bluuebunny/crossref_metadata_2025 huggingface dataset:
“A longitudinal study of healthcare workers’ surveillance during the ongoing COVID-19 Epidemics in Italy: is SARS-CoV-2 still a threat for the Health-care System?”
Authors: Barbaro F , Della Rocca F , Padoan A , Aita A , Cianci V , Basso D , Cattelan A , Donato D , Plebani M , Dall’Olmo L
Published: February 2021

Objectives

In spring 2020, Northern Italy was the first area outside China to be involved in the SARS-CoV-2 pandemic. This observational study depicts SARS-CoV-2 prevalence and serological curves among first-line healthcare workers (HCWs) at Padua University Hospital (PdUH), North-East Italy.

Method

344 HCWs, working at the PdUH Emergency Department and Infectious Disease Unit, underwent a SARS-CoV-2 RNA nasopharyngeal swab with paired IgM and IgG antibody detection for 4 consecutive weeks. At every session, a questionnaire recorded symptoms, signs and recent contacts with SARS-CoV-2 patients. Positive cases were followed up for 5 months.

Results

Twenty-seven HCWs (7.84%) had positive serology (Abs) with 12 positive swabs during the study period. Two additional HCWs were positive by swab but without Abs. Fourteen cases (4%) had SARS-CoV-2 infection before the beginning of the study. An HCW with autoimmune disease showed false Ab results. 46% of individuals with Abs reported no symptoms, in accordance with previous population studies. Fever, nasal congestion, diarrhoea and contacts with SARS-CoV-2 individuals correlated to SARS-CoV-2 infection. 96% of Abs+ cases showed persistent positive antibodies 5 months later and none was re-infected.

Discussion

Correct use of PPEs and separate paths for positive/negative patients in the hospital can result in a low percentage of SARS-CoV-2 infections among HCWs, even in high risk settings. Frequent testing for SARS-CoV-2 with nasopharyngeal swabs is worthwhile, irrespective of HCWs’ symptoms, due to the lack of specificity together with the high percentage of asymptomatic cases. Further studies are needed to elucidate the neutralizing effect of SARS-CoV-2 antibodies.
Prior COVID-19 Infection and Antibody Response to Single Versus Double Dose mRNA SARS-CoV-2 Vaccination
Authors: Ebinger Joseph E. , Fert-Bober Justyna , Printsev Ignat , Wu Min , Sun Nancy , Figueiredo Jane C. , Eyk Jennifer E. Van , Braun Jonathan G. , Cheng Susan , Sobhani Kimia
Published: February 2021

The double dose regimen for mRNA vaccines against SARS-CoV-2 presents both a hope and a challenge for global efforts to curb the COVID-19 pandemic. With supply chain logistics impacting the rollout of population-scale vaccination programs, increasing attention has turned to the potential efficacy of single versus double dose vaccine administration for select individuals. To this end, we examined response to Pfizer-BioNTech mRNA vaccine in a large cohort of healthcare workers including those with versus without prior COVID-19 infection. For all participants, we quantified circulating levels of SARS-CoV-2 anti-spike (S) protein IgG at baseline prior to vaccine, after vaccine dose 1, and after vaccine dose 2. We observed that the anti-S IgG antibody response following a single vaccine dose in persons who had recovered from confirmed prior COVID-19 infection was similar to the antibody response following two doses of vaccine in persons without prior infection (P≥0.58). Patterns were similar for the post-vaccine symptoms experienced by infection recovered persons following their first dose compared to the symptoms experienced by infection naïve persons following their second dose (P=0.66). These results support the premise that a single dose of mRNA vaccine could provoke in COVID-19 recovered individuals a level of immunity that is comparable to that seen in infection naïve persons following a double dose regimen. Additional studies are needed to validate our findings, which could allow for public health programs to expand the reach of population wide vaccination efforts.
Depression and anxiety before and during the COVID-19 lockdown: a longitudinal cohort study with university students
Authors: da Conceição Virgínia , Rothes Inês , Gusmão Ricardo , Barros Henrique
Published: February 2021

Background

For young people, just as in the general population, COVID-19 caused many changes in their lives, including an increased risk for mental illness symptoms. We aimed to study the impact of the COVID-19 pandemic in anxiety and depression symptoms in a cohort of university students.

Methods

This study is part of broader longitudinal research on university students’ mental health with data of the Portuguese version of The Patient Health Questionnaire (PHQ-9) and the Portuguese version of the Generalised Anxiety Disorder (GAD-7) with evaluations on January, May and October 2019 and June 2020, as well as socio-demographic information.

Results

341 university students (257 females and 84 males) were included, with a mean age of 19.91 (SD=1.58). In June 2020, the mean for perceived wellbeing loss was 60.47% (SD=26.56) and 59.54% (SD=28.95) for mental health loss. The proportion of students with scores equal to or above 15 in the PHQ-9 ranged between 22.6% and 25.5% in 2019 and 37.0% in June 2020. The proportion of GAD-7 scores above cut-off ten ranged between 46.0% and 47.8% in 2019 and 64.5% in 2020. Compared with preceding trends, PHQ-9 scores were 3.11 (CI=2.40-3.83) higher than expected, and GAD-7 scores were 3.56 (CI=2.75-5.37) higher.

