bluuebunny/crossref_metadata_2025 huggingface dataset:
Farmers’ Perception of Climate Change: A Review of the Literature for Latin America
Authors: Fierros-González Isael , López-Feldman Alejandro
Published: June 2021

Global climate is changing rapidly, and it is not clear if agricultural producers in developing countries will be able to adapt fast enough in order to mitigate its negative effects. In order to be willing to take adaptation measures, farmers need to perceive that the climate is changing or could change, and they need to attribute enough weight to this perception to take action. During the last two decades, the literature that examines farmers’ perception of climate change has gained ground, but it is still scant. This is particularly true for Latin America, which is highly vulnerable to climate change. Based on a review of original research articles published between 2000 and 2020, this article presents the status of knowledge about the topic in the region to identify research gaps and inform future research. The review found that the available research has been based mostly on qualitative analyses of case studies for a few countries. More research that identifies causal relationships is necessary. Data from surveys that are representative at the national or subnational levels, as well as longitudinal data, will be very helpful to better understand farmer’s perceptions. Finally, the use of field experiments and choice experiments can complement the use of observational data.
A Study of Hybridization Between Marmota baibacina and M. sibirica in Their Secondary Contact Zone in Mongolian Altai
Authors: Brandler Oleg V. , Kapustina Svetlana Yu. , Nikol’skii Alexander A. , Kolesnikov Viacheslav V. , Badmaev Bair B. , Adiya Yansanjav
Published: June 2021

The role of hybridization as one of the factors of speciation in mammals has been underestimated for a long time, but now there is a lot of data on its impact in mammalian evolution. Hybridization of species often occurs in their secondary contact zones, which is a natural model for testing factors that ensure species integrity. Studies of hybrid zones are increasingly revealing the essential role of ecological and behavioral features both in initiating crossbreeding and in maintaining interspecific barriers. We studied the hybridization of two species of marmots Marmota baibacina and M. sibirica in the zone of sympatry in Mongolian Altai Mountains. We used a bioacoustic approach to determine the localization of individuals of different species and their cohabitation sites. Genetic typing with two diploid nuclear markers and one marker each of paternal and maternal lines was used to identify hybrids. Habitat preferences of marmots were studied to understand the conditions for the formation of heterospecific pairs. We found a high proportion of hybrid individuals in boulder screes where conditions for the formation of heterospecific pairs probably exist. Our data indicate the viability and fertility of F1 hybrids and their descendants. We hypothesize that the environmental preferences and behavioral features of both species of marmots are important factors that both create conditions for hybridization and limit hybrid dispersal.
Diaphragmatic Hernia as a Prenatal Feature of Glycosylphosphatidylinositol Biosynthesis Defects and the Overlap With Fryns Syndrome – Literature Review
Authors: Kosinski Przemyslaw , Greczan Milena , Jezela-Stanek Aleksandra
Published: June 2021

Fryns syndrome is an autosomal recessive multiple congenital anomaly syndrome, with diaphragmatic defects and secondary lung hypoplasia as cardinal features. Despite it was reported first in 1979, its exact etiology has not been established to date. With this review, we would like to draw attention to the prenatal presentation of multiple congenital anomalies syndromes, resulting from defects in the synthesis of glycosylphosphatidylinositol anchors, to be considered in a prenatal assessment of fetuses with DH and Fryns-like phenotype.
Causal Inference Between Chronic Periodontitis and Chronic Kidney Disease: A Bidirectional Mendelian Randomization Analysis in a European Population
Authors: Yang Jie , Chen Tianyi , Zhu Yahong , Bai Mingxia , Li Xingang
Published: June 2021

Background

Previous epidemiological studies have shown significant associations between chronic periodontitis (CP) and chronic kidney disease (CKD), but the causal relationship remains uncertain. Aiming to examine the causal relationship between these two diseases, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis with multiple MR methods.

Methods

For the casual effect of CP on CKD, we selected seven single-nucleotide polymorphisms (SNPs) specific to CP as genetic instrumental variables from the genome-wide association studies (GWAS) in the GLIDE Consortium. The summary statistics of complementary kidney function measures, i.e., estimated glomerular filtration rate (eGFR) and blood urea nitrogen (BUN), were derived from the GWAS in the CKDGen Consortium. For the reversed causal inference, six SNPs associated with eGFR and nine with BUN from the CKDGen Consortium were included and the summary statistics were extracted from the CLIDE Consortium.

Results

No significant causal association between genetically determined CP and eGFR or BUN was found (all p > 0.05). Based on the conventional inverse variance-weighted method, one of seven instrumental variables supported genetically predicted CP being associated with a higher risk of eGFR (estimate = 0.019, 95% CI: 0.012–0.026, p < 0.001).

