bluuebunny/crossref_metadata_2025 huggingface dataset:
Adhesive Behavior of Propolis on Different Substrates
Authors: Saccardi Leonie , Schiebl Jonas , Weber Katharina , Schwarz Oliver , Gorb Stanislav , Kovalev Alexander
Published: May 2021

Propolis is a sticky substance used by bees to seal their hive and protect the colony against pathogens. Its main components are plant resins, beeswax, essential oils, pollen, and other organic substances. The chemical and medicinal properties of propolis have been extensively studied, but little is known about its physical and especially adhesive properties. To gain a better understanding of propolis and its potential for adhesive applications, we performed several experiments, including adhesion tests with propolis in different conditions and on various substrates, differential scanning calorimetry analysis, and compression tests. Propolis shows clear viscoelastic behavior and temperature-dependent mechanical properties. Our results demonstrate that propolis adheres well to a wide range of substrates from glass to PTFE, but also enables stronger adhesion at higher temperatures and longer contact times. Even underwater, in wet conditions, quite a substantial adhesion was measured. The data are interpreted from a biomechanical point of view, and the significance of the obtained results for bee biology is discussed.
Vagus Nerve Stimulation: A Potential Adjunct Therapy for COVID-19
Authors: Azabou Eric , Bao Guillaume , Bounab Rania , Heming Nicholas , Annane Djillali
Published: May 2021

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) through excessive end organ inflammation. Despite improved understanding of the pathophysiology, management, and the great efforts worldwide to produce effective drugs, death rates of COVID-19 patients remain unacceptably high, and effective treatment is unfortunately lacking. Pharmacological strategies aimed at modulating inflammation in COVID-19 are being evaluated worldwide. Several drug therapies targeting this excessive inflammation, such as tocilizumab, an interleukin (IL)-6 inhibitor, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, and intravenous immunoglobulin have been identified as potentially useful and reliable approaches to counteract the cytokine storm. However, little attention is currently paid for non-drug therapeutic strategies targeting inflammatory and immunological processes that may be useful for reducing COVID-19-induced complications and improving patient outcome. Vagus nerve stimulation attenuates inflammation both in experimental models and preliminary data in human. Modulating the activity of cholinergic anti-inflammatory pathways (CAPs) described by the group of KJ Tracey has indeed become an important target of therapeutic research strategies for inflammatory diseases and sepsis. Non-invasive transcutaneous vagal nerve stimulation (t-VNS), as a non-pharmacological adjuvant, may help reduce the burden of COVID-19 and deserve to be investigated. VNS as an adjunct therapy in COVID-19 patients should be investigated in clinical trials. Two clinical trials on this topic are currently underway (NCT04382391 and NCT04368156). The results of these trials will be informative, but additional larger studies are needed.
Implications of the Novel Mutations in the SARS-CoV-2 Genome for Transmission, Disease Severity, and the Vaccine Development
Authors: Akkiz Hikmet
Published: May 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of the coronavirus disease 2019 (COVID-19), has been identified in China in late December 2019. SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA betacoronavirus of the Coronaviridae family. Coronaviruses have genetic proofreading mechanism that corrects copying mistakes and thus SARS-CoV-2 genetic diversity is extremely low. Despite lower mutation rate of the virus, researchers have detected a total of 12,706 mutations in the SARS-CoV-2 genome, the majority of which were single nucleotide polymorphisms. Sequencing data revealed that the SARS-CoV-2 accumulates two-single nucleotide mutations per month in its genome. Recently, an amino acid aspartate (D) to glycine (G) (D614G) mutation due to an adenine to guanine nucleotide change at position 23,403 at the 614th amino-acid position of the spike protein in the original reference genotype has been identified. The SARS-CoV-2 viruses that carry the spike protein D614G mutation have become dominant variant around the world. The D614G mutation has been found to be associated with 3 other mutations in the spike protein. Clinical and pseudovirus experimental studies have demonstrated that the spike protein D614G mutation alters the virus phenotype. However, the impact of the mutation on the rate of transmission between people, disease severity and the vaccine and therapeutic development remains unclear. Three variants of SARS-CoV-2 have recently been identified. They are B.1.1.7 (UK) variant, B.1.351 (N501Y.V2, South African) variant and B.1.1.28 (Brazilian) variant. Epidemiological data suggest that they have a higher transmissibility than the original variant. There are reports that some vaccines are less efficacious against the B.1.351 variant. This review article discusses the effects of novel mutations in the SARS-CoV-2 genome on transmission, clinical outcomes and vaccine development.
The Ocular Microbiome in Stevens-Johnson Syndrome
Authors: Kittipibul Thanachaporn , Puangsricharern Vilavun
Published: May 2021

