bluuebunny/crossref_metadata_2025 huggingface dataset:
The Homelessness Reduction Act 2017: furthering not fracturing marginalisation of those experiencing homelessness
Authors: Bevan Chris
Published: April 2022

The Homelessness Reduction Act 2017 represents the most significant change to the rights of homeless people in England for decades. Through an analysis of the history of homelessness legislation in England, but focusing on the ‘ground-breaking’ 2017 Act, this paper explores how the homeless population is represented and ‘constructed’ in this new legislation and what this tells us about the place of homeless people in our society. In so doing, this paper exposes how the 2017 Act – a state instrument of apparent homelessness prevention – can be read and understood as contributing to rather than obviating the marginalisation and social exclusion of homeless people.
Doherty power amplifier output networks with maximized bandwidth
Authors: Alemdar Sinan , Atalar Abdullah
Published: April 2022

A method is presented to optimize the combining network and the post-matching network of a Doherty power amplifier (DPA) for maximizing the bandwidth. For widely applicable results, RF power transistors are approximated in the large-signal regime using a simple analytical model with a few parameters. A definition of bandwidth of DPA is given, which involves gain and efficiency at full-power and 6 dB backoff. Different combining network topologies are compared in terms of this bandwidth definition. The element values are optimized using two factors, one to scale the combining node impedance and the other to scale the impedance seen by the transistors. For each optimized topology, explicit formulas are given resulting in the element values in terms of the optimized values and a few transistor parameters. The method presented also leads to a proper selection of the post-matching network.
Nutzung digitaler Medien in Kinderkrippen
Authors: Rettenbacher Karoline , Eglmaier Marina Tanja Waltraud , Hackl-Wimmer Sigrid , Paechter Manuela , Rominger Christian , Lackner Helmut Karl , Walter-Laager Catherine , Eichen Lars
Published: April 2022

Zusammenfassung. Medienbildung ist ein Teil des Bildungsauftrags österreichischer Kindertageseinrichtungen ( Charlotte-Bühler-Institut, 2009 ). In der hier vorliegenden Studie wurden 57 frühpädagogische Fachkräfte aus österreichischen Kinderkrippen mittels pilotiertem Fragebogen zu deren digitaler Ausstattung, Häufigkeit und Zweck der (digitalen) Mediennutzung mit den Kindern und Einstellungen gegenüber digitalen Medien in der Kinderkrippe befragt. Die Ergebnisse zeigen, dass es laut den Fachkräften in den Einrichtungen vor allem an digitalen medialen Ressourcen fehlt, um eine umfassende Medienbildung umzusetzen. Die Einstellungen der Fachkräfte gegenüber der Nutzung digitaler Medien in Kinderkrippen sind geteilt. Es wird darauf verwiesen, dass digitale Medien nicht genutzt werden, da andere Entwicklungs- und Bildungsbereiche im Fokus stehen.
Acute Sensitivity of Global Ocean Circulation and Heat Content to Eddy Energy Dissipation Timescale
Authors: Mak J. , Marshall D. P. , Madec G. , Maddison J. R.
Published: April 2022

The global ocean overturning circulation, critically dependent on the global density stratification, plays a central role in regulating climate evolution. While it is well known that the global stratification profile exhibits a strong dependence to Southern Ocean dynamics and in particular to wind and buoyancy forcing, we demonstrate here that the stratification is also acutely sensitive to the mesoscale eddy energy dissipation timescale. Within the context of a global ocean circulation model with an energy constrained mesoscale eddy parameterization, it is shown that modest variations in the eddy energy dissipation timescale lead to significant variations in key metrics relating to ocean circulation, namely the Antarctic Circumpolar Current transport, Atlantic Meridional Overturning Circulation strength, and global ocean heat content, over long timescales. The results highlight a need to constrain uncertainties associated with eddy energy dissipation for climate model projections over centennial timescales and also for paleoclimate simulations over millennial timescales.
Are Terrestrial Biosphere Models Fit for Simulating the Global Land Carbon Sink?
Authors: Seiler Christian , Melton Joe R. , Arora Vivek K. , Sitch Stephen , Friedlingstein Pierre , Anthoni Peter , Goll Daniel , Jain Atul K. , Joetzjer Emilie , Lienert Sebastian , Lombardozzi Danica , Luyssaert Sebastiaan , Nabel Julia E. M. S. , Tian Hanqin , Vuichard Nicolas , Walker Anthony P. , Yuan Wenping , Zaehle Sönke
Published: April 2022

