bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multivesicular body-like organelle mediates stimulus-regulated trafficking of olfactory ciliary transduction proteins
Authors: Maurya Devendra Kumar , Berghard Anna , Bohm Staffan 
Published: November 2022

AbstractStimulus transduction in cilia of olfactory sensory neurons is mediated by odorant receptors, Gαolf, adenylate cyclase-3, cyclic nucleotide-gated and chloride ion channels. Mechanisms regulating trafficking and localization of these proteins in the dendrite are unknown. By lectin/immunofluorescence staining and in vivo correlative light-electron microscopy (CLEM), we identify a retinitis pigmentosa-2 (RP2), ESCRT-0 and synaptophysin-containing multivesicular organelle that is not part of generic recycling/degradative/exosome pathways. The organelle’s intraluminal vesicles contain the olfactory transduction proteins except for Golf subunits Gγ13 and Gβ1. Instead, Gβ1 colocalizes with RP2 on the organelle’s outer membrane. The organelle accumulates in response to stimulus deprivation, while odor stimuli or adenylate cyclase activation cause outer membrane disintegration, release of intraluminal vesicles, and RP2/Gβ1 translocation to the base of olfactory cilia. Together, these findings reveal the existence of a dendritic organelle that mediates both stimulus-regulated storage of olfactory ciliary transduction proteins and membrane-delimited sorting important for G protein heterotrimerization.
Unimon qubit
Authors: Hyyppä Eric , Kundu Suman , Chan Chun Fai , Gunyhó András , Hotari Juho , Janzso David , Juliusson Kristinn , Kiuru Olavi , Kotilahti Janne , Landra Alessandro , Liu Wei , Marxer Fabian , Mäkinen Akseli , Orgiazzi Jean-Luc , Palma Mario , Savytskyi Mykhailo , Tosto Francesca , Tuorila Jani , Vadimov Vasilii , Li Tianyi , Ockeloen-Korppi Caspar , Heinsoo Johannes , Tan Kuan Yen , Hassel Juha , Möttönen Mikko 
Published: November 2022

AbstractSuperconducting qubits seem promising for useful quantum computers, but the currently wide-spread qubit designs and techniques do not yet provide high enough performance. Here, we introduce a superconducting-qubit type, the unimon, which combines the desired properties of increased anharmonicity, full insensitivity to dc charge noise, reduced sensitivity to flux noise, and a simple structure consisting only of a single Josephson junction in a resonator. In agreement with our quantum models, we measure the qubit frequency, ω01/(2π), and increased anharmonicity α/(2π) at the optimal operation point, yielding, for example, 99.9% and 99.8% fidelity for 13 ns single-qubit gates on two qubits with (ω01, α) = (4.49 GHz, 434 MHz) × 2π and (3.55 GHz, 744 MHz) × 2π, respectively. The energy relaxation seems to be dominated by dielectric losses. Thus, improvements of the design, materials, and gate time may promote the unimon to break the 99.99% fidelity target for efficient quantum error correction and possible useful quantum advantage with noisy systems.
Pinpointing the axial ligand effect on platinum single-atom-catalyst towards efficient alkaline hydrogen evolution reaction
Authors: Zhang Tianyu , Jin Jing , Chen Junmei , Fang Yingyan , Han Xu , Chen Jiayi , Li Yaping , Wang Yu , Liu Junfeng , Wang Lei 
Published: November 2022

