bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrophage and dendritic cell subset composition can distinguish endotypes in adjuvant-induced asthma mouse models
Authors: Özkan Müge , Eskiocak Yusuf Cem , Wingender Gerhard 
Published: April 2021

AbstractAsthma is a heterogeneous disease with neutrophilic and eosinophilic asthma as the main endotypes that are distinguished according to the cells recruited to the airways and the related pathology. Eosinophilic asthma is the treatment-responsive endotype, which is mainly associated with allergic asthma. Neutrophilic asthma is a treatment-resistant endotype, affecting 5-10% of asthmatics. Although eosinophilic asthma is well-studied, a clear understanding of the endotypes is essential to devise effective diagnosis and treatment approaches for neutrophilic asthma. To this end, we directly compared adjuvant-induced mouse models of neutrophilic (CFA/OVA) and eosinophilic (Alum/OVA) asthma side-by-side. The immune response in the inflamed lung was analyzed by multi-parametric flow cytometry and immunofluorescence. We found that eosinophilic asthma was characterized by a preferential recruitment of interstitial macrophages and myeloid dendritic cells, whereas in neutrophilic asthma plasmacytoid dendritic cells, exudate macrophages, and GL7+activated B cells predominated. This differential distribution of macrophage and dendritic cell subsets reveals important aspects of the pathophysiology of asthma and holds the promise to be used as biomarkers to diagnose asthma endotypes.
Antibiotic Susceptibility Profile ofCampylobacter Sppfrom Poultry
Authors: Khalifa Khalda A. , Atif Elbrissi , Adel Rahim Igbal S. , Abdel Rahman Amgad M. , Ahmed Salwa A. 
Published: April 2021

AbstractCampylobacteriosis is found among the four important worldwide food borne pathogens. In intensive poultry rearing systems in Sudan the use of oral antibiotics is essential to preserve health. Accordingly, there is a high threat for the thermophilicCampylobacter sppinhabitant in the intestinal tract of food animals to develop resistance to commonly used antibiotics. Contamination of broiler meat with pathogenic strains of resistantCampylobactercould, therefore, result in a form of campylobacteriosis in humans that is difficult to treat. To the best of our knowledge, there are no data available relating antibiotic resistant against these bacteria in poultry in Sudan, hence the aim of this study was to determine the antimicrobial susceptibility profile of thermophilicCampylobacterspp. isolated from broiler in Khartoum by disk diffusion. Sensitivity of fourteen isolates against seven antibiotics namely Neomycin, Nitrofurantoin, Nalidixic acid, Gentamycin, Streptomycin, Tetracycline and Erythromycin were studied. The result showed that Nitrofurantoin was found as highly sensitive (64.3%). It was also observed that Erythromycin, Gentamycin, Streptomycin and Neomycin verified the following resistant against isolates recovered 92.9%, 71.4%, 71.4%, 64.3% respectively. Multidrug resistant against five, four, three and two antibiotics was also reported. It was concluded that poultry meat in Khartoum could complicate the antimicrobial therapy in human as multidrug resistant of campylobacter was detected.
The effect of a canine semen activator supplementation or addiction on the long-term refrigeration quality of dog spermatozoa
Authors: Martínez-Barbitta Marcelo , Salinas Claudio Rivera 
Published: April 2021

