bluuebunny/crossref_metadata_2025_split huggingface dataset:
ER stress-linked autophagy stabilizes apoptosis effector PERP and triggers its co-localization with SERCA2b at ER–plasma membrane junctions
Authors: McDonnell Samantha J. , Spiller David G. , White Michael R. H. , Prior Ian A. , Paraoan Luminita 
Published: September 2019

AbstractSpecific molecular interactions that underpin the switch between ER stress-triggered autophagy-mediated cellular repair and cellular death by apoptosis are not characterized. This study reports the unexpected interaction elicited by ER stress between the plasma membrane (PM)-localized apoptosis effector PERP and the ER Ca2+ pump SERCA2b. We show that the p53 effector PERP, which specifically induces apoptosis when expressed above a threshold level, has a heterogeneous distribution across the PM of un-stressed cells and is actively turned over by the lysosome. PERP is upregulated following sustained starvation-induced autophagy, which precedes the onset of apoptosis indicating that PERP protein levels are controlled by a lysosomal pathway that is sensitive to cellular physiological state. Furthermore, ER stress stabilizes PERP at the PM and induces its increasing co-localization with SERCA2b at ER–PM junctions. The findings highlight a novel crosstalk between pro-survival autophagy and pro-death apoptosis pathways and identify, for the first time, accumulation of an apoptosis effector to ER–PM junctions in response to ER stress.
Association between habitual yogurt consumption and newly diagnosed non-alcoholic fatty liver disease
Authors: Zhang Shunming , Fu Jingzhu , Zhang Qing , Liu Li , Lu Min , Meng Ge , Yao Zhanxin , Wu Hongmei , Xia Yang , Bao Xue , Gu Yeqing , Sun Shaomei , Wang Xing , Zhou Ming , Jia Qiyu , Song Kun , Wu Yuntang , Xiang Huiling , Niu Kaijun 
Published: September 2019

Abstract

Background/Objectives
Many studies have suggested that probiotics may be applied as a therapeutic agent for non-alcoholic fatty liver disease (NAFLD). However, the effects of frequent yogurt consumption (as a natural probiotic source) on NAFLD remain poorly understood. This study was to examine the association of habitual yogurt consumption with newly diagnosed NAFLD in the general adult population.

Subject/Methods
Overall, 24,389 adults were included in this cross-sectional study. Yogurt consumption was estimated by using a validated self-administered food frequency questionnaire. NAFLD was diagnosed by abdominal ultrasonography. We used logistic regression models to assess the association between yogurt consumption categories and newly diagnosed NAFLD.

Results
The multivariable odds ratios with 95% confidence interval of newly diagnosed NAFLD were 1.00 (0.88, 1.14) for 1 time/week, 0.91 (0.81, 1.02) for 2–3 times/week, and 0.86 (0.76, 0.98) for ≥4 times/week (P for trend = 0.01), compared with those who consumed <1 time/week yogurt. The inverse association was observed in a sensitivity analysis.

Conclusion
Higher yogurt consumption was inversely associated with the prevalence of newly diagnosed NAFLD. These results are needed to be confirmed in randomized controlled trials or prospective studies.
Single-cell transcriptomics reveals multi-step adaptations to endocrine therapy
Authors: Hong Sung Pil , Chan Thalia E. , Lombardo Ylenia , Corleone Giacomo , Rotmensz Nicole , Bravaccini Sara , Rocca Andrea , Pruneri Giancarlo , McEwen Kirsten R. , Coombes R. Charles , Barozzi Iros , Magnani Luca 
Published: September 2019

AbstractResistant tumours are thought to arise from the action of Darwinian selection on genetically heterogenous cancer cell populations. However, simple clonal selection is inadequate to describe the late relapses often characterising luminal breast cancers treated with endocrine therapy (ET), suggesting a more complex interplay between genetic and non-genetic factors. Here, we dissect the contributions of clonal genetic diversity and transcriptional plasticity during the early and late phases of ET at single-cell resolution. Using single-cell RNA-sequencing and imaging we disentangle the transcriptional variability of plastic cells and define a rare subpopulation of pre-adapted (PA) cells which undergoes further transcriptomic reprogramming and copy number changes to acquire full resistance. We find evidence for sub-clonal expression of a PA signature in primary tumours and for dominant expression in clustered circulating tumour cells. We propose a multi-step model for ET resistance development and advocate the use of stage-specific biomarkers.
The structural basis of lipid scrambling and inactivation in the endoplasmic reticulum scramblase TMEM16K
Authors: Bushell Simon R. , Pike Ashley C. W. , Falzone Maria E. , Rorsman Nils J. G. , Ta Chau M. , Corey Robin A. , Newport Thomas D. , Christianson John C. , Scofano Lara F. , Shintre Chitra A. , Tessitore Annamaria , Chu Amy , Wang Qinrui , Shrestha Leela , Mukhopadhyay Shubhashish M. M. , Love James D. , Burgess-Brown Nicola A. , Sitsapesan Rebecca , Stansfeld Phillip J. , Huiskonen Juha T. , Tammaro Paolo , Accardi Alessio , Carpenter Elisabeth P. 
Published: September 2019

