bluuebunny/crossref_metadata_2025 huggingface dataset:
A revision of theRostania occultata(Collemataceae) complex in Fennoscandia
Authors: Košuthová Alica , Westberg Martin , Wedin Mats
Published: February 2022

TheRostania occultataspecies complex (‘Collema occultatums. lat.’) is revised in Fennoscandia and found to consist of four species, all epiphytes on deciduous trees:Rostania effusaA. Košuth., M. Westb. & Wedin sp. nov.,R. occultata(Bagl.) Otáloraet al.,R. pallidaA. Košuth., M. Westb. & Wedin sp. nov. andR. populina(Th. Fr.) A. Košuth., M. Westb. & Wedin comb. nov.Rostania effusaandR. pallidaare newly described from humid habitats in old-growth boreal coniferous forests, usually with a mixture of deciduous trees, and from similar areas in the subalpine birch-dominated forests of Fennoscandia.Rostania effusais characterized by apothecia with red-brown apothecium discs and an excipulum thallinum with a simple pseudocortex and cubic to oblong, muriform spores.Rostania pallidahas apothecia with whitish to pale yellowish discs and an excipulum thallinum with a distinct cellular pseudocortex, and ellipsoid, muriform mature spores that are often constricted at the centre. A lectotype is designated forCollema quadratumJ. Lahm ex Körb. The new combinationRostania populinais introduced for the species recognized until now as the varietyRostania occultatavar.populina(Th. Fr.) Perlmutter & Rivas Plata. A key to the six species inRostanias. str. is included.
Haemodynamic impact of chest compressions in the delivery room
Authors: Natarajan Girija , Bajaj Monika , Aggarwal Sanjeev
Published: February 2022

Among 65 neonates with encephalopathy undergoing cooling, 30 (46.1%) received chest compressions during delivery room resuscitation. Despite differences in encephalopathy severity, early (<24 hours) biventricular function on echocardiogram (fractional area change, myocardial performance indices, systolic to diastolic duration ratios, tricuspid annular plane systolic excursion) was comparable between groups with and without chest compressions. Epinephrine receipt was associated with abnormal tricuspid annular plane systolic excursion.
The Impact of Trade Barrier Reductions on Global Value Chains for Agricultural Products in China and Countries along the ‘Belt and Road’
Authors: Zhang Zhen , Gao Yue , Wei Taoyuan
Published: February 2022

The Belt and Road Initiative (BRI) may potentially reduce trade barriers between China and countries along the Belt and Road (BR) route, affecting the positions in Global Value Chains (GVCs) of agricultural products of these countries. This study explores the BRI influence on the GVC positions using a global computable general equilibrium (CGE) model and focusing on China and the BR countries. The study finds that the reduction of tariff barriers and non-tariff barriers between countries along ‘the Belt and Road’ results in increased producer prices and volumes of almost all agricultural products exported from China, which improves the position of China in the GVCs of these agricultural products in our best estimate scenario. Countries along the BR route also benefit from the reduction in trade barriers, with improved positions in the GVCs of agricultural products in the best estimate scenario, especially those products that have comparative advantages in GVCs.
Secondary 12‐Day Planetary Wave in the Mesospheric Water Vapor During the 2016/2017 Unusual Canadian Stratospheric Warming
Authors: Qin Yusong , Gu Sheng‐Yang , Dou Xiankang , Teng Chen‐Ke‐Min , Yang Zhenlin
Published: February 2022

The anomalous strengthening of the stratospheric Aleutian High during the early boreal winter of 2016/2017 led to a rare Canadian stratospheric warming (CSW) event, during which the extent of the wind reversal in the Arctic region is the strongest among CSWs since 2001. Unlike sudden stratospheric warmings, the polar vortex during this CSW is merely distorted, not displaced off the pole or split into two pieces, and the polar mean temperature only has a modest increase of a few kelvins. Using the Aura satellite Microwave Limb Sounder measurements, an exceptionally strong 12‐day wave (12DW) with westward zonal wavenumber 1 is captured in the mesospheric water vapor mixing ratio during the recovery phase of this CSW. Further diagnostic analysis suggests that the baroclinic/barotropic instability related to this CSW triggers the 12DW in the Arctic stratosphere, and meridional advection plays a leading role in the modulation of 12DW on mesospheric water vapor.
Bidecadal Temperature Anomalies Over the Tibetan Plateau and Arctic in Response to the 1450s Volcanic Eruptions
Authors: Liu Wei , Shi Feng , Xiao Guoqiao , Xue Huihong , Yin Qiuzhen , Liu Fei , Duan Anmin , Xiao Cunde , Guo Zhengtang
Published: February 2022

Volcanic eruptions have been the most dominant natural forcing of climate change over the past millennium, affecting temperature change at multiple timescales. However, how volcanic eruptions affect regional temperature variability on the decadal timescale remains unclear. We analyzed the bidecadal effects of volcanic eruptions in the mid‐fifteenth century on two representative regions (the Tibetan plateau [TP] and the Arctic) in the Northern Hemisphere by combining proxy reconstructions, model ensemble simulations, and model sensitive experiments. The results show that the TP experienced bidecadal cooling during the mid‐fifteenth century as a result of the long‐term heat uptake in the midlatitude ocean that reduced latent heat transfer to the atmosphere. A positive sea ice–albedo feedback led to a bidecadal summer temperature decrease in the Arctic comparable to that on the TP, whereas the Arctic winter experienced stronger bidecadal cooling caused by a reduced ocean–atmosphere energy exchange and atmospheric poleward energy transport. In addition, our results show that it took ∼20 years for the temperature in these two regions to return to the level that existed before the first eruption, and this was linked to the strengthening of the Atlantic Meridional Overturning Circulation and ocean heat transport.
Unraveling the Contribution of Turbulence and Bubbles to Air‐Water Gas Exchange in Running Waters
Authors: Klaus M. , Labasque T. , Botter G. , Durighetto N. , Schelker J.
Published: February 2022