Conclusion

Evidence from our bidirectional causal inference does not support a causal relation between CP and CKD risk and therefore suggests that associations reported by previous observational studies may represent confounding.
Human MicroRNAs Interacting With SARS-CoV-2 RNA Sequences: Computational Analysis and Experimental Target Validation
Authors: Siniscalchi Chiara , Di Palo Armando , Russo Aniello , Potenza Nicoletta
Published: June 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel RNA virus affecting humans, causing a form of acute pulmonary respiratory disorder named COVID-19, declared a pandemic by the World Health Organization. MicroRNAs (miRNA) play an emerging and important role in the interplay between viruses and host cells. Although the impact of host miRNAs on SARS-CoV-2 infection has been predicted, experimental data are still missing. This study started by a bioinformatics prediction of cellular miRNAs potentially targeting viral RNAs; then, a number of criteria also based on experimental evidence and virus biology were applied, giving rise to eight promising binding miRNAs. Their interaction with viral sequences was experimentally validated by transfecting luciferase-based reporter plasmids carrying viral target sequences or their inverted sequences into the lung A549 cell line. Transfection of the reporter plasmids resulted in a reduction of luciferase activity for five out of the eight potential binding sites, suggesting responsiveness to endogenously expressed miRNAs. Co-transfection of the reporter plasmids along with miRNA mimics led to a further and strong reduction of luciferase activity, validating the interaction between miR-219a-2-3p, miR-30c-5p, miR-378d, miR-29a-3p, miR-15b-5p, and viral sequences. miR-15b was also able to repress plasmid-driven Spike expression. Intriguingly, the viral target sequences are fully conserved in more recent variants such as United Kingdom variant B.1.1.7 and South Africa 501Y.V2. Overall, this study provides a first experimental evidence of the interaction between specific cellular miRNAs and SARS-CoV-2 sequences, thus contributing to understanding the molecular mechanisms underlying virus infection and pathogenesis to envisage innovative therapeutic interventions and diagnostic tools.
Regulated Intramembrane Proteolysis of ACE2: A Potential Mechanism Contributing to COVID-19 Pathogenesis?
Authors: Gonzalez Sandra M. , Siddik Abu Bakar , Su Ruey-Chyi
Published: June 2021

Since being identified as a key receptor for SARS-CoV-2, Angiotensin converting enzyme 2 (ACE2) has been studied as one of the potential targets for the development of preventative and/or treatment options. Tissue expression of ACE2 and the amino acids interacting with the spike protein of SARS-CoV-2 have been mapped. Furthermore, the recombinant soluble extracellular domain of ACE2 is already in phase 2 trials as a treatment for SARS-CoV-2 infection. Most studies have continued to focus on the ACE2 extracellular domain, which is known to play key roles in the renin angiotensin system and in amino acid uptake. However, few also found ACE2 to have an immune-modulatory function and its intracellular tail may be one of the signaling molecules in regulating cellular activation. The implication of its immune-modulatory role in preventing the cytokine-storm, observed in severe COVID-19 disease outcomes requires further investigation. This review focuses on the regulated proteolytic cleavage of ACE2 upon binding to inducer(s), such as the spike protein of SARS-CoV, the potential of cleaved ACE2 intracellular subdomain in regulating cellular function, and the ACE2’s immune-modulatory function. This knowledge is critical for targeting ACE2 levels for developing prophylactic treatment or preventative measures in SARS-CoV infections.
Intestinal Microbiota in Common Chronic Inflammatory Disorders Affecting Children
Authors: Torun Anna , Hupalowska Anna , Trzonkowski Piotr , Kierkus Jaroslaw , Pyrzynska Beata
Published: June 2021

The incidence and prevalence rate of chronic inflammatory disorders is on the rise in the pediatric population. Recent research indicates the crucial role of interactions between the altered intestinal microbiome and the immune system in the pathogenesis of several chronic inflammatory disorders in children, such as inflammatory bowel disease (IBD) and autoimmune diseases, such as type 1 diabetes mellitus (T1DM) and celiac disease (CeD). Here, we review recent knowledge concerning the pathogenic mechanisms underlying these disorders, and summarize the facts suggesting that the initiation and progression of IBD, T1DM, and CeD can be partially attributed to disturbances in the patterns of composition and abundance of the gut microbiota. The standard available therapies for chronic inflammatory disorders in children largely aim to treat symptoms. Although constant efforts are being made to maximize the quality of life for children in the long-term, sustained improvements are still difficult to achieve. Additional challenges are the changing physiology associated with growth and development of children, a population that is particularly susceptible to medication-related adverse effects. In this review, we explore new promising therapeutic approaches aimed at modulation of either gut microbiota or the activity of the immune system to induce a long-lasting remission of chronic inflammatory disorders. Recent preclinical studies and clinical trials have evaluated new approaches, for instance the adoptive transfer of immune cells, with genetically engineered regulatory T cells expressing antigen-specific chimeric antigen receptors. These approaches have revolutionized cancer treatments and have the potential for the protection of high-risk children from developing autoimmune diseases and effective management of inflammatory disorders. The review also focuses on the findings of studies that indicate that the responses to a variety of immunotherapies can be enhanced by strategic manipulation of gut microbiota, thus emphasizing on the importance of proper interaction between the gut microbiota and immune system for sustained health benefits and improvement of the quality of life of pediatric patients.
Single-Cell TCR and Transcriptome Analysis: An Indispensable Tool for Studying T-Cell Biology and Cancer Immunotherapy
Authors: Pasetto Anna , Lu Yong-Chen
Published: June 2021

T cells have been known to be the driving force for immune response and cancer immunotherapy. Recent advances on single-cell sequencing techniques have empowered scientists to discover new biology at the single-cell level. Here, we review the single-cell techniques used for T-cell studies, including T-cell receptor (TCR) and transcriptome analysis. In addition, we summarize the approaches used for the identification of T-cell neoantigens, an important aspect for T-cell mediated cancer immunotherapy. More importantly, we discuss the applications of single-cell techniques for T-cell studies, including T-cell development and differentiation, as well as the role of T cells in autoimmunity, infectious disease and cancer immunotherapy. Taken together, this powerful tool not only can validate previous observation by conventional approaches, but also can pave the way for new discovery, such as previous unidentified T-cell subpopulations that potentially responsible for clinical outcomes in patients with autoimmunity or cancer.
Cytokine/Chemokine Expression Is Closely Associated Disease Severity of Human Adenovirus Infections in Immunocompetent Adults and Predicts Disease Progression
Authors: Li Jin , Wei Jinli , Xu Zhixiang , Jiang Chunmei , Li Mianhuan , Chen Jie , Li Yanjie , Yang Minghui , Gu Yuchen , Wang Fuxiang , Shu Yuelong , Yang Yang , Sun Litao , Liu Yingxia
Published: June 2021