Discussion

COVID-19 impacted negatively depressive and anxiety symptoms, confirming previous studies and young people’s vulnerability in such uncertain times.
Changes in lipids and inflammation in adults with super-refractory status epilepticus on a ketogenic diet
Authors: Dickens Alex M , Johnson Tory , Lamichhane Santosh , Kumar Anupama , Pardo Carlos A. , Gutierrez Erie G. , Haughey Norman , Cervenka Mackenzie C.
Published: February 2021

Objective

To test the hypothesis that increased ketone body production with a ketogenic diet (KD) will correlate with reductions in pro-inflammatory cytokines, lipid subspecies, and improved clinical outcomes in adults treated with an adjunctive ketogenic diet for super-refractory status epilepticus (SRSE).

Methods

Adults (18 years or older) were treated with a 4:1 (fat:carbohydrate and protein) ratio enteral KD as adjunctive therapy to pharmacologic seizure suppression for SRSE. Blood and urine samples and clinical measurements were collected at baseline (n=10), after 1 week (n=8), and after 2 weeks of KD (n=5). Urine acetoacetate, serum β-hydroxybutyrate, lipidomics, pro-inflammatory cytokines (IL-1β, IL-6), chemokines (CCL3, CCL4, CXCL13), and clinical measurements were obtained at these 3 time points. Univariate and multivariate data analyses were performed to determine the correlation between ketone body production and circulating lipids, inflammatory biomarkers, and clinical outcome.

Results

Changes in lipids included an increase in ceramides, mono-hexosyl ceramide, sphingomyelin, phosphocholine, and phosphoserines, and there was a significant reduction in pro-inflammatory mediators IL-6 and CXCL13 seen at 1 and 2 weeks of KD. Higher blood β-hydroxybutyrate levels at baseline correlated with better clinical outcome however, ketone body production did not correlate with other variables during treatment. Higher chemokine CCL3 levels following treatment correlated with greater length of intensive care unit stay, higher modified Rankin Scale score (worse neurologic disability) at discharge and 6-month follow up.

Conclusions

Adults receiving an adjunctive enteral ketogenic diet for super-refractory status epilepticus have alterations in select pro-inflammatory cytokines and lipid species that may predict response to treatment.
Identification of promising oilseed rape genotypes for the tropical regions of Iran using multivariate analysis
Authors: Bakhshi Behnam , Oghan Hassan Amiri , Alizadeh Bahram , Rameeh Valiollah , Payghamzadeh Kamal , Kiani Davood , Rabiee Mohammad , Rezaizad Abbas , Shiresmaeili Gholamhossein , Dalili Alireza , Kia Shahriar
Published: February 2021

producing new adapted oilseed rape cultivars among the available resources of rapeseed would be a valuable method to increase the cultivar diversity in the tropical regions. Low adaptable and high yield cultivars resources of oilseed rapes are now available in the tropical regions of Iran. The current study aimed to identify new high yield and adaptable genotypes adaptable across various tropical regions. To this end, 20 new genotypes and a check variety (Dalgan) were cultivated in the tropical regions of Iran based on a randomized complete block design (RCBD) with three replications during the 2019 to 2020 cropping season. The experimental sites are composed of five locations, including Gorgan, Sari, Rasht, Borazjan and Zabol. During the growth season, several phenological and quantitative traits were recorded. Combined ANOVA revealed significant genotype by environment interaction for all studied quantitative traits. Days to start flowering and days to end flowering showed the highest heritability. Correlation analysis showed a significant positive relationship between yield and flowering period, the number of sub-branches and also the number of pods per plant, but a negative and significant correlation with the days to maturity. Path analysis showed that the days to maturity had the most negative direct effect on yield and the days to start flowering, while the number of sub-branches had the most positive direct effect on yield. Canonical correlation showed that yield is correlated positively with phenological traits. The principal component analysis showed that the two first components covered 68.07% of all data variations which 12 genotypes were correlated with these two components. Cluster analysis categorized evaluated genotypes into three main groups. Finally, eight genotypes (from class 2 of the cluster) were selected in the current study, which had high yield and adaptability in the tropical regions of Iran.
The Organelle in the Ointment: cryptic mitochondria account for many unknown sequences in cross-species microbiome comparisons
Authors: Sonett Dylan , Brown Tanya , Bengtsson-Palme Johan , Padilla-Gamiño Jacqueline L. , Zaneveld Jesse R.
Published: February 2021