The ocular surface microbiome is an essential factor that maintains ocular surface homeostasis. Since the ocular surface is continuously exposed to the external environment, its microbiome, tears, and local immunity are vital for maintaining normal conditions. Additionally, this microbiome helps prevent pathogen colonization, which commonly leads to opportunistic infection. The abnormal ocular surface microbiome has previously been reported in several conditions, including dry eyes, allergy, blepharitis, graft-versus-host disease (GVHD), and Stevens-Johnson syndrome (SJS). Several approaches were applied to identify the ocular microbiome, including conventional culture techniques and molecular sequencing techniques. By using 16s rRNA sequencing, alterations in the type, proportion, and composition of bacterial communities, described by alpha (α)-and beta (β)-diversity, were observed in SJS patients compared to the healthy group. Conventional culture techniques indicated a higher number of positive bacterial cultures in the SJS group, with a predominance of gram-positive cocci and gram-positive bacilli. Besides, there are increased variations and multiple detections of bacterial genera. Taken together, SJS causes structural changes in the ocular surface and significantly affects its microbiome. Further studies into the area of temporal relationship, metagenomics, proteomics, and metabolomics analysis of the microbiome will lead to a better understanding of this disease. Finally, the treatment using prebiotics and probiotics to re-establish the normal ocular ecosystem and bring back a healthy ocular surface await confirmation.
Relationship Between Sarcopenia and Electrocardiographic Abnormalities in Older People: The Bushehr Elderly Health Program
Authors: Heshmat Ramin , Shafiee Gita , Ostovar Afshin , Fahimfar Noushin , Maleki Birjandi Saba , Jabbari Mohammad , Sharifi Farshad , Nabipour Iraj , Larijani Bagher
Published: May 2021

Background: Sarcopenia is characterized by low skeletal muscle mass and function, which is associated with cardiovascular risk factors and may even be related to adverse cardiovascular events and mortality. This study aimed to evaluate whether sarcopenia is related to electrocardiographic (ECG) abnormalities in a large sample of older adults.

Methods: We performed a cross-sectional study based on the data collected during the Bushehr Elderly Health (BEH) cohort study. Body composition was measured by dual X-ray absorptiometry (DXA) and muscle strength was measured using a digital dynamometer for each hand of every participant. A person who had low muscle strength, as well as low muscle mass was identified as having sarcopenia. The subjects were classified into three groups according to the Minnesota Code (MC) as major, minor ECG abnormalities and participants with no abnormalities ECG.

Results: Of the 2,426 participants, 354 (14.6%) had major ECG abnormalities and 193 (8%) had minor ECG abnormalities. Sarcopenia was associated with an increased risk of major ECG abnormality in all models. After adjustment for confounders of CHD in full model, the OR for major ECG abnormality was 1.47 (95% CI 1.11–1.95) in those with sarcopenia. Low muscle strength and low muscle performance were both with an increased risk of major ECG abnormality in all models. Sarcopenia and low muscle strength increased 28% and 62% risk of any ECG abnormality in the full models [sarcopenia: 1.28(1.01–1.63), low muscle strength: 1.62(1.30–2.03)], respectively.