Quantifying air‐water gas exchange is critical for estimating greenhouse gas fluxes and metabolism in aquatic ecosystems. In high‐energy streams, the gas exchange rate k is poorly constrained, due to an incomplete understanding of turbulence and bubble contributions to k. We performed a flume experiment with air bubble additions to evaluate the combined effects of turbulence and bubbles on k for helium, argon, xenon, and methane. We created contrasting hydraulic conditions by varying channel slope, bed roughness, water discharge, and bubble flux. We found that k increased from 1–4 to 17–66 m d−1 with increases in turbulence and bubble flux metrics. Mechanistic models that explicitly account for these metrics, as well as gas diffusivity and solubility, agreed well with the data and indicated that bubble‐mediated gas exchange accounted for 64–93% of k. Bubble contributions increased with bubble flux but were independent of gas type, as bubbles did not equilibrate with the water. This was evident through modeled bubble life and equilibration times inferred from bubble size distributions obtained from underwater sound spectra. Sound spectral properties correlated well with turbulence and bubble flux metrics. Our results demonstrate that (a) mechanistic models can be applied to separate free surface‐ and bubble‐mediated gas exchange in running waters, (b) bubble life and equilibration times are critical for accurate scaling of k between different gases, and (c) ambient sound spectra can be used to approximate contributions of turbulence and bubbles.
Coal Seam Fires Burn Beneath Communities in Zimbabwe
Authors: Mambondiyani Andrew
Published: February 2022

Underground fires threaten the health of people and livestock living near mines supporting the country’s growing coal industry.
Protein C receptor maintains cancer stem cell properties via activating lipid synthesis in nasopharyngeal carcinoma
Authors: Zhang Panpan , He Qiuping , Wang Yaqin , Zhou Guanqun , Chen Yupei , Tang Linglong , Zhang Yuan , Hong Xiaohong , Mao Yanping , He Qingmei , Yang Xiaojing , Liu Na , Ma Jun
Published: February 2022

Metastasis and recurrence account for 95% of deaths from nasopharyngeal carcinoma (NPC). Cancer stem cells (CSCs) are regarded as one of the main reasons for tumor cell resistance to clinical therapy, and cancer metastasis or recurrence, while little is known about CSCs in NPC. The present study uncovers a subpopulation of cells labeled as CD45−EPCAM+PROCR+ in NPC biopsy samples that exhibit stem cell-like characteristics. A relatively low number of these cells initiate xenograft tumors in mice. Functional analysis reveals that protein C receptor (PROCR) not only serves as a stem cell marker in NPC, but also maintains tumor cells’ stemness potential through regulating lipid metabolism and mitochondrial fission. Epistatic studies reveal that cAMP-protein kinase A stimulates Ca2+ release to manipulate lipid metabolism related genes’ expression. Finally, in a cohort of 207 NPC samples, PROCR expression is correlated with tumor metastasis or recurrence, and predicts poor prognosis. These novel findings link PROCR labeled CSCs with lipid metabolism and mitochondrial plasticity, and provides new clinical target against metastatic or recurrent NPC.
Active anaerobic methane oxidation and sulfur disproportionation in the deep terrestrial subsurface
Authors: Bell Emma , Lamminmäki Tiina , Alneberg Johannes , Qian Chen , Xiong Weili , Hettich Robert L , Frutschi Manon , Bernier-Latmani Rizlan
Published: February 2022

Microbial life is widespread in the terrestrial subsurface and present down to several kilometers depth, but the energy sources that fuel metabolism in deep oligotrophic and anoxic environments remain unclear. In the deep crystalline bedrock of the Fennoscandian Shield at Olkiluoto, Finland, opposing gradients of abiotic methane and ancient seawater-derived sulfate create a terrestrial sulfate-methane transition zone (SMTZ). We used chemical and isotopic data coupled to genome-resolved metaproteogenomics to demonstrate active life and, for the first time, provide direct evidence of active anaerobic oxidation of methane (AOM) in a deep terrestrial bedrock. Proteins from Methanoperedens (formerly ANME-2d) are readily identifiable despite the low abundance (≤1%) of this genus and confirm the occurrence of AOM. This finding is supported by 13C-depleted dissolved inorganic carbon. Proteins from Desulfocapsaceae and Desulfurivibrionaceae, in addition to 34S-enriched sulfate, suggest that these organisms use inorganic sulfur compounds as both electron donor and acceptor. Zerovalent sulfur in the groundwater may derive from abiotic rock interactions, or from a non-obligate syntrophy with Methanoperedens, potentially linking methane and sulfur cycles in Olkiluoto groundwater. Finally, putative episymbionts from the candidate phyla radiation (CPR) and DPANN archaea represented a significant diversity in the groundwater (26/84 genomes) with roles in sulfur and carbon cycling. Our results highlight AOM and sulfur disproportionation as active metabolisms and show that methane and sulfur fuel microbial activity in the deep terrestrial subsurface.
Long non-coding ROR promotes the progression of papillary thyroid carcinoma through regulation of the TESC/ALDH1A1/TUBB3/PTEN axis
Authors: Fan Yuxia , Fan Xin , Yan Hao , Liu Zheng , Wang Xiaoming , Yuan Qingling , Xie Jie , Lu Xiubo , Yang Yang
Published: February 2022

