laboratory mice remains a limitation. In an attempt to standardize the gut microbiome in preclinical mouse studies, here we report the development of a simplified mouse microbiota composed of 15 strains from 7 of the 20 most prevalent bacterial families representative of the fecal microbiota of C57BL/6J Specific (and Opportunistic) Pathogen-Free (SPF/SOPF) animals and the derivation of a standardized gnotobiotic mouse model called GM15. GM15 recapitulates extensively the functionalities found in the C57BL/6J SOPF microbiota metagenome, and GM15 animals are phenotypically similar to SOPF or SPF animals in two different facilities. They are also less sensitive to the deleterious effects of post-weaning malnutrition. In this work, we show that the GM15 model provides increased reproducibility and robustness of preclinical studies by limiting the confounding effect of fluctuation in microbiota composition, and offers opportunities for research focused on how the microbiota shapes host physiology in health and disease.
Hox genes regulate asexual reproductive behavior and tissue segmentation in adult animals
Authors: Arnold Christopher P. , Lozano Analí Migueles , Mann Frederick G. , Nowotarski Stephanie H. , Haug Julianna O. , Lange Jeffrey J. , Seidel Chris W. , Alvarado Alejandro Sánchez 
Published: November 2021

AbstractHox genes are highly conserved transcription factors renowned for their roles in the segmental patterning of the embryonic anterior-posterior (A/P) axis. We report functions for Hox genes in A/P tissue segmentation and transverse fission behavior underlying asexual reproduction in adult planarian flatworms,Schmidtea mediterranea. Silencing of each of theHoxfamily members identifies 5 Hox genes required for asexual reproduction. Among these, silencing ofhox3genes results in supernumerary fission segments, while silencing ofpost2beliminates segmentation altogether. The opposing roles ofhox3andpost2bin segmentation are paralleled in their respective regulation of fission behavior. Silencing ofhox3increases the frequency of fission behavior initiation while silencing ofpost2beliminates fission behavior entirely. Furthermore, we identify a network of downstream effector genes mediating Hox gene functions, providing insight into their respective mechanisms of action. In particular, we resolve roles forpost2band effector genes in the functions of the marginal adhesive organ in fission behavior regulation. Collectively, our study establishes adult stage roles for Hox genes in the regulation of tissue segmentation and behavior associated with asexual reproduction.
Increasing donor-acceptor spacing for reduced voltage loss in organic solar cells
Authors: Wang Jing , Jiang Xudong , Wu Hongbo , Feng Guitao , Wu Hanyu , Li Junyu , Yi Yuanping , Feng Xunda , Ma Zaifei , Li Weiwei , Vandewal Koen , Tang Zheng 
Published: November 2021

AbstractThe high voltage losses ($${V}_{{loss}}$$

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), originating from inevitable electron-phonon coupling in organic materials, limit the power conversion efficiency of organic solar cells to lower values than that of inorganic or perovskite solar cells. In this work, we demonstrate that this $${V}_{{loss}}$$

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can in fact be suppressed by controlling the spacing between the donor (D) and the acceptor (A) materials (DA spacing). We show that in typical organic solar cells, the DA spacing is generally too small, being the origin of the too-fast non-radiative decay of charge carriers ($${k}_{{nr}}$$

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), and it can be increased by engineering the non-conjugated groups, i.e., alkyl chain spacers in single component DA systems and side chains in high-efficiency bulk-heterojunction systems. Increasing DA spacing allows us to realize significantly reduced $${k}_{{nr}}$$

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and improved device voltage. This points out a new research direction for breaking the performance bottleneck of organic solar cells.
Twinning-assisted dynamic adjustment of grain boundary mobility
Authors: Huang Qishan , Zhu Qi , Chen Yingbin , Gong Mingyu , Li Jixue , Zhang Ze , Yang Wei , Wang Jian , Zhou Haofei , Wang Jiangwei 
Published: November 2021