ABSTRACTWithin modern biotechnology, different tools have been developed to maximize canine semen conservation protocol to optimizing reproductive results and making their handling more flexible. In the last decades, the survival of refrigerated semen has been prolonged from 2-3d with the first basic diluents, to 10-14d using the most modern extenders. However, their main limitation is that sperm quality decreases during cold storage. Semen activators (SA) have been produced to provide the molecules necessary to maximize the sperm survival and quality with the aim to enhance fertility and prolificacy. In this study, the effect of SA was recorded by daily evaluation of chilled semen 14d. For this experiment, six adult healthy Neapolitan Mastiff dogs, were used as donors and the semen was manually collected. Spermatozoa-rich fractions of each suject was chilled using a new generation extender for long periods of time (d0) starting from the d1 to d14, different aliquot, with (experimental trial) and without SA (control trial), were evaluated daily for motility vigor, morphology and membrane integrity. The initial sperm concentration of extended semen was 417.3±170.4×106/mL (mean ± SEM) with 85.89±4.76% of MNS (morphologically normal sperm), 84.47±5.22 % vital sperm and a pH of 6.2±2.8. The initial vigor was 3.83±0.48, but after one min with SA, it rose to 4.45 ± 0.45 (P<0.001). The semen motility parameter increase significantly (P<0.05) in experimental trial, respect to control, starting to d2 at finish (except for d7). The vigor analysis significantly increase in experimental trial (P<0.05) during the most day of the study with the exclusion of d3 and d14. For evaluate the semen characteristics over time, the experiment was divided into T1 (d0-d5), T2 (d6-d10) and T3 (d11-d14) (P<0.001) in evaluation of morphology and membrane stability. The MNS reached 70% at d10 and finally 65% at d14, being considered normal and possibly fertile. With Host-s, 65% of MNS were also achieved at d14. The presence of glucose and fructose in the diluents used for refrigeration can exert very important effects given the fact that metabolic routes have been found in both sugars, providing both different and complementing effects. It can be concluded that the use of SA prior to artificial insemination improves the quality of chilled semen significantly, although it does not reverse the effects of deterioration due to cellular metabolism over time.
Intranasal gene therapy to prevent infection by SARS-CoV-2 variants
Authors: Sims Joshua J. , Greig Jenny A. , Michalson Kristofer T. , Lian Sharon , Martino R. Alexander , Meggersee Rosemary , Turner Kevin B. , Nambiar Kalyani , Dyer Cecilia , Hinderer Christian , Horiuchi Makoto , Yan Hanying , Huang Xin , Chen Shu-Jen , Wilson James M. 
Published: April 2021

AbstractSARS-CoV-2 variants have emerged with enhanced pathogenicity and transmissibility, and escape from pre-existing immunity, suggesting first-generation vaccines and monoclonal antibodies may now be less effective. This manuscript demonstrates an approach for preventing clinical sequelae and the spread of SARS-CoV-2 variants. First, we affinity-matured an angiotensin-converting enzyme 2 (ACE2) decoy protein, achieving 1000-fold binding improvements that extend across a wide range of SARS-CoV-2 variants and distantly related, ACE2-dependent coronaviruses. Next, we demonstrated the expression of this decoy in proximal airway when delivered via intranasal administration of an AAV vector. This intervention significantly diminished clinical and pathologic consequences of SARS-CoV-2 challenge in a mouse model and achieved therapeutic levels of decoy expression at the surface of proximal airways when delivered intranasally to nonhuman primates. Importantly, this long-lasting, passive protection approach is applicable in vulnerable populations such as the elderly and immune-compromised that do not respond well to traditional vaccination. This approach could be useful in combating COVID-19 surges caused by SARS-CoV-2 variants and should be considered as a countermeasure to future pandemics caused by pre-emergent members, ACE2-dependent CoVs that are poised for zoonosis.Author summarySARS-CoV-2 variants have emerged with enhanced pathogenicity and transmissibility, and escape from pre-existing immunity, suggesting first-generation vaccines and monoclonal antibodies may now be less effective. This manuscript demonstrates an approach for preventing clinical sequelae and the spread of SARS-CoV-2 variants. First, we affinity-matured an angiotensin-converting enzyme 2 (ACE2) decoy protein, achieving 1000-fold binding improvements that extend across a wide range of SARS-CoV-2 variants and distantly related, ACE2-dependent coronaviruses. Next, we demonstrated the expression of this decoy in proximal airway when delivered via intranasal administration of an AAV vector. This intervention significantly diminished clinical and pathologic consequences of SARS-CoV-2 challenge in a mouse model and achieved therapeutic levels of decoy expression at the surface of proximal airways when delivered intranasally to nonhuman primates. Importantly, this long-lasting, passive protection approach is applicable in vulnerable populations such as the elderly and immune-compromised that do not respond well to traditional vaccination. This approach could be useful in combating COVID-19 surges caused by SARS-CoV-2 variants and should be considered as a countermeasure to future pandemics caused by pre-emergent members, ACE2-dependent CoVs that are poised for zoonosis.
Controlling gene expression timing through gene regulatory architecture
Authors: Ali Md Zulfikar , Brewster Robert C. 
Published: April 2021