The genomes of mitochondria and chloroplasts contain ribosomal RNA (rRNA) genes, reflecting their evolutionary ancestry as free-living bacteria prior to endosymbiosis. In microbiome studies of animals, plants, or other eukaryotic hosts, these organellar rRNAs are often amplified. If identified, they can be discarded, merely reducing sequencing depth. However, incorrectly annotated mitochondrial reads may compromise statistical analysis by distorting relative abundances of free-living microbes. We quantified this by reanalyzing 7,459 samples from seven 16S rRNA sequencing studies, including the microbiomes of 927 unique animal genera. We find that under-annotation of cryptic mitochondrial reads affects multiple of these large-scale cross-species microbiome comparisons, and can be severe in some samples. It also varies between host species, potentially biasing cross-species microbiome comparisons. We propose a straightforward solution: by supplementing existing taxonomies with diverse mitochondrial rRNA sequences, we resolve up to 97% of unique unclassified sequences in some entire studies as mitochondrial (14% averaged across all studies), without increasing false positive annotations in mitochondria-free mock communities. Overall, improved annotation decreases the proportion of unknown sequences by ≥10-fold in 2,262 of 7,459 samples (30%), including representatives from 5 of 7 studies examined. While standard DADA2 analyses are severely affected, the default positive filter in Deblur run through QIIME2 discards many divergent mitochondrial sequences, preventing bias in analysis, but also making analysis of these sequences more difficult. We recommend leveraging mitochondrial sequence diversity to better identify, remove and analyze mitochondrial rRNA gene sequences in microbiome studies.
Small-molecule inhibitors of the RNA m6A demethylase FTO potently support the survival of dopamine neurons
Authors: Selberg Simona , Yu Li-Ying , Bondarenko Olesja , Kankuri Esko , Seli Neinar , Kovaleva Vera , Herodes Koit , Saarma Mart , Karelson Mati
Published: February 2021

The fat mass and obesity-associated protein (FTO), an RNA N6-methyladenosine (m6A) demethylase, is an important regulator of central nervous system development, neuronal signalling and disease. We present here the target-tailored development and biological characterization of small-molecule inhibitors of FTO. The active compounds were identified using high-throughput molecular docking and molecular dynamics screening of the ZINC compound library. In FTO binding and activity-inhibition assays the two best inhibitors demonstrated Kd= 185 nM; IC50= 1.46 μM (compound2) and Kd= 337 nM; IC50= 28.9 μM (compound3). Importantly, the treatment of mouse midbrain dopamine neurons with the compounds promoted cellular survival and rescued them from growth factor deprivation induced apoptosis already at nanomolar concentrations. Moreover, these inhibitors demonstrated good blood-brain-barrier penetration in the model system, 31.7% and 30.8%, respectively. The compounds2and3protected dopamine neurons with greater potency than our recently developed alkylation repair homolog protein 5 (AlkBH5) m6A demethylase inhibitors. Inhibition of m6A RNA demethylation by small-molecule drugs, as presented here, has therapeutic potential and provides tools for the identification of disease-modifying m6A RNAs in neurogenesis and neuroregeneration. Further refinement of the lead compounds identified in this study, can also lead to unprecedented breakthroughs in the treatment of neurodegenerative diseases.
Core circadian clock transcription factor BMAL1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis
Authors: Casey Theresa , Suarez-Trujillo Aridany , Cummings Shelby , Huff Katelyn , Crodian Jennifer , Bhide Ketaki , Aduwari Clare , Teeple Kelsey , Shamay Avi , Mabjeesh Sameer J. , Miguel Phillip San , Thimmapuram Jyothi , Plaut Karen
Published: February 2021

The role the mammary epithelial circadian clock plays in gland development and lactation is unknown. We hypothesized that mammary epithelial clocks function to regulate mammogenesis and lactogenesis, and propose the core clock transcription factor BMAL1:CLOCK regulates genes that control mammary epithelial development and milk synthesis. Our objective was to identify transcriptional targets of BMAL1 in undifferentiated (UNDIFF) and lactogen differentiated (DIFF) mammary epithelial cells (HC11) using ChIP-seq. Ensembl gene IDs with the nearest transcriptional start site to peaks were explored as potential targets, and represented 846 protein coding genes common to UNDIFF and DIFF cells and 2773 unique to DIFF samples. Genes with overlapping peaks between samples (1343) enriched cell-cell adhesion, membrane transporters and lipid metabolism categories. To functionally verify targets, an HC11 line withBmal1gene knocked out (BMAL1-KO) using CRISPR-CAS was created. BMAL1-KO cultures had lower cell densities over an eight-day growth curve, which was associated with increased (p<0.05) levels of reactive oxygen species and lower expression of superoxide dismutase 3 (Sod3). Q-PCR analysis also found lower expression of the putative targets, prolactin receptor (Prlr),Ppara, and beta-casein (Csn2). Findings support our hypothesis and highlight potential importance of clock in mammary development and substrate transport.
Effect of exogenously applied alpha-tocopherol on vital agronomic, physiological and biochemical attributes of Lentil (Lens culinarisMedik.) under induced drought stress
Authors: Shah Wadood , Ullah Sami , Ali Sajjad , Idrees Muhammad , Khan Muhammad Nauman , Ali Kasif , Khan Ajmal , Ali Muhammad , Younas Frhan
Published: February 2021