Papillary thyroidal carcinoma (PTC) is a common endocrine cancer that plagues people across the world. The potential roles of long non-coding RNAs (lncRNAs) in PTC have gained increasing attention. In this study, we aimed to explore whether lncRNA ROR affects the progression of PTC, with the involvement of tescalcin (TESC)/aldehyde dehydrogenase isoform 1A1 (ALDH1A1)/βIII-tubulin (TUBB3)/tensin homolog (PTEN) axis. PTC tumor and adjacent tissues were obtained, followed by measurement of lncRNA ROR and TESC, ALDH1A1, and TUBB3 expression. Interactions among lncRNA ROR, TESC, ALDH1A1, TUBB3, and PTEN were evaluated by ChIP assay, RT-qPCR, or western blot analysis. After ectopic expression and depletion experiments in PTC cells, MTT and colony formation assay, Transwell assay, and flow cytometry were performed to detect cell viability and colony formation, cell migration and invasion, and apoptosis, respectively. In addition, xenograft in nude mice was performed to test the effects of lncRNA ROR and PTEN on tumor growth in PTC in vivo. LncRNA ROR, TESC, ALDH1A1, and TUBB3 were highly expressed in PTC tissues and cells. Overexpression of lncRNA ROR activated TESC by inhibiting the G9a recruitment on the promoter of TESC and histone H3-lysine 9me methylation. Moreover, TESC upregulated ALDH1A1 expression to increase TUBB3 expression, which then reduced PTEN expression. Overexpression of lncRNA ROR, TESC, ALDH1A1 or TUBB3 and silencing of PTEN promoted PTC cell viability, colony formation, migration, and invasion while suppressing apoptosis. Moreover, overexpression of lncRNA ROR increased tumor growth by inhibiting PTEN in vivo. Taken together, the current study demonstrated that lncRNA ROR mediated TESC/ALDH1A1/TUBB3/PTEN axis, thereby facilitating the development of PTC.
CHCHD2 and CHCHD10 regulate mitochondrial dynamics and integrated stress response
Authors: Ruan Yu , Hu Jiaqiao , Che Yaping , Liu Yanyan , Luo Zhenhuan , Cheng Jin , Han Qi , He He , Zhou Qinghua
Published: February 2022

Mitochondrial dysfunction is becoming one of the main pathology factors involved in the etiology of neurological disorders. Recently, mutations of the coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) and 10 (CHCHD10) which encode two homologous proteins that belong to the mitochondrial CHCH domain protein family, are linked to Parkinson’s disease and amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD), respectively. However, the physiological and pathological roles of these twin proteins have not been well elaborated. Here, we show that, in physiological conditions, CHCHD2 and CHCHD10 interact with OMA1 and suppress its enzyme activity, which not only restrains the initiation of the mitochondrial integrated response stress (mtISR), but also suppresses the processing of OPA1 for mitochondrial fusion. Further, during mitochondria stress-induced by carbonyl cyanide m-chlorophenylhydrazone (CCCP) treatment, CHCHD2 and CHCHD10 translocate to the cytosol and interacte with eIF2a, which attenuates mtISR overactivation by suppressing eIF2a phosphorylation and its downstream response. As such, knockdown of CHCHD2 and CHCHD10 triggers mitochondrial ISR, and such cellular response is enhanced by CCCP treatment. Therefore, our findings demonstrate the first “mtISR suppressor” localized in mitochondria for regulating stress responses in mammalian cells, which has a profound pathological impact on the CHCH2/CHCH10-linked neurodegenerative disorder.
An efficient urine peptidomics workflow identifies chemically defined dietary gluten peptides from patients with celiac disease
Authors: Palanski Brad A. , Weng Nielson , Zhang Lichao , Hilmer Andrew J. , Fall Lalla A. , Swaminathan Kavya , Jabri Bana , Sousa Carolina , Fernandez-Becker Nielsen Q. , Khosla Chaitan , Elias Joshua E.
Published: February 2022

Celiac disease (CeD) is an autoimmune disorder induced by consuming gluten proteins from wheat, barley, and rye. Glutens resist gastrointestinal proteolysis, resulting in peptides that elicit inflammation in patients with CeD. Despite well-established connections between glutens and CeD, chemically defined, bioavailable peptides produced from dietary proteins have never been identified from humans in an unbiased manner. This is largely attributable to technical challenges, impeding our knowledge of potentially diverse peptide species that encounter the immune system. Here, we develop a liquid chromatographic-mass spectrometric workflow for untargeted sequence analysis of the urinary peptidome. We detect over 600 distinct dietary peptides, of which ~35% have a CeD-relevant T cell epitope and ~5% are known to stimulate innate immune responses. Remarkably, gluten peptides from patients with CeD qualitatively and quantitatively differ from controls. Our results provide a new foundation for understanding gluten immunogenicity, improving CeD management, and characterizing the dietary and urinary peptidomes.
Dual clathrin and integrin signaling systems regulate growth factor receptor activation
Authors: Alfonzo-Méndez Marco A. , Sochacki Kem A. , Strub Marie-Paule , Taraska Justin W.
Published: February 2022