AbstractDeveloping active single-atom-catalyst (SAC) for alkaline hydrogen evolution reaction (HER) is a promising solution to lower the green hydrogen cost. However, the correlations are not clear between the chemical environments around the active-sites and their desired catalytic activity. Here we study a group of SACs prepared by anchoring platinum atoms on NiFe-layered-double-hydroxide. While maintaining the homogeneity of the Pt-SACs, various axial ligands (−F, −Cl, −Br, −I, −OH) are employedviaa facile irradiation-impregnation procedure, enabling us to discover definite chemical-environments/performance correlations. Owing to its high first-electron-affinity, chloride chelated Pt-SAC exhibits optimized bindings with hydrogen and hydroxide, which favor the sluggish water dissociation and further promote the alkaline HER. Specifically, it shows high mass-activity of 30.6 A mgPt−1and turnover frequency of 30.3  H2s−1at 100 mV overpotential, which are significantly higher than those of the state-of-the-art Pt-SACs and commercial Pt/C catalyst. Moreover, high energy efficiency of 80% is obtained for the alkaline water electrolyser assembled using the above catalyst under practical-relevant conditions.
The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration
Authors: Opie-Martin Sarah , Iacoangeli Alfredo , Topp Simon D. , Abel Olubunmi , Mayl Keith , Mehta Puja R. , Shatunov Aleksey , Fogh Isabella , Bowles Harry , Limbachiya Naomi , Spargo Thomas P. , Al-Khleifat Ahmad , Williams Kelly L. , Jockel-Balsarotti Jennifer , Bali Taha , Self Wade , Henden Lyndal , Nicholson Garth A. , Ticozzi Nicola , McKenna-Yasek Diane , Tang Lu , Shaw Pamela J. , Chio Adriano , Ludolph Albert , Weishaupt Jochen H. , Landers John E. , Glass Jonathan D. , Mora Jesus S. , Robberecht Wim , Damme Philip Van , McLaughlin Russell , Hardiman Orla , van den Berg Leonard , Veldink Jan H. , Corcia Phillippe , Stevic Zorica , Siddique Nailah , Silani Vincenzo , Blair Ian P. , Fan Dong-sheng , Esselin Florence , de la Cruz Elisa , Camu William , Basak Nazli A. , Siddique Teepu , Miller Timothy , Brown Robert H. , Al-Chalabi Ammar , Shaw Christopher E. 
Published: November 2022

AbstractSuperoxide dismutase (SOD1) gene variants may cause amyotrophic lateral sclerosis, some of which are associated with a distinct phenotype. Most studies assess limited variants or sample sizes. In this international, retrospective observational study, we compare phenotypic and demographic characteristics between people with SOD1-ALS and people with ALS and no recorded SOD1 variant. We investigate which variants are associated with age at symptom onset and time from onset to death or censoring using Cox proportional-hazards regression. The SOD1-ALS dataset reports age of onset for 1122 and disease duration for 883 people; the comparator population includes 10,214 and 9010 people respectively. Eight variants are associated with younger age of onset and distinct survival trajectories; a further eight associated with younger onset only and one with distinct survival only. Here we show that onset and survival are decoupled in SOD1-ALS. Future research should characterise rarer variants and molecular mechanisms causing the observed variability.
Stress-driven potentiation of lateral hypothalamic synapses onto ventral tegmental area dopamine neurons causes increased consumption of palatable food
Authors: Linders Louisa E. , Patrikiou Lefkothea , Soiza-Reilly Mariano , Schut Evelien H. S. , van Schaffelaar Bram F. , Böger Leonard , Wolterink-Donselaar Inge G. , Luijendijk Mieneke C. M. , Adan Roger A. H. , Meye Frank J. 
Published: November 2022

AbstractStress can cause overconsumption of palatable high caloric food. Despite the important role of stress eating in obesity and (binge) eating disorders, its underlying neural mechanisms remain unclear. Here we demonstrate in mice that stress alters lateral hypothalamic area (LHA) control over the ventral tegmental area (VTA), thereby promoting overconsumption of palatable food. Specifically, we show that glutamatergic LHA neurons projecting to the VTA are activated by social stress, after which their synapses onto dopamine neurons are potentiated via AMPA receptor subunit alterations. We find that stress-driven strengthening of these specific synapses increases LHA control over dopamine output in key target areas like the prefrontal cortex. Finally, we demonstrate that while inducing LHA-VTA glutamatergic potentiation increases palatable fat intake, reducing stress-driven potentiation of this connection prevents such stress eating. Overall, this study provides insights in the neural circuit adaptations caused by stress that drive overconsumption of palatable food.
IL-33 induces thymic involution-associated naive T cell aging and impairs host control of severe infection
Authors: Xu Lei , Wei Chuan , Chen Ying , Wu Yue , Shou Xiaoli , Chen Wenjie , Lu Di , Sun Haoran , Li Wei , Yu Beibei , Wang Xiaowei , Zhang Xiaojun , Yu Yanxiong , Lei Zhigang , Tang Rui , Zhu Jifeng , Li Yalin , Lu Linrong , Zhou Hong , Zhou Sha , Su Chuan , Chen Xiaojun 
Published: November 2022