AbstractGrain boundary (GB) plasticity dominates the mechanical behaviours of nanocrystalline materials. Under mechanical loading, GB configuration and its local deformation geometry change dynamically with the deformation; the dynamic variation of GB deformability, however, remains largely elusive, especially regarding its relation with the frequently-observed GB-associated deformation twins in nanocrystalline materials. Attention here is focused on the GB dynamics in metallic nanocrystals, by means of well-designed in situ nanomechanical testing integrated with molecular dynamics simulations. GBs with low mobility are found to dynamically adjust their configurations and local deformation geometries via crystallographic twinning, which instantly changes the GB dynamics and enhances the GB mobility. This self-adjust twin-assisted GB dynamics is found common in a wide range of face-centred cubic nanocrystalline metals under different deformation conditions. These findings enrich our understanding of GB-mediated plasticity, especially the dynamic behaviour of GBs, and bear practical implication for developing high performance nanocrystalline materials through interface engineering.
Diversity, multifaceted evolution, and facultative saprotrophism in the European Batrachochytrium salamandrivorans epidemic
Authors: Kelly Moira , Pasmans Frank , Muñoz Jose F. , Shea Terrance P. , Carranza Salvador , Cuomo Christina A. , Martel An 
Published: November 2021

AbstractWhile emerging fungi threaten global biodiversity, the paucity of fungal genome assemblies impedes thoroughly characterizing epidemics and developing effective mitigation strategies. Here, we generatede novogenomic assemblies for six outbreaks of the emerging pathogenBatrachochytrium salamandrivorans(Bsal). We reveal the European epidemic currently damaging amphibian populations to comprise multiple, highly divergent lineages demonstrating isolate-specific adaptations and metabolic capacities. In particular, we show extensive gene family expansions and acquisitions, through a variety of evolutionary mechanisms, and an isolate-specific saprotrophic lifecycle. This finding both explains the chytrid’s ability to divorce transmission from host density, producingBsal’s enigmatic host population declines, and is a key consideration in developing successful mitigation measures.
Observation of spin-space quantum transport induced by an atomic quantum point contact
Authors: Ono Koki , Higomoto Toshiya , Saito Yugo , Uchino Shun , Nishida Yusuke , Takahashi Yoshiro 
Published: November 2021

AbstractQuantum transport is ubiquitous in physics. So far, quantum transport between terminals has been extensively studied in solid state systems from the fundamental point of views such as the quantized conductance to the applications to quantum devices. Recent works have demonstrated a cold-atom analog of a mesoscopic conductor by engineering a narrow conducting channel with optical potentials, which opens the door for a wealth of research of atomtronics emulating mesoscopic electronic devices and beyond. Here we realize an alternative scheme of the quantum transport experiment with ytterbium atoms in a two-orbital optical lattice system. Our system consists of a multi-component Fermi gas and a localized impurity, where the current can be created in the spin space by introducing the spin-dependent interaction with the impurity. We demonstrate a rich variety of localized-impurity-induced quantum transports, which paves the way for atomtronics exploiting spin degrees of freedom.
Complementary resource preferences spontaneously emerge in diauxic microbial communities
Authors: Wang Zihan , Goyal Akshit , Dubinkina Veronika , George Ashish B. , Wang Tong , Fridman Yulia , Maslov Sergei 
Published: November 2021

AbstractMany microbes grow diauxically, utilizing the available resources one at a time rather than simultaneously. The properties of communities of microbes growing diauxically remain poorly understood, largely due to a lack of theory and models of such communities. Here, we develop and study a minimal model of diauxic microbial communities assembling in a serially diluted culture. We find that unlike co-utilizing communities, diauxic community assembly repeatably and spontaneously leads to communities with complementary resource preferences, namely communities where species prefer different resources as their top choice. Simulations and theory explain that the emergence of complementarity is driven by the disproportionate contribution of the top choice resource to the growth of a diauxic species. Additionally, we develop a geometric approach for analyzing serially diluted communities, with or without diauxie, which intuitively explains several additional emergent community properties, such as the apparent lack of species which grow fastest on a resource other than their most preferred resource. Overall, our work provides testable predictions for the assembly of natural as well as synthetic communities of diauxically shifting microbes.
G3BP1 inhibits Cul3SPOP to amplify AR signaling and promote prostate cancer
Authors: Mukhopadhyay Chandrani , Yang Chenyi , Xu Limei , Liu Deli , Wang Yu , Huang Dennis , Deonarine Lesa Dayal , Cyrta Joanna , Davicioni Elai , Sboner Andrea , Robinson Brian. D. , Chinnaiyan Arul M. , Rubin Mark A. , Barbieri Christopher E. , Zhou Pengbo 
Published: November 2021

