bluuebunny/crossref_metadata_2025 huggingface dataset:
Room-temperature third-order nonlinear Hall effect in Weyl semimetal TaIrTe4
Authors: Wang Cong , Xiao Rui-Chun , Liu Huiying , Zhang Zhaowei , Lai Shen , Zhu Chao , Cai Hongbing , Wang Naizhou , Chen Shengyao , Deng Ya , Liu Zheng , Yang Shengyuan A , Gao Wei-Bo
Published: February 2022

The second-order nonlinear Hall effect observed in the time-reversal symmetric system has not only shown abundant physical content, but also exhibited potential application prospects. Recently, a third-order nonlinear Hall effect has been observed in MoTe2 and WTe2. However, few-layer MoTe2 and WTe2 are usually unstable in air and the observed third-order nonlinear Hall effect can be measured only at low temperature, which hinders further investigation as well as potential application. Thus, exploring new air-stable material systems with a sizable third-order nonlinear Hall effect at room temperature is an urgent task. Here, in type-II Weyl semimetal TaIrTe4, we observed a pronounced third-order nonlinear Hall effect, which can exist at room temperature and remain stable for months. The third-order nonlinear Hall effect is connected to the Berry-connection polarizability tensor instead of the Berry curvature. The possible mechanism of the observation of the third-order nonlinear Hall effect in TaIrTe4 at room temperature has been discussed. Our findings will open an avenue towards exploring room-temperature nonlinear devices in new quantum materials.
A Review of Hemophagocytic Lymphohistiocytosis in Patients With HIV
Authors: Tabaja Hussam , Kanj Amjad , El Zein Said , Comba Isin Yagmur , Chehab Omar , Mahmood Maryam
Published: February 2022

We provide an elaborate review of cases published between January 2005 and April 2021 on hemophagocytic lymphohistiocytosis (HLH) in HIV patients. Seventy articles describing 81 adult patients (age ≥19 years) were included. The median age was 40 years, and 78% were males. Only 65% were known to have HIV before presentation. CD4 count was ≥200 cells/mm3 in 23%, and HIV viral load was <200 copies/mL in 41%. The lack of meticulous reporting of ≥5 of 8 criteria for HLH diagnosis was evident in a third of cases. At least 1 infectious agent—other than HIV—was believed to trigger HLH in 78% of patients. The most common were Epstein-Barr virus (26%), human herpesvirus 8 (21%), and Histoplasma capsulatum (17%). Sixty percent survived. Among those, 93% received treatment for identified secondary trigger(s), while 51% received HLH-directed therapy. There was significant heterogeneity in the treatment regimens used for HLH.
Targeting Communication Effectiveness in Adults Who Stutter
Authors: Byrd Courtney T. , Coalson Geoffrey A. , Young Megan M.
Published: February 2022

The purpose of this study was to examine the benefits of a treatment approach for adults who stutter that focuses on core communication competencies rather than attempt to modify speech fluency. Eleven adults who stutter completed a 12-week treatment program at The Arthur M. Blank Center for Stuttering Education and Research. Pre- and posttreatment measures included (a) self-reported cognitive and affective aspects of stuttering (Overall Assessment of the Speaker's Experience of Stuttering [OASES], Self-Perceived Communication Competence [SPCC], Devereux Adult Resilience Survey [DARS], and Self-Compassion Scale [SCS]) and (b) ratings of 9 core communication competencies by an unfamiliar clinician blind to pre/posttreatment status. Participants reported significant mitigation of the adverse impact of stuttering (OASES) and greater resilience (DARS) after treatment. Participants also demonstrated significant gains in 8 of the 9 clinician-perceived communication competencies. Lower pretreatment stuttering frequencies were not significantly associated with posttreatment gains in clinician-perceived communication competencies. Preliminary findings suggest that, similar to findings for children and adolescents who stutter in previous studies, significant psychosocial and communicative benefit can be obtained for adults who stutter following treatment designed to focus on communication effectiveness rather than fluency, and that these gains are not contingent on the participants' stuttering frequency prior to enrollment.
Lung Transplant Candidates With Pretransplant Gastroesophageal Reflux and Antibodies to Lung Self-antigens Have Shorter CLAD-free Survival After Transplant
Authors: Razia Deepika , Mittal Sumeet K. , Bansal Sandhya , Ravichandran Ranjithkumar , Smith Michael A. , Walia Rajat , Bremner Ross M. , Mohanakumar Thalachallour , Tokman Sofya
Published: February 2022

Background.

Pre–lung transplant (LTx) gastroesophageal reflux (GER) and circulating antibodies against the lung self-antigens (SAbs) collagen V and K-alpha-1 tubulin may predispose recipients to chronic lung allograft dysfunction (CLAD). We aimed to study the association of pre-LTx GER or pre-LTx SAbs with CLAD.

Methods.

In this retrospective analysis of patients who underwent LTx between 2015 and 2019, pre-LTx GER and SAbs were dichotomously defined as present or absent. The study group comprised recipients with either GER‚ SAbs, or both, and the control group comprised recipients without GER or SAbs. Endpoints included CLAD and survival.

Results.