AbstractSevere infection commonly results in immunosuppression, which leads to impaired pathogen clearance or increased secondary infection in both humans and animals. However, the exact mechanisms remain poorly understood. Here, we demonstrate that IL-33 results in immunosuppression by inducing thymic involution-associated naive T cell dysfunction with aberrant expression of aging-associated genes and impairs host control of infection in mouse disease models of schistosomiasis or sepsis. Furthermore, we illustrate that IL-33 triggers the excessive generation of medullary thymic epithelial cell (mTEC) IV (thymic tuft cells) in a Pou2f3-dependent manner, as a consequence, disturbs mTEC/cortical TEC (cTEC) compartment and causes thymic involution during severe infection. More importantly, IL-33 deficiency, the anti-IL-33 neutralizing antibody treatment, or IL-33 receptor ST2 deficient thymus transplantation rescues T cell immunity to better control infection in mice. Our findings not only uncover a link between severe infection-induced IL-33 and thymic involution-mediated naive T cell aging, but also suggest that targeting IL-33 or ST2 is a promising strategy to rejuvenate T cell immunity to better control severe infection.
Ozone impact from solar energetic particles cools the polar stratosphere
Authors: Szela̧g Monika E. , Marsh Daniel R. , Verronen Pekka T. , Seppälä Annika , Kalakoski Niilo 
Published: November 2022

AbstractUnderstanding atmospheric impacts of solar energetic particle precipitation (EPP) remains challenging, from quantification of the response in ozone, to implications on temperature. Both are necessary to understand links between EPP and regional climate variability. Here we use a chemistry-climate model to assess the importance of EPP on late winter/spring polar stratosphere. In transient simulations, the impact on NOy, ozone, and temperature is underestimated when using EPP forcing from the current recommendation of the Coupled Model Intercomparison Project (CMIP6). The resulting temperature response is largely masked by overall dynamical variability. An idealised experiment with EPP forcing that reproduces observed levels of NOyresults in a significant reduction of ozone (up to 25%), cooling the stratosphere (up to 3 K) during late winter/spring. Our results unravel the inconsistency regarding the temperature response to EPP-driven springtime ozone decrease, and highlight the need for an improved EPP forcing in climate simulations.
Enterotoxigenic Escherichia coli heat-labile toxin drives enteropathic changes in small intestinal epithelia
Authors: Sheikh Alaullah , Tumala Brunda , Vickers Tim J. , Martin John C. , Rosa Bruce A. , Sabui Subrata , Basu Supratim , Simoes Rita D. , Mitreva Makedonka , Storer Chad , Tyksen Erik , Head Richard D. , Beatty Wandy , Said Hamid M. , Fleckenstein James M. 
Published: November 2022

AbstractEnterotoxigenicE. coli(ETEC) produce heat-labile (LT) and/or heat-stable (ST) enterotoxins, and commonly cause diarrhea in resource-poor regions. ETEC have been linked repeatedly to sequelae in children including enteropathy, malnutrition, and growth impairment. Although cellular actions of ETEC enterotoxins leading to diarrhea are well-established, their contributions to sequelae remain unclear. LT increases cellular cAMP to activate protein kinase A (PKA) that phosphorylates ion channels driving intestinal export of salt and water resulting in diarrhea. As PKA also modulates transcription of many genes, we interrogated transcriptional profiles of LT-treated intestinal epithelia. Here we show that LT significantly alters intestinal epithelial gene expression directing biogenesis of the brush border, the major site for nutrient absorption, suppresses transcription factors HNF4 and SMAD4 critical to enterocyte differentiation, and profoundly disrupts microvillus architecture and essential nutrient transport. In addition, ETEC-challenged neonatal mice exhibit substantial brush border derangement that is prevented by maternal vaccination with LT. Finally, mice repeatedly challenged with toxigenic ETEC exhibit impaired growth recapitulating the multiplicative impact of recurring ETEC infections in children. These findings highlight impacts of ETEC enterotoxins beyond acute diarrheal illness and may inform approaches to prevent major sequelae of these common infections including malnutrition that impact millions of children.
Generative deep learning enables the discovery of a potent and selective RIPK1 inhibitor
Authors: Li Yueshan , Zhang Liting , Wang Yifei , Zou Jun , Yang Ruicheng , Luo Xinling , Wu Chengyong , Yang Wei , Tian Chenyu , Xu Haixing , Wang Falu , Yang Xin , Li Linli , Yang Shengyong 
Published: November 2022