Water being a vital part of cell protoplasm plays a significant role in sustaining life on earth; drastic changes in climatic condition leads to limit the availability of water and causing other environmental chaos. Alpha-tocopherol being a powerful antioxidant plays a vital role in scavenging the ill effects of oxidative stress. A pot experiment was conducted by exposing lentil cultivar (Punjab-2009) to varying levels of induced drought stress, sprinkled with α-tocopherol 100, 200 and 300 mg/L. Induced water deficit stress conditions caused a pronounced decline in growth parameters including absolute growth rate (AGR), leaf area index (LAI), leaf area ratio (LAR), root shoot ratio (RSR), relative growth rate (RGR), chlorophyll a, b, total chlorophyll content, carotenoids and soluble protein content (SPC) which were significantly enhanced by exogenously applied α-tocopherol. Moreover, a significant increase was reported in total proline content (TPC), soluble sugar content (SSC), glycine betaine (GB) content, endogenous tocopherol levels, ascorbate peroxidase (APX), catalase (CAT) peroxidase (POD) and superoxide dismutase (SOD) activities. On contrary, exogenously applied α-tocopherol significantly reduced the concentrations of malondialdehyde (MDA) and hydrogen peroxide (H2O2). In conclusion, it was confirmed that exogenously applied α-tocopherol under induced drought stress regimes ameliorated drought stress tolerance potential of lentil cultivar to a great extent; by enhancing growth, physiological and biochemical attributes.
Difference in hoof conformation between shod and barefoot-managed hooves
Authors: De Klerk J.N.
Published: February 2021

Reasons for performing the study

Hoof conformation is linked to biomechanics of the hoof and injury occurrence. There is no scientific data if conformation differs between shod and barefoot-managed hooves.

Objectives

To investigate if and how shod and barefoot hooves differ in conformation.

Study design

Retrospective cohort study.

Methods

Standardised lateral, dorsopalmar/dorsoplantar and solar photographs of 98 shod and 69 barefoot-managed hooves were included. Thirty-six of the barefoot horses were farrier-managed, 33 were podiatrist-managed. Length and angular measurements produced nine conformation parameters; dorsopalmar/plantar balance, solar symmetry, toe angle, heel angle, heel/toe angle difference, heel width, splaying index, flaring index and frog size.

Results

Barefoot hooves showed significantly fewer underrun heels, steeper heel angles, wider heels, increased splaying, increased flaring and larger frog size compared to hooves of shod horses. Solar symmetry showed a significant difference in front hooves but not hind hooves (P=0.038, P=0.104) and toe angle was not significantly different (P=0.368, P=0.425). There was no significant difference in the conformation of barefoot farrier and podiatrist-managed front hooves, however there was a significant difference in the hind hooves: farrier-managed hooves had longer frogs and shorter toes, compared to podiatrist-managed hooves.

Conclusions

The significant differences in hoof conformation found should be considered when managing the individual horse, since hoof conformation affects loading of the internal structure of the hoof and hence influences aetiopathogenesis of hoof pathology.
Hypusinated eIF5A is required for the translation of collagen
Authors: Barba-Aliaga Marina , Mena Adriana , Espinoza Vanessa , Apostolova Nadezda , Costell Mercedes , Alepuz Paula
Published: February 2021

The evolutionary conserved elongation factor eIF5A is required for the translation of mRNAs that encode protein sequences with consecutive prolines or combined with glycine and charged amino acids. Mammalian collagens are enriched in putative eIF5A-dependent Pro-Gly-containing tripeptides. Here, we show that eIF5A is needed for heterologous expression of collagen in yeast, and using a dual luciferase reporter system we confirmed that eIF5A depletion interrupts translation at Pro-Gly-collagenic motifs. Using mouse fibroblasts, we showed that depletion of active eIF5A reduced collagen 1α (Col1a1) content, which became concentrated around the nuclei, in contrast to a stronger and all over the cell collagen signal in untreated cells. Active eIF5A-depleted mouse fibroblast showed upregulation of endoplasmic reticulum (ER) stress markers, suggesting retention of partially synthesized Col1a1 in the ER. A dramatically lower level of Col1α1 protein was also observed in functional eIF5A-depleted human hepatic stellate cells treated with the profibrotic cytokine TGF-β1. Our results show that collagen expression requires eIF5A and imply its potential as a target for regulating collagen production in fibrotic diseases.
GPI-anchored FGF directs cytoneme-mediated bidirectional signaling to self-regulate tissue-specific dispersion
Authors: Du Lijuan , Sohr Alex , Li Yujia , Roy Sougata
Published: February 2021

How signaling proteins generate a multitude of information to organize tissue patterns is critical to understanding morphogenesis. InDrosophila, FGF produced in wing-disc cells regulates the development of the disc-associated air-sac-primordium (ASP). Here, we show that FGF is Glycosylphosphatidylinositol-anchored to the producing cell surface and that this modification both inhibits free FGF secretion and activates target-specific bidirectional FGF-FGFR signaling through cytonemes. FGF-source and recipient ASP cells extend cytonemes that present FGF and FGFR on their surfaces and reciprocally recognize each other over distance by contacting through CAM-like FGF-FGFR binding. Contact-mediated FGF-FGFR binding induces bidirectional signaling, which, in turn, promotes ASP and source cells to polarize cytonemes toward each other and reinforce signaling contacts. Subsequent un-anchoring of FGFR-bound-FGF from the source cell membrane dissociates cytoneme contacts and delivers FGF target-specifically to ASP cytonemes for paracrine functions. Thus, GPI-anchored FGF organizes both source and recipient cells and self-regulates its cytoneme-mediated tissue-specific dispersion and signaling.
Morphological Landscapes from High Content Imaging Identify Optimal Priming Strategies that Enhance MSC Immunosuppression
Authors: Andrews Seth H. , Klinker Matthew W. , Bauer Steven R. , Marklein Ross A.
Published: February 2021