AbstractSPOP, an E3 ubiquitin ligase, acts as a prostate-specific tumor suppressor with several key substrates mediating oncogenic function. However, the mechanisms underlying SPOP regulation are largely unknown. Here, we have identified G3BP1 as an interactor of SPOP and functions as a competitive inhibitor of Cul3SPOP, suggesting a distinctive mode of Cul3SPOP inactivation in prostate cancer (PCa). Transcriptomic analysis and functional studies reveal a G3BP1-SPOP ubiquitin signaling axis that promotes PCa progression through activating AR signaling. Moreover, AR directly upregulates G3BP1 transcription to further amplify G3BP1-SPOP signaling in a feed-forward manner. Our study supports a fundamental role of G3BP1 in disabling the tumor suppressive Cul3SPOP, thus defining a PCa cohort independent of SPOP mutation. Therefore, there are significantly more PCa that are defective for SPOP ubiquitin ligase than previously appreciated, and these G3BP1high PCa are more susceptible to AR-targeted therapy.
Phosphorylation activates the yeast small heat shock protein Hsp26 by weakening domain contacts in the oligomer ensemble
Authors: Mühlhofer Moritz , Peters Carsten , Kriehuber Thomas , Kreuzeder Marina , Kazman Pamina , Rodina Natalia , Reif Bernd , Haslbeck Martin , Weinkauf Sevil , Buchner Johannes 
Published: November 2021

AbstractHsp26 is a small heat shock protein (sHsp) from S. cerevisiae. Its chaperone activity is activated by oligomer dissociation at heat shock temperatures. Hsp26 contains 9 phosphorylation sites in different structural elements. Our analysis of phospho-mimetic mutations shows that phosphorylation activates Hsp26 at permissive temperatures. The cryo-EM structure of the Hsp26 40mer revealed contacts between the conserved core domain of Hsp26 and the so-called thermosensor domain in the N-terminal part of the protein, which are targeted by phosphorylation. Furthermore, several phosphorylation sites in the C-terminal extension, which link subunits within the oligomer, are sensitive to the introduction of negative charges. In all cases, the intrinsic inhibition of chaperone activity is relieved and the N-terminal domain becomes accessible for substrate protein binding. The weakening of domain interactions within and between subunits by phosphorylation to activate the chaperone activity in response to proteotoxic stresses independent of heat stress could be a general regulation principle of sHsps.
Defactinib inhibits PYK2 phosphorylation of IRF5 and reduces intestinal inflammation
Authors: Ryzhakov Grigory , Almuttaqi Hannah , Corbin Alastair L. , Berthold Dorothée L. , Khoyratty Tariq , Eames Hayley L. , Bullers Samuel , Pearson Claire , Ai Zhichao , Zec Kristina , Bonham Sarah , Fischer Roman , Jostins-Dean Luke , Travis Simon P. L. , Kessler Benedikt M. , Udalova Irina A. 
Published: November 2021

AbstractInterferon regulating factor 5 (IRF5) is a multifunctional regulator of immune responses, and has a key pathogenic function in gut inflammation, but how IRF5 is modulated is still unclear. Having performed a kinase inhibitor library screening in macrophages, here we identify protein-tyrosine kinase 2-beta (PTK2B/PYK2) as a putative IRF5 kinase. PYK2-deficient macrophages display impaired endogenous IRF5 activation, leading to reduction of inflammatory gene expression. Meanwhile, a PYK2 inhibitor, defactinib, has a similar effect on IRF5 activation in vitro, and induces a transcriptomic signature in macrophages similar to that caused by IRF5 deficiency. Finally, defactinib reduces pro-inflammatory cytokines in human colon biopsies from patients with ulcerative colitis, as well as in a mouse colitis model. Our results thus implicate a function of PYK2 in regulating the inflammatory response in the gut via the IRF5 innate sensing pathway, thereby opening opportunities for related therapeutic interventions for inflammatory bowel diseases and other inflammatory conditions.
A somatic proteoglycan controls Notch-directed germ cell fate
Authors: Gopal Sandeep , Amran Aqilah , Elton Andre , Ng Leelee , Pocock Roger 
Published: November 2021