The Global Carbon Project estimates that the terrestrial biosphere has absorbed about one‐third of anthropogenic CO2 emissions during the 1959–2019 period. This sink‐estimate is produced by an ensemble of terrestrial biosphere models and is consistent with the land uptake inferred from the residual of emissions and ocean uptake. The purpose of our study is to understand how well terrestrial biosphere models reproduce the processes that drive the terrestrial carbon sink. One challenge is to decide what level of agreement between model output and observation‐based reference data is adequate considering that reference data are prone to uncertainties. To define such a level of agreement, we compute benchmark scores that quantify the similarity between independently derived reference data sets using multiple statistical metrics. Models are considered to perform well if their model scores reach benchmark scores. Our results show that reference data can differ considerably, causing benchmark scores to be low. Model scores are often of similar magnitude as benchmark scores, implying that model performance is reasonable given how different reference data are. While model performance is encouraging, ample potential for improvements remains, including a reduction in a positive leaf area index bias, improved representations of processes that govern soil organic carbon in high latitudes, and an assessment of causes that drive the inter‐model spread of gross primary productivity in boreal regions and humid tropics. The success of future model development will increasingly depend on our capacity to reduce and account for observational uncertainties.
SIX5-activated LINC01468 promotes lung adenocarcinoma progression by recruiting SERBP1 to regulate SERPINE1 mRNA stability and recruiting USP5 to facilitate PAI1 protein deubiquitylation
Authors: Yuan Yuan , Zhou Danyang , Chen Feifei , Yang Zhenhua , Gu Wei , Zhang Kai
Published: April 2022

Increasing research has uncovered the involvement of long noncoding RNAs (lncRNAs) in the progression of multiple cancers including lung adenocarcinoma (LUAD). RT-qPCR and western blot were done to measure RNAs and proteins. Functional assays assessed LUAD cell biological behaviors under knockdown or overexpression of LINC01468, SIX5, SERBP1 or SERPINE1, and the specific function of those genes in regulating LUAD progression was evaluated via animal experiments. Supported by bioinformatics analysis, the interaction among genes was verified via mechanism assays. Upregulation of LINC01468 in LUAD tissues and cells as well as its association with poor clinical outcome was predicted. LINC01468, transcriptionally activated by SIX5, could strengthen proliferative, migratory and invasive abilities of LUAD cells. The oncogenic role of LINC01468 was further validated via animal experiments. SIX5 was a positive transcription regulator of LINC01468 and could exacerbate LUAD cell malignant behaviors. LINC01468 could recruit SERBP1 to enhance SERPINE1 mRNA stability and interact with USP5 to affect PAI1 protein ubiquitination. The oncogenic role of SERBP1 and SERPINE1 was also confirmed. Rescue experiments finally verified LINC01468 modulated proliferation, migration and invasion of LUAD cells via upregulation of SERPINE1. Our observations could contribute to deeper understanding of LUAD.
Mitochondria bridge HIF signaling and ferroptosis blockage in acute kidney injury
Authors: Li Wenju , Xiang Zhidan , Xing Yuexian , Li Shen , Shi Shaolin
Published: April 2022

Ferroptosis, a form of regulated cell death, plays an important role in acute kidney injury (AKI). Previous studies have shown that prolyl hydroxylase domain protein (PHD) inhibitors that activate HIF signaling provide strong protection against AKI, which is characterized by marked cell death. However, the relationship between PHD inhibition/HIF signaling and ferroptosis in AKI has not been elucidated. Here, we review recent studies to explore the issue. First, we will review the literature concerning the functions of HIF in promoting mitophagy, suppressing mitochondrial respiration and modulating redox homeostasis. Second, we will describe the current understanding of ferroptosis and its role in AKI, particularly from the perspective of mitochondrial dysfunction. Finally, we will discuss the possibility that mitochondria link PHD inhibition/HIF signaling and ferroptosis in AKI. In conclusion, we propose that HIF may protect renal cells against ferroptosis in AKI by reducing mitochondrial oxidative stress and damage.
Efficient iron single-atom catalysts for selective ammoxidation of alcohols to nitriles
Authors: Sun Kangkang , Shan Hongbin , Neumann Helfried , Lu Guo-Ping , Beller Matthias
Published: April 2022