AbstractThe retrieval of hit/lead compounds with novel scaffolds during early drug development is an important but challenging task. Various generative models have been proposed to create drug-like molecules. However, the capacity of these generative models to design wet-lab-validated and target-specific molecules with novel scaffolds has hardly been verified. We herein propose a generative deep learning (GDL) model, a distribution-learning conditional recurrent neural network (cRNN), to generate tailor-made virtual compound libraries for given biological targets. The GDL model is then applied to RIPK1. Virtual screening against the generated tailor-made compound library and subsequent bioactivity evaluation lead to the discovery of a potent and selective RIPK1 inhibitor with a previously unreported scaffold, RI-962. This compound displays potent in vitro activity in protecting cells from necroptosis, and good in vivo efficacy in two inflammatory models. Collectively, the findings prove the capacity of our GDL model in generating hit/lead compounds with unreported scaffolds, highlighting a great potential of deep learning in drug discovery.
Prognostic and predictive value of a pathomics signature in gastric cancer
Authors: Chen Dexin , Fu Meiting , Chi Liangjie , Lin Liyan , Cheng Jiaxin , Xue Weisong , Long Chenyan , Jiang Wei , Dong Xiaoyu , Sui Jian , Lin Dajia , Lu Jianping , Zhuo Shuangmu , Liu Side , Li Guoxin , Chen Gang , Yan Jun 
Published: November 2022

AbstractThe current tumour-node-metastasis (TNM) staging system alone cannot provide adequate information for prognosis and adjuvant chemotherapy benefits in patients with gastric cancer (GC). Pathomics, which is based on the development of digital pathology, is an emerging field that might improve clinical management. Herein, we propose a pathomics signature (PSGC) that is derived from multiple pathomics features of haematoxylin and eosin-stained slides. We find that the PSGC is an independent predictor of prognosis. A nomogram incorporating the PSGC and TNM staging system shows significantly improved accuracy in predicting the prognosis compared to the TNM staging system alone. Moreover, in stage II and III GC patients with a low PSGC (but not in those with a high PSGC), satisfactory chemotherapy benefits are observed. Therefore, the PSGC could serve as a prognostic predictor in patients with GC and might be a potential predictive indicator for decision-making regarding adjuvant chemotherapy.
REM sleep is associated with distinct global cortical dynamics and controlled by occipital cortex
Authors: Wang Ziyue , Fei Xiang , Liu Xiaotong , Wang Yanjie , Hu Yue , Peng Wanling , Wang Ying-wei , Zhang Siyu , Xu Min 
Published: November 2022

AbstractThe cerebral cortex is spontaneously active during sleep, yet it is unclear how this global cortical activity is spatiotemporally organized, and whether such activity not only reflects sleep states but also contributes to sleep state switching. Here we report that cortex-wide calcium imaging in mice revealed distinct sleep stage-dependent spatiotemporal patterns of global cortical activity, and modulation of such patterns could regulate sleep state switching. In particular, elevated activation in the occipital cortical regions (including the retrosplenial cortex and visual areas) became dominant during rapid-eye-movement (REM) sleep. Furthermore, such pontogeniculooccipital (PGO) wave-like activity was associated with transitions to REM sleep, and optogenetic inhibition of occipital activity strongly promoted deep sleep by suppressing the NREM-to-REM transition. Thus, whereas subcortical networks are critical for initiating and maintaining sleep and wakefulness states, distinct global cortical activity also plays an active role in controlling sleep states.
Dust emission reduction enhanced gas-to-particle conversion of ammonia in the North China Plain
Authors: Liu Yongchun , Zhan Junlei , Zheng Feixue , Song Boying , Zhang Yusheng , Ma Wei , Hua Chenjie , Xie Jiali , Bao Xiaolei , Yan Chao , Bianchi Federico , Petäjä Tuukka , Ding Aijun , Song Yu , He Hong , Kulmala Markku 
Published: November 2022