AbstractCommunication between the soma and germline optimizes germ cell fate programs. Notch receptors are key determinants of germ cell fate but how somatic signals direct Notch-dependent germ cell behavior is undefined. Here we demonstrate that SDN-1 (syndecan-1), a somatic transmembrane proteoglycan, controls expression of the GLP-1 (germline proliferation-1) Notch receptor in the Caenorhabditis elegans germline. We find that SDN-1 control of a somatic TRP calcium channel governs calcium-dependent binding of an AP-2 transcription factor (APTF-2) to the glp-1 promoter. Hence, SDN-1 signaling promotes GLP-1 expression and mitotic germ cell fate. Together, these data reveal SDN-1 as a putative communication nexus between the germline and its somatic environment to control germ cell fate decisions.
Magic in twisted transition metal dichalcogenide bilayers
Authors: Devakul Trithep , Crépel Valentin , Zhang Yang , Fu Liang 
Published: November 2021

AbstractThe long-wavelength moiré superlattices in twisted 2D structures have emerged as a highly tunable platform for strongly correlated electron physics. We study the moiré bands in twisted transition metal dichalcogenide homobilayers, focusing on WSe2, at small twist angles using a combination of first principles density functional theory, continuum modeling, and Hartree-Fock approximation. We reveal the rich physics at small twist angles θ < 4∘, and identify a particular magic angle at which the top valence moiré band achieves almost perfect flatness. In the vicinity of this magic angle, we predict the realization of a generalized Kane-Mele model with a topological flat band, interaction-driven Haldane insulator, and Mott insulators at the filling of one hole per moiré unit cell. The combination of flat dispersion and uniformity of Berry curvature near the magic angle holds promise for realizing fractional quantum anomalous Hall effect at fractional filling. We also identify twist angles favorable for quantum spin Hall insulators and interaction-induced quantum anomalous Hall insulators at other integer fillings.
HPF1 dynamically controls the PARP1/2 balance between initiating and elongating ADP-ribose modifications
Authors: Langelier Marie-France , Billur Ramya , Sverzhinsky Aleksandr , Black Ben E. , Pascal John M. 
Published: November 2021

AbstractPARP1 and PARP2 produce poly(ADP-ribose) in response to DNA breaks. HPF1 regulates PARP1/2 catalytic output, most notably permitting serine modification with ADP-ribose. However, PARP1 is substantially more abundant in cells than HPF1, challenging whether HPF1 can pervasively modulate PARP1. Here, we show biochemically that HPF1 efficiently regulates PARP1/2 catalytic output at sub-stoichiometric ratios matching their relative cellular abundances. HPF1 rapidly associates/dissociates from multiple PARP1 molecules, initiating serine modification before modification initiates on glutamate/aspartate, and accelerating initiation to be more comparable to elongation reactions forming poly(ADP-ribose). This “hit and run” mechanism ensures HPF1 contributions to PARP1/2 during initiation do not persist and interfere with PAR chain elongation. We provide structural insights into HPF1/PARP1 assembled on a DNA break, and assess HPF1 impact on PARP1 retention on DNA. Our data support the prevalence of serine-ADP-ribose modification in cells and the efficiency of serine-ADP-ribose modification required for an acute DNA damage response.
Generation of a Gluconobacter oxydans knockout collection for improved extraction of rare earth elements
Authors: Schmitz Alexa M. , Pian Brooke , Medin Sean , Reid Matthew C. , Wu Mingming , Gazel Esteban , Barstow Buz 
Published: November 2021

AbstractBioleaching of rare earth elements (REEs), using microorganisms such as Gluconobacter oxydans, offers a sustainable alternative to environmentally harmful thermochemical extraction, but is currently not very efficient. Here, we generate a whole-genome knockout collection of single-gene transposon disruption mutants for G. oxydans B58, to identify genes affecting the efficacy of REE bioleaching. We find 304 genes whose disruption alters the production of acidic biolixiviant. Disruption of genes underlying synthesis of the cofactor pyrroloquinoline quinone (PQQ) and the PQQ-dependent membrane-bound glucose dehydrogenase nearly eliminates bioleaching. Disruption of phosphate-specific transport system genes enhances bioleaching by up to 18%. Our results provide a comprehensive roadmap for engineering the genome of G. oxydans to further increase its bioleaching efficiency.
Silicon: quantum dot photovoltage triodes
Authors: Zhou Wen , Zheng Li , Ning Zhijun , Cheng Xinhong , Wang Fang , Xu Kaimin , Xu Rui , Liu Zhongyu , Luo Man , Hu Weida , Guo Huijun , Zhou Wenjia , Yu Yuehui 
Published: November 2021