Conclusions: This study showed that sarcopenia and its components are associated with ECG abnormalities in Iranian older people. Although some older adults have higher cardiovascular risk factors, these data showed that further factors such as sarcopenia may be identified as a particular risk factor for future cardiovascular events. Therefore, sarcopenia could be added to the screening of the older population to reduce the risk of cardiovascular events.
Tapering of Biological Agents in Juvenile ERA Patients in Daily Clinical Practice
Authors: Liao Chun-Hua , Chiang Bor-Luen , Yang Yao-Hsu
Published: May 2021

Objectives: We aim to evaluate the proportion and characteristics of enthesitis-related arthritis (ERA) patients in whom medications can be withdrawn in daily practice and to analyze the factors associated with flare-ups during medication tapering of these patients.

Methods: We retrospectively reviewed records of patients under 16 years old diagnosed with ERA from April 2001 to March 2020 in one tertiary medical center in Taiwan. Patients were categorized by different medication uses: conventional disease modifying anti-rheumatic drugs (cDMARDs) only and cDMARDs plus biologics. Demographics, laboratory data, presence of uveitis, and medication withdrawal rate were analyzed. Subgroup analysis was performed in the patients with cDMARDs plus biologics to identify factors associated with flare-ups during medication tapering of these patients. Statistical analysis was performed using R (v3.6.0).

Results: There were 75 juvenile ERA patients with a median onset age of 10.28 years old. Nineteen (25.3%) patients used cDMARDs for disease control; 56 (74.7%) patients depended on cDMARDs plus biologics. Poly-articular involvement was noted in 29 (38.7%) patients, and it occurred more frequently in the cDMARDs plus biologics subgroup (cDMARDs only, 5.3%; cDMARDs plus biologics, 53.6%; P = 0.0001). ANA positivity was observed in 18 (24.0%) patients, and it occurred more frequently in the cDMARDs plus biologics subgroup (cDMARDs, 0%; cDMARDs plus biologics, 32.1%; P = 0.0038). The overall medication withdrawal rate was 34.7%, and it occurred more frequently in patients with cDMARDs only (cDMARDs only, 84.2%; cDMARDs plus biologics, 17.9%; P < 0.001). In the subgroup analysis of patients with cDMARDs plus biologics, patients on biologics tapering with flare-up had a significantly longer time interval between disease onset and initiation of cDMARDs (biologics tapering without flare-up: 0.27 (0.11–0.73) years; biologics tapering with flare-up: 1.14 (0.39–2.02) years; ever withdrawing biologics: 0.26 (0.18–0.42) years, P = 0.0104).

Conclusion: Juvenile ERA patients with polyarticular involvement had a higher risk of developing cDMARDs refractory and progressing to biologics use. Patients with a long time interval between disease onset and initiation of cDMARDs were prone to experience flare-up during tapering of biologics.
Development of a Core Outcome Set for the Benefits and Adverse Events of Acute Heart Failure in Clinical Trials of Traditional Chinese Medicine and Western Medicine: A Study Protocol
Authors: Qiu Ruijin , Han Songjie , Wei Xuxu , Zhong Changming , Li Min , Hu Jiayuan , Wang Pengqian , Zhao Chen , Chen Jing , Shang Hongcai
Published: May 2021

Aims: To identify a minimum set of efficacy and adverse events for patients with acute heart failure (AHF) among different stakeholders in clinical trials of traditional Chinese medicine and Western medicine.

Methods and Analysis: First, we will develop a preliminary long list of outcomes that includes efficacy and adverse events/reactions via three steps: (i) systematic reviews of efficacy and safety outcomes for clinical trials of AHF; (ii) drugs included in the National Medical Insurance Catalog, the National Essential Medicines Catalog, and the WHO Essential Medicines List will be collected and safety outcomes extracted from the package inserts; and (iii) patients' or caregivers' semi-structured interviews will be carried out to add new viewpoints to the list. Second, after merging outcomes and grouping them under different outcome domains, questionnaires for health professionals and patients will be separately developed. Further, two rounds of Delphi survey for health professionals and a survey for patients and the public will be carried out. Third, different stakeholders will discuss and determine the final core outcome set (COS) for AHF in a consensus meeting.

