bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ca2+-activated sphingomyelin scrambling and turnover mediate ESCRT-independent lysosomal repair
Authors: Niekamp Patrick , Scharte Felix , Sokoya Tolulope , Vittadello Laura , Kim Yeongho , Deng Yongqiang , Südhoff Elisabeth , Hilderink Angelika , Imlau Mirco , Clarke Christopher J. , Hensel Michael , Burd Christopher G. , Holthuis Joost C. M. 
Published: April 2022

AbstractLysosomes are vital organelles vulnerable to injuries from diverse materials. Failure to repair or sequester damaged lysosomes poses a threat to cell viability. Here we report that cells exploit a sphingomyelin-based lysosomal repair pathway that operates independently of ESCRT to reverse potentially lethal membrane damage. Various conditions perturbing organelle integrity trigger a rapid calcium-activated scrambling and cytosolic exposure of sphingomyelin. Subsequent metabolic conversion of sphingomyelin by neutral sphingomyelinases on the cytosolic surface of injured lysosomes promotes their repair, also when ESCRT function is compromised. Conversely, blocking turnover of cytosolic sphingomyelin renders cells more sensitive to lysosome-damaging drugs. Our data indicate that calcium-activated scramblases, sphingomyelin, and neutral sphingomyelinases are core components of a previously unrecognized membrane restoration pathway by which cells preserve the functional integrity of lysosomes.
Mitochondrially targeted tamoxifen alleviates markers of obesity and type 2 diabetes mellitus in mice
Authors: Vacurova Eliska , Trnovska Jaroslava , Svoboda Petr , Skop Vojtech , Novosadova Vendula , Reguera David Pajuelo , Petrezselyová Silvia , Piavaux Benoit , Endaya Berwini , Spoutil Frantisek , Zudova Dagmar , Stursa Jan , Melcova Magdalena , Bielcikova Zuzana , Werner Lukas , Prochazka Jan , Sedlacek Radislav , Huttl Martina , Hubackova Sona Stemberkova , Haluzik Martin , Neuzil Jiri 
Published: April 2022

AbstractType 2 diabetes mellitus represents a major health problem with increasing prevalence worldwide. Limited efficacy of current therapies has prompted a search for novel therapeutic options. Here we show that treatment of pre-diabetic mice with mitochondrially targeted tamoxifen, a potential anti-cancer agent with senolytic activity, improves glucose tolerance and reduces body weight with most pronounced reduction of visceral adipose tissue due to reduced food intake, suppressed adipogenesis and elimination of senescent cells. Glucose-lowering effect of mitochondrially targeted tamoxifen is linked to improvement of type 2 diabetes mellitus-related hormones profile and is accompanied by reduced lipid accumulation in liver. Lower senescent cell burden in various tissues, as well as its inhibitory effect on pre-adipocyte differentiation, results in lower level of circulating inflammatory mediators that typically enhance metabolic dysfunction. Targeting senescence with mitochodrially targeted tamoxifen thus represents an approach to the treatment of type 2 diabetes mellitus and its related comorbidities, promising a complex impact on senescence-related pathologies in aging population of patients with type 2 diabetes mellitus with potential translation into the clinic.
Waffle Method: A general and flexible approach for improving throughput in FIB-milling
Authors: Kelley Kotaro , Raczkowski Ashleigh M. , Klykov Oleg , Jaroenlak Pattana , Bobe Daija , Kopylov Mykhailo , Eng Edward T. , Bhabha Gira , Potter Clinton S. , Carragher Bridget , Noble Alex J. 
Published: April 2022

AbstractCryo-FIB/SEM combined with cryo-ET has emerged from within the field of cryo-EM as the method for obtaining the highest resolution structural information of complex biological samples in-situ in native and non-native environments. However, challenges remain in conventional cryo-FIB/SEM workflows, including milling thick specimens with vitrification issues, specimens with preferred orientation, low-throughput when milling small and/or low concentration specimens, and specimens that distribute poorly across grid squares. Here we present a general approach called the ‘Waffle Method’ which leverages high-pressure freezing to address these challenges. We illustrate the mitigation of these challenges by applying the Waffle Method and cryo-ET to reveal the macrostructure of the polar tube in microsporidian spores in multiple complementary orientations, which was previously not possible due to preferred orientation. We demonstrate the broadness of the Waffle Method by applying it to three additional cellular samples and a single particle sample using a variety of cryo-FIB-milling hardware, with manual and automated approaches. We also present a unique and critical stress-relief gap designed specifically for waffled lamellae. We propose the Waffle Method as a way to achieve many advantages of cryo-liftout on the specimen grid while avoiding the long, challenging, and technically-demanding process required for cryo-liftout.
Citrullination of glucokinase is linked to autoimmune diabetes
Authors: Yang Mei-Ling , Horstman Sheryl , Gee Renelle , Guyer Perrin , Lam TuKiet T. , Kanyo Jean , Perdigoto Ana L. , Speake Cate , Greenbaum Carla J. , Callebaut Aïsha , Overbergh Lut , Kibbey Richard G. , Herold Kevan C. , James Eddie A. , Mamula Mark J. 
Published: April 2022

