bluuebunny/crossref_metadata_2025 huggingface dataset:
High-resolution yeast quiescence profiling in human-like media reveals interacting influences of auxotrophy and nutrient availability
Authors: Santos Sean L , Laflin Samantha , Broadway Audrie , Burnett Cosby , Hartheimer Joline , Rodgers John W , Smith Daniel L , Hartman John L
Published: May 2020

Yeast cells survive in stationary phase culture by entering quiescence, which is measured by colony forming capacity upon nutrient re-exposure. Yeast chronological lifespan (CLS) studies, employing the comprehensive collection of gene knockout strains, have correlated weakly between independent laboratories, which is hypothesized to reflect differential interaction between the deleted genes, auxotrophy, media composition and other assay conditions influencing quiescence. This hypothesis was investigated by high-throughput quiescence profiling of the parental prototrophic strain, from which the gene deletion strain libraries were constructed, and all possible auxotrophic allele combinations in that background. Defined media resembling human cell culture media promoted long-term quiescence, and was used to assess effects of glucose, ammonium sulfate, auxotrophic nutrient availability, Target of Rapamycin signaling, and replication stress. Frequent, high-replicate measurements of colony forming capacity from cultures aged past 60 days provided profiles of quiescence phenomena such as gasping and hormesis. Media acidification was assayed in parallel to assess correlation. Influences of leucine, methionine, glucose, and ammonium sulfate metabolism were clarified, and a role for lysine metabolism newly characterized, while histidine and uracil perturbations had less impact. Interactions occurred between glucose, ammonium sulfate, auxotrophy, auxotrophic nutrient limitation, aeration, TOR signaling, and/or replication stress. Weak correlation existed between media acidification and maintenance of quiescence. In summary, experimental factors, uncontrolled across previous genome-wide yeast CLS studies, influence quiescence and interact extensively, revealing quiescence as a complex metabolic and developmental process that should be studied in a prototrophic context, omitting ammonium sulfate from defined media, and employing highly replicable protocols.
The island rule explains consistent patterns of body size evolution in terrestrial vertebrates
Authors: Benítez-López Ana , Santini Luca , Gallego-Zamorano Juan , Milá Borja , Walkden Patrick , Huijbregts Mark A.J. , Tobias Joseph A.
Published: May 2020

Island faunas can be characterized by gigantism in small animals and dwarfism in large animals, but the extent to which this so-called ‘island rule’ provides a general explanation for evolutionary trajectories on islands remains contentious. Here we use a phylogenetic meta-analysis to assess patterns and drivers of body size evolution across a global sample of paired island-mainland populations of terrestrial vertebrates. We show that ‘island rule’ effects are widespread in mammals, birds and reptiles, but less evident in amphibians, which mostly tend towards gigantism. We also found that the magnitude of insular dwarfism and gigantism is mediated by climate as well as island size and isolation, with more pronounced effects in smaller, more remote islands for mammals and reptiles. We conclude that the island rule is pervasive across vertebrates, but that the implications for body size evolution are nuanced and depend on an array of context-dependent ecological pressures and environmental conditions.
AC. elegansZona Pellucida domain protein functions via its ZPc domain
Authors: Cohen Jennifer D. , Bermudez Jessica G. , Good Matthew C. , Sundaram Meera V.
Published: May 2020

Zona Pellucida domain (ZP) proteins are critical components of the body’s external-most protective layers, apical extracellular matrices (aECMs). Although their loss or dysfunction is associated with many diseases, it remains unclear how ZP proteins assemble in aECMs. Current models suggest that ZP proteins polymerize via their ZPn subdomains, while ZPc subdomains modulate ZPn behavior. Using the model organismC. elegans, we investigated the aECM assembly of one ZP protein, LET-653, which shapes several tubes. Contrary to prevailing models, we find that LET-653 localizes and functions via its ZPc domain. Furthermore, the ZPc domain is inhibited by the ZPn domain and cleavage of the LET-653 C-terminus relieves this inhibition.In vitro, the ZPc, but not ZPn, domain formed crystalline aggregates. These data offer a new model for ZP function whereby the ZPc domain is primarily responsible for matrix incorporation and tissue shaping.
Multi-site Validation of a SARS-CoV-2 IgG/IgM Rapid Antibody Detection Kit
Authors: Minteer Christopher , Casanovas-Massana Arnau , Li Tao , McDonald David , Wang Linda , Pan Si Hui , Caianiello David , Collinski Jesse , deRamon Edward , Hale Robert , Howell Rebecca , Ray Jason , Vinetz Joseph , Levine Morgan , Ko Albert I. , Spiegel David A.
Published: May 2020