AbstractMembranes in cells have defined distributions of lipids in each leaflet, controlled by lipid scramblases and flip/floppases. However, for some intracellular membranes such as the endoplasmic reticulum (ER) the scramblases have not been identified. Members of the TMEM16 family have either lipid scramblase or chloride channel activity. Although TMEM16K is widely distributed and associated with the neurological disorder autosomal recessive spinocerebellar ataxia type 10 (SCAR10), its location in cells, function and structure are largely uncharacterised. Here we show that TMEM16K is an ER-resident lipid scramblase with a requirement for short chain lipids and calcium for robust activity. Crystal structures of TMEM16K show a scramblase fold, with an open lipid transporting groove. Additional cryo-EM structures reveal extensive conformational changes from the cytoplasmic to the ER side of the membrane, giving a state with a closed lipid permeation pathway. Molecular dynamics simulations showed that the open-groove conformation is necessary for scramblase activity.
Replication stress triggers microsatellite destabilization and hypermutation leading to clonal expansion in vitro
Authors: Matsuno Yusuke , Atsumi Yuko , Shimizu Atsuhiro , Katayama Kotoe , Fujimori Haruka , Hyodo Mai , Minakawa Yusuke , Nakatsu Yoshimichi , Kaneko Syuzo , Hamamoto Ryuji , Shimamura Teppei , Miyano Satoru , Tsuzuki Teruhisa , Hanaoka Fumio , Yoshioka Ken-ichi 
Published: September 2019

AbstractMismatch repair (MMR)-deficient cancers are characterized by microsatellite instability (MSI) and hypermutation. However, it remains unclear how MSI and hypermutation arise and contribute to cancer development. Here, we show that MSI and hypermutation are triggered by replication stress in an MMR-deficient background, enabling clonal expansion of cells harboring ARF/p53-module mutations and cells that are resistant to the anti-cancer drug camptothecin. While replication stress-associated DNA double-strand breaks (DSBs) caused chromosomal instability (CIN) in an MMR-proficient background, they induced MSI with concomitant suppression of CIN via a PARP-mediated repair pathway in an MMR-deficient background. This was associated with the induction of mutations, including cancer-driver mutations in the ARF/p53 module, via chromosomal deletions and base substitutions. Immortalization of MMR-deficient mouse embryonic fibroblasts (MEFs) in association with ARF/p53-module mutations was ~60-fold more efficient than that of wild-type MEFs. Thus, replication stress-triggered MSI and hypermutation efficiently lead to clonal expansion of cells with abrogated defense systems.
An electrostatic switching mechanism to control the lipid transfer activity of Osh6p
Authors: Lipp Nicolas-Frédéric , Gautier Romain , Magdeleine Maud , Renard Maxime , Albanèse Véronique , Čopič Alenka , Drin Guillaume 
Published: September 2019

AbstractA central assumption is that lipid transfer proteins (LTPs) bind transiently to organelle membranes to distribute lipids in the eukaryotic cell. Osh6p and Osh7p are yeast LTPs that transfer phosphatidylserine (PS) from the endoplasmic reticulum (ER) to the plasma membrane (PM) via PS/phosphatidylinositol-4-phosphate (PI4P) exchange cycles. It is unknown how, at each cycle, they escape from the electrostatic attraction of the PM, highly anionic, to return to the ER. Using cellular and in vitro approaches, we show that Osh6p reduces its avidity for anionic membranes once it captures PS or PI4P, due to a molecular lid closing its lipid-binding pocket. Thus, Osh6p maintains its transport activity between ER- and PM-like membranes. Further investigations reveal that the lid governs the membrane docking and activity of Osh6p because it is anionic. Our study unveils how an LTP self-limits its residency time on membranes, via an electrostatic switching mechanism, to transfer lipids efficiently.
Anti-relapse neurons in the infralimbic cortex of rats drive relapse-suppression by drug omission cues
Authors: Laque Amanda , L. De Ness Genna , Wagner Grant E. , Nedelescu Hermina , Carroll Ayla , Watry Debbie , M. Kerr Tony , Koya Eisuke , Hope Bruce T. , Weiss Friedbert , Elmer Greg I. , Suto Nobuyoshi 
Published: September 2019