Ninety-five LTx recipients were divided into a study group (n = 71; 75%) and a control group (n = 24; 25%). Pretransplant GER was associated with pre-LTx SAbs (odds ratio [95% confidence intervals], 5.022 [1.419-17.770]; P = 0.012). In addition, the study group (either GER‚ SAbs, or both) had a higher risk of CLAD (hazard ratio [95% confidence intervals], 8.787 [1.694-45.567]; P = 0.010) and lower CLAD-free survival after LTx than the control group (P = 0.007); however, overall survival was similar between the 2 groups (P = 0.618).

Conclusions.

GER was associated with elevated SAbs in LTx candidates, and either GER, SAbs, or both were associated with CLAD in LTx recipients. This association suggests that GER may cause an immune response to normally sequestered lung-associated self-antigens that drives ongoing lung injury.
High attack rate in a Tong Lau house outbreak of COVID-19 with subdivided units in Hong Kong
Authors: Wang Qun , Lung David Christopher , Chan Pak-To , Jia Wei , Dung Chung-Hin , Miao Te , Huang Jianxiang , Chen Wenzhao , Wang Zixuan , Leung Kai-Ming , Xu Pengcheng , Lin Zhang , Wong Daniel , Tse Herman , Ying Wong Sally Cheuk , Choi Garnet Kwan-Yue , To Kelvin Kai-Wang , Cheng Vincent Chi-Chung , Yuen Kwok-Yung , Li Yuguo
Published: February 2022

Poor housing conditions are known to be associated with infectious diseases such as high Coronavirus disease 2019 (COVID-19) incidences. Transmission causes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in poor housing conditions can be complex. An understanding of the exact mechanism of transmission can help to pinpoint contributing environmental issues. Here, we investigated a Hong Kong COVID-19 outbreak in early 2021 in four traditional Tong Lau houses with subdivided units. There are more than 80 subdivided units of less than 20 m2floor area each on average. With a total of 34 confirmed COVID-19 cases, the outbreak had an attack rate of 25.4%, being one of the highest attack rates observed in Hong Kong, and ranked among the highest attack rates in reported outbreaks internationally. Tracer gas leakage and decay measurements were performed in the drainage system and in the subdivided units to determine the transport of infectious aerosols by the owner-modified sophisticated wastewater drainage pipe networks and the poor ventilation conditions in some subdivided units. The results show that the outbreak was probably due to multiple transmission routes, i.e. by the drainage pipe spread of stack aerosols, which is enhanced by poor ventilation in the subdivided units.
Spread of infectious agents through the air in complex spaces
Authors: Eames Ian , Flór Jan-Bert
Published: February 2022

The fluid mechanical processes that govern the spread of infectious agents through the air in complex spaces are reviewed and the scientific gaps and challenges identified and discussed. Air, expelled from the nose and mouth, creates turbulent jets that form loosely coherent structures which quickly slow. For the transport and dispersion of aerosols, the suitability of the Eulerian as well as the Lagrangian approaches are brought into context. The effects of buoyancy and external turbulence are explored and shown to influence the horizontal extent of expulsion through distinct mechanisms which both inhibit penetration and enhance mixing. The general influence of inhomogeneous turbulence and stratification on the spread of infectious agents in enclosed complex spaces is discussed.
Emergence of Neisseria meningitidis W South American sublineage strain variant in Brazil: disease and carriage
Authors: Lemos Ana Paula Silva de , Gorla Maria Cecilia Outeiro , de Moraes Camile , Willemann Maria Cristina , Sacchi Claudio Tavares , Fukasawa Lucila Okuyama , Camargo Carlos Henrique , Barreto Gisele , Rodrigues Dauri Santos , Gonçalves Maria Gisele , Higa Fábio Takenori , Salgado Maristela Marques , de Moraes José Cássio
Published: February 2022

Introduction. Invasive meningococcal disease is a major health problem, impacting morbidity and mortality worldwide. Exploratory genomics has revealed insights into adaptation, transmissibility and virulence to elucidate endemic, outbreaks or epidemics caused by

Neisseria meningitidis

serogroup W (MenW) strains.

Gap Statement. Limited information on the genomics of Neisseria meningitis serogroup W ST11/cc11 is available from emerging countries, especially in contemporary isolates.

Aim. To (i) describe the antigenic diversity and distribution of genetic lineages of

N. meningitidis

serogroup W circulating in Brazil; (ii) study the carriage prevalence of hypervirulent clones in adolescents students and (iii) analyse the potential risk factors for meningococcal carriage.

Methodology. Using whole-genome sequencing, we analysed the genomic diversity of 92 invasive

N. meningitidis

serogroup W isolates circulating in Brazil from 2016 to 2019. A cross-sectional survey of meningococcal carriage was conducted in 2019, in the city of Florianópolis, Brazil, among a representative sample of 538 students.

Results. A predominance (58.5 %, 41/82) of ST11/cc11 presenting PorB2-144, PorA VR1–5, VR2-2, FetA 1–1, and a novel fHbp peptide 1241 was found on invasive

N. meningitidis

W isolates, on the other hand, a high diversity of clonal complexes was found among carriage isolates. The overall carriage rate was 7.5 % (40/538). A total of 28 of 538 swab samples collected were culture positive for

N. meningitidis

, including four serogroup/genogroup B isolates (14.8 %;4/27), 1 serogroup/genogroup Y isolate (3.7 %;1/27), 22 (81.5 %; 22/27) non-groupable isolates. No MenW isolate was identified among carriages isolates.