AbstractInflammation, including reactive oxygen species and inflammatory cytokines in tissues amplify various post-translational modifications of self-proteins. A number of post-translational modifications have been identified as autoimmune biomarkers in the initiation and progression of Type 1 diabetes. Here we show the citrullination of pancreatic glucokinase as a result of inflammation, triggering autoimmunity and affecting glucokinase biological functions. Glucokinase is expressed in hepatocytes to regulate glycogen synthesis, and in pancreatic beta cells as a glucose sensor to initiate glycolysis and insulin signaling. We identify autoantibodies and autoreactive CD4+T cells to glucokinase epitopes in the circulation of Type 1 diabetes patients and NOD mice. Finally, citrullination alters glucokinase biologic activity and suppresses glucose-stimulated insulin secretion. Our study define glucokinase as a Type 1 diabetes biomarker, providing new insights of how inflammation drives post-translational modifications to create both neoautoantigens and affect beta cell metabolism.
Direct measurements of mRNA translation kinetics in living cells
Authors: Metelev Mikhail , Lundin Erik , Volkov Ivan L. , Gynnå Arvid H. , Elf Johan , Johansson Magnus 
Published: April 2022

AbstractRibosome mediated mRNA translation is central to life. The cycle of translation, however, has been characterized mostly using reconstituted systems, with only few techniques applicable for studies in the living cell. Here we describe a live-cell ribosome-labeling method, which allows us to characterize the whole processes of finding and translating an mRNA, using single-molecule tracking techniques. We find that more than 90% of both bacterial ribosomal subunits are engaged in translation at any particular time, and that the 30S and 50S ribosomal subunits spend the same average time bound to an mRNA, revealing that 30S re-initiation on poly-cistronic mRNAs is not prevalent in E. coli. Instead, our results are best explained by substantial 70S re-initiation of translation of poly-cistronic mRNAs, which is further corroborated by experiments with translation initiation inhibitors. Finally, we find that a variety of previously described orthogonal ribosomes, with altered anti-Shine-Dalgarno sequences, show significant binding to endogenous mRNAs.
Enabling fast-charging selenium-based aqueous batteries via conversion reaction with copper ions
Authors: Dai Chunlong , Hu Linyu , Chen Hao , Jin Xuting , Han Yuyang , Wang Ying , Li Xiangyang , Zhang Xinqun , Song Li , Xu Maowen , Cheng Huhu , Zhao Yang , Zhang Zhipan , Liu Feng , Qu Liangti 
Published: April 2022

AbstractSelenium (Se) is an appealing alternative cathode material for secondary battery systems that recently attracted research interests in the electrochemical energy storage field due to its high theoretical specific capacity and good electronic conductivity. However, despite the relevant capacity contents reported in the literature, Se-based cathodes generally show poor rate capability behavior. To circumvent this issue, we propose a series of selenium@carbon (Se@C) composite positive electrode active materials capable of delivering a four-electron redox reaction when placed in contact with an aqueous copper-ion electrolyte solution (i.e., 0.5 M CuSO4) and copper or zinc foils as negative electrodes. The lab-scale Zn | |Se@C cell delivers a discharge voltage of about 1.2 V at 0.5 A g−1 and an initial discharge capacity of 1263 mAh gSe−1. Interestingly, when a specific charging current of 6 A g−1 is applied, the Zn | |Se@C cell delivers a stable discharge capacity of around 900 mAh gSe−1 independently from the discharge rate. Via physicochemical characterizations and first-principle calculations, we demonstrate that battery performance is strongly associated with the reversible structural changes occurring at the Se-based cathode.
Multiple yet switchable hydrogen-bonded organic frameworks with white-light emission
Authors: Shi Yadong , Wang Shuodong , Tao Wei , Guo Jingjing , Xie Sheng , Ding Yanglan , Xu Guoyong , Chen Cheng , Sun Xiaoyu , Zhang Zengming , He Zikai , Wei Peifa , Tang Ben Zhong 
Published: April 2022