AbstractDrug addiction is a chronic relapsing disorder of compulsive drug use. Studies of the neurobehavioral factors that promote drug relapse have yet to produce an effective treatment. Here we take a different approach and examine the factors that suppress—rather than promote—relapse. Adapting Pavlovian procedures to suppress operant drug response, we determined the anti-relapse action of environmental cues that signal drug omission (unavailability) in rats. Under laboratory conditions linked to compulsive drug use and heightened relapse risk, drug omission cues suppressed three major modes of relapse-promotion (drug-predictive cues, stress, and drug exposure) for cocaine and alcohol. This relapse-suppression is, in part, driven by omission cue-reactive neurons, which constitute small subsets of glutamatergic and GABAergic cells, in the infralimbic cortex. Future studies of such neural activity-based cellular units (neuronal ensembles/memory engram cells) for relapse-suppression can be used to identify alternate targets for addiction medicine through functional characterization of anti-relapse mechanisms.
Capillary orbits
Authors: Gauthier Anaïs , van der Meer Devaraj , Snoeijer Jacco H. , Lajoinie Guillaume 
Published: September 2019

AbstractMillimeter-sized objects trapped at a liquid surface distort the interface by their weight, which in turn attracts them towards each other. This ubiquitous phenomenon, colloquially called the “Cheerios effect” is seen in the clumping of cereals in a breakfast bowl, and turns out to be a highly promising route towards controlled self-assembly of colloidal particles at the water surface. Here, we study capillary attraction between levitating droplets, maintained in an inverse Leidenfrost state above liquid nitrogen. We reveal that the drops spontaneously orbit around each other – mirroring a miniature celestial system. In this unique situation of negligible friction, the trajectories are solely shaped by the Cheerios-interaction potential, which we obtain directly from the droplet’s dynamics. Our findings offer an original perspective on contactless and contamination-free droplet cryopreservation processing, where the Leidenfrost effect and capillarity would be used in synergy to vitrify and transport biological samples.
Nano-confined crystallization of organic ultrathin nanostructure arrays with programmable geometries
Authors: Gao Hanfei , Qiu Yuchen , Feng Jiangang , Li Shuang , Wang Huijie , Zhao Yuyan , Wei Xiao , Jiang Xiangyu , Su Yewang , Wu Yuchen , Jiang Lei 
Published: September 2019

AbstractFabricating ultrathin organic semiconductor nanostructures attracts wide attention towards integrated electronic and optoelectronic applications. However, the fabrication of ultrathin organic nanostructures with precise alignment, tunable morphology and high crystallinity for device integration remains challenging. Herein, an assembly technique for fabricating ultrathin organic single-crystal arrays with different sizes and shapes is achieved by confining the crystallization process in a sub-hundred nanometer space. The confined crystallization is realized by controlling the deformation of the elastic topographical templates with tunable applied pressures, which produces organic nanostructures with ordered crystallographic orientation and controllable thickness from less than 10 nm to ca. 1 μm. The generality is verified for patterning various typical solution-processable materials with long-range order and pure orientation, including organic small molecules, polymers, metal-halide perovskites and nanoparticles. It is anticipated that this technique with controlling the crystallization kinetics by the governable confined space could facilitate the electronic integration of organic semiconductors.
YAP1 subgroup supratentorial ependymoma requires TEAD and nuclear factor I-mediated transcriptional programmes for tumorigenesis
Authors: Pajtler Kristian W. , Wei Yiju , Okonechnikov Konstantin , Silva Patricia B. G. , Vouri Mikaella , Zhang Lei , Brabetz Sebastian , Sieber Laura , Gulley Melissa , Mauermann Monika , Wedig Tatjana , Mack Norman , Imamura Kawasawa Yuka , Sharma Tanvi , Zuckermann Marc , Andreiuolo Felipe , Holland Eric , Maass Kendra , Körkel-Qu Huiqin , Liu Hai-Kun , Sahm Felix , Capper David , Bunt Jens , Richards Linda J. , Jones David T. W. , Korshunov Andrey , Chavez Lukas , Lichter Peter , Hoshino Mikio , Pfister Stefan M. , Kool Marcel , Li Wei , Kawauchi Daisuke 
Published: September 2019