Deaths from coronavirus disease (COVID-19) have exceeded 300,000 persons globally, calling for rapid development of mobile diagnostics that can assay widespread prevalence and infection rates. Data provided in this study supports the utility of a newly-designed lateral flow immunoassay (LFA) for detecting SARS-CoV-2 IgM and IgG antibodies. We employed a clinical cohort of 1,892 SARS-CoV-2 patients and controls, including individuals diagnosed by RT-qPCR at Yale New Haven Hospital, The First Affiliated Hospital of Anhui Medical University, the Chinese Center for Disease Control and Prevention of Hefei City (Hefei CDC), Anhui Province (Anhui Province CDC), and Fuyang City (Fuyang CDC). The LFA studied here detects SARS-CoV-2 IgM and IgG antibodies with a specificity of 97.9–100% for IgM, 99.7–100% for IgG, and sensitivities ranging from 94.1–100% for patients >14-days post symptom onset. Sensitivity decreases in patients <14-days post symptom onset, which is likely due to lower IgG/IgM antibody levels in this population. Finally, we developed a visual intensity reporting system that we believe will be suitable for laboratory and point-of-care settings, and will provide granular information about antibody levels. Overall our results support the widespread utility of this and other LFAs in assessing population-level epidemiological statistics.
Gsta4 controls apoptosis of differentiating adult oligodendrocytes during homeostasis and remyelination via the mitochondria-associated Fas/Casp8/Bid-axis
Authors: Carlström Karl E , Zhu Keying , Ewing Ewoud , Krabbendam Inge E , Harris Robert A , Falcão Ana Mendanha , Jagodic Maja , Castelo-Branco Gonçalo , Piehl Fredrik
Published: May 2020

Arrest of oligodendrocyte (OL) differentiation and remyelination following myelin damage in Multiple Sclerosis (MS) are associated with disease progression but the underlying mechanism are elusive. We show that Glutathione S-transferase 4α (Gsta4) is highly expressed during adult OL differentiation and that its loss prevents differentiation into myelinating OLs. Also, Gsta4 appeared to be a novel target for Clemastine, in clinical trial for MS. Over-expression of Gsta4 reduced the expression of Fas and activity along the mitochondria-associated Casp8/Bid-axis in adult pre-OLs from the corpus callosum, together promoting enhanced pre-OL survival during differentiation. The Gsta4-mediated input on apoptosis during adult OL differentiation was further verified in the LPC and EAE model, where Casp8 were reduced in pre-OLs with high Gsta4 expression in an immune response-independent fashion. Our results place Gsta4 as a key regulator of intrinsic mechanisms beneficial for OL differentiation and remyelination, and as a possible target for future MS therapies.
Dynamics of a mutual inhibition between pyramidal neurons compared to human perceptual competition
Authors: Kogo N. , Kern F. B. , Nowotny T. , van Ee R. , van Wezel R. , Aihara T.
Published: May 2020

Neural competition plays an essential role in active selection processes of noisy and ambiguous input signals and it is assumed to underlie emergent properties of brain functioning such as perceptual organization and decision making. Despite ample theoretical research on neural competition, experimental tools to allow neurophysiological investigation of competing neurons have not been available. We developed a “hybrid” system where real-life neurons and a computer-simulated neural circuit interacted. It enabled us to construct a mutual inhibition circuit between two real life pyramidal neurons. We then asked what dynamics this minimal unit of neural competition exhibits and compared them to the known behavioral-level dynamics of neural competition. We found that the pair of neurons shows bi-stability when activated simultaneously by current injections. The addition of modelled noise and changes in the activation strength showed that the dynamics of the circuit are strikingly similar to the known properties of bi-stable visual perception.
Angiotensin-converting enzyme 2, a SARS-CoV-2 receptor, is upregulated by interleukin-6 via STAT3 signaling in rheumatoid synovium
Authors: Mokuda Sho , Tokunaga Tadahiro , Masumoto Junya , Sugiyama Eiji
Published: May 2020

Detected in December 2019, the coronavirus disease 2019 (COVID-19) has since spread all over the world, resulting in a global pandemic. The disease is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), and its symptoms usually include cough, fever, and gastrointestinal problems. Although the prevalence of rheumatoid arthritis (RA) is about 1 % of the global population and RA patients naturally have a chance of acquiring COVID-19 in this pandemic, no studies have considered the expression of angiotensin-converting enzyme 2 (ACE2) (a receptor for SARS-CoV-2) in synovial tissues. Our presenting data revealed that ACE2 expression was elevated in active rheumatoid synovium, and siRNA against STAT3 was able to downregulate ACE2 expression, which was in turn induced by IL-6 signaling.
Plis de passage in the Superior Temporal Sulcus: Morphology and local connectivity
Authors: Bodin C. , Pron A. , Le Mao M. , Régis J , Belin P. , Coulon O.
Published: May 2020

While there is a profusion of functional investigations involving the superior temporal sulcus (STS), our knowledge of the anatomy of this sulcus is still limited by a large variability across individuals. Several “plis de passage” (PPs), annectant gyri buried inside the fold, can separate the STS into distinct segments and could explain part of the observed variability. However, an accurate characterization is lacking to properly extract and fully understand the nature of PPs. The aim of the present study is twofold:i.to characterize the STS PPs by directly identifying them within individual STS, using the geometry of the surrounding surface and considering both deep and superficial PPs.ii.to test the hypothesis that PPs constitute local increases of the short-range structural connectivity. Performed on 90 subjects from the Human Connectome Project database, our study revealed that PPs constitute surface landmarks that can be identified from the geometry of the STS walls and that they constitute critical pathways of the U-shaped white-matter connecting the two banks of the STS. Specifically, a larger amount of fibers was extracted at the location of PPs compared to other locations in the STS. This quantity was also larger for superficial PPs than for deep buried ones. These findings raise new hypotheses regarding the relation between the cortical surface geometry and structural connectivity, as well as the possible role of PPs in the functional organization of the STS.
Impact of Comorbidities on SARS-CoV-2 Viral Entry-Related Genes
Authors: Breidenbach Joshua D. , Dube Prabhatchandra , Ghosh Subhanwita , Modyanov Nikolai N. , Malhotra Deepak , Dworkin Lance D. , Haller Steven T. , Kennedy David J.
Published: May 2020