The crosstalk between growth factor and adhesion receptors is key for cell growth and migration. In pathological settings, these receptors are drivers of cancer. Yet, how growth and adhesion signals are spatially organized and integrated is poorly understood. Here we use quantitative fluorescence and electron microscopy to reveal a mechanism where flat clathrin lattices partition and activate growth factor signals via a coordinated response that involves crosstalk between epidermal growth factor receptor (EGFR) and the adhesion receptor β5-integrin. We show that ligand-activated EGFR, Grb2, Src, and β5-integrin are captured by clathrin coated-structures at the plasma membrane. Clathrin structures dramatically grow in response to EGF into large flat plaques and provide a signaling platform that link EGFR and β5-integrin through Src-mediated phosphorylation. Disrupting this EGFR/Src/β5-integrin axis prevents both clathrin plaque growth and dampens receptor signaling. Our study reveals a reciprocal regulation between clathrin lattices and two different receptor systems to coordinate and enhance signaling. These findings have broad implications for the regulation of growth factor signaling, adhesion, and endocytosis.
Structural snapshots of La Crosse virus polymerase reveal the mechanisms underlying Peribunyaviridae replication and transcription
Authors: Arragain Benoît , Durieux Trouilleton Quentin , Baudin Florence , Provaznik Jan , Azevedo Nayara , Cusack Stephen , Schoehn Guy , Malet Hélène
Published: February 2022

Segmented negative-strand RNA bunyaviruses encode a multi-functional polymerase that performs genome replication and transcription. Here, we establish conditions for in vitro activity of La Crosse virus polymerase and visualize its conformational dynamics by cryo-electron microscopy, unveiling the precise molecular mechanics underlying its essential activities. We find that replication initiation is coupled to distal duplex promoter formation, endonuclease movement, prime-and-realign loop extension and closure of the polymerase core that direct the template towards the active site. Transcription initiation depends on C-terminal region closure and endonuclease movements that prompt primer cleavage prior to primer entry in the active site. Product realignment after priming, observed in replication and transcription, is triggered by the prime-and-realign loop. Switch to elongation results in polymerase reorganization and core region opening to facilitate template-product duplex formation in the active site cavity. The uncovered detailed mechanics should be helpful for the future design of antivirals counteracting bunyaviral life threatening pathogens.
Differential V2-directed antibody responses in non-human primates infected with SHIVs or immunized with diverse HIV vaccines
Authors: Weiss Svenja , Itri Vincenza , Pan Ruimin , Jiang Xunqing , Luo Christina C. , Morris Lynn , Malherbe Delphine C. , Barnette Philip , Alexander Jeff , Kong Xiang-Peng , Haigwood Nancy L. , Hessell Ann J. , Duerr Ralf , Zolla-Pazner Susan
Published: February 2022

V2p and V2i antibodies (Abs) that are specific for epitopes in the V1V2 region of the HIV gp120 envelope (Env) do not effectively neutralize HIV but mediate Fc-dependent anti-viral activities that have been correlated with protection from, or control of HIV, SIV and SHIV infections. Here, we describe a novel molecular toolbox that allows the discrimination of antigenically and functionally distinct polyclonal V2 Ab responses. We identify different patterns of V2 Ab induction by SHIV infection and three separate vaccine regimens that aid in fine-tuning an optimized immunization protocol for inducing V2p and V2i Abs. We observe no, or weak and sporadic V2p and V2i Abs in non-vaccinated SHIV-infected NHPs, but strong V2p and/or V2i Ab responses after immunization with a V2-targeting vaccine protocol. The V2-focused vaccination is superior to both natural infection and to immunization with whole Env constructs for inducing functional V2p- and V2i-specific responses. Strikingly, levels of V2-directed Abs correlate inversely with Abs specific for peptides of V3 and C5. These data demonstrate that a V1V2-targeting vaccine has advantages over the imprecise targeting of SIV/SHIV infections and of whole Env-based immunization regimens for inducing a more focused functional V2p- and V2i-specific Ab response.
Early alveolar macrophage response and IL-1R-dependent T cell priming determine transmissibility of Mycobacterium tuberculosis strains
Authors: Lovey Arianne , Verma Sheetal , Kaipilyawar Vaishnavi , Ribeiro-Rodrigues Rodrigo , Husain Seema , Palaci Moises , Dietze Reynaldo , Ma Shuyi , Morrison Robert D. , Sherman David. R. , Ellner Jerrold J. , Salgame Padmini
Published: February 2022

Mechanisms underlying variability in transmission of Mycobacterium tuberculosis strains remain undefined. By characterizing high and low transmission strains of M.tuberculosis in mice, we show here that high transmission M.tuberculosis strain induce rapid IL-1R-dependent alveolar macrophage migration from the alveolar space into the interstitium and that this action is key to subsequent temporal events of early dissemination of bacteria to the lymph nodes, Th1 priming, granulomatous response and bacterial control. In contrast, IL-1R-dependent alveolar macrophage migration and early dissemination of bacteria to lymph nodes is significantly impeded in infection with low transmission M.tuberculosis strain; these events promote the development of Th17 immunity, fostering neutrophilic inflammation and increased bacterial replication. Our results suggest that by inducing granulomas with the potential to develop into cavitary lesions that aids bacterial escape into the airways, high transmission M.tuberculosis strain is poised for greater transmissibility. These findings implicate bacterial heterogeneity as an important modifier of TB disease manifestations and transmission.
Disuse-associated loss of the protease LONP1 in muscle impairs mitochondrial function and causes reduced skeletal muscle mass and strength
Authors: Xu Zhisheng , Fu Tingting , Guo Qiqi , Zhou Danxia , Sun Wanping , Zhou Zheng , Chen Xinyi , Zhang Jingzi , Liu Lin , Xiao Liwei , Yin Yujing , Jia Yuhuan , Pang Erkai , Chen Yuncong , Pan Xin , Fang Lei , Zhu Min-sheng , Fei Wenyong , Lu Bin , Gan Zhenji
Published: February 2022