AbstractThe development of new strategies to construct on-demand porous lattice frameworks from simple motifs is desirable. However, mitigating complexity while combing multiplicity and reversibility in the porous architectures is a challenging task. Herein, based on the synergy of dynamic intermolecular interactions and flexible molecular conformation of a simple cyano-modified tetraphenylethylene tecton, eleven kinetic-stable hydrogen-bonded organic frameworks (HOFs) with various shapes and two thermo-stable non-porous structures with rare perpendicular conformation are obtained. Multimode reversible structural transformations along with visible fluorescence output between porous and non-porous or between different porous forms is realized under different external stimuli. Furthermore, the collaborative of flexible framework and soft long-chain guests facilitate the relaxation from intrinsic blue emission to yellow emission in the excited state, which represents a strategy for generating white-light emission. The dynamic intermolecular interactions, facilitated by flexible molecular conformation and soft guests, diversifies the strategies of construction of versatile smart molecular frameworks.
Capturing a rhodopsin receptor signalling cascade across a native membrane
Authors: Chen Siyun , Getter Tamar , Salom David , Wu Di , Quetschlich Daniel , Chorev Dror S. , Palczewski Krzysztof , Robinson Carol V. 
Published: April 2022

AbstractG protein-coupled receptors (GPCRs) are cell-surface receptors that respond to various stimuli to induce signalling pathways across cell membranes. Recent progress has yielded atomic structures of key intermediates1,2 and roles for lipids in signalling3,4. However, capturing signalling events of a wild-type receptor in real time, across a native membrane to its downstream effectors, has remained elusive. Here we probe the archetypal class A GPCR, rhodopsin, directly from fragments of native disc membranes using mass spectrometry. We monitor real-time photoconversion of dark-adapted rhodopsin to opsin, delineating retinal isomerization and hydrolysis steps, and further showing that the reaction is significantly slower in its native membrane than in detergent micelles. Considering the lipids ejected with rhodopsin, we demonstrate that opsin can be regenerated in membranes through photoisomerized retinal–lipid conjugates, and we provide evidence for increased association of rhodopsin with unsaturated long-chain phosphatidylcholine during signalling. Capturing the secondary steps of the signalling cascade, we monitor light activation of transducin (Gt) through loss of GDP to generate an intermediate apo-trimeric G protein, and observe Gαt•GTP subunits interacting with PDE6 to hydrolyse cyclic GMP. We also show how rhodopsin-targeting compounds either stimulate or dampen signalling through rhodopsin–opsin and transducin signalling pathways. Our results not only reveal the effect of native lipids on rhodopsin signalling and regeneration but also enable us to propose a paradigm for GPCR drug discovery in native membrane environments.
Characteristics of immunophenotypes and immunological in tumor microenvironment and analysis of immune implication of CXCR4 in gastric cancer
Authors: Wen Fang , Lu Xiaona , Huang Wenjie , Chen Xiaoxue , Ruan Shuai , Gu SuPing , Gu Peixing , Li Ye , Liu Jiatong , Liu Shenlin , Shu Peng 
Published: April 2022

AbstractThe formation of gastric cancer (GC) is a complicated process involving multiple factors and multiple steps. The tumor–immune microenvironment is essential for the growth of GC and affects the prognosis of patients. We performed multiple machine learning algorithms to identify immunophenotypes and immunological characteristics in GC patients’ information from the TCGA database and extracted immune genes relevance of the GC immune microenvironment. C-X-C motif chemokine receptor 4 (CXCR4), belongs to the C-X-C chemokine receptor family, which can promote the invasion and migration of tumor cells. CXCR4 expression is significantly correlated to metastasis and the worse prognosis. In this work, we assessed the condition of immune cells and identified the connection between CXCR4 and GC immune microenvironment, as well as the signaling pathways that mediate the immune responses involved in CXCR4. The work showed the risk scores generated by CXCR4-related immunomodulators could distinguish risk groups consisting of differential expression genes and could use for the personalized prognosis prediction. The findings suggested that CXCR4 is involved in tumor immunity of GC, and CXCR4 is considered as a potential prognostic biomarker and immunotherapy target of GC. The prognostic immune markers from CXCR4-associated immunomodulators can independently predict the overall survival of GC.
A pilot study of disease related education and psychotherapeutic support for unresolved grief in parents of children with CF
Authors: Schultz André , Barrett Andrea , Balding Elizabeth , Billingham Wesley , Branch-Smith Cindy , Grover Zubin , Yikilmaz Gisele , Bourke Crystal , Depiazzi Julie , Sander Nicole , Foster Juliet , Cooper Matthew , Zepf Florian 
Published: April 2022