AbstractGene networks typically involve the regulatory control of multiple genes with related function. This connectivity enables correlated control of the levels and timing of gene expression. Here we study how gene expression timing in the single-input module motif can be encoded in the regulatory DNA of a gene. Using stochastic simulations, we examine the role of binding affinity, TF regulatory function and network size in controlling the mean first-passage time to reach a fixed fraction of steady-state expression for both an auto-regulated TF gene and a target gene. We also examine how the variability in first-passage time depends on these factors. We find that both network size and binding affinity can dramatically speed up or slow down the response time of network genes, in some cases predicting more than a 100-fold change compared to that for a constitutive gene. Furthermore, these factors can also significantly impact the fidelity of this response. Importantly, these effects do not occur at “extremes” of network size or binding affinity, but rather in an intermediate window of either quantity.Author summaryRegulated genes are able to respond to stimuli in order to ramp up or down production of specific proteins. Although there is considerable focus on the magnitude (or fold-change) of the response and how that depends on the architectural details of the regulatory DNA, the dynamics, which dictates the response time of the gene, is another key feature of a gene that is encoded within the DNA. Unraveling the rules that dictate both the response time of a gene and the precision of that response encoded in the DNA poses a fundamental problem. In this manuscript, we systematically investigate how the response time of genes in auto-regulatory networks is controlled by the molecular details of the network. In particular, we find that network size and TF-binding affinity are key parameters that can slow, in the case of auto-activation, or speed up, in the case of auto-repression, the response time of not only the auto-regulated gene but also the genes that are controlled by the auto-regulated TF. In addition, we find that the precision of the response depends crucially on these characteristics.
Theoretical causes of the Brazilian P.1 and P.2 lineages of the SARS-CoV-2 virus through molecular dynamics
Authors: Oliveira Micael D. L. , Oliveira Kelson M. T. , Silva Jonathas N. , Santos Clarice , Bessa João , de Freitas Rosiane 
Published: April 2021

ABSTRACTThe newβ-coronavirus has been causing sad losses around the world and the emergence of new variants has caused great concern. This pandemic is of a proportion not seen since the Spanish Flu in 1918. Thus, throughout this research, the B.1.1.28 lineage of the P.1 clade (K417T, N501Y, E484K) that emerged in Brazil was studied, as well as the latest Delta variant. This is because the molecular mechanisms by which phenotypic changes in transmissibility or mortality remain unknown. Through molecular dynamics simulations with the NAMD 3 algorithm in the 50nsinterval, it was possible to understand the impact on structural stabilization on the interaction of the ACE2-RBD complex, as well as simulations in 30nsfor the neutralizing antibody P2B-2F6, with this antibody was derived from immune cells from patients infected with SARS-CoV-2. Although not all molecular dynamics analyzes support the hypothesis of greater stability in the face of mutations, there was a predominance of low fluctuations. Thus, 3 (three) analyzes corroborate the hypothesis of greater ACE2-RBD stability as a result of P.1, among them: Low mean RMSF values, greater formation of hydrogen bonds and low solvent exposure measured by the SASA value. An inverse behavior occurs in the interaction with neutralizing antibodies, since the mutations induce greater instability and thus hinder the recognition of antibodies in neutralizing the Spike protein, where we noticed a smaller number of hydrogen bonds as a result of P.1. Through MM-PBSA energy decomposition, we found that Van der Waals interactions predominated and were more favorable when the structure has P.1 strain mutations. Therefore, we believe that greater stabilization of the ACE2-RBD complex may be a plausible explanation for why some mutations are converging in different strains, such as E484K and N501Y. The P.1 concern variant still makes the Spike protein recognizable by antibodies, and therefore, even if the vaccines’ efficacy can be diminished, there are no results in the literature that nullify them.
Structure ofEscherichia colirespiratory complex I reconstituted into lipid nanodiscs reveals an uncoupled conformation
Authors: Kolata Piotr , Efremov Rouslan G. 
Published: April 2021