Successful clinical translation of mesenchymal stromal cell (MSC) products has not been achieved in the United States and may be in large part due to MSC functional heterogeneity. Efforts have been made to identify ‘priming’ conditions that produce MSCs with consistent immunomodulatory function; however, challenges remain with predicting and understanding how priming impacts MSC behavior. The purpose of this study was to develop a high throughput, image-based approach to assess MSC morphology in response to combinatorial priming treatments and establish morphological profiling as an effective approach to screen the effect of manufacturing changes (i.e. priming) on MSC immunomodulation. We characterized the morphological response of multiple MSC lines/passages to an array of Interferon-gamma (IFN-γ) and Tumor Necrosis Factor alpha (TNF-α) priming conditions, as well as the effects of priming on MSC modulation of activated T cells and MSC secretome. Although considerable functional heterogeneity, in terms of T cell suppression, was observed between different MSC lines and at different passages, this heterogeneity was significantly reduced with combined IFN-γ/TNF-α priming. The magnitude of this change correlated strongly with multiple morphological features and was also reflected by MSC secretion of immunomodulatory factors e.g. PGE2, ICAM-1, and CXCL16. Overall, this study further demonstrates the ability of priming to enhance MSC function, as well as the ability of morphology to better understand MSC heterogeneity and predict changes in function due to manufacturing.
Combinatorial transcription factor profiles predict mature and functional human islet α and β cells
Authors: Shrestha Shristi , Saunders Diane C. , Walker John T. , Camunas-Soler Joan , Dai Xiao-Qing , Haliyur Rachana , Aramandla Radhika , Poffenberger Greg , Prasad Nripesh , Bottino Rita , Stein Roland , Cartailler Jean-Philippe , Parker Stephen C. J. , MacDonald Patrick E. , Levy Shawn E. , Powers Alvin C. , Brissova Marcela
Published: February 2021

Islet-enriched transcription factors (TFs) exert broad control over cellular processes in pancreatic α and β cells and changes in their expression are associated with developmental state and diabetes. However, the implications of heterogeneity in TF expression across islet cell populations are not well understood. To define this TF heterogeneity and its consequences for cellular function, we profiled >40,000 cells from normal human islets by scRNA-seq and stratified α and β cells based on combinatorial TF expression. Subpopulations of islet cells co-expressingARX/MAFB(α cells) andMAFA/MAFB(β cells) exhibited greater expression of key genes related to glucose sensing and hormone secretion relative to subpopulations expressing only one or neither TF. Moreover, all subpopulations were identified in native pancreatic tissue from multiple donors. By Patch-seq,MAFA/MAFBco-expressing β cells showed enhanced electrophysiological activity. Thus, these results indicate combinatorial TF expression in islet α and β cells predicts highly functional, mature subpopulations.
Multiple mechanisms of photoreceptor spectral tuning following loss of UV color vision inHeliconiusbutterflies
Authors: McCulloch Kyle J. , Macias-Muñoz Aide , Mortazavi Ali , Briscoe Adriana D.
Published: February 2021

Color vision modifications occur in animals via a process known as spectral tuning. InHeliconiusbutterflies, a genus-specificUVRhopsin duplication led to the evolution of UV color discrimination inHeliconius eratofemales, a rare trait among butterflies. In theH. melpomeneandH. ismeniuslineages, the UV2 receptor has been lost. Here we compare how loss of the UV2 photoreceptor has altered the visual system of these butterflies. We compare visual system evolution in threeHeliconiusbutterfly species using a combination of intracellular recordings, ATAC-seq, and antibody staining. We identify several spectral tuning mechanisms including adaptive evolution of opsins, deployment of two types of filtering pigments, and co-expression of two distinct opsins in the same cell. Our data show that opsin gain and loss is driving rapid divergence inHeliconiusvisual systems via tuning of multiple spectral classes of photoreceptor in distinct lineages, potentially contributing to ongoing speciation in this genus.
PredictProtein – Predicting Protein Structure and Function for 29 Years
Authors: Bernhofer Michael , Dallago Christian , Karl Tim , Satagopam Venkata , Heinzinger Michael , Littmann Maria , Olenyi Tobias , Qiu Jiajun , Schütze Konstantin , Yachdav Guy , Ashkenazy Haim , Ben-Tal Nir , Bromberg Yana , Goldberg Tatyana , Kajan Laszlo , O’Donoghue Sean , Sander Chris , Schafferhans Andrea , Schlessinger Avner , Vriend Gerrit , Mirdita Milot , Gawron Piotr , Gu Wei , Jarosz Yohan , Trefois Christophe , Steinegger Martin , Schneider Reinhard , Rost Burkhard
Published: February 2021

Since 1992PredictProtein(https://predictprotein.org) is a one-stop online resource for protein sequence analysis with its main site hosted at the Luxembourg Centre for Systems Biomedicine (LCSB) and queried monthly by over 3,000 users in 2020.PredictProteinwas the first Internet server for protein predictions. It pioneered combining evolutionary information and machine learning. Given a protein sequence as input, the server outputs multiple sequence alignments, predictions of protein structure in 1D and 2D (secondary structure, solvent accessibility, transmembrane segments, disordered regions, protein flexibility, and disulfide bridges) and predictions of protein function (functional effects of sequence variation or point mutations, Gene Ontology (GO) terms, subcellular localization, and protein-, RNA-, and DNA binding). PredictProtein’s infrastructure has moved to the LCSB increasing throughput; the use of MMseqs2 sequence search reduced runtime five-fold; user interface elements improved usability, and new prediction methods were added. PredictProtein recently included predictions from deep learning embeddings (GO and secondary structure) and a method for the prediction of proteins and residues binding DNA, RNA, or other proteins. PredictProtein.org aspires to provide reliable predictions to computational and experimental biologists alike. All scripts and methods are freely available for offline execution in high-throughput settings.