Zeolitic imidazolate frameworks derived Fe1-N-C catalysts with isolated single iron atoms have been synthesized and applied for selective ammoxidation reactions. For the preparation of the different Fe-based materials, benzylamine as an additive proved to be essential to tune the morphology and size of ZIFs resulting in uniform and smaller particles, which allow stable atomically dispersed Fe–N4 active sites. The optimal catalyst Fe1-N-C achieves an efficient synthesis of various aryl, heterocyclic, allylic, and aliphatic nitriles from alcohols in water under very mild conditions. With its chemoselectivity, recyclability, high efficiency under mild conditions this new system complements the toolbox of catalysts for nitrile synthesis, which are important intermediates with many applications in life sciences and industry.
CRISPR-mediated multiplexed live cell imaging of nonrepetitive genomic loci with one guide RNA per locus
Authors: Clow Patricia A. , Du Menghan , Jillette Nathaniel , Taghbalout Aziz , Zhu Jacqueline J. , Cheng Albert W.
Published: April 2022

Three-dimensional (3D) structures of the genome are dynamic, heterogeneous and functionally important. Live cell imaging has become the leading method for chromatin dynamics tracking. However, existing CRISPR- and TALE-based genomic labeling techniques have been hampered by laborious protocols and are ineffective in labeling non-repetitive sequences. Here, we report a versatile CRISPR/Casilio-based imaging method that allows for a nonrepetitive genomic locus to be labeled using one guide RNA. We construct Casilio dual-color probes to visualize the dynamic interactions of DNA elements in single live cells in the presence or absence of the cohesin subunit RAD21. Using a three-color palette, we track the dynamic 3D locations of multiple reference points along a chromatin loop. Casilio imaging reveals intercellular heterogeneity and interallelic asynchrony in chromatin interaction dynamics, underscoring the importance of studying genome structures in 4D.
Paramagnetic relaxation enhancement NMR as a tool to probe guest binding and exchange in metallohosts
Authors: Swartjes Anne , White Paul B. , Bruekers Jeroen P. J. , Elemans Johannes A. A. W. , Nolte Roeland J. M.
Published: April 2022

Paramagnetic metallohost systems can bind guest molecules and find application as biomimetic catalysts. Due to the presence of the paramagnetic metal center, rigorous characterization of these systems by NMR spectroscopy can be very difficult. We report here that metallohost-guest systems can be studied by using the paramagnetic relaxation enhancement (PRE) effect. Manganese(III) porphyrin cage compounds are shown through their PRE to thread and bind viologen guests, including a polymeric one. The binding constants and dethreading activation parameters are lower than those of the metal-free porphyrin cage compounds, which is proposed to be a result of charge repulsion of the trivalent metal center and dicationic viologen guest. The threading rate of the manganese(III) porphyrin cage onto the polymer is more than 10 times faster than that of the non-metallated one, which is ascribed to initial binding of the cage to the polymer chain prior to threading, and to an entron effect.
Electrochemical CO2 reduction to ethylene by ultrathin CuO nanoplate arrays
Authors: Liu Wei , Zhai Pengbo , Li Aowen , Wei Bo , Si Kunpeng , Wei Yi , Wang Xingguo , Zhu Guangda , Chen Qian , Gu Xiaokang , Zhang Ruifeng , Zhou Wu , Gong Yongji
Published: April 2022

Electrochemical reduction of CO2 to multi-carbon fuels and chemical feedstocks is an appealing approach to mitigate excessive CO2 emissions. However, the reported catalysts always show either a low Faradaic efficiency of the C2+ product or poor long-term stability. Herein, we report a facile and scalable anodic corrosion method to synthesize oxygen-rich ultrathin CuO nanoplate arrays, which form Cu/Cu2O heterogeneous interfaces through self-evolution during electrocatalysis. The catalyst exhibits a high C2H4 Faradaic efficiency of 84.5%, stable electrolysis for ~55 h in a flow cell using a neutral KCl electrolyte, and a full-cell ethylene energy efficiency of 27.6% at 200 mA cm−2 in a membrane electrode assembly electrolyzer. Mechanism analyses reveal that the stable nanostructures, stable Cu/Cu2O interfaces, and enhanced adsorption of the *OCCOH intermediate preserve selective and prolonged C2H4 production. The robust and scalable produced catalyst coupled with mild electrolytic conditions facilitates the practical application of electrochemical CO2 reduction.
Predictive biomarkers for survival benefit with ramucirumab in urothelial cancer in the RANGE trial
Authors: van der Heijden Michiel S. , Powles Thomas , Petrylak Daniel , de Wit Ronald , Necchi Andrea , Sternberg Cora N. , Matsubara Nobuaki , Nishiyama Hiroyuki , Castellano Daniel , Hussain Syed A. , Bamias Aristotelis , Gakis Georgios , Lee Jae-Lyun , Tagawa Scott T. , Vaishampayan Ulka , Aragon-Ching Jeanny B. , Eigl Bernie J. , Hozak Rebecca R. , Rasmussen Erik R. , Xia Meng Summer , Rhodes Ryan , Wijayawardana Sameera , Bell-McGuinn Katherine M. , Aggarwal Amit , Drakaki Alexandra
Published: April 2022