Conclusion. This report describes the emergence of the new MenW ST11/cc11 South America sublineage variant, named here, 2016 strain, carrying a novel fHbp peptide 1241, but its emergence, was not associated with an increased MenW carriage prevalence. Continuous surveillance is necessary to ascertain the role of this sublineage diversification and how its emergence can impact transmission.
Inducible Nitric Oxide Synthase deficiency leads to early demyelination by altering the balance between pro- and anti-inflammatory responses against Murine-β-Coronavirus
Authors: Kamble Mithila , Saadi Fareeha , Kumar Saurav , Saha Bhaskar , Sarma Jayasri Das
Published: February 2022

The neurological disease Multiple sclerosis (MS) is characterized by neuroinflammation and demyelination orchestrated by the activated glial cells, the CNS infiltrating leukocytes, and their reciprocal interaction through inflammatory signals. Inducible nitric oxide synthase (iNOS), an enzyme that catalyzes sustained nitric oxide production in response to an inflammatory stimulus, is a pro-inflammatory marker expressed particularly by the microglia/macrophages (MG/Mφ) during neuroinflammation. In MS, iNOS has been reportedly associated with the disease pathology; however, studies dissecting its role in the underlying mechanisms, specifically demyelination, are limited. Therefore, we studied the role of iNOS in a recombinant beta-coronavirus-MHV-RSA59-induced neuroinflammation, which is a prototypic animal model used to investigate the pathological hallmarks of MS, neuroinflammatory demyelination, and axonal degeneration. During the acute phase of infection with RSA59, wildtype C57BL/6 (WT) mice had significantly upregulated iNOS expression in macrophages, natural killer cells, and natural killer T cells suggesting a role for iNOS in RSA59-induced neuroinflammation. Studies comparing RSA59-infected WT and iNOS-deficient mice revealed that iNOS deficiency aggravated the disease with increased CNS infiltration of macrophages and neutrophils and enhanced mortality. As early as 9-10 days after the infection, the CNS of iNOS-deficient mice had substantially higher demyelination marked with morphologically defined MG/Mφ in the demyelinating regions. Transcript analysis confirmed the significant upregulation of type2 macrophage (M2) markers-Arginase 1, CD206, and TREM2-in the CNS of iNOS-deficient mice. Corroborating to the phenotype, the iNOS-deficient mice showed a significantly higher expression of TGFβ-an anti-inflammatory cytokine- and increased T regulatory (Treg) cell infiltration, indicating an anti-inflammatory milieu established early after the infection. These observations highlight a protective role of iNOS in virus-induced neuroinflammation whereas its absence leads to MG/Mφ polarization towards a phenotype that may be involved in the exacerbated demyelination pathology.

Author summary

Contrary to the reported pathogenic role of inducible nitric oxide synthase (iNOS) in multiple sclerosis and related autoimmune animal models, we show that the mice deficient in iNOS show an exacerbated disease with accelerated demyelination accompanied by heightened production of an anti-inflammatory and phagocytic markers and more numbers of Tregs in a mouse model of a recombinant mouse hepatitis virus RSA59 infection. Therefore, iNOS may play protective and regulatory roles in this beta-coronavirus infection.
Visual Acuity alterations in heavily impaired Congenital Zika Syndrome (CZS) children
Authors: Baran Luiz C. P. , Lima Diego da S. , Silva Leonardo A. , Tabares Heydi S. , Dias Sarah L. , Zin Andrea Araújo , Moreira Maria Elisabeth Lopes , Costa Marcelo F. , Ventura Dora F.
Published: February 2022

We aim to assess visual acuity (VA) in Congenital Zika Syndrome (CZS)-children to evaluate visual loss. To that end we evaluated 41 CZS- children, from Rio de Janeiro using Teller Acuity Cards. They had Zika virus-infection confirmed by reverse transcription–polymerase chain reaction (RT-PCR) or clinical evaluation. VA below normative values was present in 39/41 (95%). In 10 cases, VA was only marginally below normal; in the remaining 29 cases, VA was more than 0.15 logMAR below the lower limit. There was no relationship between VA and cognitive domain tasks, although there was a relationship between VA and motor domain tasks. Thirty-seven children performed at least one task in the cognitive set, 14 children did not perform any task in the motor set. Children with VA above the lower limit performed better in the cognitive and motor tasks. We concluded that ZIKV- infected children with CSZ were highly VA impaired which correlated with motor performance, but not with cognitive performance. Part of the children had VA within the normal limits and displayed better performance in the cognitive and motor set. Therefore, even if heavily impaired, most children had some degree of visual acuity and visual function and may benefit from visual rehabilitation.
Pilot Plant-Based Lifestyle Medicine Program in an Urban Public Healthcare System: Evaluating Demand and Implementation
Authors: Albert Stephanie L. , Massar Rachel , Kwok Lorraine , Correa Lily , Polito-Moller Krisann , Joshi Shivam , Shah Sapana , McMacken Michelle
Published: February 2022

Background

Lifestyle interventions that optimize nutrition, physical activity, sleep health, social connections, and stress management, and address substance use can reduce cardiometabolic risk. Despite substantial evidence that healthful plant-based diets are beneficial for long-term cardiometabolic health and longevity, uncertainty lies in how to implement plant-based lifestyle programs in traditional clinical settings, especially in safety-net contexts with finite resources.

Methods

In this mixed-methods implementation evaluation of the Plant-Based Lifestyle Medicine Program piloted in a large public healthcare system, we surveyed participants and conducted qualitative interviews and focus groups with stakeholders to assess program demand in the eligible population, and feasibility of implementation within the safety-net setting.