Viral entry mechanisms for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an important aspect of virulence. Proposed mechanisms involve host cell membrane-bound angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine proteases (TTSPs), such as transmembrane serine protease isoform 2 (TMPRSS2). The distribution of expression of these genes across cell types representing multiple organ systems in healthy individuals has been recently demonstrated. However, comorbidities such as diabetes and cardiovascular disease are highly prevalent in patients with Coronavirus Disease 2019 (COVID-19) and associated with worse outcomes. Whether these conditions contribute directly to SARS-CoV-2 virulence remain unclear. Here we show that the expression levels ofACE2, TMPRSS2and other viral entry-related genes are modulated in target organs of select disease states. In tissues such as heart, which normally expressACE2but minimalTMPRSS2, we found thatTMPRSS2as well as other TTSPs are elevated in individuals with comorbidities vs healthy individuals. Additionally, we found increased expression of viral entry-related genes in the settings of hypertension, cancer or smoking across target organ systems. Our results demonstrate that common comorbidities may contribute directly to SARS-CoV-2 virulence and suggest new therapeutic targets to improve outcomes in vulnerable patient populations.
Diabetes is associated with increased risk for in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis comprising 18,506 patients
Authors: Palaiodimos Leonidas , Chamorro-Pareja Natalia , Karamanis Dimitrios , Li Weijia , Zavras Phaedon D. , Mathias Priyanka , Kokkinidis Damianos G.
Published: May 2020

Background

Infectious diseases are more frequent and can be associated with worse outcomes in patients with diabetes. Our aim was to systematically review and synthesize with a meta-analysis the available observational studies reporting the effect of diabetes in mortality among hospitalized patients with COVID-19.

Methods

Medline, Embase, Google Scholar, and medRxiv databases were reviewed. A random-effect model meta-analysis was used and I-square was utilized to assess the heterogeneity. In-hospital mortality was defined as the endpoint. Sensitivity, subgroup, and meta-regression analyses were performed.

Results

18,506 patients were included in this meta-analysis (3,713 diabetics and 14,793 non-diabetics). Patients with diabetes were associated with a higher risk of death compared to patients without diabetes (OR: 1.65; 95% CI: 1.35-1.96; I2 77.4%). The heterogeneity was high. A study level meta-regression analysis was performed for all the important covariates and no significant interactions were found between the covariates and the outcome of mortality.

Conclusion

This meta-analysis shows that that the likelihood of death is 65% higher in diabetic hospitalized patients with COVID-19 compared to non-diabetics. Further studies are needed to assess whether this association is independent or not, as well as to investigate to role of glucose control prior or during the disease.
Increase of non-vaccine human papillomavirus types in a group of HPV-vaccinated Mexican women. Evidence of Pathogenic Strain Replacement
Authors: Cabrera-Becerril Augusto , Alonso Ramiro , Vargas-De-León Cruz , Miramontes Pedro , Romero Pablo , Taniguchi Keiko , Marrero Daniel , Capistrán Marco , Jiménez Sheila , Dávila Sonia , Salcedo Mauricio , Peralta Raúl
Published: May 2020

High risk HPV infection is the etiological factor of Cervical Cancer (CC) and other types of cancer of epithelial origin. HPV 16 and 18 infections are associated with 70% of CC worldwide. At the present time, there is a vaccine that prevents this infections. In Mexico, the HPV vaccine was introduced in 2009. Even if the current vaccine is effective, some models indicate a possible scenario of Vaccine-induced Pathogen Strain Replacement (VPSR). In this report, we performed the molecular detection of HPV in a group of HPV-vaccinated Mexican women to explore a putative scenario of VPSR. We used biological samples from women who went for their routine Pap. The study included eighteen women older than 18 years of age and HPV-vaccinated. As the number of cases analyzed is relatively small, we supplemented the study with an agent-based direct computer simulation. The outcome of the numerical experiments and the analyzed cases complement each other and show that in three different scenarios, there is an increase in HPV cases approx 10 years after vaccination of the first cohort of women. The prevalence of non-vaccine HPV types increases when compared to prevalence of vaccine HPV types. This result could be interpreted as the phenomenon of Vaccine-induced Pathogenic Strain Replacement.
COVID-19 (SARS-CoV-2) Ventilator Resource Management Using a Network Optimization Model and Predictive System Demand
Authors: Billingham Samuel , Widrick Rebecca , Edwards Nathan J. , Klaus Sybil A.
Published: May 2020