Mitochondrial proteolysis is an evolutionarily conserved quality-control mechanism to maintain proper mitochondrial integrity and function. However, the physiological relevance of stress-induced impaired mitochondrial protein quality remains unclear. Here, we demonstrate that LONP1, a major mitochondrial protease resides in the matrix, plays a role in controlling mitochondrial function as well as skeletal muscle mass and strength in response to muscle disuse. In humans and mice, disuse-related muscle loss is associated with decreased mitochondrial LONP1 protein. Skeletal muscle-specific ablation of LONP1 in mice resulted in impaired mitochondrial protein turnover, leading to mitochondrial dysfunction. This caused reduced muscle fiber size and strength. Mechanistically, aberrant accumulation of mitochondrial-retained protein in muscle upon loss of LONP1 induces the activation of autophagy-lysosome degradation program of muscle loss. Overexpressing a mitochondrial-retained mutant ornithine transcarbamylase (ΔOTC), a known protein degraded by LONP1, in skeletal muscle induces mitochondrial dysfunction, autophagy activation, and cause muscle loss and weakness. Thus, these findings reveal a role of LONP1-dependent mitochondrial protein quality-control in safeguarding mitochondrial function and preserving skeletal muscle mass and strength, and unravel a link between mitochondrial protein quality and muscle mass maintenance during muscle disuse.
Non-thermal plasma-assisted rapid hydrogenolysis of polystyrene to high yield ethylene
Authors: Yao Libo , King Jaelynne , Wu Dezhen , Ma Jiayang , Li Jialu , Xie Rongxuan , Chuang Steven S. C. , Miyoshi Toshikazu , Peng Zhenmeng
Published: February 2022

The evergrowing plastic production and the caused concerns of plastic waste accumulation have stimulated the need for waste plastic chemical recycling/valorization. Current methods suffer from harsh reaction conditions and long reaction time. Herein we demonstrate a non-thermal plasma-assisted method for rapid hydrogenolysis of polystyrene (PS) at ambient temperature and atmospheric pressure, generating high yield (>40 wt%) of C1–C3 hydrocarbons and ethylene being the dominant gas product (Selectivity of ethylene, SC2H4 > 70%) within ~10 min. The fast reaction kinetics is attributed to highly active hydrogen plasma, which can effectively break bonds in polymer and initiate hydrogenolysis under mild condition. Efficient hydrogenolysis of post-consumer PS materials using this method is also demonstrated, suggesting a promising approach for fast retrieval of small molecular hydrocarbon modules from plastic materials as well as a good capability to process waste plastics in complicated conditions.
Cardiac outcomes of subjects on adjuvant trastuzumab emtansine vs paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer (ATEMPT) study (TBCRC033): a randomized controlled trial
Authors: Barroso-Sousa Romualdo , Tarantino Paolo , Tayob Nabihah , Dang Chau , Yardley Denise A. , Isakoff Steven J. , Valero Vicente , Faggen Meredith , Mulvey Therese , Bose Ron , Hu Jiani , Weckstein Douglas , Wolff Antonio C. , Reeder-Hayes Katherine , Rugo Hope S. , Ramaswamy Bhuvaneswari , Zuckerman Dan , Hart Lowell , Gadi Vijayakrishna K. , Constantine Michael , Cheng Kit , Briccetti Frederick , Schneider Bryan , Garrett Audrey Merrill , Marcom Kelly , Albain Kathy , DeFusco Patricia , Tung Nadine , Ardman Blair , Nanda Rita , Jankowitz Rachel C. , Rimawi Mothaffar , Abramson Vandana , Pohlmann Paula R. , Van Poznak Catherine , Forero-Torres Andres , Liu Minetta , Ruddy Kathryn J. , Zheng Yue , Rosenberg Shoshana M. , Gelber Richard D. , Trippa Lorenzo , Barry William , DeMeo Michelle , Burstein Harold , Partridge Ann , Winer Eric P. , Krop Ian , Tolaney Sara M.
Published: February 2022

The excellent outcomes seen in patients treated with adjuvant trastuzumab emtansine (T-DM1) in the ATEMPT trial and the favorable toxicity profile associated with this agent make T-DM1 a potential therapeutic option for select patients with stage I HER2-positive breast cancer. Moreover, T-DM1 is an established adjuvant treatment for patients with HER2-positive breast cancer with the residual invasive disease after neoadjuvant therapy. Given that cardiotoxicity is the most significant adverse event of trastuzumab, which is a main molecular component of T-DM1, we conducted a sub-analysis of the ATEMPT trial to determine the cardiac safety of adjuvant T-DM1. In this analysis, the incidence of grade 3–4 left ventricular systolic dysfunction (LVSD) in T-DM1 or trastuzumab plus paclitaxel arms were respectively 0.8 and 1.8%. In addition, three (0.8%) patients in the T-DM1 arm and six (5.3%) patients in the adjuvant paclitaxel with trastuzumab (TH) arm experienced a significant asymptomatic left ventricular ejection fraction (LVEF) decline that per-protocol required holding T-DM1 or trastuzumab. All patients with available follow-up data experienced full resolution of cardiac symptoms and LVEF normalization. Furthermore, we performed an exploratory analysis to assess the relationship between age, baseline LVEF, and body mass index with cardiac outcomes. No significant association between these baseline characteristics and the incidence of significant asymptomatic LVEF decline or symptomatic LVSD was identified. The low incidence of significant cardiac adverse events in this population during therapy with adjuvant T-DM1 suggests that studies on the cost-effectiveness of cardiac monitoring during adjuvant therapy using anthracycline-free regimens are needed.