Findings

Program demand was high and exceeded capacity. Participants’ main motivations for joining the program included gaining more control over life, reducing medication, and losing weight. The program team, approach, and resources were successful facilitators. However, the program faced administrative and payor-related challenges within the safety-net setting, and participants reported barriers to access.

Conclusions

Stakeholders found the program to be valuable, despite challenges in program delivery and access. Findings provide guidance for replication. Future research should focus on randomized controlled trials to assess clinical outcomes as a result of program participation.
HiDiver: A Suite of Methods to Merge Magnetic Resonance Histology, Light Sheet Microscopy, and Complete Brain Delineations
Authors: Johnson G. Allan , Tian Yuqi , Cofer Gary P. , Cook James C. , Gee James C. , Hall Adam , Hornburg Kathryn , Qi Yi , Yeh Fang-Cheng , Wang Nian , White Leonard E. , Williams Robert W.
Published: February 2022

We have developed new imaging and computational workflows to produce accurately aligned multimodal 3D images of the mouse brain that exploit high resolution magnetic resonance histology (MRH) and light sheet microscopy (LSM) with fully rendered 3D reference delineations of brain structures. The suite of methods starts with the acquisition of geometrically accurate (in-skull) brain MRIs using multi-gradient echo (MGRE) and new diffusion tensor imaging (DTI) at an isotropic spatial resolution of 15 μm. Whole brain connectomes are generated using over 100 diffusion weighted images acquired with gradients at uniformly spaced angles. Track density images are generated at a super-resolution of 5 μm. Brains are dissected from the cranium, cleared with SHIELD, stained by immunohistochemistry, and imaged by LSM at 1.8 μm/pixel. LSM channels are registered into the reference MRH space along with the Allen Brain Atlas (ABA) Common Coordinate Framework version 3 (CCFv3). The result is a high-dimensional integrated volume with registration (HiDiver) that has a global alignment accuracy of 10–50 μm. HiDiver enables 3D quantitative and global analyses of cells, circuits, connectomes, and CNS regions of interest (ROIs). Throughput is sufficiently high that HiDiver is now being used in comprehensive quantitative studies of the impact of gene variants and aging on rodent brain cytoarchitecture.
Plant phenotypic plasticity changes pollinator-mediated selection
Authors: Dorey Thomas , Schiestl Florian P.
Published: February 2022

Many organisms change their phenotype in response to the environment, a phenomenon called phenotypic plasticity. Yet we hardly understand how such plasticity can affect biotic interactions and the resulting phenotypic selection. Here we use fast cycling Brassica rapa plants in a proof-of-concept experiment in the greenhouse to study the link between plasticity and selection. We detected strong plasticity in morphology, nectar, and floral scent in response to different soil types and aphid herbivory. We found positive selection on nectar and several morphological traits. Bumblebee-mediated selection on a principle component representing plant height, flower number, and flowering time (mPC3) differed depending on soil type and herbivory. For plants growing in richer soil, selection was stronger in the absence of herbivores, whereas for plants growing in poorer soil selection was stronger with herbivory. We showed that bumblebees visited tall plants with many flowers over-proportionally when they were rare (i.e. in plants in poor soil with herbivory), thus causing stronger positive selection on this trait-combination. We suggest that with strong plasticity under most stressful conditions, a shift in pollinator behavior may speed up adaptation to local environmental factors.
NICEgame: A workflow for annotating the knowledge gaps in metabolic reconstructions, using known and hypothetical reactions
Authors: Vayena Evangelia , Chiappino-Pepe Anush , MohammadiPeyhani Homa , Francioli Yannick , Hadadi Noushin , Ataman Meriç , Hafner Jasmin , Pavlou Stavros , Hatzimanikatis Vassily
Published: February 2022

Advances in medicine and biotechnology rely on the further understanding of biological processes. Despite the increasingly available types and amounts of omics data, significant biochemical knowledge gaps remain uncharacterized. Several approaches have been developed during the past years to identify missing metabolic annotations in genome-scale. However, these approaches suggest missing metabolic reactions within a limited set of already characterized metabolic capabilities. In this study, we introduce NICEgame (Network Integrated Computational Explorer for Gap Annotation of Metabolism), a workflow to characterize missing metabolic capabilities in genome-scale metabolic models using the ATLAS of Biochemistry. NICEgame suggests alternative sets of known and hypothetical reactions to resolve gaps in metabolic networks, assesses their thermodynamic feasibility, and suggests candidate genes and proteins to catalyze the introduced reactions. We use gene essentiality data use to identify metabolic gaps in the latest genome-scale model of Escherichia coli, iML1515. We apply our gap-filling approach and further enhance its genome annotation, by suggesting reactions and putative genes to resolve 46 % of the false negative gene essentiality predictions.
Mechanism of RNA Polymerase I selection by transcription factor UAF
Authors: Baudin Florence , Murciano Brice , Fung Herman K.H. , Fromm Simon A. , Mattei Simone , Mahamid Julia , Müller Christoph W.
Published: February 2022