The COVID-19 (SARS-CoV-2) pandemic is overwhelming global healthcare delivery systems due to the exponential spike in cases requiring specialty tests, facilities and equipment, including complex, precision devices like ventilators. In particular, the surge in critically ill patients has revealed a significant deficiency in regional availability of respiratory care ventilators. The authors offer a mathematical framework for ventilator distribution under scarcity conditions using an optimized network model and solver. The framework is interoperable with existing COVID-19 healthcare demand models and scales for different user-defined system sizes, including hospital networks, city, state, regional and national-scale prioritization. The authors’ approach improves current capabilities for medical device resource management within the existing incident command system while accounting for availability of devices, ventilation treatment time periods, disinfection and cleaning between patients, as well as shipping logistics time. The authors present a proof of concept using a high fidelity COVID-19 data set from Colorado, discusses how to scale nationally, and emphasizes the importance of applying ethical human-in-the-loop decision making when using this or similar approaches to managing medical device resources during epidemic emergencies.
Reference genome and demographic history of the most endangered marine mammal, the vaquita
Authors: Morin Phillip A. , Archer Frederick I. , Avila Catherine D. , Balacco Jennifer R. , Bukhman Yury V. , Chow William , Fedrigo Olivier , Formenti Giulio , Fronczek Julie A. , Fungtammasan Arkarachai , Gulland Frances M.D. , Haase Bettina , Heide-Jorgensen Mads Peter , Houck Marlys L. , Howe Kerstin , Misuraca Ann C. , Mountcastle Jacquelyn , Musser Whitney , Paez Sadye , Pelan Sarah , Phillippy Adam , Rhie Arang , Robinson Jacqueline , Rojas-Bracho Lorenzo , Rowles Teri K. , Ryder Oliver A. , Smith Cynthia R. , Stevenson Sacha , Taylor Barbara L. , Teilmann Jonas , Torrance James , Wells Randall S. , Westgate Andrew , Jarvis Erich D.
Published: May 2020

The vaquita is the most critically endangered marine mammal, with fewer than 19 remaining in the wild. First described in 1958, the vaquita has been in rapid decline resulting from inadvertent deaths due to the increasing use of large-mesh gillnets for more than 20 years. To understand the evolutionary and demographic history of the vaquita, we used combined long-read sequencing and long-range scaffolding methods with long- and short-read RNA sequencing to generate a near error-free annotated reference genome assembly from cell lines derived from a female individual. The genome assembly consists of 99.92% of the assembled sequence contained in 21 nearly gapless chromosome-length autosome scaffolds and the X-chromosome scaffold, with a scaffold N50 of 115 Mb. Genome-wide heterozygosity is the lowest (0.01%) of any mammalian species analyzed to date, but heterozygosity is evenly distributed across the chromosomes, consistent with long-term small population size at genetic equilibrium, rather than low diversity resulting from a recent population bottleneck or inbreeding. Historical demography of the vaquita indicates long-term population stability at less than 5000 (Ne) for over 200,000 years. Together, these analyses indicate that the vaquita genome has had ample opportunity to purge highly deleterious alleles and potentially maintain diversity necessary for population health.
Site-specific recombination between inverted target sites generates dicentric/acentric chromosomes
Authors: Titen Simon W. A. , Johnson Makenna T. B. , Capecchi Mario , Golic Kent G.
Published: May 2020

Site-specific recombinases are widely used tools for analysis of genetics, development and cell biology, and many schemes have been devised to alter gene expression by recombinase-mediated DNA rearrangements. Because theFRTandloxtarget sites for the commonly used FLP and Cre recombinases are asymmetrical, and must pair in the same direction to recombine, construct design must take into account orientation of the target sites. Both direct and inverted configurations have been used. However, the consequence of recombination between target sites on sister chromatids is frequently overlooked. This is especially consequential with inverted target sites, where exchange between oppositely oriented target sites on sisters will produce dicentric and acentric chromosomes. By using constructs that have inverted target sites inDrosophila melanogasterand in mice, we show here that dicentric chromosomes are produced in the presence of recombinase, and that the frequency of this event is quite high. The negative effects on cell viability and behavior can be significant, and should be considered when using such constructs.
Spatial separation ofStreptomycesaerial mycelium during fermentation enhances secondary metabolite production
Authors: Muralikrishnan Balaji , R J Retnakumar , Ramachandran Ranjit , J S Vinodh , M Nijisha , K B Arun , Paul Laiza , Dastager Syed , Dan Vipin Mohan , Ramakrishnan Ajay Kumar
Published: May 2020

Conditioning of morphology is an effective technique to enhance secondary metabolite production byStreptomyces. Here we report a novel conditioning method employing glass marbles in batch cultures to enhance secondary metabolite production byStreptomyces sp. The marbles seem to spatially separate aerial and submerged mycelia in the flask which was necessary for the qualitative and quantitative enhancement of metabolite production of secondary metabolites. The method also offers shorter incubation period compared to conventional methods for effective production. Further, using a combination of this method and response surface methodology we could enhance the production of antimycobacterial molecules chrysomycin A and B significantly.

Importance

Rediscovery of existing molecules and lack of techniques to induce production of secondary metabolites are the major bottlenecks associated with drug discovery of novel bioactive molecules fromStreptomyces, the major source of marketable drugs today. We found a new method to increase the diversity and quantity of secondary metabolites in twoStreptomycesspecies. This method thus enhances the chance of finding novel active principles fromStreptomyces.
Using Genome-Wide Association Study to Identify Genes and Pathways associated with Hypersensitivity Pneumonitis
Authors: Wang Ling , Millerick Melissa May , Rosenman Kenneth D. , Cui Yuehua , Uhal Bruce , Wang Jianrong , Gerlach John
Published: May 2020

Background

Hypersensitivity Pneumonitis (HP) is an interstitial lung disease caused by an immune response to the inhalation of antigens. Since only a small proportion of individuals exposed to HP-related antigens develop the disease, a genetic variation may play a role in disease development.