Availability

Freely accessible webserverPredictProtein.org; Source and docker images:github.com/rostlab
Metagenomic diagnosis and pathogenic network profile of SARS-CoV-2 in patients co-morbidly affected by type 2 diabetes
Authors: Al-Emran Hassan M. , Rahman M. Shaminur , Hasan Md. Shazid , Rubayet Ul Alam A. S. M. , Islam Ovinu Kibria , Anwar Ajwad , Jahid Iqbal Kabir , Hossain M. Anwar
Published: February 2021

Background

The mortality of COVID-19 disease is very high among males or elderly or individuals having comorbidities with obesity, cardiovascular diseases, lung infections, hypertension, and/or diabetes. Our study characterizes SARS-CoV-2 infected patients’ metagenomic features with or without type 2 diabetes to identify the microbial interactions associated with its fatal consequences.

Method

This study compared the baseline nasopharyngeal microbiome of SARS-CoV-2 infected diabetic and non-diabetic patients with controls adjusted with age and gender. The mNGS were performed using Ion GeneStudio S5 Series and the data were analyzed by the Vegan-package in R.

Results

All three groups possessed significant bacterial diversity and dissimilarity indexes (p<0.05). Spearman’s correlation coefficient network analysis illustrated 183 significant positive correlations and 13 negative correlations of pathogenic bacteria (r=0.6-1.0, p<0.05), and 109 positive correlations among normal-flora and probiotic bacteria (r>0.6, p<0.05). The SARS-CoV-2 diabetic group exhibited a significant increase of pathogens (p<0.05) and opportunistic pathogens (p<0.05) with a simultaneous decrease of normal-flora (p<0.05). The molecular docking analysis of Salivaricin, KLD4 (alpha), and enterocin produced by several enriched probiotic strains presented strong binding affinity with Shiga toxin, outer membrane proteins (ompA, omp33) or hemolysin.

Conclusion

The dysbiosis of the bacterial community might be linked with severe consequences of COVID-19 infected diabetic patients, although few probiotic strains inhibited numerous pathogens in the same pathological niches. This study suggested that the promotion of normal-flora and probiotics through dietary changes and reduction of excessive pro-inflammatory states by preventing pathogenic environment might lead to a better outcome for those co-morbid patients.
Automated classification of signal sources in mesoscale calcium imaging
Authors: Mullen Brian R. , Weiser Sydney C. , Ascencio Desiderio , Ackman James B.
Published: February 2021

Functional imaging of neural cell populations is critical for mapping intra− and inter−regional network dynamics across the neocortex. Recently we showed that an unsupervised machine learning decomposition of densely sampled recordings of cortical calcium dynamics results in a collection of components comprised of neuronal signal sources distinct from optical, movement, and vascular artifacts. Here we build a supervised learning classifier that automatically separates neural activity and artifact components, using a set of extracted spatial and temporal metrics that characterize the respective components. We demonstrate that the performance of the machine classifier matches human identification of signal components in novel data sets. Further, we analyze control data recorded in glial cell reporter and non−fluorescent mouse lines that validates human and machine identification of functional component class. This combined workflow of data−driven video decomposition and machine classification of signal sources will aid robust and scalable mapping of complex cerebral dynamics.
Cerebellar connectivity maps embody individual adaptive behavior
Authors: Spaeth Ludovic , Bahuguna Jyotika , Gagneux Theo , Dorgans Kevin , Sugihara Izumi , Poulain Bernard , Battaglia Demian , Isope Philippe
Published: February 2021

From planification to execution, cerebellar microcircuits encode different features of skilled movements. However, it is unknown whether cerebellar synaptic connectivity maps encode movement features in a motor context specific manner. Here we investigated the spatial organization of excitatory synaptic connectivity in mice cerebellar cortex in different locomotor contexts: during development and in normal, trained or altered locomotor conditions. We combined optical, electrophysiological and graph modelling approaches to describe synaptic connectivity between granule cells (GCs) and Purkinje cells (PCs). Synaptic map maturation during development revealed a critical period in juvenile animals before the establishment of a stereotyped functional organization in adults. However, different locomotor conditions lead to specific GC-PC connectivity maps in PCs. Ultimately, we demonstrated that the variability in connectivity maps directly accounts for individual specific behavioral features of mice locomotion, suggesting that GC-PC networks encode a general motor context as well as individual specific internal models underlying motor adaptation.
Intracellular pools of DAG-activated TRPC3 channels are essential for TLR4 activation
Authors: Casas Javier , Meana Clara , López-López José Ramón , Balsinde Jesús , Balboa María A.
Published: February 2021