AbstractRespiratory complex I is a multi-subunit membrane protein complex that reversibly couples NADH oxidation and ubiquinone reduction with proton translocation against trans-membrane potential. Complex I fromEscherichia coliis among the best functionally characterized complexes, but its structure remains unknown, hindering further mechanistic studies to understand the enzyme coupling mechanism. Here we describe the single particle cryo-electron microscopy (cryo-EM) structure of the entire catalytically activeE. colicomplex I reconstituted into lipid nanodiscs. The structure of this mesophilic bacterial complex I displays highly dynamic connection between the peripheral and membrane domains. The peripheral domain assembly is stabilized by unique terminal extensions and an insertion loop. The membrane domain structure reveals novel dynamic features. Unusual conformation of the conserved interface between the cytoplasmic and membrane domains suggests an uncoupled conformation of the complex. Based on these structural data we suggest a new simple and testable coupling mechanism for the molecular machine.
Functional genome and microbiome in blood of goats affected by the gastrointestinal pathogenHaemonchus contortus
Authors: Tilahun Yonathan 
Published: April 2021

AbstractThe Alpine goatCapra aegagrus hircusis parasitized by the barber pole worm (Haemonchus contortus). This relationship results in changes that affect the gene expression of the host, the pest, and the microbiome of both. Hematological parameters indicating genes that are expressed and/or the % Composition of abundant and diverse microbial flora are reflective of infestation. We explored the similarity/dissimilarity between and among blood samples of non-infected, infected, infected zoledronic acid-treated, and infected antibody (anti-γσ T cells) treated wethers under controlled conditions. We identified responses to barber pole worms using blood-based analysis of transcripts and the microbiome. Seven (7) days post-inoculation (dpi) we identified 7,627 genes associated with different treatment types. Across all treatments we identified fewer raw read counts and a reduced diversity in microbial flora on 7 dpi than in 21 dpi wethers. We also identified that there were differences in % Composition of microbial flora known to be associated with inflammation. This study identifies treatment specific genes, and an increase in microflora abundance and diversity as wethers age post infestation. Further,Firmicutes/Bacteriodetes(F/B) ratio reflect metabolic health, based on depression or elevation above thresholds defined by the baseline of non-infected hosts depending on the type of intrusion exhibited by the pest.
Early construction of the thalamocortical axon pathway requires JNK signaling within the ventral forebrain
Authors: Cunningham Jessica G. , Scripter James D. , Nti Stephany A. , Tucker Eric S. 
Published: April 2021

AbstractThalamocortical connectivity is essential for normal brain function. This important pathway is established during development, when thalamic axons extend a long distance through the forebrain before reaching the cerebral cortex. In this study, we identify a novel role for the c-Jun N-terminal Kinase (JNK) signaling pathway in guiding thalamocortical axons through intermediate target territories. Complete genetic removal of JNK signaling from theDistal-less 5/6(Dlx5/6) domain in mice prevents thalamocortical axons from crossing the diencephalon-telencephalon boundary (DTB) and the internal capsule fails to form. Ventral telencephalic cells critical for thalamocortical axon extension including corridor and guidepost neurons are also disrupted. In addition, corticothalamic, striatonigral, and nigrostriatal axons fail to cross the DTB. Analyses of different JNK mutants demonstrates that thalamocortical axon pathfinding has a non-autonomous requirement for JNK signaling. We conclude that JNK signaling within theDlx5/6territory enables the construction of major axonal pathways in the developing forebrain.Impact statementWe find an obligate, non-autonomous requirement for JNK signaling in early thalamocortical axon pathfinding, providing new mechanistic insight into the establishment of axonal connections in the developing forebrain.
Mutagenesis of human cytomegalovirus glycoprotein L disproportionately disrupts gH/gL/gO over gH/gL/pUL128-131
Authors: Schultz Eric P. , Yu Qin , Stegmann Cora , Day Le Zhang , Lanchy Jean-Marc , Ryckman Brent J. 
Published: April 2021