Methods

In this small-scale study, 24 patients diagnosed with HP were matched with control group who shared the patient’s environment and were exposed to the same HP-associated antigens. Logistic regression was employed to identify Single-Nucleotide Polymorphisms (SNPs) associated with HP. Next genes associated with HP were identified using sequence kernel association test (SKAT) analysis. Last, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Oncology (GO) enrichment analysis were employed to find HP signaling pathways using SNPs coded on genes and on non-coding genes, respectively.

Results

Given the small sample size, no single SNPs or genes were identified to be significantly associated with HP after adjustment for multiple testing. After P-value adjustment, the KEGG and GO pathway enrichment analysis identified 11 and 20 significant pathways respectively using SNPs coded on genes. Among these pathways, Cell cycle, Proteasome and Base excision repair had previously reported to be associated with lung function.

Conclusion

This is the first GWAS study identifying genetic factors associated with HP. Although no significant associations at SNPs/gene level were identified, there were significant pathways that are identified associated with HP which need further investigation in large cohorts.
Searching for biological feedstock material: 3D printing of wood particles from house borer and drywood termite frass
Authors: Plarre Rudy , Zocca Andrea , Spitzer Andrea , Benemann Sigrid , Gorbushina Anna A. , Li Yuexuan , Wilbig Janka , Günste Jens
Published: May 2020

Frass (fine powdery refuse or fragile perforated wood produced by the activity of boring insects) of larvae of the European house borer and of drywood termites was tested as a natural and novel feedstock for 3D-printing of wood-based materials. Small particles produced by the drywood termiteIncisitermes marginipennisand the European house borer (EHB)Hylotrupes bajulusduring feeding in construction timber, were used. Frass is a powdery material of particularly consistent quality that is essentially biologically processed wood mixed with debris of wood and faeces. The filigree-like particles flow easily permitting the build-up of wood-based structures in a layer wise fashion using the Binder Jetting printing process. The quality of powders produced by different insect species was compared along with the processing steps and properties of the printed parts. Drywood termite frass with a HR = 1.1 with ρBulk = 0.67 g.cm-3and ρTap = 0.74 g.cm-3was perfectly suited to deposition of uniformly packed layers in 3D printing. We suggest that a variety of naturally available feedstocks could be used in environmentally responsible approaches to scientific material sciences/additive manufacturing.
SARS-CoV-2 envelope protein topology in eukaryotic membranes
Authors: Duart Gerard , García-Murria Ma Jesús , Grau Brayan , Acosta-Cáceres José M. , Martínez-Gil Luis , Mingarro Ismael
Published: May 2020

Coronavirus E protein is a small membrane protein found in the virus envelope. Different coronavirus E proteins share striking biochemical and functional similarities, but sequence conservation is limited. In this report, we studied the E protein topology from the new SARS-CoV-2 virus both in microsomal membranes and in mammalian cells. Experimental data reveal that E protein is a single-spanning membrane protein with the N-terminus being translocated across the membrane, while the C-terminus is exposed to the cytoplasmic side (Ntlum/Ctcyt). The defined membrane protein topology of SARS-CoV-2 E protein may provide a useful framework to understand its interaction with other viral and host components and establish the basis to tackle the pathogenesis of SARS-CoV-2.
Assessment of ACE2, CXCL10 and Their co-expressed Genes: An In-silico Approach to Evaluate the Susceptibility and Fatality of Lung Cancer Patients towards COVID-19 Infection
Authors: Mahmood Tousif Bin , Chowdhury Afrin Sultana , Hasan Mehedee , Aakil Md. Mezbah-Ul-Islam , Hossan Mohammad Imran
Published: May 2020

Background

COVID-19 is a recent pandemic that started to spread out worldwide from Wuhan, China. This disease is caused by a newly discovered strain of the coronavirus, namely SARS CoV-2. Lung cancer patients are reported to be more susceptible to COVID-19 infection. To evaluate the probable reasons behind the excessive susceptibility and fatality of lung cancer patients to COVID-19 infection, we targeted two most crucial biomarkers of COVID-19, ACE2 and CXCL10. ACE2 plays a vital role in the SARS CoV-2 entry into the host cell while CXCL10 is a cytokine mainly responsible for the lung cell damage involving in a cytokine storm.

Methods

Firstly, we used the TIMER, UALCAN and GEPIA2 databases to analyze the expression and correlation of ACE2 and CXCL10 in LUAD and LUSC. After that, using the cBioPortal database, we performed an analytical study to determine the genetic changes in ACE2 and CXCL10 protein sequences that are responsible for lung cancer development. Finally, we analyzed different functional approaches of ACE2, CXCL10 and their co-expressed genes associated with lung cancer and COVID-19 development by using the PANTHER database.