AbstractYAP1 fusion-positive supratentorial ependymomas predominantly occur in infants, but the molecular mechanisms of oncogenesis are unknown. Here we show YAP1-MAMLD1 fusions are sufficient to drive malignant transformation in mice, and the resulting tumors share histo-molecular characteristics of human ependymomas. Nuclear localization of YAP1-MAMLD1 protein is mediated by MAMLD1 and independent of YAP1-Ser127 phosphorylation. Chromatin immunoprecipitation-sequencing analyses of human YAP1-MAMLD1-positive ependymoma reveal enrichment of NFI and TEAD transcription factor binding site motifs in YAP1-bound regulatory elements, suggesting a role for these transcription factors in YAP1-MAMLD1-driven tumorigenesis. Mutation of the TEAD binding site in the YAP1 fusion or repression of NFI targets prevents tumor induction in mice. Together, these results demonstrate that the YAP1-MAMLD1 fusion functions as an oncogenic driver of ependymoma through recruitment of TEADs and NFIs, indicating a rationale for preclinical studies to block the interaction between YAP1 fusions and NFI and TEAD transcription factors.
Enhanced ion tolerance of electrokinetic locomotion in polyelectrolyte-coated microswimmer
Authors: Zhan Xiaojun , Wang Jizhuang , Xiong Ze , Zhang Xuan , Zhou Ying , Zheng Jing , Chen Jianan , Feng Shien-Ping , Tang Jinyao 
Published: September 2019

AbstractOver the last decade, researchers have endeavored to mimic the naturally motile microorganisms and develop artificial nano/microswimmers, which propel themselves in aqueous media. However, most of these nano/microswimmers are propelled by the self-electrophoretic mechanism, which has one critical incompetency: the inability to operate in a high concentration electrolyte solution, such as the most important body fluid, blood. This ionic quenching behavior is well backed by the classical Helmholtz–Smoluchowski theory and seems to be an insurmountable challenge which has shadowed the otherwise promising biomedical applications for artificial nano/microswimmers. Here, we propose that the active nano/microswimmer’s self-electrophoresis is fundamentally different from the passive nanoparticle electrophoresis. By significantly increasing the Dukhin number with polyelectrolyte coating and geometry optimization, a favorable deviation from the Helmholtz–Smoluchowski behavior can be realized, and ion tolerance is enhanced by over 100 times for a visible light-powered self-electrophoretic microswimmer.
The marginal cells of the Caenorhabditis elegans pharynx scavenge cholesterol and other hydrophobic small molecules
Authors: Kamal Muntasir , Moshiri Houtan , Magomedova Lilia , Han Duhyun , Nguyen Ken C. Q. , Yeo May , Knox Jessica , Bagg Rachel , Won Amy M. , Szlapa Karolina , Yip Christopher M. , Cummins Carolyn L. , Hall David H. , Roy Peter J. 
Published: September 2019

AbstractThe nematode Caenorhabditis elegans is a bacterivore filter feeder. Through the contraction of the worm’s pharynx, a bacterial suspension is sucked into the pharynx’s lumen. Excess liquid is then shunted out of the buccal cavity through ancillary channels made by surrounding marginal cells. We find that many worm-bioactive small molecules (a.k.a. wactives) accumulate inside of the marginal cells as crystals or globular spheres. Through screens for mutants that resist the lethality associated with one crystallizing wactive we identify a presumptive sphingomyelin-synthesis pathway that is necessary for crystal and sphere accumulation. We find that expression of sphingomyelin synthase 5 (SMS-5) in the marginal cells is not only sufficient for wactive accumulation but is also important for absorbing exogenous cholesterol, without which C. elegans cannot develop. We conclude that sphingomyelin-rich marginal cells act as a sink to scavenge important nutrients from filtered liquid that might otherwise be shunted back into the environment.
Effects of the serine protease inhibitor rBmTI-A in an experimental mouse model of chronic allergic pulmonary inflammation
Authors: Florencio Ariana Corrêa , de Almeida Robson S. , Arantes-Costa Fernanda M. , Saraiva-Romanholo Beatriz M. , Duran Adriana F. , Sasaki Sérgio D. , Martins Mílton A. , Lopes Fernanda D. T. Q. S. , Tibério Iolanda F. L. C. , Leick Edna A. 
Published: September 2019