ABSTRACTCell-free and cell-to-cell spread of herpesviruses involves a core fusion apparatus comprised of the fusion protein glycoprotein B (gB) and the regulatory factor gH/gL. The human cytomegalovirus (HCMV) gH/gL/gO and gH/gL/pUL128-131 facilitate spread in different cell types. The gO and pUL128-131 components bind distinct receptors, but the how the gH/gL portion of the complexes functionally compare is not understood. We previously characterized a panel of gL mutants by transient expression and showed that many were impaired for gH/gL-gB dependent cell-cell fusion, but were still able to form gH/gL/pUL128-131 and induce receptor-interference. Here, the gL mutants were engineered into the HCMV BAC clones TB40/e-BAC4 (TB), TR and Merlin (ME), which differ in their utilization of the two complexes for entry and spread. Several of the gL mutations disproportionately impacted gH/gL/gO-dependent entry and spread over gH/gL/pUL128-131 processes. Effects of some mutants could be explained by impaired gH/gL/gO assembly, but other mutants impacted gH/gL/gO function. Soluble gH/gL/gO containing the L201 mutant failed to block HCMV infection despite unimpaired binding to PDGFRα, indicating the existence of other important gH/gL/gO receptors. Another mutant (L139) enhanced the gH/gL/gO-dependent cell-free spread of TR, suggesting a “hyperactive” gH/gL/gO. Recently published crystallography and cryo-EM studies suggest structural conservation of the gH/gL underlying gH/gL/gO and gH/gL/pUL128-131. However, our data suggest important differences in the gH/gL of the two complexes and support a model in which gH/gL/gO can provide an activation signal for gB.IMPORTANCEThe endemicbeta-herpesvirus HCMV circulates in human populations as a complex mixture of genetically distinct variants, establishes lifelong persistent infections, and causes significant disease in neonates and immunocompromised adults. This study capitalizes on our recent characterizations of three genetically distinct HCMV BAC clones to discern the functions of the envelope glycoprotein complexes gH/gL/gO and gH/gL/pUL128-13, which are promising vaccine targets that share the herpesvirus core fusion apparatus component, gH/gL. Mutations in the shared gL subunit disproportionally affected gH/gL/gO, demonstrating mechanistic differences between the two complexes and may provide a basis for more refined evaluations of neutralizing antibodies.
Social and environmental accounting in developing countries: contextual challenges and insights
Authors: Qian Wei , Tilt Carol , Belal Ataur 
Published: April 2021

PurposeThe purpose of this paper is to review most recent developments of social and environmental accounting (SEA) in the context of developing countries and to offer insights for the latest research in this field. It also provides an introduction to the AAAJ special issue.Design/methodology/approachThe authors have undertaken a conceptual overview of the field developed in the past two decades (2001–2020) with a view to identify major themes, trends and future research directions.FindingsThe overview reveals that only 43 SEA papers addressing contextual challenges of developing countries have been published in leading accounting journals in the last 20 years. The coverage of these publications is concentrated in a small number of countries and regions. Interdisciplinary accounting journals, especially AAAJ, are the main publishing outlets in this field. The topic areas are dominated by social accounting challenges, with much less focus on environmental accounting, although developing countries are particularly exposed to the threats of climate change, water pollution and biodiversity loss. The literature reviewed uses elaborating, problematising and theorising contexts as three main contextualisation approaches to analyse contextual themes framed around regulatory, political, cultural and religious, and social-economic systems. Although various conceptual lenses have been adopted in the developing country SEA literature, the use of institutional theory and its various extensions to address political and cultural complexities seems to become more prominent, as shown in most of the contributions included in this special issue.Research limitations/implicationsThis review is limited to leading accounting journals. SEA research increasingly published in other disciplines such as in management, social and environmental areas might provide a more comprehensive view in this research field.Originality/valueIn this paper,inter alia, the authors review and synthesise the previous literature in a conceptual framework, illustrating and highlighting the importance of contextual framing of SEA in developing countries. Based on this review, the authors propose some ideas for a future research agenda aiming to advance the field. The authors expect this paper and the special issue to act as a reference point for emerging SEA researchers from developing countries to raise more scholarly impactful enquiries in this area.