Results

Initially, we observed that ACE2 and CXCL10 are mostly overexpressed in LUAD and LUSC. We also found the functional significance of ACE2 and CXCL10 in lung cancer development by determining the genetic alteration frequency in their amino acid sequences. Lastly, by doing the functional assessment of the targeted genes, we identified that ACE2 and CXCL10 along with their commonly co-expressed genes are respectively involved in the binding activity and immune responses in case of lung cancer and COVID-19 infection.

Conclusions

Finally, on the basis of this systemic analysis, we came to the conclusion that ACE2 and CXCL10 are possible biomarkers responsible for the higher susceptibility and fatality of lung cancer patients towards the COVID-19.
Novel antioxidant therapy with the immediate precursor to glutathione, γ-glutamylcysteine (GGC), ameliorates LPS-induced cellular stress in anin vitrocystic fibrosis model
Authors: Hewson Chris K , Capraro Alexander , Wong Sharon L , Pandzic Elvis , Fernando Bentotage S.M , Awatade Nikhil T , Zhong Ling , Hart-Smith Gene , Whan Renee M , Thomas Shane R , Jaffe Adam , Bridge Wallace J , Waters Shafagh A
Published: May 2020

Introduction

Glutathione deficiency and chronic bacterial inflammation exacerbates the oxidative stress damage to airways in cystic fibrosis. Improvements to current antioxidant therapeutic strategies are needed. Dietary supplement, γ-glutamylcysteine (GGC), the immediate precursor to glutathione, rapidly boosts cellular glutathione levels following a single dose in healthy individuals. Efficacy of GGC againstPseudomonas aeruginosaderived lipopolysaccharide (LPS), a prominent factor in mediating both bacterial virulence and host responses, in CF remains unassessed.

Methods

Primary F508del/F508del mucociliary differentiated bronchial and nasal epithelial cells were created to model LPS-induced oxidative stress and inflammation of CF. The proteomic signature of GGC treated cells was resolved by qLC-MS/MS. Parameters including cell redox state (glutathione, ROS), anti-inflammatory mediators (IL-8, IDO-1) and cellular health (membrane integrity, stress granule formation and cell viability) were assayed.

Results

Proteomic analysis identified perturbation of several pathways related to cellular respiration and stress responses upon LPS challenge. Most of these were resolved when cells were treated with GGC. While GGC did not resolve LPS-induced IL-8 and IDO-1 activity, it effectively attenuated LPS-induced ROS and stress granule formation, while significantly increasing intracellular glutathione levels and improving epithelial cell barrier integrity. Moreover, we compared the effect of GGC with thiols NAC and glutathione on cell viability. GGC was the only thiol that increased cell viability; protecting cells against LPS induced cell death. Both therapeutic and prophylactic treatments were successful.

Conclusion

Together, these findings indicate that GGC has therapeutic potential for treatment and prevention of oxidative stress related damage to airways in Cystic Fibrosis.
The crystal structure of SnTox3 from the necrotrophic fungusParastagonospora nodorumreveals a unique effector fold and insights into Kex2 protease processing of fungal effectors
Authors: Outram Megan A. , Sung Yi-Chang , Yu Daniel , Dagvadorj Bayantes , Rima Sharmin A. , Jones David A. , Ericsson Daniel J. , Sperschneider Jana , Solomon Peter S. , Kobe Bostjan , Williams Simon J.
Published: May 2020

Plant pathogens cause disease through secreted effector proteins, which act to modulate host physiology and promote infection. Typically, the sequences of effectors provide little functional information and further targeted experimentation is required. Here, we utilised a structure/function approach to study SnTox3, an effector from the necrotrophic fungal pathogenParastagonospora nodorum, which causes cell death in wheat-lines carrying the sensitivity geneSnn3.

We developed a workflow for the production of SnTox3 in a heterologous host that enabled crystal structure determination. We show this approach can be successfully applied to effectors from other pathogenic fungi. Complementing this, anin-silicostudy uncovered the prevalence of an expanded subclass of effectors from fungi.

The β-barrel fold of SnTox3 is a novel fold among fungal effectors. We demonstrate that SnTox3 is a pre-pro-protein and that the protease Kex2 removes the pro-domain. Ourin-silicostudies suggest that Kex2-processed pro-domain (designated here as K2PP) effectors are common in fungi, and we demonstrate this experimentally for effectors fromFusarium oxysporumf sp.lycopersici.

We propose that K2PP effectors are highly prevalent among fungal effectors. The identification and classification of K2PP effectors has broad implications for the approaches used to study their function in fungal virulence.
Safety-Stock: Predicting the demand for supplies in Brazilian hospitals during the COVID-19 pandemic
Authors: Gonzatto Oilson Alberto , Nascimento Diego Carvalho , Russo Cibele Maria , Henriques Marcos Jardel , Tomazella Caio Paziani , Santos Maristela Oliveira , Neves Denis , Assad Diego , Guerra Rafaela , Bertazo Evelyn Keise , Cuminato José Alberto , Neto Francisco Louzada
Published: May 2020

Background

Many challenges lie ahead when dealing with COVID-19, not only related to the acceleration of the pandemic, but also to the prediction of personal protective equipment consumption to accommodate the explosive demand. Due to this situation of uncertainty, the hospital administration encourages the excess stock of these materials, over-stocking products in some hospitals, and provoke shortage in others. The number of available personal protective equipment is one of the three main factors that limit the number of patients at a hospital, along with the number of available beds and the number of professionals per shift.