Clinical Trial Registration:ClinicalTrials.gov, NCT01853748
Visualizing protein breathing motions associated with aromatic ring flipping
Authors: Mariño Pérez Laura , Ielasi Francesco S. , Bessa Luiza M. , Maurin Damien , Kragelj Jaka , Blackledge Martin , Salvi Nicola , Bouvignies Guillaume , Palencia Andrés , Jensen Malene Ringkjøbing
Published: February 2022

Aromatic residues cluster in the core of folded proteins, where they stabilize the structure through multiple interactions. Nuclear magnetic resonance (NMR) studies in the 1970s showed that aromatic side chains can undergo ring flips—that is, 180° rotations—despite their role in maintaining the protein fold1–3. It was suggested that large-scale ‘breathing’ motions of the surrounding protein environment would be necessary to accommodate these ring flipping events1. However, the structural details of these motions have remained unclear. Here we uncover the structural rearrangements that accompany ring flipping of a buried tyrosine residue in an SH3 domain. Using NMR, we show that the tyrosine side chain flips to a low-populated, minor state and, through a proteome-wide sequence analysis, we design mutants that stabilize this state, which allows us to capture its high-resolution structure by X-ray crystallography. A void volume is generated around the tyrosine ring during the structural transition between the major and minor state, and this allows fast flipping to take place. Our results provide structural insights into the protein breathing motions that are associated with ring flipping. More generally, our study has implications for protein design and structure prediction by showing how the local protein environment influences amino acid side chain conformations and vice versa.
Twin study reveals non-heritable immune perturbations in multiple sclerosis
Authors: Ingelfinger Florian , Gerdes Lisa Ann , Kavaka Vladyslav , Krishnarajah Sinduya , Friebel Ekaterina , Galli Edoardo , Zwicky Pascale , Furrer Reinhard , Peukert Christian , Dutertre Charles-Antoine , Eglseer Klara Magdalena , Ginhoux Florent , Flierl-Hecht Andrea , Kümpfel Tania , De Feo Donatella , Schreiner Bettina , Mundt Sarah , Kerschensteiner Martin , Hohlfeld Reinhard , Beltrán Eduardo , Becher Burkhard
Published: February 2022

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system underpinned by partially understood genetic risk factors and environmental triggers and their undefined interactions1,2. Here we investigated the peripheral immune signatures of 61 monozygotic twin pairs discordant for MS to dissect the influence of genetic predisposition and environmental factors. Using complementary multimodal high-throughput and high-dimensional single-cell technologies in conjunction with data-driven computational tools, we identified an inflammatory shift in a monocyte cluster of twins with MS, coupled with the emergence of a population of IL-2 hyper-responsive transitional naive helper T cells as MS-related immune alterations. By integrating data on the immune profiles of healthy monozygotic and dizygotic twin pairs, we estimated the variance in CD25 expression by helper T cells displaying a naive phenotype to be largely driven by genetic and shared early environmental influences. Nonetheless, the expanding helper T cells of twins with MS, which were also elevated in non-twin patients with MS, emerged independent of the individual genetic makeup. These cells expressed central nervous system-homing receptors, exhibited a dysregulated CD25–IL-2 axis, and their proliferative capacity positively correlated with MS severity. Together, our matched-pair analysis of the extended twin approach allowed us to discern genetically and environmentally determined features of an MS-associated immune signature.
Effects of field enhanced charge transfer on the luminescence properties of Si/SiO2 superlattices
Authors: Yazicioglu Deniz , Gutsch Sebastian , Zacharias Margit
Published: February 2022

The effect of an externally applied electric field on exciton splitting and carrier transport was studied on 3.5 nm Si nanocrystals embedded in SiO2superlattices with barrier oxide thicknesses varied between 2 and 4 nm. Through a series of photoluminescence measurements performed at both room temperature and with liquid N2cooling, it was shown that the application of an electric field resulted in a reduction of luminescence intensity due to exciton splitting and charging of nanocrystals within the superlattices. This effect was found to be enhanced when surface defects at the Si/SiO2interface were not passivated by H2treatment and severely reduced for inter layer barrier oxide thicknesses above 3 nm. The findings point to the surface defects assisting in carrier transport, lowering the energy required for exciton splitting. Said enhancement was found to be diminished at low temperatures due to the freezing-in of phonons. We propose potential device design parameters for photon detection and tandem solar cell applications utilizing the quantum confinement effect based on the findings of the present study.
Conserved topology of virus glycoepitopes presents novel targets for repurposing HIV antibody 2G12
Authors: Miller Nathaniel L. , Subramanian Vidya , Clark Thomas , Raman Rahul , Sasisekharan Ram
Published: February 2022

Complex glycans decorate viral surface proteins and play a critical role in virus–host interactions. Viral surface glycans shield vulnerable protein epitopes from host immunity yet can also present distinct “glycoepitopes” that can be targeted by host antibodies such as the potent anti-HIV antibody 2G12 that binds high-mannose glycans on gp120. Two recent publications demonstrate 2G12 binding to high mannose glycans on SARS-CoV-2 and select Influenza A (Flu) H3N2 viruses. Previously, our lab observed 2G12 binding and functional inhibition of a range of Flu viruses that include H3N2 and H1N1 lineages. In this manuscript, we present these data alongside structural analyses to offer an expanded picture of 2G12-Flu interactions. Further, based on the remarkable breadth of 2G12 N-glycan recognition and the structural factors promoting glycoprotein oligomannosylation, we hypothesize that 2G12 glycoepitopes can be defined from protein structure alone according to N-glycan site topology. We develop a model describing 2G12 glycoepitopes based on N-glycan site topology, and apply the model to identify viruses within the Protein Data Bank presenting putative 2G12 glycoepitopes for 2G12 repurposing toward analytical, diagnostic, and therapeutic applications.
Dietary carbohydrate and the risk of type 2 diabetes: an updated systematic review and dose–response meta-analysis of prospective cohort studies
Authors: Hosseini Fatemeh , Jayedi Ahmad , Khan Tauseef Ahmad , Shab-Bidar Sakineh
Published: February 2022