The RANGE study (NCT02426125) evaluated ramucirumab (an anti-VEGFR2 monoclonal antibody) in patients with platinum-refractory advanced urothelial carcinoma (UC). Here, we use programmed cell death-ligand 1 (PD-L1) immunohistochemistry (IHC) and transcriptome analysis to evaluate the association of immune and angiogenesis pathways, and molecular subtypes, with overall survival (OS) in UC. Higher PD-L1 IHC and immune pathway scores, but not angiogenesis scores, are associated with greater ramucirumab OS benefit. Additionally, Basal subtypes, which have higher PD-L1 IHC and immune/angiogenesis pathway scores, show greater ramucirumab OS benefit compared to Luminal subtypes, which have relatively lower scores. Multivariable analysis suggests patients from East Asia as having lower immune/angiogenesis signature scores, which correlates with decreased ramucirumab OS benefit. Our data highlight the utility of multiple biomarkers including PD-L1, molecular subtype, and immune phenotype in identifying patients with UC who might derive the greatest benefit from treatment with ramucirumab.
Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis
Authors: Mentrup Torben , Stumpff-Niggemann Anna Yamina , Leinung Nadja , Schlosser Christine , Schubert Katja , Wehner Rebekka , Tunger Antje , Schatz Valentin , Neubert Patrick , Gradtke Ann-Christine , Wolf Janina , Rose-John Stefan , Saftig Paul , Dalpke Alexander , Jantsch Jonathan , Schmitz Marc , Fluhrer Regina , Jacobsen Ilse D. , Schröder Bernd
Published: April 2022

Sensing of pathogens by pattern recognition receptors (PRR) is critical to initiate protective host defence reactions. However, activation of the immune system has to be carefully titrated to avoid tissue damage necessitating mechanisms to control and terminate PRR signalling. Dectin-1 is a PRR for fungal β-glucans on immune cells that is rapidly internalised after ligand-binding. Here, we demonstrate that pathogen recognition by the Dectin-1a isoform results in the formation of a stable receptor fragment devoid of the ligand binding domain. This fragment persists in phagosomal membranes and contributes to signal transduction which is terminated by the intramembrane proteases Signal Peptide Peptidase-like (SPPL) 2a and 2b. Consequently, immune cells lacking SPPL2b demonstrate increased anti-fungal ROS production, killing capacity and cytokine responses. The identified mechanism allows to uncouple the PRR signalling response from delivery of the pathogen to degradative compartments and identifies intramembrane proteases as part of a regulatory circuit to control anti-fungal immune responses.
DELE1 tracks perturbed protein import and processing in human mitochondria
Authors: Fessler Evelyn , Krumwiede Luisa , Jae Lucas T.
Published: April 2022

Protein homeostatic control of mitochondria is key to age-related diseases and organismal decline. However, it is unknown how the diverse types of stress experienced by mitochondria can be integrated and appropriately responded to in human cells. Here we identify perturbations in the ancient conserved processes of mitochondrial protein import and processing as sources of DELE1 activation: DELE1 is continuously sorted across both mitochondrial membranes into the matrix and detects different types of perturbations along the way. DELE1 molecules in transit can become licensed for mitochondrial release and stress signaling through proteolytic removal of N-terminal sorting signals. Import defects that occur at the mitochondrial surface allow DELE1 precursors to bind and activate downstream factor HRI without the need for cleavage. Genome-wide genetics reveal that DELE1 additionally responds to compromised presequence processing by the matrix proteases PITRM1 and MPP, which are mutated in neurodegenerative diseases. These mechanisms rationalize DELE1-dependent mitochondrial stress integration in the human system and may inform future therapies of neuropathies.
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

Lysosomes 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

Type 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

Cryo-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

Inflammation, 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

Ribosome 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

Selenium (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

The 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

G 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

The 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

Diagnosis 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

Complement 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

Social 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

Augmented 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

Abrupt 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.
Assessment of the predictive potential of cognitive scores from retinal images and retinal fundus metadata via deep learning using the CLSA database
Authors: Corbin Denis , Lesage Frédéric
Published: April 2022