Objective

In this scenario, a challenge is to build an easy-to-use expert system to predict the demand for personal protective equipment in hospitals during the COVID-19 pandemic, which can be updated in real-time for short term planning.

Methods

We propose naive statistical modeling, which combines historical data of the consumption of personal protective equipment by hospitals, current protocols for their uses and epidemiological data related to the disease, to build predictive models for the demand for personal protective equipment in Brazilian hospitals during the pandemic. We then embed our modeling in the free Safety-Stock expert system, which can provide the safety stock levels for a particular hospital.

Results

The Safety-Stock system provides the prediction of consumption/demand for personal protective equipment over time, indicating the moment when the hospital reaches maximum consumption, the estimate of how long it will work in this state, and when it will leave it.

Conclusion

With our predictions, a hospital may have its needs related to specific personal protective equipment estimated, taking into account its historical stock levels and possible scheduled purchases. The tool allows for the adoption of strategies to control and keep the stock at safety levels to the demand, mitigating the risk of stock-out. As a direct consequence, it also enables the interchange and cooperation between hospitals, aiming to maximize the availability of equipment during the pandemic situation.
The dissemination mechanisms of Industry 4.0 knowledge in traditional industrial districts:evidence from Italy
Authors: Pagano Alessandro , Carloni Elisa , Galvani Serena , Bocconcelli Roberta
Published: May 2020

Purpose

This paper aims to provide a contribution on the diffusion of Industry 4 (I4.0)-related knowledge in industrial districts (IDs). The main goal is to examine the dissemination of I4.0 knowledge, exploring the main mechanisms for its spreading and highlighting the main factors shaping such processes. Focus is on dissemination processes in IDs active in traditional industries, which could represent the “periphery” of I4.0 application context.

Design/methodology/approach

The methodology is qualitative. Notably, this paper presents a case study of the Pesaro ID specialized in furniture/woodworking machinery sector. A total of 18 in-depth one-to-one interviews have been conducted with relevant informants from a variety of organizations within the cluster: companies, institutions and universities.

Findings

The complexity of I4.0 requires a combination of traditional mechanisms with innovative ones within IDs characterized by the emergence of new players, activities and resources. These changes led to three main evolving patterns: the horizon of I4.0 upgrading shows blurred boundaries in terms of sectors and geographic location, the I4.0 diffusion appears fragmented in terms of initiatives and projects by both firms and institutions and the dissemination of I4.0 knowledge pushes ID firms and institutions to pursue deliberate initiatives leading to innovative forms of “collective” cooperation.

Originality/value

This paper contributes to both theory and practice. From the theoretical point of view, this paper contributes to the literature on innovation in IDs and clusters on two interrelated grounds. First, it provides further research on I4.0 and IDs and clusters. Second, it contributes to the stream of research on knowledge creation and diffusion in IDs and clusters, providing empirically based insights over emerging local learning processes in IDs. Moreover, relevant managerial and policy implications stem from the analysis.
Effect of factors of organizational structure influencing nonphysical waste in road projects of developing countries
Authors: Irfan Muhammad , Malik Muhammad Sohail Anwar , Kaka Khel Syyed Sami Ul Haq
Published: May 2020

Purpose

The purpose of this research is to rank the most significant factors of organizational structure that can reduce time and cost overruns (nonphysical waste) in road projects of the developing countries. Additionally, the effect of factors of organizational structure on nonphysical waste in road projects is also measured.

Design/methodology/approach

Factors of organizational structure causing time and cost overrun are extracted through a content analysis of the published literature. Moreover, a questionnaire survey is carried out involving 128 professionals to assess the effect of organizational structure factors on time and cost overrun. Finally, to obtain a more objective evaluation, relative importance index and regression analysis techniques are utilized, and the most severe factors influencing time and cost overrun are indicated.

Findings

This study found out that top management support and procurement procedures are the most significant factors influencing time and cost overruns in road projects of the developing countries.

Originality/value

A small number of studies have been conducted to investigate the effect of factors of organizational structure on time and cost overrun in the construction industry. And even more, its relation with respect to road projects of the developing countries is limited. This research highlights the effect of most significant factors of organizational structure that influence the nonphysical waste in road projects of the developing countries. Therefore, this study adds to the body of knowledge by recommending that all the stakeholders of construction project should pay close attention toward these factors to control the enigma of time and cost overrun. It might also prove helpful, if implemented to its full extent, in all the road construction activities undertaken.
Roles and functions of stakeholders in implementing energy retrofits in the hotel sector
Authors: Fasna M.F.F. , Gunatilake Sachie
Published: May 2020

Purpose

The success of energy retrofits (ER) projects is highly dependent on the involvement of right stakeholders at the right stage. So far, little insight is available from previous literature on the involvement of different stakeholders during various stages of the ER decision-making process, and their roles and functions in the respective stages. This is specifically true in the context of Energy Service Company (ESCO) led ER projects, which is an emerging trend in the current context. Hence, this paper aims to investigate the roles and functions of stakeholders during different stages of an ESCO-led ER project in the hotel sector.