Increasing human Adenovirus (HAdV) infections complicated with acute respiratory distress syndrome (ARDS) even fatal outcome were reported in immunocompetent adolescent and adult patients. Here, we characterized the cytokine/chemokine expression profiles of immunocompetent patients complicated with ARDS during HAdV infection and identified biomarkers for disease severity/progression. Forty-eight cytokines/chemokines in the plasma samples from 19 HAdV-infected immunocompetent adolescent and adult patients (ten complicated with ARDS) were measured and analyzed in combination with clinical indices. Immunocompetent patients with ARDS caused by severe acute respiratory disease coronavirus (SARS-CoV)-2, 2009 pandemic H1N1 (panH1N1) or bacteria were included for comparative analyses. Similar indices of disease course/progression were found in immunocompetent patients with ARDS caused by HAdV, SARS-CoV-2 or panH1N infections, whereas the HAdV-infected group showed a higher prevalence of viremia, as well as increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK). Expression levels of 33 cytokines/chemokines were increased significantly in HAdV-infected patients with ARDS compared with that in healthy controls, and many of them were also significantly higher than those in SARS-CoV-2-infected and panH1N1-infected patients. Expression of interferon (IFN)-γ, interleukin (IL)-1β, hepatocyte growth factor (HGF), monokine induced by IFN-γ (MIG), IL-6, macrophage-colony stimulating factor (M-CSF), IL-10, IL-1α and IL-2Ra was significantly higher in HAdV-infected patients with ARDS than that in those without ARDS, and negatively associated with the ratio of the partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2). Analyses of the receiver operating characteristic curve (ROC) showed that expression of IL-10, M-CSF, MIG, HGF, IL-1β, IFN-γ and IL-2Ra could predict the progression of HAdV infection, with the highest area under the curve (AUC) of 0.944 obtained for IL-10. Of note, the AUC value for the combination of IL-10, IFN-γ, and M-CSF reached 1. In conclusion, the “cytokine storm” occurred during HAdV infection in immunocompetent patients, and expression of IL-10, M-CSF, MIG, HGF, IL-1β, IFN-γ and IL-2Ra was closely associated with disease severity and could predict disease progression.
Viable Putative Vibrio vulnificus and parahaemolyticus in the Pensacola and Perdido Bays: Water Column, Sediments, and Invertebrate Biofilms
Authors: Potdukhe Trupti V. , Caffrey Jane M. , Rothfus Mackenzie J. , Daniel Carrie E. , Swords Michael E. , Albrecht Barbara B. , Jeffrey Wade H. , Waidner Lisa A.
Published: June 2021

Vibriosis is the general term for human illnesses caused by infection of pathogenicVibriospecies.Vibrio vulnificus(Vv) andparahaemolyticus(Vp) are two problematic waterborne pathogens that have yet to be enumerated in northwest Florida coastal Gulf of Mexico estuaries. In this regionally novel study, we surveyed 43 locations in two subtropical estuarine systems, Perdido Bay and Pensacola Bay, over seven dates in winter 2020. Sampling included three substrate types: surface waters, sediments, and invertebrate biofilms. We determined baseline abundances of presumptive viableVvandVpappearing as colonies on CHROMagar (Vv, blue;Vp, purple).Vvwas detected in 37 out of 43 water samples, with maximum levels of 3,556 CFU/mL.Vpwas only detected in 15 water samples, with a maximum concentration of 8,919 CFU/mL. Sediments containedVvin all but one sample, with concentrations ranging from 121 to 607,222 CFU/mL. In contrast,Vpwere only detected in 33 sediment samples, where concentrations ranged from 28 to 77,333 CFU/mL. Opportunistically-sampled surface swabs (biofilms), collected from shells (either oyster or barnacle) and polychaete worms found in sediment samples, contained on average 7,735 and 1,490 CFU/mL ofVvandVp, respectively. Surface waterVvabundances covaried with bottom water pH, maximum prior cumulative wind speeds, and tidal coefficient on the day of sampling.Vpsurface water abundances negatively correlated with surface water salinity, surface water pH, and bottom water pH and positively correlated with total surface dissolved inorganic and total Kjeldahl nitrogen concentrations, and wind. Spatially, there was large variation inVibriodensities in surface waters; abundances of both species were strongly correlated with wind, suggesting resuspension was important. Sedimentary abundances of both putativeVvandVpshared a correlation with one parameter: salinity stratification. Due to the length of this study, temperature was not considered a major factor. This short-term (1 month) study was designed not to enumerate pathogenicVvorVp, but rather to establish the first winter baseline ofVibrioabundances for this region. Determination of these baseline winter cultivable putativeVibrioabundances will be valuable in predicting relative risk factors in each waterbody of interest.
Perioperative Sleep Disorder: A Review
Authors: Lin Dandan , Huang Xiao , Sun Yi , Wei Changwei , Wu Anshi
Published: June 2021