Pre-ribosomal RNA is selectively transcribed by RNA Polymerase (Pol) I in eukaryotes. The yeast transcription factor Upstream Activating Factor (UAF) represses Pol II transcription and mediates Pol I preinitiation complex (PIC) formation during the early stages of transcription initiation at the 35S ribosomal RNA gene. To unravel the DNA recognition and Pol I selection mechanisms of UAF, we determined the structure of UAF bound to native promoter DNA and transcription factor TBP. We found that UAF recognizes DNA using a hexameric histone-like scaffold with markedly different interactions than the nucleosome and the histone-fold-rich TFIID. UAF strategically sequesters TBP from DNA and Pol II/III-specific factors, and positions it for Core Factor binding, supporting Pol I recruitment. Our findings therefore reveal the molecular basis of Pol I selection for ribosome biogenesis. As well, they reveal an unexpected potential within the histone fold as a motif for specific protein-DNA interactions inside the cell.
SARS-CoV-2 Nsp1 N-terminal and linker regions as a platform for host translational shutoff
Authors: Graziadei Andrea , Schildhauer Fabian , Spahn Christian , Kraushar Matthew , Rappsilber Juri
Published: February 2022

In the early stages of SARS-CoV-2 infection, non-structural protein 1 (Nsp1) inhibits the innate immune response by inserting its C-terminal helices into the mRNA entry channel of the ribosome and promoting mRNA degradation. Nevertheless, the mechanism by which Nsp1 achieves host translational shutoff while allowing for viral protein synthesis remains elusive. We set out to characterize the interactome of full-length Nsp1 and its topology by crosslinking mass spectrometry in order to investigate the role of the N-terminal domain and linker regions in host translational shutoff. We find that these regions are in contact with 40S proteins lining the mRNA entry channel and detect a novel interaction with the G subunit of the eIF3 complex. The crosslink-derived distance restraints allowed us to derive an integrative model of full-length Nsp1 on the 40S subunit, reporting on the dynamic interface between Nsp1, the ribosome and the eIF3 complex. The significance of the Nsp1-eIF3G interaction is supported by further evidence that Nsp1 predominantly binds to 40-43S complexes. Our results point towards a mechanism by which Nsp1 is preferentially recruited to canonical initiation complexes, leading to subsequent mRNA degradation.
Mechanism of commitment to a mating partner in Saccharomyces cerevisiae
Authors: Jacobs Katherine C. , Gorman Olivia , Lew Daniel J.
Published: February 2022

Many cells detect and follow gradients of chemical signals to perform their functions. Yeast cells use gradients of extracellular pheromones to locate mating partners, providing a tractable model to understand how cells decode the spatial information in gradients. To mate, yeast cells must orient polarity toward the mating partner. Polarity sites are mobile, exploring the cell cortex until they reach the proper position, where they stop moving and “commit” to the partner. A simple model to explain commitment posits that a high concentration of pheromone is only detected upon alignment of partner cells’ polarity sites, and causes polarity site movement to stop. Here we explore how yeast cells respond to partners that make different amounts of pheromone. Commitment was surprisingly robust to varying pheromone levels, ruling out the simple model. We also tested whether adaptive pathways were responsible for the robustness of commitment, but our results show that cells lacking those pathways were still able to accommodate changes in pheromone. To explain this robustness, we suggest that the steep pheromone gradients near each mating partner’s polarity site trap the polarity site in place. This mechanism has evolutionary implications because it enables sexual selection for cells making more pheromone.
Heparins enhance C1 esterase inhibitor activity: a promising remedy for acute hereditary angioedema
Authors: Zhou Yingyan , Majluf-Cruz Abraham , Dennis Jaclyn , Woroch Eric , Hor Lilian , Hellbusch Brandon , Archuleta Erin , Fornis Lorelenn , Garcia Cindy , Aerts Shanae L. , Bai Xiyuan , Bevers Shaun , Schmidt Eric P. , Bates Melanie , Fugit Randolph V. , Nieto-Martinez Sandra , Galvan Manuel , Giclas Patricia , Frazer-Abel Ashley , Chan Edward D.
Published: February 2022

Rationale

Hereditary angioedema (HAE) is a potentially life-threatening illness most commonly due to deficiency or dysfunction of C1-esterase inhibitor (C1-INH). While specific treatments are available to thwart acute exacerbations, they are extremely costly and some can be associated with rare but serious side effects. The heparins are long known to augment C1-INH activity and case reports / series have documented their efficacy in treating HAE.

Objective

to determine if unfractionated heparin and two low-molecular weight heparins (enoxaparin and nadroparin) can augment C1-INH activityex vivoin the sera of patients with HAE and in anin vitrobiochemical assay.

Methods

C1-INH activity in the absence or presence of the heparin formulations were analyzed by two different methods. To measure C1-INH activityex vivo, a commercially available assay was utilized with patient sera, excess amounts of C1s, and a substrate of C1s which, upon cleavage by C1s, produces a chromogenic product. To determine biochemically the C1-INH activityin vitro, a pharmacologic grade C1-INH, recombinant C1s (C1s-CCP12SP), and a peptide substrate of C1s were employed. Microscale thermophoresis was used to determine whether C1-INH binds to heparin.

Main results

in patient sera, nadroparin was superior to enoxaparin and unfractionated heparin in augmenting C1-INH activity, followed by enoxaparin and then unfractionated heparin. In thein vitrobiochemical assay, all three heparins augmented C1-INH-C1s binding linearly in a dose-dependent fashion. Microscale thermophoresis assay demonstrated that nadroparin binds to C1-INH, providing a mechanism by which heparin facilitates the interaction between C1-INH and the proteases known to produce bradykinin, the mediator of HAE.