AbstractAmmonium salt is an important component of particulate matter with aerodynamic diameter less than 2.5 µm (PM2.5) and has significant impacts on air quality, climate, and natural ecosystems. However, a fundamental understanding of the conversion kinetics from ammonia to ammonium in unique environments of high aerosol loading is lacking. Here, we report the uptake coefficient of ammonia (γNH3) on ambient PM2.5 varying from 2.2 × 10−4 to 6.0 × 10−4 in the North China Plain. It is significantly lower than those on the model particles under simple conditions reported in the literature. The probability-weighted γNH3 increases obviously, which is well explained by the annual decrease in aerosol pH due to the significant decline in alkali and alkali earth metal contents from the emission source of dust. Our results elaborate on the complex interactions between primary emissions and the secondary formation of aerosols and the important role of dust in atmospheric chemistry.
Hypothermia evoked by stimulation of medial preoptic nucleus protects the brain in a mouse model of ischaemia
Authors: Zhang Shuai , Zhang Xinpei , Zhong Haolin , Li Xuanyi , Wu Yujie , Ju Jun , Liu Bo , Zhang Zhenyu , Yan Hai , Wang Yizheng , Song Kun , Hou Sheng-Tao 
Published: November 2022

AbstractTherapeutic hypothermia at 32-34 °C during or after cerebral ischaemia is neuroprotective. However, peripheral cold sensor-triggered hypothermia is ineffective and evokes vigorous counteractive shivering thermogenesis and complications that are difficult to tolerate in awake patients. Here, we show in mice that deep brain stimulation (DBS) of warm-sensitive neurones (WSNs) in the medial preoptic nucleus (MPN) produces tolerable hypothermia. In contrast to surface cooling-evoked hypothermia, DBS mice exhibit a torpor-like state without counteractive shivering. Like hypothermia evoked by chemogenetic activation of WSNs, DBS in free-moving mice elicits a rapid lowering of the core body temperature to 32-34 °C, which confers significant brain protection and motor function reservation. Mechanistically, activation of WSNs contributes to DBS-evoked hypothermia. Inhibition of WSNs prevents DBS-evoked hypothermia. Maintaining the core body temperature at normothermia during DBS abolishes DBS-mediated brain protection. Thus, the MPN is a DBS target to evoke tolerable therapeutic hypothermia for stroke treatment.
Structural basis for mechanotransduction in a potassium-dependent mechanosensitive ion channel
Authors: Mount Jonathan , Maksaev Grigory , Summers Brock T. , Fitzpatrick James A. J. , Yuan Peng 
Published: November 2022

AbstractMechanosensitive channels of small conductance, found in many living organisms, open under elevated membrane tension and thus play crucial roles in biological response to mechanical stress. Amongst these channels, MscK is unique in that its activation also requires external potassium ions. To better understand this dual gating mechanism by force and ligand, we elucidate distinct structures of MscK along the gating cycle using cryo-electron microscopy. The heptameric channel comprises three layers: a cytoplasmic domain, a periplasmic gating ring, and a markedly curved transmembrane domain that flattens and expands upon channel opening, which is accompanied by dilation of the periplasmic ring. Furthermore, our results support a potentially unifying mechanotransduction mechanism in ion channels depicted as flattening and expansion of the transmembrane domain.
Simultaneous enhancement in electrical conductivity and Seebeck coefficient by single- to double-valley transition in a Dirac-like band
Authors: Dai Yu , Zhou Wenjiang , Kim Hyun-Jung , Song Qichen , Qian Xin , Liu Te-Huan , Yang Ronggui 
Published: November 2022

AbstractSnTe possesses a single- to double-valley transition in the conduction band minimum when a compressive strain is applied. Through a tight-binding analysis, it is shown that the variation of the band structure is attributed to the strain-induced delocalization of both the Sn-5s orbitals and Te-5p orbitals with different angular momenta. This effect can largely increase the electron density of states near the band edge and thus keep the Fermi level of the compressed SnTe closer to it, where the electrons have lower scattering rates. The strain-induced double valleys lead to simultaneous increases in the electrical conductivity and the Seebeck coefficient and thereby nearly four times the enhancement of the power factor at the doping concentration of 5×1019 cm–3. This work suggests a feasible concept that can be employed to promote the power factor of a Dirac semiconductor via manipulating the valley degeneracy in the conduction band minimum.