Patients in the perioperative period usually present with different types and degrees of sleep disorders, which can severely affect their post-operative outcomes. Multiple risk factors may lead to the occurrence of perioperative sleep disorders, including personal factors, psychological factors, surgery factors, and environmental factors. In this review, we summarize the potential risk factors for perioperative sleep disorders during hospitalization. And it also provides an overview of perioperative outcomes and potential therapeutic prevention of perioperative sleep disorders. However, the further search is necessary to investigate the effectiveness and safety of preventions in the clinical practice and push forward the therapies.
Convalescent Plasma Therapy for COVID-19: A Graphical Mosaic of the Worldwide Evidence
Authors: Klassen Stephen A. , Senefeld Jonathon W. , Senese Katherine A. , Johnson Patrick W. , Wiggins Chad C. , Baker Sarah E. , van Helmond Noud , Bruno Katelyn A. , Pirofski Liise-anne , Shoham Shmuel , Grossman Brenda J. , Henderson Jeffrey P. , Wright R. Scott , Fairweather DeLisa , Paneth Nigel S. , Carter Rickey E. , Casadevall Arturo , Joyner Michael J.
Published: June 2021

Convalescent plasma has been used worldwide to treat patients hospitalized with coronavirus disease 2019 (COVID-19) and prevent disease progression. Despite global usage, uncertainty remains regarding plasma efficacy, as randomized controlled trials (RCTs) have provided divergent evidence regarding the survival benefit of convalescent plasma. Here, we argue that during a global health emergency, the mosaic of evidence originating from multiple levels of the epistemic hierarchy should inform contemporary policy and healthcare decisions. Indeed, worldwide matched-control studies have generally found convalescent plasma to improve COVID-19 patient survival, and RCTs have demonstrated a survival benefit when transfused early in the disease course but limited or no benefit later in the disease course when patients required greater supportive therapies. RCTs have also revealed that convalescent plasma transfusion contributes to improved symptomatology and viral clearance. To further investigate the effect of convalescent plasma on patient mortality, we performed a meta-analytical approach to pool daily survival data from all controlled studies that reported Kaplan–Meier survival plots. Qualitative inspection of all available Kaplan–Meier survival data and an aggregate Kaplan–Meier survival plot revealed a directionally consistent pattern among studies arising from multiple levels of the epistemic hierarchy, whereby convalescent plasma transfusion was generally associated with greater patient survival. Given that convalescent plasma has a similar safety profile as standard plasma, convalescent plasma should be implemented within weeks of the onset of future infectious disease outbreaks.
Staphylococcus saprophyticus From Clinical and Environmental Origins Have Distinct Biofilm Composition
Authors: Lawal Opeyemi U. , Barata Marta , Fraqueza Maria J. , Worning Peder , Bartels Mette D. , Goncalves Luisa , Paixão Paulo , Goncalves Elsa , Toscano Cristina , Empel Joanna , Urbaś Malgorzata , Domiìnguez Maria A. , Westh Henrik , de Lencastre Hermínia , Miragaia Maria
Published: June 2021

Biofilm formation has been shown to be critical to the success of uropathogens. Although Staphylococcus saprophyticus is a common cause of urinary tract infections, its biofilm production capacity, composition, genetic basis, and origin are poorly understood. We investigated biofilm formation in a large and diverse collection of S. saprophyticus (n = 422). Biofilm matrix composition was assessed in representative strains (n = 63) belonging to two main S. saprophyticus lineages (G and S) recovered from human infection, colonization, and food-related environment using biofilm detachment approach. To identify factors that could be associated with biofilm formation and structure variation, we used a pangenome-wide association study approach. Almost all the isolates (91%; n = 384/422) produced biofilm. Among the 63 representative strains, we identified eight biofilm matrix phenotypes, but the most common were composed of protein or protein–extracellular DNA (eDNA)–polysaccharides (38%, 24/63 each). Biofilms containing protein–eDNA–polysaccharides were linked to lineage G and environmental isolates, whereas protein-based biofilms were produced by lineage S and infection isolates (p < 0.05). Putative biofilm-associated genes, namely, aas, atl, ebpS, uafA, sasF, sasD, sdrH, splE, sdrE, sdrC, sraP, and ica genes, were found with different frequencies (3–100%), but there was no correlation between their presence and biofilm production or matrix types. Notably, icaC_1 was ubiquitous in the collection, while icaR was lineage G-associated, and only four strains carried a complete ica gene cluster (icaADBCR) except one that was without icaR. We provided evidence, using a comparative genomic approach, that the complete icaADBCR cluster was acquired multiple times by S. saprophyticus and originated from other coagulase-negative staphylococci. Overall, the composition of S. saprophyticus biofilms was distinct in environmental and clinical isolates, suggesting that modulation of biofilm structure could be a key step in the pathogenicity of these bacteria. Moreover, biofilm production in S. saprophyticus is ica-independent, and the complete icaADBCR was acquired from other staphylococci.
Next-Generation Sequencing for Whole-Genome Characterization of Weissella cibaria UTNGt21O Strain Originated From Wild Solanum quitoense Lam. Fruits: An Atlas of Metabolites With Biotechnological Significance
Authors: Tenea Gabriela N. , Hurtado Pamela
Published: June 2021