Conclusion

low-molecular weight heparin augments C1-INH activity and should be studied as a potential treatment for acute HAE.
Modulating neutrophils leads to changes in CNS output
Authors: Coulibaly A.P. , Salken I. , Provencio J.J.
Published: February 2022

It has become increasingly evident that immune cells play a role in modulating brain function. Neutrophils are the most abundant innate immune cell in mammals. Until recently, our understanding of the physiological role of these cells was limited to infection and cancer. Recently, it has emerged that neutrophils play critical roles in modulating tissue health and physiology. There has been evidence that neutrophils populate the rodent meninges. As such, we hypothesized that like other meningeal immune cells, neutrophils play a neuromodulatory role. Using a depletion paradigm, anti-Ly6G antibody injection, we demonstrate that the loss of neutrophils leads to changes in cognitive flexibility and social interactions in mice. Furthermore, the depletion paradigm led to a 50% decrease in the number of neutrophils in the meninges, which in turn led to the proliferation of resident immature neutrophils within the meninges. Finally, our data show that this immature population reenters the cell cycle only in response to specific physiological stimuli (neutrophil depletion, and stress). In conclusion, this study demonstrates that there are resident neutrophils within the meninges and that elucidating their function in the nervous system will deepen our understanding of immune regulation of brain function.
Spatially Resolved and Highly Complexed Protein and RNA in situ Detection by Combining CODEX with RNAscope In Situ Hybridization
Authors: Cheng Yilun , Burrack Rachel M. , Li Qingsheng
Published: February 2022

Highly multiplexed protein and RNA in situ concurrent detection on a single tissue section is highly desirable for both basic and applied biomedical research. CODEX is a new and powerful platform to visualize up to 60 protein biomarkers in situ and RNAscope in situ hybridization (RNAscope) is a novel RNA detection system with single-copy sensitivity and unprecedent specificity at a single cell level. Nevertheless, to our knowledge, the combination CODEX and RNAscope remained unreported until this study. Here we report a simple and reproducible combination of CODEX and RNAscope (Comb-CODEX-RNAscope). We also determined the cross-reactivities of CODEX anti-human antibodies to rhesus macaques, a widely used animal model of human disease.
Inactivation of Nphp2 in renal epithelial cells drives infantile nephronophthisis like phenotypes in mouse
Authors: Li Yuanyuan , Xu Wenyan , Makova Svetlana , Brueckner Martina , Sun Zhaoxia
Published: February 2022

Background

Nephronophthisis (NPHP) is a ciliopathy characterized by renal fibrosis and cyst formation, and accounts for a significant portion of end stage renal disease in children and young adults. Currently no targeted therapy is available for this disease. NPHP2 is one of the 25 NPHP genes identified to date. In mouse, global knockout of Nphp2 leads to renal fibrosis and cysts. However, the precise contribution of different cell types and the relationship between epithelial cysts and interstitial fibrosis remains undefined.

Methods

Here, we generated cell-type specific knockout mouse models of Nphp2 and characterized kidney morphology and phenotype. We additionally investigated the impact of removing cilia via deletion of the cilia biogenesis gene Ift88 on phenotype severity in Nphp2 mutants.

Results

Epithelial specific knockout of Nphp2 in Nphp2flox/flox; Ksp-Cre mutant mice resulted in renal cyst formation and severe fibrosis, while Nphp2flox/flox; Foxd1-Cre mice, where Nphp2 is deleted in stromal cells, displayed no observable phenotypes. Further, myofibroblast activation occurred early during disease progression and preceded detectable cyst formation in the Nphp2flox/flox; Ksp-Cre kidney. Moreover, concomitant removal of cilia partially suppressed the phenotypes of the Nphp2flox/flox; Ksp-Cre mutant kidney, supporting a significant role of cilia in Nphp2 function in vivo.

Conclusions

Our results highlight the critical role of renal epithelial cilia and epithelial-stromal communication in NPHP.

Significance statement

Nephronophthisis (NPHP) is a ciliopathy characterized by interstitial fibrosis and epithelial cysts in the kidney. A significant portion of end stage renal disease occurring before age 30 results from NPHP. However, the molecular etiology of NPHP remains to be elucidated. By generating and analyzing tissue specific knockout mouse models of Nphp2/Inversin, authors pinpoint defective epithelial cells as the driver for both epithelial cysts and interstitial fibrosis. Moreover, the profibrotic response is triggered before cyst formation in the epithelial-specific Nphp2 knockout model. Mechanistically, authors provide evidence that Nphp2 may function to inhibit a cilia-dependent pro-fibrotic and pro-cystic pathway.
Omicron (BA.1) and Sub-Variants (BA.1, BA.2 and BA.3) of SARS-CoV-2 Spike Infectivity and Pathogenicity: A Comparative Sequence and Structural-based Computational Assessment
Authors: Kumar Suresh , Karuppanan Kalimuthu , Subramaniam Gunasekaran
Published: February 2022