AbstractDiagnosis of chronic disease in a child can result in unresolved grief (UG) in parents. This study aimed to evaluate the efficacy of psychological insight-oriented therapy (IOT) as a treatment for UG compared to disease related education in parents of children with cystic fibrosis (CF). Sequence of delivery, first IOT then disease related education (or vice versa) was also examined, to let all participants experience both interventions. Parents were screened for UG. Parents with UG were randomised to either five 1-h sessions of IOT or five 1-h sessions of education. Measures were assessed pre-intervention, after the first intervention period (primary efficacy assessment), and after the second intervention period (swapping intervention). Forty-seven parents were screened of which 46.8% (22/47) had UG. Median duration of UG was 5 years (range: 6 months–14 years). Anxiety (50% vs. 20%, p = 0.03) and stress (59% vs. 28%, p = 0.03) were significantly more prevalent in parents with UG. There was no difference between arms in the odds of UG resolving either following the first intervention period (OR 0.88; 95% CI 0.5, 1.5) or the second intervention period (OR 0.91; 95% CI 0.5, 1.6). While not statistically significant, adjusted mean values for seven of the eight mental health measures were lower in the IOT (first) arm compared to the ED (first) arm, following the first intervention period. UG is a significant burden for families affected by CF. Provision of disease related education and psychological support, regardless of sequence, can result in resolution of grief.Trial registration number: ACTRN12621000796886, date of registration 24/06/2021, retrospectively registered.
Association of mannose-binding lectin 2 gene polymorphisms with Guillain-Barré syndrome
Authors: Jahan Israt , Hayat Shoma , Khalid Mir M. , Ahammad Rijwan U. , Asad Asaduzzaman , Islam Badrul , Mohammad Quazi D. , Jacobs Bart C. , Islam Zhahirul 
Published: April 2022

AbstractComplement activation plays a critical role in the pathogenesis of Guillain-Barré syndrome (GBS), a debilitating immune-mediated neuropathy. Mannose-binding lectin (MBL) is a complement activation factor of lectin pathway which as genetic host factor may influence the susceptibility or severity of GBS. We investigated the frequency ofMBL2promoter (− 550H/L and − 221X/Y) and functional region (exon 1 A/O) polymorphisms and their association with disease susceptibility, clinical features and serum MBL among GBS patients (n = 300) and healthy controls (n = 300) in Bangladesh. The median patient age was 30 years (IQR: 18–42; males, 68%).MBL2polymorphisms were not significantly associated with GBS susceptibility compared to healthy controls. HL heterozygosity in GBS patients was significantly associated with mild functional disability at enrolment (P = 0.0145, OR, 95% CI 2.1, 1.17–3.82). The HY, YA, HA and HYA heterozygous haplotypes were more common among mildly affected (P = 0.0067,P = 0.0086,P = 0.0075,P = 0.0032, respectively) than severely affected patients with GBS. Reduced serum MBL was significantly associated with the LL, OO and no HYA variants and GBS disease severity. No significant association was observed betweenMBL2polymorphisms and electrophysiological variants, recentCampylobacter jejuniinfection or anti-ganglioside (GM1) antibody responses in GBS. In conclusion,MBL2gene polymorphisms are related to reduced serum MBL and associated with the severity of GBS.
In.To. COVID-19 socio-epidemiological co-causality
Authors: Galbraith Elroy , Li Jie , Rio-Vilas Victor J. Del , Convertino Matteo 
Published: April 2022