The whole genome of Weissella cibaria strain UTNGt21O isolated from wild fruits of Solanum quitoense (naranjilla) shrub was sequenced and annotated. The similarity proportions based on the genus level, as a result of the best hits for the entire contig, were 54.84% with Weissella, 6.45% with Leuconostoc, 3.23% with Lactococcus, and 35.48% no match. The closest genome was W. cibaria SP7 (GCF_004521965.1) with 86.21% average nucleotide identity (ANI) and 3.2% alignment coverage. The genome contains 1,867 protein-coding genes, among which 1,620 were assigned with the EggNOG database. On the basis of the results, 438 proteins were classified with unknown function from which 247 new hypothetical proteins have no match in the nucleotide Basic Local Alignment Search Tool (BLASTN) database. It also contains 78 tRNAs, six copies of 5S rRNA, one copy of 16S rRNA, one copy of 23S rRNA, and one copy of tmRNA. The W. cibaria UTNGt21O strain harbors several genes responsible for carbohydrate metabolism, cellular process, general stress responses, cofactors, and vitamins, conferring probiotic features. A pangenome analysis indicated the presence of various strain-specific genes encoded for proteins responsible for the defense mechanisms as well as gene encoded for enzymes with biotechnological value, such as penicillin acylase and folates; thus, W. cibaria exhibited high genetic diversity. The genome characterization indicated the presence of a putative CRISPR-Cas array and five prophage regions and the absence of acquired antibiotic resistance genes, virulence, and pathogenic factors; thus, UTNGt21O might be considered a safe strain. Besides, the interaction between the peptide extracts from UTNGt21O and Staphylococcus aureus results in cell death caused by the target cell integrity loss and the release of aromatic molecules from the cytoplasm. The results indicated that W. cibaria UTNGt21O can be considered a beneficial strain to be further exploited for developing novel antimicrobials and probiotic products with improved technological characteristics.
Cronobacter sakazakii ATCC 29544 Translocated Human Brain Microvascular Endothelial Cells via Endocytosis, Apoptosis Induction, and Disruption of Tight Junction
Authors: Jin Tong , Guan Ning , Du Yuhang , Zhang Xinpeng , Li Jiahui , Xia Xiaodong
Published: June 2021

Cronobacter sakazakii (C. sakazakii) is an emerging opportunistic foodborne pathogen that can cause neonatal necrotizing enterocolitis, meningitis, sepsis in neonates and infants with a relatively high mortality rate. Bacterial transcytosis across the human brain microvascular endothelial cells (HBMEC) is vital for C. sakazakii to induce neonatal meningitis. However, few studies focus on the mechanisms by which C. sakazakii translocates HBMEC. In this study, the translocation processes of C. sakazakii on HBMEC were explored. C. sakazakii strains could effectively adhere to, invade and intracellularly survive in HBMEC. The strain ATCC 29544 exhibited the highest translocation efficiency across HBMEC monolayer among four tested strains. Bacteria-contained intracellular endosomes were detected in C. sakazakii-infected HBMEC by a transmission electron microscope. Endocytosis-related proteins CD44, Rab5, Rab7, and LAMP2 were increased after infection, while the level of Cathepsin L did not change. C. sakazakii induced TLR4/NF-κB inflammatory signal pathway activation in HBMEC, with increased NO production and elevated mRNA levels of IL-8, IL-6, TNF-α, IL-1β, iNOS, and COX-2. C. sakazakii infection also caused LDH release, caspase-3 activation, and HBMEC apoptosis. Meanwhile, increased Dextran-FITC permeability and decreased trans epithelial electric resistance indicated that C. sakazakii disrupted tight junction of HBMEC monolayers, which was confirmed by the decreased levels of tight junction-related proteins ZO-1 and Occludin. These findings suggest that C. sakazakii induced intracellular bacterial endocytosis, stimulated inflammation and apoptosis, disrupted monolayer tight junction in HBMEC, which all together contribute to bacterial translocation.
OpaR Controls the Metabolism of c-di-GMP in Vibrio parahaemolyticus
Authors: Zhang Yiquan , Qiu Yue , Gao He , Sun Junfang , Li Xue , Zhang Miaomiao , Xue Xingfan , Yang Wenhui , Ni Bin , Hu Lingfei , Yin Zhe , Lu Renfei , Zhou Dongsheng
Published: June 2021

Vibrio parahaemolyticus, the leading cause of seafood-associated gastroenteritis worldwide, has a strong ability to form biofilms on surfaces. Quorum sensing (QS) is a process widely used by bacteria to communicate with each other and control gene expression via the secretion and detection of autoinducers. OpaR is the master QS regulator of V. parahaemolyticus operating under high cell density (HCD). OpaR regulation of V. parahaemolyticus biofilm formation has been reported, but the regulatory mechanisms are still not fully understood. bis-(3′-5′)-cyclic di-GMP (c-di-GMP) is an omnipresent intracellular second messenger that regulates diverse behaviors of bacteria including activation of biofilm formation. In this work, we showed that OpaR repressed biofilm formation and decreased the intracellular concentration of c-di-GMP in V. parahaemolyticus RIMD2210633. The OpaR box-like sequences were detected within the regulatory DNA regions of scrA, scrG, VP0117, VPA0198, VPA1176, VP0699, and VP2979, encoding a group of GGDEF and/or EAL-type proteins. The results of qPCR, LacZ fusion, EMSA, and DNase I footprinting assays demonstrated that OpaR bound to the upstream DNA regions of scrA, VP0117, VPA0198, VPA1176, and VP0699 to repress their transcription, whereas it positively and directly regulated the transcription of scrG and VP2979. Thus, transcriptional regulation of these genes by OpaR led directly to changes in the intracellular concentration of c-di-GMP. The direct association between QS and c-di-GMP metabolism in V. parahaemolyticus RIMD2210633 would be conducive to precise control of gene transcription and bacterial behaviors such as biofilm formation.
Membrane Stress Caused by Unprocessed Outer Membrane Lipoprotein Intermediate Pro-Lpp Affects DnaA and Fis-Dependent Growth
Authors: Patil Digvijay , Xun Dan , Schueritz Markus , Bansal Shivani , Cheema Amrita , Crooke Elliott , Saxena Rahul
Published: June 2021