Toll-like receptor 4, the receptor for bacterial lipopolysaccharide (LPS), drives inflammatory responses that protect against pathogens and boost the adaptive immunity. LPS responses are known to depend on calcium fluxes, but the molecular mechanisms involved are poorly understood. Here we present evidence that the transient receptor potential canonical channel 3 (TRPC3) is activated intracellularly during macrophage exposure to LPS and is essential for Ca2+release from internal stores. In this way TRPC3 participates in cytosolic Ca2+elevations, TLR4 endocytosis, activation of inflammatory transcription factors and cytokine upregulation. We also report that TRPC3 is activated by diacylglycerol (DAG) generated by the phosphatidic acid phosphatase lipin-1. In accord with this, lipin-1-deficient cells show reduced Ca2+responses to LPS challenge. A cameleon indicator directed to the endoplasmic reticulum shows that this is the organelle from which TRPC3 mediates the Ca2+release. Finally, pharmacological inhibition of TRPC3 reduces systemic inflammation induced by LPS in mice. Collectively, our study unveils a central component of LPS-triggered Ca2+signaling that involves intracellular sensing of lipin-1-derived DAG by TRPC3.
The oncogenic transcription factor FUS-CHOP can undergo nuclear liquid-liquid phase separation
Authors: Owen Izzy , Yee Debra , Wyne Hala , Perdikari Theodora Myrto , Johnson Victoria , Smyth Jeremy , Kortum Robert , Fawzi Nicolas L. , Shewmaker Frank
Published: February 2021

Myxoid liposarcoma is caused by a chromosomal translocation resulting in a fusion protein comprised of the N-terminus of FUS (fused in sarcoma) and the full-length transcription factor CHOP (CCAAT/Enhancer Binding Protein Homologous Protein). FUS functions in RNA metabolism and CHOP is a stress-induced transcription factor. The FUS-CHOP fusion protein causes unique gene expression and oncogenic transformation. The FUS segment is required for oncogenic transformation, but the mechanism of FUS-CHOP-induced transcriptional activation is unknown. Recently, some transcription factors and super enhancers were proposed to undergo liquid-liquid phase separation and form membraneless compartments that recruit transcription machinery to gene promoters. Since phase separation of FUS depends on its N-terminus, transcriptional activation by FUS-CHOP could result from the N-terminus driving nuclear phase transitions. Here, we characterized FUS-CHOP in cells andin vitro, and observed novel phase-separating properties relative to unmodified CHOP. Our data indicate FUS-CHOP forms phase-separated condensates at super enhancer transcriptional sites. We provide strong evidence that the FUS-CHOP phase transition is a novel oncogenic mechanism and potential therapeutic target for treatment of myxoid liposarcoma.
Structure and functional properties of the cold-adapted catalase from Acinetobacter sp. Ver3 native to the Atacama plateau in northern Argentina
Authors: Sartorio Mariana G. , Cortez Néstor , González Javier M.
Published: February 2021

Heme catalases remove hydrogen peroxide by catalyzing its dismutation into water and molecular oxygen, thereby protecting the cell from oxidative damage. The Atacama plateau in northern Argentina, located 4000 m above sea level, is a desert area characterized by extreme UV radiation, high salinity and a large temperature variation between day and night. Here, the heme catalase KatE1 from an Atacama Acinetobacter sp. isolate was cloned, expressed and purified, with the aim of investigating its extremophilic properties. Kinetic and stability assays indicate that KatE1 is maximally active at 50°C in alkaline media, with a nearly unchanged specific activity between 0°C and 40°C in the pH range 5.5–11.0. In addition, its three-dimensional crystallographic structure was solved, revealing minimal structural differences compared with its mesophilic and thermophilic analogues, except for a conserved methionine residue on the distal heme side, which is proposed to comprise a molecular adaptation to oxidative damage.
Assessment of visibility in industrial construction projects: a viewpoint from supply chain stakeholders
Authors: Dharmapalan Vineeth , O’Brien William J. , Morrice Douglas , Jung Minhyuk
Published: February 2021

Purpose

Stakeholders of construction projects exhibit different perceptions regarding the visibility of materials in the supply chain, which affects the timely delivery and installation of materials. This study aims to quantitatively investigate the differences in viewpoints of owners, contractors, designers and suppliers about the visibility of materials at supply chain locations and different material types during the construction of industrial projects.

Design/methodology/approach

Survey data about visibility at nine typical supply chain locations and three common material types were collected from owner, contractor, designer and supplier groups and analyzed using frequency statistics, relative importance index and tests for equality of odds.

Findings

Offsite Tier-2 supplier, ports and kitting site shows the lowest visibility level for the owner, contractor, supplier and designer groups. Also, the supplier group tends to have adequate to extreme visibility at the Tier-2 supplier, kitting site and during transportation compared to owner, contractor and designer groups. An example finding concerning the visibility of material types is that owners and contractors perceive prefabricated material requires higher visibility than all other material types.

Research limitations/implications

The findings are limited to construction projects in the industrial sector. Further, the survey participants were based in North America at the time of participation.

Practical implications

The study’s findings indicate how visibility is spread across supply chain locations and for material types for the owners, contractors, suppliers and designers of industrial projects. As such, academia and industry’s research and investment efforts can be more focused on locations and material types that need improvement.