The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread throughout the world. We used computational tools to assess the spike infectivity, transmission, and pathogenicity of Omicron (BA.1) and sub-variants (BA.1.1, BA.2, and BA.3) in this study. BA.1 has 39 mutations, BA.1.1 has 40 mutations, BA.2 has 31 mutations, and BA.3 has 34 mutations, with 21 shared mutations between all. We observed 11 common mutations in Omicron’s receptor-binding domain and sub-variants. In pathogenicity analysis, the Y505H, N786K, T95I, N211I, N856K, and V213R mutations in omicron and sub-variants are predicted to be deleterious. Due to the major effect of the mutations characterising, in the receptor-binding domain (RBD), we found that Omicron and sub-variants had a higher positive electrostatic surface potential. This could increase interaction between RBD and electronegative human angiotensin-converting enzyme 2 (hACE2). Omicron and sub-variants had a higher affinity for hACE2 and the potential for increased transmission when compared to the wild type. Among Omicron sub-lineages, BA.2 and BA.3 have a higher transmission potential than BA.1 and BA.1.1. We predicted that mutated residues in BA.1.1 (K478), BA.2 (R400, R490, R495), and BA.3 (R397 and H499) formation of new salt bridges and hydrogen bonds. Omicron and sub-variant mutations at Receptor-binding Motif (RBM) residues such as Q493R, N501Y, Q498, T478K, and Y505H all contribute significantly to binding affinity with human ACE2. Interactions with Omicron variant mutations at residues 493, 496, 498, and 501 seem to restore ACE2 binding effectiveness lost due to other mutations like K417N and Y505H.
Phosphorylation by casein kinase 2 ensures ER-phagy receptor TEX264 binding to ATG8 proteins
Authors: Chino Haruka , Yamasaki Akinori , Ode Koji L , Ueda Hiroki R , Noda Nobuo N , Mizushima Noboru
Published: February 2022

Selective autophagy cargos are recruited to autophagosomes primarily by interacting with autophagosomal ATG8 family proteins via the LC3-interacting region (LIR). The upstream sequence of most LIRs contains negatively charged residues such as Asp, Glu, and phosphorylated Ser and Thr. However, the significance of LIR phosphorylation (compared with having acidic amino acids) and the structural basis of phosphorylated LIR–ATG8 binding are not entirely understood. Here, we show that the serine residues upstream of the core LIR of the endoplasmic reticulum (ER)-phagy receptor TEX264 are phosphorylated by casein kinase 2, which is critical for its interaction with ATG8s, autophagosomal localization, and ER-phagy. Structural analysis showed that phosphorylation of these serine residues increased binding affinity by producing multiple hydrogen bonds with ATG8s that cannot be mimicked by acidic residues. This binding mode is different from those of other ER-phagy receptors that utilize a downstream helix, which is absent from TEX264, to increase affinity. These results suggest that phosphorylation of the LIR is critically important for strong LIR–ATG8 interactions, even in the absence of auxiliary interactions.
Bird-strike damage analysis of composite panels with different stiffeners
Authors: Zhang Yile , Zhou Yadong , Sun Youchao
Published: February 2022

Purpose

The purpose of this paper is to analyze the bird impact damage of fuselage composite stiffened structures by numerical method and to evaluate the damage and the bird impact resistance of different structures.

Design/methodology/approach

The deformation and damage of composite stiffened plates during bird impact are numerically analyzed by the explicit finite element software LS-DYNA. A comparative study on the numerical calculation results was conducted by using SPH (Smoothed Particle Hydrodynamics)-FEM (Finite Element Method) modeling and simulation. First, the I-shaped, T-shaped, straight stiffened plates and unstiffened plate were designed. Second, the accuracy of the bird model was verified and further used to evaluate bird strikes on composite stiffened plate. Third, the results of damage modes as well as displacements of the stiffened plates were compared.

Findings

The stiffeners can increase the local stiffness of the composite panel, which can effectively inhibit the bird’s movement along the impact direction. Adding stiffeners can change the panel matrix tension damage from global distribution to local distribution mode; however, the impact damage distribution and the ability to inhibit damage propagation can differ for different stiffened panels. Especially, the I-stiffened panel exhibits a better anti-bird strike performance.

Originality/value

The analysis of geometric parameters of structural components by numerical methods can reduce the cost of the design phase and has been widely used in aircraft design. The present study evaluated the bird impact damage of composite stiffened plates with different structures, which provides a guideline for selecting the stiffened plate structure in the fuselage skin.
Thermal behavior of grain-oriented electrical steel wound core solid-state transformer
Authors: Ichou Houssam , Roger Daniel , Rossi Mathieu
Published: February 2022

Purpose

This paper aims to propose a new design for high-power compact solid-state transformers (SSTs) made with grain-oriented electrical steel (GOES) wound cores that benefit from the natural reduction of iron losses at high temperatures.

Design/methodology/approach

An experimental approach, coupled with numerical and analytical investigations, is widely used for proving the validity of the proposed concept.

Findings

With cores much hotter than coils, the new design of medium frequency transformers can be used for building compact SSTs that rated powers and common-mode insulation voltages much higher than existing ones with similar efficiencies.

Research limitations/implications

The thermal design must provide a large difference between core and coil temperatures in a reasonable volume.

Practical implications

The increasing number of intermittent renewable sources place electric grid stability at risk. Smart nodes, made of SSTs, improve the global grid stability because they are able to provide real-time control of energy fluxes at critical points. In railway applications, high-power SST cells can be distributed along the train providing a larger volume for passengers.

Social implications

The increasing part of electricity in a flexible grid requires performant and high-power SSTs made with components that have an environmental footprint as low as possible.