We did this study to clarify the association between carbohydrate intake and the risk of type 2 diabetes (T2D) and potential effect modification by geographical location. PubMed, Scopus and Web of Science were searched to find prospective cohort studies of dietary carbohydrate intake and T2D risk. A random-effects dose–response meta-analysis was performed to calculate the summary hazard ratios (HRs) and 95%CIs. The quality of cohort studies and the certainty of evidence was rated using the Newcastle–Ottawa Scale and GRADE tool, respectively. Eighteen prospective cohort studies with 29,229 cases among 607,882 participants were included. Thirteen studies were rated to have high quality, and five as moderate quality. The HR for the highest compared with the lowest category of carbohydrate intake was 1.02 (95%CI: 0.91, 1.15; I2 = 67%, GRADE = low certainty). The HRs were 0.93 (95%CI: 0.82, 1.05; I2 = 58%, n = 7) and 1.26 (95%CI: 1.11, 1.44; I2 = 6%, n = 6) in Western and Asian countries, respectively. Dose–response analysis indicated a J shaped association, with the lowest risk at 50% carbohydrate intake (HR50%: 0.95, 95%CI: 0.90, 0.99) and with risk increasing significantly at 70% carbohydrate intake (HR70%: 1.18, 95%CI: 1.03, 1.35). There was no association between low carbohydrate diet score and the risk of T2D (HR: 1.14, 95%CI: 0.89, 1.47; I2 = 90%, n = 5). Carbohydrate intake within the recommended 45–65% of calorie intake was not associated with an increased risk of T2D. Carbohydrate intake more than 70% calorie intake might be associated with a higher risk.
Strength criterion of rock mass considering the damage and effect of joint dip angle
Authors: Li Yugen , Zhang Huimei , Chen Min , Meng Xiangzhen , Shen Yanjun , Liu Hui , Lu Yani
Published: February 2022

It is highly significant to theoretically assess the effect, under load, of initial stress and structure on the mass damage of rock mass. In this reported study, first a multi-factor coupling damage constitutive model under the action of joint-load was established by fully considering the non-uniformity, anisotropy and initial structure of a rock mass based on the Weibull distribution and D-P criterion. The relationship between the damage evolution and joint angle in the rock mass was elaborated. Then, a jointed rock mass strength criterion was built in line with the D–P criterion and the limit state of rock mass failure by the method of multivariate function total differential as based on the constitutive model. The results showed that the established constitutive model was in good agreement with the test results, which accurately reflected the damage characteristics of jointed rock mass during the entire loading process. The initial damage value of the rock mass increased with increasing joint dip angles, and the damage evolution of the jointed rock mass could be divided into the initial, stable, accelerated and failure damage stages. Comparing the results of this approach with other methods it was found that the strength criterion better reflected the effects of minimum principal stress σ3, volume stress σm, shear stress J21/2 and joint dip angle β on rock mass strength than other existing strength criteria, which showed that the proposed method offered important guiding principles for the engineering practice.
Using absolutist word frequency from online searches to measure population mental health dynamics
Authors: Adam-Troian Jais , Bonetto Eric , Arciszewski Thomas
Published: February 2022

The assessment of population mental health relies on survey data from representative samples, which come with considerable costs. Drawing on research which established that absolutist words (e.g. never) are semantic markers for depression, we propose a new measure of population mental health based on the frequency of absolutist words in online search data (absolute thinking index; ATI). Our aims were to first validate the ATI, and to use it to model public mental health dynamics in France and the UK during the current COVID-19 pandemic. To do so, we extracted time series for a validated dictionary of 19 absolutist words, from which the ATI was computed (weekly averages, 2019–2020,n = 208) using Google Trends. We then tested the relationship between ATI and longitudinal survey data of population mental health in the UK (n = 36,520) and France (n = 32,000). After assessing the relationship between ATI and survey measures of depression and anxiety in both populations, and dynamic similarities between ATI and survey measures (France), we tested the ATI’s construct validity by showing how it was affected by the pandemic and how it can be predicted by COVID-19-related indicators. A final step consisted in replicating ATI’s construct validity tests in Japan, thereby providing evidence for the ATI’s cross-cultural generalizability. ATI was linked with survey depression scores in the UK,r = 0.68, 95%CI[0.34,0.86],β = 0.23, 95%CI[0.09,0.37] in France and displayed similar trends. We finally assessed the pandemic’s impact on ATI using Bayesian structural time-series models. These revealed that the pandemic increased ATI by 3.2%, 95%CI[2.1,4.2] in France and 3.7%, 95%CI[2.9,4.4] in the UK. Mixed-effects models showed that ATI was related to COVID-19 new deaths in both countriesβ = 0.14, 95%CI[0.14,0.21]. These patterns were replicated in Japan, with a pandemic impact of 4.9%, 95%CI[3.1,6.7] and an influence of COVID-19 death ofβ = 0.90, 95%CI[0.36,1.44]. Our results demonstrate the validity of the ATI as a measure of population mental health (depression) in France, the UK and to some extent in Japan. We propose that researchers use it as cost-effective public mental health “thermometer” for applied and research purposes.
Dietary carbohydrate intake is associated with the subgingival plaque oral microbiome abundance and diversity in a cohort of postmenopausal women
Authors: Millen Amy E. , Dahhan Runda , Freudenheim Jo L. , Hovey Kathleen M. , Li Lu , McSkimming Daniel I. , Andrews Chris A. , Buck Michael J. , LaMonte Michael J. , Kirkwood Keith L. , Sun Yijun , Murugaiyan Vijaya , Tsompana Maria , Wactawski-Wende Jean
Published: February 2022