AbstractSocial media can forecast disease dynamics, but infoveillance remains focused on infection spread, with little consideration of media content reliability and its relationship to behavior-driven epidemiological outcomes. Sentiment-encoded social media indicators have been poorly developed for expressed text to forecast healthcare pressure and infer population risk-perception patterns. Here we introduce Infodemic Tomography (InTo) as the first web-based interactive infoveillance cybertechnology that forecasts and visualizes spatio-temporal sentiments and healthcare pressure as a function of social media positivity (i.e., Twitter here), considering both epidemic information and potential misinformation. Information spread is measured on volume and retweets, and the Value of Misinformation (VoMi) is introduced as the impact on forecast accuracy where misinformation has the highest dissimilarity in information dynamics. We validated InTo for COVID-19 in New Delhi and Mumbai by inferring distinct socio-epidemiological risk-perception patterns. We forecast weekly hospitalization and cases using ARIMA models and interpolate spatial hospitalization using geostatistical kriging on inferred risk perception curves between tweet positivity and epidemiological outcomes. Geospatial tweet positivity tracks accurately $$\sim $$
∼
60$$\%$$
%
of hospitalizations and forecasts hospitalization risk hotspots along risk aversion gradients. VoMi is higher for risk-prone areas and time periods, where misinformation has the highest non-linear predictability, with high incidence and positivity manifesting popularity-seeking social dynamics. Hospitalization gradients, VoMi, effective healthcare pressure and spatial model-data gaps can be used to predict hospitalization fluxes, misinformation, healthcare capacity gaps and surveillance uncertainty. Thus, InTo is a participatory instrument to better prepare and respond to public health crises by extracting and combining salient epidemiological and social surveillance at any desired space-time scale.
Metasurface wavefront control for high-performance user-natural augmented reality waveguide glasses
Authors: Boo Hyunpil , Lee Yoo Seung , Yang Hangbo , Matthews Brian , Lee Tom G. , Wong Chee Wei 
Published: April 2022

AbstractAugmented reality (AR) devices, as smart glasses, enable users to see both the real world and virtual images simultaneously, contributing to an immersive experience in interactions and visualization. Recently, to reduce the size and weight of smart glasses, waveguides incorporating holographic optical elements in the form of advanced grating structures have been utilized to provide light-weight solutions instead of bulky helmet-type headsets. However current waveguide displays often have limited display resolution, efficiency and field-of-view, with complex multi-step fabrication processes of lower yield. In addition, current AR displays often have vergence-accommodation conflict in the augmented and virtual images, resulting in focusing-visual fatigue and eye strain. Here we report metasurface optical elements designed and experimentally implemented as a platform solution to overcome these limitations. Through careful dispersion control in the excited propagation and diffraction modes, we design and implement our high-resolution full-color prototype, via the combination of analytical–numerical simulations, nanofabrication and device measurements. With the metasurface control of the light propagation, our prototype device achieves a 1080-pixel resolution, a field-of-view more than 40°, an overall input–output efficiency more than 1%, and addresses the vergence-accommodation conflict through our focal-free implementation. Furthermore, our AR waveguide is achieved in a single metasurface-waveguide layer, aiding the scalability and process yield control.
An effective modular approach for crowd counting in an image using convolutional neural networks
Authors: Ilyas Naveed , Ahmad Zaheer , Lee Boreom , Kim Kiseon 
Published: April 2022

AbstractAbrupt and continuous nature of scale variation in a crowded scene is a challenging task to enhance crowd counting accuracy in an image. Existing crowd counting techniques generally used multi-column or single-column dilated convolution to tackle scale variation due to perspective distortion. However, due to multi-column nature, they obtain identical features, whereas, the standard dilated convolution (SDC) with expanded receptive field size has sparse pixel sampling rate. Due to sparse nature of SDC, it is highly challenging to obtain relevant contextual information. Further, features at multiple scale are not extracted despite some inception-based model is not used (which is cost effective). To mitigate theses drawbacks in SDC, we therefore, propose a hierarchical dense dilated deep pyramid feature extraction through convolution neural network (CNN) for single image crowd counting (HDPF). It comprises of three modules: general feature extraction module (GFEM), deep pyramid feature extraction module (PFEM) and fusion module (FM). The GFEM is responsible to obtain task independent general features. Whereas, PFEM plays a vital role to obtain the relevant contextual information due to dense pixel sampling rate caused by densely connected dense stacked dilated convolutional modules (DSDCs). Further, due to dense connections among DSDCs, the final feature map acquires multi-scale information with expanded receptive field as compared to SDC. Due to dense pyramid nature, it is very effective to propagate the extracted feature from lower dilated convolutional layers (DCLs) to middle and higher DCLs, which result in better estimation accuracy. The FM is used to fuse the incoming features extracted by other modules. The proposed technique is tested through simulations on three well known datasets: Shanghaitech (Part-A), Shanghaitech (Part-B) and Venice. Results justify its relative effectiveness in terms of selected performance.