Originality/value

This paper proves that the design of high-power transformers with GOES wound cores much hotter than coils is possible. It proposes also a thermal equivalent circuit that helps the design.
Maritime resilience during the COVID-19 pandemic: impacts and solutions
Authors: Chua Jie Ying , Foo Ryan , Tan Kim Hock , Yuen Kum Fai
Published: February 2022

Purpose

This study aims to study the resilience of the maritime industry by analyzing the impacts of COVID-19 on the maritime industry, in particular, on the shipping management aspect and offshore sector, investigate the effectiveness of current solutions and recommend future solutions for the industry to reduce or mitigate the negative impacts.

Design/methodology/approach

In order to better appreciate resilience in the maritime industry, the study conducted secondary research and semi-structured online interviews to (1) identify the impacts of COVID-19 on the shipping management and offshore sector, (2) analyze the effectiveness of current solutions and (3) provide some strategies to enhance the effectiveness of the current measures.

Findings

he results are congruent with existing literature which indicate that the pandemic has negatively affected the global economy, changed the global trade network and contributed to the sharp decline in demand for oil. In response to the pandemic, governments have implemented safety and health-related measures such as lockdown, safe-distancing and travel restrictions. Often, measures differ from countries to countries and these non-standardized and changing regulations further increase the challenges faced by the industry. From the shipping management perspective, the industry experienced issues such as crew changing, trade contraction and the expiration of shipping certificates, which supported and validated current research. Meanwhile, the offshore industry is challenged by the increasing market volatility and uncertainty, increasing need to source for alternative fuels and the declining oil exploration activities. Current strategies adopted by shipping management companies include crew change management, capacity management and the extension of ship certificates, whereas offshore industry chose to collaborate with oil majors.

Research limitations/implications

By identifying the impacts and challenges and studying the effectiveness of solutions adopted by the maritime industry, this paper allows maritime industry stakeholders and policymakers to develop strategies to mitigate the effects of the global health crisis and strengthen the resilience of the industry. However, as the pandemic continues to develop and evolve, strategies need to be reviewed continuously in response to the changing situations.

Originality/value

This research analyses the impacts and solutions in response to the COVID-19 pandemic, which contributes to the development and formulation of strategies to strengthen the resilience of maritime transport.
Research that sparked attention on the social Web in 2020: an Altmetric analysis of “top 100” articles
Authors: Rehman Ikhlaq ur , Ganaie Shabir Ahmad , Wani Javaid Ahmad
Published: February 2022

Purpose

The study aims to analyse the “Top 100” articles that were most discussed on social media in 2020.

Design/methodology/approach

This study is based on the data retrieved from the Altmetric database. The data were tabulated in Microsoft Excel for further analysis. Moreover, articles were examined at an individual level to retrieve author affiliations for research collaboration analysis.

Findings

The most discussed article on social media for the year 2020 has an Article Attention Score (AAS) of 34775. COVID-19 related studies have dominated the list and it comes as no surprise since COVID-19 became the focal point of many researchers and publishers ever since the pandemic started. These articles have been published across 63 journals with the highest contributions from reputed journals such as Nature, PLoS ONE and Science. The majority (46%) of articles has been published in open access. Finally, the majority of publications are a result of research collaboration.

Originality/value

This study reflects the societal impact of research that could be used as an indicator of research performance.
Winery diversification options for Native American tribal enterprises
Authors: Hutchens Randi , Way Kelly , Becnel Jennifer N.
Published: February 2022

Purpose

This study examined the perceptions of tribal members regarding the strengths, challenges and opportunities presented by tribal winery operation. Issues of business diversification, marketing, perceived barriers to success, potential benefits to the tribe and the role of agriculture in the preservation of tribal heritage were considered.

Design/methodology/approach

A modified mixed-methods exploratory sequential research model was used to collect and organize data in two studies. In Study 1 quantitative data was used to inform the development of Study 2 which included a qualitative interview protocol. Qualitative interviews followed to elaborate on the various aspects of each of these areas of consideration.

Findings

Results indicate that there is neutral to positive opinion on tribal wineries and that any venture would have to be carefully thought out in terms of marketing and preserving tribal heritage.

Practical implications

This research examined the potential strengths, challenges and opportunities provided by tribal winery operation that can be used to inform future business practices.

Originality/value

The results of this research provide a framework for consideration of the potential strengths and opportunities provided by tribal winery operation.
Mental toughness for employees: towards conceptual clarity and scale development
Authors: Ruparel Namita , Choubisa Rajneesh , Seth Himanshu , Dubey Shubha
Published: February 2022

Purpose

Time and again, scholars have emphasized the vitality of mental toughness for success in performance-oriented contexts. Despite the awareness about the significance of mental toughness, there is ambiguity in the conceptual consensus of the factors that comprise of the construct in an organizational setup. Second, there is a dearth of a psychometrically sound measure that assesses mental toughness among employees.

Design/methodology/approach

The study follows a multi-method approach to develop a mental toughness questionnaire. First, to arrive at a consensus of the factors that construe mental toughness, a meta-ethnography was done. Subsequently, a measure of mental toughness was developed and tested following scale development norms.

Findings

Drawing from the results of qualitative inquiry, four factors of mental toughness were derived, namely, perseverance, control, challenge and commitment. Then, the scale development process was followed. Results of psychometric testing using three samples were above the acceptable range, justifying the use of developed scale for academic and professional purposes.

Originality/value

This study is a novel attempt in the literature to extract factors of mental toughness through meta-ethnography and consequently develop a scale.