Design/methodology/approach

An in-depth case study was conducted in a selected hotel building to gain insights into the roles and functions of stakeholders throughout the project stages. To collect the required data, face-to-face semi-structured interviews were conducted with seven selected respondents within the case.

Findings

The study identified nine key stakeholders that were involved during five different project stages along with their functions. Based on these identified functions, four main roles (i.e. decision-maker, performer, monitor/observer, and supporter) emerged that were reflective of the nature of the stakeholders' involvement in different stages of the decision-making process. Owner/client, facilities manager (FM), ESCO and architect attached to ESCO emerged as the key “decision-makers” during project implementation process.

Originality/value

The outcomes of this research would be useful in ensuring the proactive involvement of all the identified stakeholders in respective project stages of ESCO led ER projects in the hotel sector.
Influence of values, brand consciousness and behavioral intentions in predicting luxury fashion consumption
Authors: Kautish Pradeep , Khare Arpita , Sharma Rajesh
Published: May 2020

Purpose

This paper aims to examine the relationships among two distinct yet interconnected forms of value orientations, namely, terminal and instrumental values, brand consciousness and behavioral intentions. This study validated the conceptual model for branded fashion apparel consumption in an emerging market, e.g. India.

Design/methodology/approach

The research design followed a two-step approach to test the measurement and structural models for partial least squares structural equation modeling with SmartPLS (v.3.0) as recommended by Anderson and Gerbing (1988).

Findings

The results illustrated that both the instrumental and terminal values influence brand consciousness and, consequently, brand consciousness had an impact on behavioral intentions for fashion apparel consumption. Instrumental values had a greater influence on brand consciousness and behavioral intentions than terminal values. Brand consciousness mediated the relationship between instrumental/terminal values and behavioral intentions.

Research limitations/implications

This study defined two value orientations (i.e. instrumental versus terminal) using cross-sectional data from an emerging market. Future studies may examine the research findings’ generalizability using diverse data sets (longitudinal and cross-sectional) and evaluate the value orientation and customers’ favorable behavioral intentions for luxury fashion consumption.

Practical implications

This study provides insights into luxury marketers and practitioners to understand the contribution of instrumental and terminal values on brand consciousness and behavioral intentions for luxury fashion apparel. The findings would assist in developing marketing strategies for an emerging market, i.e. India.

Social implications

With the rapid proliferation of materialism, the Indian market has witnessed the dawn of a new era of luxury fashion acceptance. The research offers evidence that in emerging markets such as India, consumers exhibit value orientation toward luxury brands while holding a sense of fashion involvement in their consumption behavior.

Originality/value

This study is a pioneering attempt to understand the relationships between the value orientation, namely, instrumental and terminal values and their underlying influence on brand consciousness and behavioral intentions toward fashion apparel. Rokeach’s (1973) two-dimensional value dichotomy was adapted to understand luxury apparel consumption in an emerging market context, specifically India.
Dietary patterns and fatigue in female slimmers
Authors: Kaya Kaçar Hüsna , Avery Amanda , Bennett Sarah , McCullough Fiona
Published: May 2020

Purpose

This paper aims to understand the association of dietary patterns with perceived fatigue and identify predictors for presence of fatigue in women who are obese and trying to lose weight.

Design/methodology/approach

An online survey, hosted by slimming world (SW), comprised of a questionnaire regarding weight, level of fatigue and food frequency questionnaire before joining the weight management programme (T0) and current data (T1) was conducted. In total, 543 non-pregnant women with obesity of child-bearing age (19-49 years) completed the survey (T0-T1). The principal components analysis was used to determine dietary patterns and multinomial logistic regression was used to analyse predictors for presence of fatigue.

Findings

The participants who have a “simple carbohydrate and high fat” dietary pattern were more likely to have fatigue at T0 (p ≤ 0.001) and those who followed a “vegetables” dietary pattern were less likely to have fatigue at T1 (p ≤ 0.05). The study findings indicate that while “simple carbohydrate and high fat” dietary pattern was associated with increased risk of fatigue, “vegetables” dietary pattern was associated with reduced risk of fatigue and a higher percentage of weight loss.

Originality/value

The present study appears to be the first study to examine associations between dietary patterns and fatigue. The strengths of the study included the in-depth analysis of this association in both before joining a weight management programme (SW) and currently as a member of SW with an adequate sample size.
Dark Data
Authors: Hand David J.
Published: May 2020

On being misled by what isn't there, and what to do about it. By David J. Hand
Retraction: Effect of Fasudil on remyelination following cuprizone‐induced demyelination.
Authors: Wang Jing , Sui Ruo‐Xuan , Miao Qiang , Wang Qing , Song Li‐Juan , Yu Jie‐Zhong , Li Yan‐Hua , Xiao Bao‐Guo , Ma Cun‐Gen
Published: May 2020

Retraction: Wang J, Sui R‐X, Miao Q, et al. Effect of Fasudil on remyelination following cuprizone‐induced demyelination. CNS Neuroscience & Therapeutics, 2020;26:76–89. https://doi.org/10.1111/cns.13154. The above article published online on May 23, 2019, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, Professor Jun Chen, and John Wiley & Sons Ltd. The retraction has been agreed due to major overlap with a previously published article from the same group of authors.