Ethics and Dissemination: The entire project has been approved by the Ethics Committee of the main institution. After the final COS is developed, it will be published and discussed widely in conferences.

Clinical Trial Registration: This study is registered with the Core Outcome Measures in Effectiveness Trials database as study 1566 (available at: https://www.cometinitiative.org/Studies/Details/1566).
Experimental Evolution in Plant-Microbe Systems: A Tool for Deciphering the Functioning and Evolution of Plant-Associated Microbial Communities
Authors: Manriquez Beatriz , Muller Daniel , Prigent-Combaret Claire
Published: May 2021

In natural environments, microbial communities must constantly adapt to stressful environmental conditions. The genetic and phenotypic mechanisms underlying the adaptive response of microbial communities to new (and often complex) environments can be tackled with a combination of experimental evolution and next generation sequencing. This combination allows to analyse the real-time evolution of microbial populations in response to imposed environmental factors or during the interaction with a host, by screening for phenotypic and genotypic changes over a multitude of identical experimental cycles. Experimental evolution (EE) coupled with comparative genomics has indeed facilitated the monitoring of bacterial genetic evolution and the understanding of adaptive evolution processes. Basically, EE studies had long been done on single strains, allowing to reveal the dynamics and genetic targets of natural selection and to uncover the correlation between genetic and phenotypic adaptive changes. However, species are always evolving in relation with other species and have to adapt not only to the environment itself but also to the biotic environment dynamically shaped by the other species. Nowadays, there is a growing interest to apply EE on microbial communities evolving under natural environments. In this paper, we provide a non-exhaustive review of microbial EE studies done with systems of increasing complexity (from single species, to synthetic communities and natural communities) and with a particular focus on studies between plants and plant-associated microorganisms. We highlight some of the mechanisms controlling the functioning of microbial species and their adaptive responses to environment changes and emphasize the importance of considering bacterial communities and complex environments in EE studies.
Silver(I) and Copper(II) Complexes of 1,10-Phenanthroline-5,6-Dione Against Phialophora verrucosa: A Focus on the Interaction With Human Macrophages and Galleria mellonella Larvae
Authors: Granato Marcela Q. , Mello Thaís P. , Nascimento Renata S. , Pereira Marcos D. , Rosa Thabatta L. S. A. , Pessolani Maria C. V. , McCann Malachy , Devereux Michael , Branquinha Marta H. , Santos André L. S. , Kneipp Lucimar F.
Published: May 2021

Phialophora verrucosa is a dematiaceous fungus that causes mainly chromoblastomycosis, but also disseminated infections such as phaeohyphomycosis and mycetoma. These diseases are extremely hard to treat and often refractory to current antifungal therapies. In this work, we have evaluated the effect of 1,10-phenanthroline-5,6-dione (phendione) and its metal-based complexes, [Ag (phendione)2]ClO4 and [Cu(phendione)3](ClO4)2.4H2O, against P. verrucosa, focusing on (i) conidial viability when combined with amphotericin B (AmB); (ii) biofilm formation and disarticulation events; (iii) in vitro interaction with human macrophages; and (iv) in vivo infection of Galleria mellonella larvae. The combination of AmB with each of the test compounds promoted the additive inhibition of P. verrucosa growth, as judged by the checkerboard assay. During the biofilm formation process over polystyrene surface, sub-minimum inhibitory concentrations (MIC) of phendione and its silver(I) and copper(II) complexes were able to reduce biomass and extracellular matrix production. Moreover, a mature biofilm treated with high concentrations of the test compounds diminished biofilm viability in a concentration-dependent manner. Pre-treatment of conidial cells with the test compounds did not alter the percentage of infected THP-1 macrophages; however, [Ag(phendione)2]ClO4 caused a significant reduction in the number of intracellular fungal cells compared to the untreated system. In addition, the killing process was significantly enhanced by post-treatment of infected macrophages with the test compounds. P. verrucosa induced a typically cell density-dependent effect on G. mellonella larvae death after 7 days of infection. Interestingly, exposure to the silver(I) complex protected the larvae from P. verrucosa infection. Collectively, the results corroborate the promising therapeutic potential of phendione-based drugs against fungal infections, including those caused by P. verrucosa.
Reappraisal of Immotthia in Dictyosporiaceae, Pleosporales: Introducing Immotthia bambusae sp. nov. and Pseudocyclothyriella clematidis comb. et gen. nov. Based on Morphology and Phylogeny
Authors: Jiang Hong-Bo , Jeewon Rajesh , Karunarathna Samantha C. , Phukhamsakda Chayanard , Doilom Mingkwan , Kakumyan Pattana , Suwannarach Nakarin , Phookamsak Rungtiwa , Lumyong Saisamorn
Published: May 2021