Accumulation of beta-amyloid in the brain and cognitive decline are considered hallmarks of Alzheimer’s disease. Knowing from previous studies that these two factors can manifest in the retina, the aim was to investigate whether a deep learning method was able to predict the cognition of an individual from a RGB image of his retina and metadata. A deep learning model, EfficientNet, was used to predict cognitive scores from the Canadian Longitudinal Study on Aging (CLSA) database. The proposed model explained 22.4% of the variance in cognitive scores on the test dataset using fundus images and metadata. Metadata alone proved to be more effective in explaining the variance in the sample (20.4%) versus fundus images (9.3%) alone. Attention maps highlighted the optic nerve head as the most influential feature in predicting cognitive scores. The results demonstrate that RGB fundus images are limited in predicting cognition.
Prolonged and extended impacts of SARS-CoV-2 on the olfactory neurocircuit
Authors: Kishimoto-Urata Megumi , Urata Shinji , Kagoya Ryoji , Imamura Fumiaki , Nagayama Shin , Reyna Rachel A. , Maruyama Junki , Yamasoba Tatsuya , Kondo Kenji , Hasegawa-Ishii Sanae , Paessler Slobodan
Published: April 2022

The impact of SARS-CoV-2 on the olfactory pathway was studied over several time points using Syrian golden hamsters. We found an incomplete recovery of the olfactory sensory neurons, prolonged activation of glial cells in the olfactory bulb, and a decrease in the density of dendritic spines within the hippocampus. These data may be useful for elucidating the mechanism underlying long-lasting olfactory dysfunction and cognitive impairment as a post-acute COVID-19 syndrome.
Pigmented villonodular synovitis of the temporomandibular joint with skull base extension: a retrospective case series
Authors: He Qiang , Zan Xin , Chen Fei , You Chao , Xu Jianguo
Published: April 2022

Most studies on pigmented villonodular synovitis (PVNS) of the temporomandibular joint (TMJ) with skull base extension mostly are case report. Here, we summarize the clinical features, treatments, and outcomes of PVNS of the TMJ with skull base extension in a large case series. We reviewed the clinical information relating to patients diagnosed with PVNS of the TMJ with skull base extension information of patients in our center between 2011 and 2020. We reviewed 10 patients (4 males and 6 females). All cases had presented with a unilateral lesion extending the middle skull base. PVNS of the TMJ with skull base extension occurred on the left side in 6 patients (60%) and on the right side in 4 patients (40%). Of the 10 patients, pain and mass were the most prevalent symptoms. All patients received surgery and no recurrence was seen after 35.90 ± 25.35 months follow-up. Despite destructive biological behavior, surgery can achieve an excellent outcome for patients with PVNS of the TMJ with skull base extension. An en bloc resection may prevent recurrence and provide long-term relief. Radiotherapy may be reserved for subtotal excision and recurrent lesions but require further investigation.
Natural diversity in phenolic components and antioxidant properties of oregano (Origanum vulgare L.) accessions, grown under the same conditions
Authors: Jafari Khorsand Ghazaleh , Morshedloo Mohammad Reza , Mumivand Hasan , Emami Bistgani Zohreh , Maggi Filippo , Khademi Abdolvahab
Published: April 2022

Oregano (Origanum vulgareL.) is a rich source of biologically active components such as phenolic compounds. Here, seven pot grownO. vulgareaccessions belonging to three subspecies (subsp.virens, subsp.vulgareand subsp.gracile) were investigated for their content in sixteen bioactive phenolic compounds as well as their antioxidant capacities (DPPH•and FRAP tests), total phenolic content (TPC) and total flavonoid content (TFC) in order to identify the most suitable ones on an industrial level. HPLC analyses showed that rosmarinic acid (659.6–1646.9 mg/100 g DW) was by far the most abundant constituent, followed by luteolin (46.5–345.4 mg/100 g DW), chicoric acid (36.3–212.5 mg/100 g DW), coumarin (65.7–193.9 mg/100 g DW) and quercetin (10.6–106.1 mg/100 g DW), with variability in concentration depending on the accession and subspecies. The highest level of rosmarinic acid and TPC was obtained from Ardabil accession (subsp.virens). There was a significant and positive correlation between rosmarinic acid and antioxidant activity (r = 0.46). TFC significantly correlated to TPC (r = 0.57) as well as to chicoric acid (r = 0.73). Cluster (CA) and principal component (PCA) analyses classified the investigated accessions in three different groups. Such natural variabilities in phenolics provide the possibility of using elite plants for nutraceutical and pharmaceutical industries and domestication of highly antioxidative accessions of oregano.