Limited research exists on carbohydrate intake and oral microbiome diversity and composition assessed with next-generation sequencing. We aimed to better understand the association between habitual carbohydrate intake and the oral microbiome, as the oral microbiome has been associated with caries, periodontal disease, and systemic diseases. We investigated if total carbohydrates, starch, monosaccharides, disaccharides, fiber, or glycemic load (GL) were associated with the diversity and composition of oral bacteria in subgingival plaque samples of 1204 post-menopausal women. Carbohydrate intake and GL were assessed from a food frequency questionnaire, and adjusted for energy intake. The V3–V4 region of the 16S rRNA gene from subgingival plaque samples were sequenced to identify the relative abundance of microbiome compositional data expressed as operational taxonomic units (OTUs). The abundance of OTUs were centered log(2)-ratio transformed to account for the compositional data structure. Associations between carbohydrate/GL intake and microbiome alpha-diversity measures were examined using linear regression. PERMANOVA analyses were conducted to examine microbiome beta-diversity measures across quartiles of carbohydrate/GL intake. Associations between intake of carbohydrates and GL and the abundance of the 245 identified OTUs were examined by using linear regression. Total carbohydrates, GL, starch, lactose, and sucrose intake were inversely associated with alpha-diversity measures. Beta-diversity across quartiles of total carbohydrates, fiber, GL, sucrose, and galactose, were all statistically significant (p for PERMANOVA p < 0.05). Positive associations were observed between total carbohydrates, GL, sucrose and Streptococcus mutans; GL and both Sphingomonas HOT 006 and Scardovia wiggsiae; and sucrose and Streptococcus lactarius. A negative association was observed between lactose and Aggregatibacter segnis, and between sucrose and both TM7_[G-1] HOT 346 and Leptotrichia HOT 223. Intake of total carbohydrate, GL, and sucrose were inversely associated with subgingival bacteria alpha-diversity, the microbial beta-diversity varied by their intake, and they were associated with the relative abundance of specific OTUs. Higher intake of sucrose, or high GL foods, may influence poor oral health outcomes (and perhaps systemic health outcomes) in older women via their influence on the oral microbiome.
Facile synthesis of hierarchically structured MIL-53(Al) with superior properties using an environmentally-friendly ultrasonic method for separating lead ions from aqueous solutions
Authors: Ahadi Niusha , Askari Sima , Fouladitajar Amir , Akbari Iman
Published: February 2022

The present study aims at investigating sonochemically synthesized MIL-53(Al) and its applications in adsorption lead ions from aqueous solution. XRD, FESEM, BET, and FTIR analyses were employed to identify and characterize MIL-53(Al). The ultrasonic-assisted synthesis procedure results in reducing the synthesis time to 24 h; however, the conventional synthesis of MIL-53(Al) takes 3 days. Applying ultrasonic waves also leads to increase of the specific surface area up to 50% more than that of synthesized by the conventional method, as well as creating the hierarchical MIL-53(Al) structure which reduces the mass transfer limitation of ions into internal micropores. The optimum conditions for removing lead ions are pH of 6, Pb+2 ion concentration of 20 mg/L, contact time of 60 min, adsorbent dose of 0.04 g, and temperature of 318 K with the removal efficiency of 97.63%. The experimental adsorption equilibrium and kinetic data fit the Langmuir isotherm and pseudo-second-order kinetic models, respectively. Moreover, the usage of sonochemically synthesized MIL-53(Al), for the first time as an adsorbent in heavy metal removal points to the great potential of this new environmentally-friendly adsorbent in removing lead ions from aqueous solutions
Prediction of serine phosphorylation sites mapping on Schizosaccharomyces Pombe by fusing three encoding schemes with the random forest classifier
Authors: Tasmia Samme Amena , Kibria Md. Kaderi , Tuly Khanis Farhana , Islam Md. Ariful , Khatun Mst Shamima , Hasan Md. Mehedi , Mollah Md. Nurul Haque
Published: February 2022

Serine phosphorylation is one type of protein post-translational modifications (PTMs), which plays an essential role in various cellular processes and disease pathogenesis. Numerous methods are used for the prediction of phosphorylation sites. However, the traditional wet-lab based experimental approaches are time-consuming, laborious, and expensive. In this work, a computational predictor was proposed to predict serine phosphorylation sites mapping onSchizosaccharomyces pombe(SP) by the fusion of three encoding schemes namely k-spaced amino acid pair composition (CKSAAP), binary and amino acid composition (AAC) with the random forest (RF) classifier. So far, the proposed method is firstly developed to predict serine phosphorylation sites forSP. Both the training and independent test performance scores were used to investigate the success of the proposed RF based fusion prediction model compared to others. We also investigated their performances by 5-fold cross-validation (CV). In all cases, it was observed that the recommended predictor achieves the largest scores of true positive rate (TPR), true negative rate (TNR), accuracy (ACC), Mathew coefficient of correlation (MCC), Area under the ROC curve (AUC) and pAUC (partial AUC) at false positive rate (FPR) = 0.20. Thus, the prediction performance as discussed in this paper indicates that the proposed approach may be a beneficial and motivating computational resource for predicting serine phosphorylation sites in the case of Fungi. The online interface of the software for the proposed prediction model is publicly available athttp://mollah-bioinformaticslab-stat.ru.ac.bd/PredSPS/.