Immotthia is a poorly known genus, and currently, no DNA sequence data are available to ascertain its proper phylogenetic placement and evolutionary relationships with other bitunicate fungi. To date, there are only two species accepted in the genus. During our ongoing research study of bambusicolous fungi in southwest China and Thailand, a fungus associated with stromata of Hypoxylon sp. was found on dead bamboo culms in Loei Province, Thailand. Preliminary morphological identification revealed that the fungal collection belongs to Immotthia. A novel species, Immotthia bambusae, is introduced herein based on a comparison of morphological characteristics with the type specimen of I. hypoxylon (≡ Amphisphaeria hypoxylon Ellis and Everh.), a synonym of I. atrograna (Cooke and Ellis) M. E. Barr. Phylogenetic analyses of a concatenated ITS, LSU, SSU, and TEF1-α DNA sequence matrix showed that Immotthia belongs to Dictyosporiaceae, Pleosporales. Despite I. bambusae strains constituting a supported subclade, they are nested with the genus Pseudocoleophoma. Pseudocoleophoma clematidis is morphologically different from all other Pseudocoleophoma species, while its conidial characteristics are similar to Cyclothyriella. Multigene phylogenetic analyses showed that P. clematidis formed a clade basal to Immotthia, separated from Pseudocoleophoma with strong statistical support. Therefore, we introduce a monotypic genus, Pseudocyclothyriella Phukhams. and Phookamsak, gen. nov. to accommodate the single species, Pseudocyclothyriella clematidis (Phukhams. and K. D. Hyde) Phukhams. and Phookamsak, comb. nov. Detailed descriptions, color micrographs, and phylogenetic trees to show the placement of the new taxa are provided. In addition, an updated taxonomic treatment of the genera Immotthia and Pseudocyclothyriella is also provided based on the study of the type materials and phylogeny generated from DNA sequence data.
The Dissemination and Molecular Characterization of Clonal Complex 361 (CC361) Methicillin-Resistant Staphylococcus aureus (MRSA) in Kuwait Hospitals
Authors: Sarkhoo Eiman , Udo Edet E. , Boswihi Samar S. , Monecke Stefan , Mueller Elke , Ehricht Ralf
Published: May 2021