AbstractTo evaluate whether a recombinant serine protease inhibitor (rBmTI-A) modulates inflammation in an experimental model of chronic allergic lung inflammation. Balb/c mice were divided into four groups: SAL (saline), OVA (sensitized with ovalbumin), SAL + rBmTI-A (control treated with rBmTI-A) and OVA + rBmTI-A (sensitized with ovalbumin and treated with rBmTI-A). The animals received an intraperitoneal injection of saline or ovalbumin, according to the group. The groups received inhalation with saline or ovalbumin and were treated with rBmTI-A or saline by nasal instillation. After 29 days, we evaluated the respiratory mechanics; bronchoalveolar lavage fluid (BALF); cytokines; MMP-9, TIMP-1; eosinophils; collagen and elastic fibre expression in the airways; and the trypsin-like, MMP-1, and MMP-9 lung tissue proteolytic activity. Treatment with rBmTI-A reduced the trypsin-like proteolytic activity, the elastance and resistance maximum response, the polymorphonuclear cells, IL-5, IL-10, IL-13 and IL-17A in the BALF, the expression of IL-5, IL-13, IL-17, CD4+, MMP-9, TIMP-1, eosinophils, collagen and elastic fibres in the airways of the OVA + rBmTI-A group compared to the OVA group (p < 0.05). rBmTI-A attenuated bronchial hyperresponsiveness, inflammation and remodelling in this experimental model of chronic allergic pulmonary inflammation. This inhibitor may serve as a potential therapeutic tool for asthma treatment.
River channel conveyance capacity adjusts to modes of climate variability
Authors: Slater L. J. , Khouakhi A. , Wilby R. L. 
Published: September 2019

AbstractRiver networks are typically treated as conduits of fixed discharge conveyance capacity in flood models and engineering design, despite knowledge that alluvial channel networks adjust their geometry, conveyance, planform, extent and drainage density over time in response to shifts in the magnitude and frequency of streamflows and sediment supply. Consistent relationships between modes of climate variability conducive to wetter-/drier-than-average conditions and changes in channel conveyance have never been established, hindering geomorphological prediction over interannual to multidecadal timescales. This paper explores the relationship between river channel conveyance/geometry and three modes of climate variability (the El Niño–Southern Oscillation, Atlantic Multidecadal Oscillation, and Arctic Oscillation) using two-, five- and ten-year medians of channel measurements, streamflow, precipitation and climate indices over seven decades in 67 United States rivers. We find that in two thirds of these rivers, channel capacity undergoes coherent phases of expansion/contraction in response to shifts in catchment precipitation and streamflow, driven by climate modes with different periodicities. Understanding the sensitivity of channel conveyance to climate modes would enable better river management, engineering design, and flood predictability over interannual to multidecadal timescales.
A20 deficiency in hematopoietic stem cells causes lymphopenia and myeloproliferation due to elevated Interferon-γ signals
Authors: Nakagawa Masahiro Marshall , Rathinam Chozha Vendan 
Published: September 2019

AbstractInflammation and inflammatory cytokines have been shown to exert both positive and negative effects on hematopoietic stem cells (HSCs) and hematopoiesis. While the significance of inflammation driven hematopoiesis has begun to unfold, molecular players that regulate this phenomenon remain largely unknown. In the present study, we identified A20 as a critical regulator of inflammation controlled hematopoietic cell fate decisions of HSCs. A20 deficiency in HSCs leads to increased differentiation of myeloid cells and myeloproliferation. Analysis of erythroid lineage cells of A20 deficient mice indicated a striking reduction of erythrocytes in the bone marrow (BM), but elevated numbers in the spleen. Loss of A20 in HSCs causes a severe blockade of B cell differentiation in the BM and absence of peripheral B cells in the spleen, liver and blood. T cell differentiation studies revealed a reduction of both T cell progenitors and differentiated T cells in the thymus and altered T cell numbers in the spleens of A20 mutant mice. Analysis of lineage committed progenitors of the myeloid, erythroid and lymphoid lineages specified an altered composition in the A20 deficient BM. Genetic studies identified that specific loss of A20 in the myeloid lineage cells results in myeloproliferation. Bone marrow transplantation studies and mixed bone marrow chimera studies suggested an involvement of inflammatory cytokines, particularly interferon (IFN)- γ, in the onset of myeloproliferation and lymphopenia of A20 deficient mice. Finally, ablation of IFNγ signals in A20 deficient mice rescued the hematopoietic defects. In essence, these studies highlight a previously unknown role for A20 in the restriction of inflammation driven pathologic hematopoiesis. We believe that our studies based on A20 mutant mice will be helpful in understanding the pathophysiology and in the treatment of patients with A20 (TNFAIP3) mutations.