InEscherichia coli, repression of phosphatidylglycerol synthase A gene (pgsA) lowers the levels of membrane acidic phospholipids, particularly phosphatidylglycerol (PG), causing growth-arrested phenotype. The interrupted synthesis of PG is known to be associated with concomitant reduction of chromosomal content and cell mass, in addition to accumulation of unprocessed outer membrane lipoprotein intermediate, pro-Lpp, at the inner membrane. However, whether a linkage exists between the two altered-membrane outcomes remains unknown. Previously, it has been shown thatpgsA+cells overexpressing mutant Lpp(C21G) protein have growth defects similar to those caused by the unprocessed pro-Lpp intermediate in cells lacking PG. Here, we found that the ectopic expression of DnaA(L366K) or deletion offis(encoding Factor for Inversion Stimulation) permits growth of cells that otherwise would be arrested for growth due to accumulated Lpp(C21G). The DnaA(L366K)-mediated restoration of growth occurs by reduced expression of Lpp(C21G)viaa σE-dependent small-regulatory RNA (sRNA), MicL-S. In contrast, restoration of growthvia fisdeletion is only partially dependent on the MicL-S pathway; deletion offisalso rescues Lpp(C21G) growth arrest in cells lacking physiological levels of PG and cardiolipin (CL), independently of MicL-S. Our results suggest a close link between the physiological state of the bacterial cell membrane and DnaA- and Fis-dependent growth.
Plant Small RNA World Growing Bigger: tRNA-Derived Fragments, Longstanding Players in Regulatory Processes
Authors: Alves Cristiane S. , Nogueira Fabio T. S.
Published: June 2021

In the past 2 decades, the discovery of a new class of small RNAs, known as tRNA-derived fragments (tRFs), shed light on a new layer of regulation implicated in many biological processes. tRFs originate from mature tRNAs and are classified according to the tRNA regions that they derive from, namely 3′tRF, 5′tRF, and tRF-halves. Additionally, another tRF subgroup deriving from tRNA precursors has been reported, the 3′U tRFs. tRF length ranges from 17 to 26 nt for the 3′and 5′tRFs, and from 30 to 40 nt for tRF-halves. tRF biogenesis is still not yet elucidated, although there is strong evidence that Dicer (and DICER-LIKE) proteins, as well as other RNases such as Angiogenin in mammal and RNS proteins family in plants, are responsible for processing specific tRFs. In plants, the abundance of those molecules varies among tissues, developmental stages, and environmental conditions. More recently, several studies have contributed to elucidate the role that these intriguing molecules may play in all organisms. Among the recent discoveries, tRFs were found to be involved in distinctive regulatory layers, such as transcription and translation regulation, RNA degradation, ribosome biogenesis, stress response, regulatory signaling in plant nodulation, and genome protection against transposable elements. Although tRF biology is still poorly understood, the field has blossomed in the past few years, and this review summarizes the most recent developments in the tRF field in plants.
Study of the Active Components and Molecular Mechanism of Tripterygium wilfordii in the Treatment of Diabetic Nephropathy
Authors: Wang Lin , Wang Zheyi , Yang Zhihua , Yang Kang , Yang Hongtao
Published: June 2021

We aimed to explore the active ingredients and molecular mechanism ofTripterygium wilfordii(TW) in the treatment of diabetic nephropathy (DN) through network pharmacology and molecular biology. First, the active ingredients and potential targets of TW were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and related literature materials, and Cytoscape 3.7.2 software was used to construct the active ingredient-target network diagram of TW. Second, the target set of DN was obtained through the disease database, and the potential targets of TW in the treatment of DN were screened through a Venn diagram. A protein interaction network diagram (PPI) was constructed with the help of the String platform and Cytoscape 3.7.2. Third, the ClueGO plug-in tool was used to enrich the GO biological process and the KEGG metabolic pathway. Finally, molecular docking experiments and cell pathway analyses were performed. As a result, a total of 52 active ingredients of TW were screened, and 141 predicted targets and 49 target genes related to DN were identified. The biological process of GO is mediated mainly through the regulation of oxygen metabolism, endothelial cell proliferation, acute inflammation, apoptotic signal transduction pathway, fibroblast proliferation, positive regulation of cyclase activity, adipocyte differentiation and other biological processes. KEGG enrichment analysis showed that the main pathways involved were AGE-RAGE, vascular endothelial growth factor, HIF-1, IL-17, relaxin signalling pathway, TNF, Fc epsilon RI, insulin resistance and other signaling pathways. It can be concluded that TW may treat DN by reducing inflammation, reducing antioxidative stress, regulating immunity, improving vascular disease, reducing insulin resistance, delaying renal fibrosis, repairing podocytes, and reducing cell apoptosis, among others, with multicomponent, multitarget and multisystem characteristics.
A Ferroptosis-Related lncRNAs Signature Predicts Prognosis and Immune Microenvironment for Breast Cancer
Authors: Zhang Kaiming , Ping Liqin , Du Tian , Liang Gehao , Huang Yun , Li Zhiling , Deng Rong , Tang Jun
Published: June 2021

Background: Ferroptosis, a regulated cell death which is driven by the iron-dependent peroxidation of lipids, plays an important role in cancer. However, studies about ferroptosis-related Long non-coding RNAs (lncRNAs) in breast cancer (BC) are limited. Besides, the prognostic role of ferroptosis-related lncRNAs and their relationship to immune microenvironment in breast cancer remain unclear. This study aimed to explore the potential prognostic value of ferroptosis-related lncRNAs and their relationship to immune microenvironment in breast cancer.