AbstractSilicon is widespread in modern electronics, but its electronic bandgap prevents the detection of infrared radiation at wavelengths above 1,100 nanometers, which limits its applications in multiple fields such as night vision, health monitoring and space navigation systems. It is therefore of interest to integrate silicon with infrared-sensitive materials to broaden its detection wavelength. Here we demonstrate a photovoltage triode that can use silicon as the emitter but is also sensitive to infrared spectra owing to the heterointegrated quantum dot light absorber. The photovoltage generated at the quantum dot base region, attracting holes from silicon, leads to high responsivity (exceeding 410 A·W−1 with Vbias of −1.5 V), and a widely self-tunable spectral response. Our device has the maximal specific detectivity (4.73 × 1013 Jones with Vbias of −0.4 V) at 1,550 nm among the infrared sensitized silicon detectors, which opens a new path towards infrared and visible imaging in one chip with silicon technology compatibility.
Identifying an optimal dihydroartemisinin-piperaquine dosing regimen for malaria prevention in young Ugandan children
Authors: Wallender Erika , Ali Ali Mohamed , Hughes Emma , Kakuru Abel , Jagannathan Prasanna , Muhindo Mary Kakuru , Opira Bishop , Whalen Meghan , Huang Liusheng , Duvalsaint Marvin , Legac Jenny , Kamya Moses R. , Dorsey Grant , Aweeka Francesca , Rosenthal Philip J. , Savic Rada M. 
Published: November 2021

AbstractIntermittent preventive treatment (IPT) with dihydroartemisinin-piperaquine (DP) is highly protective against malaria in children, but is not standard in malaria-endemic countries. Optimal DP dosing regimens will maximize efficacy and reduce toxicity and resistance selection. We analyze piperaquine (PPQ) concentrations (n = 4573), malaria incidence data (n = 326), and P. falciparum drug resistance markers from a trial of children randomized to IPT with DP every 12 weeks (n = 184) or every 4 weeks (n = 96) from 2 to 24 months of age (NCT02163447). We use nonlinear mixed effects modeling to establish malaria protective PPQ levels and risk factors for suboptimal protection. Compared to DP every 12 weeks, DP every 4 weeks is associated with 95% protective efficacy (95% CI: 84–99%). A PPQ level of 15.4 ng/mL reduces the malaria hazard by 95%. Malnutrition reduces PPQ exposure. In simulations, we show that DP every 4 weeks is optimal across a range of transmission intensities, and age-based dosing improves malaria protection in young or malnourished children.
GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain
Authors: Dar Ghulam Hassan , Mendes Cláudia C. , Kuan Wei-Li , Speciale Alfina A. , Conceição Mariana , Görgens André , Uliyakina Inna , Lobo Miguel J. , Lim Wooi F. , EL Andaloussi Samir , Mäger Imre , Roberts Thomas C. , Barker Roger A. , Goberdhan Deborah C. I. , Wilson Clive , Wood Matthew J. A. 
Published: November 2021

AbstractExtracellular vesicles (EVs) are biological nanoparticles with important roles in intercellular communication, and potential as drug delivery vehicles. Here we demonstrate a role for the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in EV assembly and secretion. We observe high levels of GAPDH binding to the outer surface of EVs via a phosphatidylserine binding motif (G58), which promotes extensive EV clustering. Further studies in a Drosophila EV biogenesis model reveal that GAPDH is required for the normal generation of intraluminal vesicles in endosomal compartments, and promotes vesicle clustering. Fusion of the GAPDH-derived G58 peptide to dsRNA-binding motifs enables highly efficient loading of small interfering RNA (siRNA) onto the EV surface. Such vesicles efficiently deliver siRNA to multiple anatomical regions of the brain in a Huntington’s disease mouse model after systemic injection, resulting in silencing of the huntingtin gene in different regions of the brain.