Social implications

Industrial projects play an essential part in improving society’s daily lives, and this study’s findings contribute to improving the efficiency of the supply chain during construction of industrial projects.

Originality/value

Although previous studies mentioned the need and importance of visibility improvement, none have sought to understand the perception of leading supply chain stakeholders about visibility at supply chain locations and of material types. This study’s findings provide specific insights and directions for advancing in these areas with regard to supply chain visibility.
User compensation as a data breach recovery action: a methodological replication and investigation of generalizability based on the Home Depot breach
Authors: Hoehle Hartmut , Wei Jia , Schuetz Sebastian , Venkatesh Viswanath
Published: February 2021

Purpose

In the aftermath of data breaches, many firms offer compensation to affected customers to recover from damaged customer sentiments. To understand the effectiveness of such compensation offerings, Goode et al. (2017) examined the effects of compensation offered by Sony following the PlayStation Network breach in 2011. Although Goode et al. (2017) present key insights on data breach compensation, it is unclear whether their findings generalize beyond the context of subscription-based gaming platforms whose customers are young and experience substantial switching costs. To address this issue, we conducted a methodological replication in a retail context with low switching costs.

Design/methodology/approach

In our replication, we examine the effects of compensation offered by Home Depot in the aftermath of its data breach in 2014. Home Depot is the largest home improvement retailer in the US and presents a substantially different context. Data were collected from 901 participants using surveys.

Findings

Our results were consistent with the original study. We found that in retail breaches, effective compensation needs to meet customers' expectations because overcompensation or undercompensation leads to negative outcomes, such as decreased repurchase intention.

Originality/value

Our study provides insights into the effectiveness of compensation in the retail context and confirms the findings of Goode et al. (2017).
Did the environmental jolt matter? Corporate entrepreneurship and firm financial performance in Egypt
Authors: Tantawy Ahmed Adel , Elaasi Sherif , Elshawadfy Mohamed
Published: February 2021

Purpose

Evidence suggests that corporate entrepreneurship (CE), namely, innovativeness, risk-taking and corporate venturing, enhances a firm’s performance. However, the study of CE in developing markets – particularly in Egypt – is still new and undeveloped. The literature stresses the importance of incorporating environmental factors into the study of CE. Therefore, the purpose of this study is to examine the relationship between CE, environmental jolts (unexpected abrupt environmental events such as the Arab Spring) and the firm’s financial performance. Based on the periods before and after the series of anti-government protests known as the Arab Spring, this paper argues that after an environmental jolt, CE will negatively affect financial performance.

Design/methodology/approach

This study analyzes and correlates CE, environmental jolts and firm performance in Egypt for a period over 10 years (from 2007 through 2016) using a sample of 94 manufacturing firms listed on the Egyptian Stock Exchange. Data were manually collected through archival/secondary data using financial and accounting information from the annual reports released by the firms. These reports were downloaded from the firms’ webpages and the Egyptian Exchange website.

Findings

The main results of this paper indicate that environmental factors play a role in the effect of CE on firm performance. Using the 2011 Arab Spring as a quasi-natural experiment, this paper finds that CE’s effect on firm performance is higher pre-jolt and lower post-jolt.

Practical implications

This study provides useful implications for managers and practitioners. Firms need to find new ways of allocating their resources to help provide innovative products and to have a competitive advantage. Although innovation, risk-taking and corporate venturing may have a delayed impact on a firm’s financial performance, managers should evaluate the implications and the success of CE activities in the long-term, not from a short-term perspective.

Originality/value

Building upon the existing literature, this is the first paper to investigate the effect of CE on a firm’s financial performance in Egypt during the Arab Spring. The manufacturing firms listed on the Egyptian Exchange were analyzed in a quasi-natural experiment, taking into account the moderating role of an environmental jolt, namely, the Arab Spring.
The role of intellectual capital on entrepreneurial opportunity recognition among SMEs in the Sultanate of Oman
Authors: Rahman Syed Abidur , Khan Golam Mostafa , AlAbri Salem , Taghizadeh Seyedeh Khadijeh
Published: February 2021

Purpose

This study aims to investigate the role of the components of intellectual capital (IC) on entrepreneurial opportunity recognition among small and medium enterprises (SMEs) in the Sultanate of Oman. The interrelationships of these components are also examined.

Design/methodology/approach

The study used quantitative research methods. Data were collected using structured questionnaires from a sample of 347 respondents from SMEs operating in Oman. Structural equation modeling was employed to examine the hypotheses using partial least square technique.

Findings

The analysis results demonstrate that structural capital, relational capital and spiritual capital have significant relationships with entrepreneurial opportunity recognition. Meanwhile, human capital has no relationship with either entrepreneurial opportunity recognition or spiritual capital. Intriguingly, significant interrelationships are observed among IC's components.

Practical implications

This study offers useful managerial implications for the related parties: firms, public institutions and other stakeholders. The findings could be a guideline for SME managers/owners to recognize the right entrepreneurial opportunity.

Originality/value

To the best of our knowledge, this study is the first to reveal the relationships between the tripartite model of IC and entrepreneurial opportunity recognition. This study is also the first to test the interrelationship of spiritual capital on other intellectual components.