Methods: RNA-sequencing data of female breast cancer patients were downloaded from TCGA database. 937 patients were randomly separated into training or validation cohort in 2:1 ratio. Ferroptosis-related lncRNAs were screened by Pearson correlation analysis with 239 reported ferroptosis-related genes. A ferroptosis-related lncRNAs signature was constructed with univariate and multivariate Cox regression analyses in the training cohort, and its prognostic value was further tested in the validation cohort.

Results: An 8-ferroptosis-related-lncRNAs signature was developed by multivariate Cox regression analysis to divide patients into two risk groups. Patients in the high-risk group had worse prognosis than patients in the low-risk group. Multivariate Cox regression analysis showed the risk score was an independent prognostic indicator. Receiver operating characteristic curve (ROC) analysis proved the predictive accuracy of the signature. The area under time-dependent ROC curve (AUC) reached 0.853 at 1 year, 0.802 at 2 years, 0.740 at 5 years in the training cohort and 0.791 at 1 year, 0.778 at 2 years, 0.722 at 5 years in the validation cohort. Further analysis demonstrated that immune-related pathways were significantly enriched in the high-risk group. Analysis of the immune cell infiltration landscape showed that breast cancer in the high-risk group tended be immunologically “cold”.

Conclusion: We identified a novel ferroptosis-related lncRNA signature which could precisely predict the prognosis of breast cancer patients. Ferroptosis-related lncRNAs may have a potential role in the process of anti-tumor immunity and serve as therapeutic targets for breast cancer.
Survival in Hostile Conditions: Pupylation and the Proteasome in Actinobacterial Stress Response Pathways
Authors: von Rosen Tatjana , Keller Lena ML , Weber-Ban Eilika
Published: June 2021

Bacteria employ a multitude of strategies to cope with the challenges they face in their natural surroundings, be it as pathogens, commensals or free-living species in rapidly changing environments like soil. Mycobacteria and other Actinobacteria acquired proteasomal genes and evolved a post-translational, ubiquitin-like modification pathway called pupylation to support their survival under rapidly changing conditions and under stress. The proteasomal 20S core particle (20S CP) interacts with ring-shaped activators like the hexameric ATPase Mpa that recruits pupylated substrates. The proteasomal subunits, Mpa and pupylation enzymes are encoded in the so-called Pup-proteasome system (PPS) gene locus. Genes in this locus become vital for bacteria to survive during periods of stress. In the successful human pathogen Mycobacterium tuberculosis, the 20S CP is essential for survival in host macrophages. Other members of the PPS and proteasomal interactors are crucial for cellular homeostasis, for example during the DNA damage response, iron and copper regulation, and heat shock. The multiple pathways that the proteasome is involved in during different stress responses suggest that the PPS plays a vital role in bacterial protein quality control and adaptation to diverse challenging environments.
Orientation of Temporal Interference for Non-invasive Deep Brain Stimulation in Epilepsy
Authors: Missey Florian , Rusina Evgeniia , Acerbo Emma , Botzanowski Boris , Trébuchon Agnès , Bartolomei Fabrice , Jirsa Viktor , Carron Romain , Williamson Adam
Published: June 2021

In patients with focal drug-resistant epilepsy, electrical stimulation from intracranial electrodes is frequently used for the localization of seizure onset zones and related pathological networks. The ability of electrically stimulated tissue to generate beta and gamma range oscillations, called rapid-discharges, is a frequent indication of an epileptogenic zone. However, a limit of intracranial stimulation is the fixed physical location and number of implanted electrodes, leaving numerous clinically and functionally relevant brain regions unexplored. Here, we demonstrate an alternative technique relying exclusively on non-penetrating surface electrodes, namely an orientation-tunable form of temporally interfering (TI) electric fields to target the CA3 of the mouse hippocampus which focally evokes seizure-like events (SLEs) having the characteristic frequencies of rapid-discharges, but without the necessity of the implanted electrodes. The orientation of the topical electrodes with respect to the orientation of the hippocampus is demonstrated to strongly control the threshold for evoking SLEs. Additionally, we demonstrate the use of Pulse-width-modulation of square waves as an alternative to sine waves for TI stimulation. An orientation-dependent analysis of classic implanted electrodes to evoke SLEs in the hippocampus is subsequently utilized to support the results of the minimally invasive temporally interfering fields. The principles of orientation-tunable TI stimulation seen here can be generally applicable in a wide range of other excitable tissues and brain regions, overcoming several limitations of fixed electrodes which penetrate tissue and overcoming several limitations of other non-invasive stimulation methods in epilepsy, such as transcranial magnetic stimulation (TMS).
Biologically Relevant Lighting: An Industry Perspective
Authors: Soler Robert , Voss Erica
Published: June 2021

Innovations in LED lighting technology have led to tremendous adoption rates and vastly improved the metrics by which they are traditionally evaluated–including color quality, longevity, and energy efficiency to name a few. Additionally, scientific insight has broadened with respect to the biological impact of light, specifically our circadian rhythm. Indoor electric lighting, despite its many attributes, fails to specifically address the biological responses to light. Traditional electric lighting environments are biologically too dim during the day, too bright at night, and with many people spending much of their lives in these environments, it can lead to circadian dysfunction. The lighting industry’s biological solution has been to create bluer days and yellower nights, but the technology created to do so caters primarily to the cones. A better call to action is to provide biologically brighter days and biologically darker nights within the built environment. However, current lighting design practices have specified the comfort and utility of electric light. Brighter intensity during the day can often be uncomfortable or glary, and reduced light intensity at night may compromise visual comfort and safety, both of which will affect user compliance. No single lighting solution will effectively create biologically brighter days and biologically darker nights, but rather a variety of parameters need to be considered. This paper discusses the contributions of spectral power distribution, hue or color temperature, spatial distribution, as well as architectural geometry and surface reflectivity, to achieve biologically relevant lighting.
Classifying Vulnerability to Sleep Deprivation Using Resting-State Functional MRI Graph Theory Metrics
Authors: Xu Yongqiang , Yu Ping , Zheng Jianmin , Wang Chen , Hu Tian , Yang Qi , Xu Ziliang , Guo Fan , Tang Xing , Ren Fang , Zhu Yuanqiang
Published: June 2021

Sleep deprivation (SD) has become very common in contemporary society, where people work around the clock. SD-induced cognitive deficits show large inter-individual differences and are trait-like with known neural correlates. However, few studies have used neuroimaging to predict vulnerability to SD. Here, resting state functional magnetic resonance imaging (fMRI) data and psychomotor vigilance task (PVT) data were collected from 60 healthy subjects after resting wakefulness and after one night of SD. The number of PVT lapses was then used to classify participants on the basis of whether they were vulnerable or resilient to SD. We explored the viability of graph-theory-based degree centrality to accurately classify vulnerability to SD. Compared with during resting wakefulness, widespread changes in degree centrality (DC) were found after SD, indicating significant reorganization of sleep homeostasis with respect to activity in resting state brain network architecture. Support vector machine (SVM) analysis using leave-one-out cross-validation achieved a correct classification rate of 84.75% [sensitivity 82.76%, specificity 86.67%, and area under the receiver operating characteristic curve (AUC) 0.94] for differentiating vulnerable subjects from resilient subjects. Brain areas that contributed most to the classification model were mainly located within the sensorimotor network, default mode network, and thalamus. Furthermore, we found a significantly negative correlation between changes in PVT lapses and DC in the thalamus after SD. These findings suggest that resting-state network measures combined with a machine learning algorithm could have broad potential applications in screening vulnerability to SD.
Determining 5HT7R’s Involvement in Modifying the Antihyperalgesic Effects of Electroacupuncture on Rats With Recurrent Migraine
Authors: Liu Lu , Xu Xiao-Bai , Qu Zheng-Yang , Zhao Luo-Peng , Zhang Claire-Shuiqing , Li Zhi-Juan , Lyu Tian-Li , Wang Xue-Fei , Jing Xiang-Hong , Li Bin
Published: June 2021

Electroacupuncture (EA) is widely used in clinical practice to relieve migraine pain. 5-HT7 receptor (5-HT7R) has been reported to play an excitatory role in neuronal systems and regulate hyperalgesic pain and neurogenic inflammation. 5-HT7R could influence phosphorylation of protein kinase A (PKA)- or extracellular signal-regulated kinase1/2 (ERK1/2)-mediated signaling pathways, which mediate sensitization of nociceptive neurons via interacting with cyclic adenosine monophosphate (cAMP). In this study, we evaluated the role of 5-HT7R in the antihyperalgesic effects of EA and the underlying mechanism through regulation of PKA and ERK1/2 in trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC). Hyperalgesia was induced in rats with dural injection of inflammatory soup (IS) to cause meningeal neurogenic inflammatory pain. Electroacupuncture was applied for 15 min every other day before IS injection. Von Frey filaments, tail-flick, hot-plate, and cold-plated tests were used to evaluate the mechanical and thermal hyperalgesia. Neuronal hyperexcitability in TNC was studied by an electrophysiological technique. The 5-HT7R antagonist (SB269970) or 5-HT7R agonist (AS19) was administered intrathecally before each IS application at 2-day intervals during the 7-day injection protocol. The changes in 5-HT7R and 5-HT7R-associated signaling pathway were examined by real-time polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) analyses. When compared with IS group, mechanical and thermal pain thresholds of the IS + EA group were significantly increased. Furthermore, EA prevented the enhancement of both spontaneous activity and evoked responses of second-order trigeminovascular neurons in TNC. Remarkable decreases in 5-HT7R mRNA expression and protein levels were detected in the IS + EA group. More importantly, 5-HT7R agonist AS19 impaired the antihyperalgesic effects of EA on p-PKA and p-ERK1/2. Injecting 5-HT7R antagonist SB-269970 into the intrathecal space of IS rats mimicked the effects of EA antihyperalgesia and inhibited p-PKA and p-ERK1/2. Our findings indicate that 5-HT7R mediates the antihyperalgesic effects of EA on IS-induced migraine pain by regulating PKA and ERK1/2 in TG and TNC.