Methicillin-resistantStaphylococcus aureus(MRSA) belonging to clonal complex 361 (CC361-MRSA) is rare among patients’ populations globally. However, CC361-MRSA has been isolated with an increasing trend among patients in Kuwait hospitals since 2010. This study investigated the molecular characteristics of CC361-MRSA isolated from patients in Kuwait hospitals in 2016–2018 to understand their genetic relatedness and virulence determinants. Of 5,223 MRSA isolates investigated by DNA microarray, 182 (3.4%) isolates obtained in 2016 (N= 55), 2017 (N= 56), and 2018 (N= 71) were identified as CC361-MRSA. The CC361-MRSA isolates were analyzed further using antibiogram,spatyping and multi locus sequence typing (MLST). Most of the isolates were resistant to fusidic acid (64.8%), kanamycin (43.4%), erythromycin (36.3%), and clindamycin (14.3%) encoded byfusC,aphA3, anderm(B)/erm(C)respectively. Nine isolates (4.9%) were resistant to linezolid mediated bycfr.The isolates belonged to 22spatypes with t3841 (N= 113), t315 (N= 16), t1309 (N= 14), and t3175 (N= 5) constituting 81.3% of thespatypes, four genotypes (strain types), CC361-MRSA-[V/VT + fus] (N= 112), CC361-MRSA-IV, WA MRSA-29 (N= 36), CC361-MRSA-V, WA MRSA-70/110 (N= 33) and CC361-MRSA-[V + fus] variant (N= 1). MLST conducted on 69 representative isolates yielded two sequence types: ST361 (11/69) and ST672 (58/69). All CC361-MRSA isolates were positive forcap8,agr1, and the enterotoxinegcgene cluster (seg, sei, selm, seln, selo, andselu). Thetst1was detected in 19 isolates. The immune evasion cluster (IEC) genes type B (scn,chp, andsak) and type E (scnandsak) were detected in 20 and 152 isolates, respectively. The CC361-MRSA circulating in Kuwait hospitals consisted of two closely related sequence types, ST361 and ST672 with ST672-MRSA [V/VT + fus] as the dominant genotype. The dissemination of these newly emerged clones and the emergence of linezolid resistance limits therapeutic options, as well as present significant challenges for the control of MRSA infections in Kuwait hospitals.
Human Cytomegalovirus Host Interactions: EGFR and Host Cell Signaling Is a Point of Convergence Between Viral Infection and Functional Changes in Infected Cells
Authors: Lee Byeong-Jae , Min Chan-Ki , Hancock Meaghan , Streblow Daniel N. , Caposio Patrizia , Goodrum Felicia D. , Yurochko Andrew D.
Published: May 2021

Viruses have evolved diverse strategies to manipulate cellular signaling pathways in order to promote infection and/or persistence. Human cytomegalovirus (HCMV) possesses a number of unique properties that allow the virus to alter cellular events required for infection of a diverse array of host cell types and long-term persistence. Of specific importance is infection of bone marrow derived and myeloid lineage cells, such as peripheral blood monocytes and CD34+ hematopoietic progenitor cells (HPCs) because of their essential role in dissemination of the virus and for the establishment of latency. Viral induced signaling through the Epidermal Growth Factor Receptor (EGFR) and other receptors such as integrins are key control points for viral-induced cellular changes and productive and latent infection in host organ systems. This review will explore the current understanding of HCMV strategies utilized to hijack cellular signaling pathways, such as EGFR, to promote the wide-spread dissemination and the classic life-long herpesvirus persistence.
Contribution of Different Mechanisms to Ciprofloxacin Resistance in Salmonella spp.
Authors: Chang Man-Xia , Zhang Jin-Fei , Sun Yin-Huan , Li Rong-Sheng , Lin Xiao-Ling , Yang Ling , Webber Mark A. , Jiang Hong-Xia
Published: May 2021

Development of fluoroquinolone resistance can involve several mechanisms that include chromosomal mutations in genes (gyrAB and parCE) encoding the target bacterial topoisomerase enzymes, increased expression of the AcrAB-TolC efflux system, and acquisition of transmissible quinolone-resistance genes. In this study, 176 Salmonella isolates from animals with a broad range of ciprofloxacin MICs were collected to analyze the contribution of these different mechanisms to different phenotypes. All isolates were classified according to their ciprofloxacin susceptibility pattern into five groups as follows: highly resistant (HR), resistant (R), intermediate (I), reduced susceptibility (RS), and susceptible (S). We found that the ParC T57S substitution was common in strains exhibiting lowest MICs of ciprofloxacin while increased MICs depended on the type of GyrA mutation. The ParC T57S substitution appeared to incur little cost to bacterial fitness on its own. The presence of PMQR genes represented an route for resistance development in the absence of target-site mutations. Switching of the plasmid-mediated quinolone resistance (PMQR) gene location from a plasmid to the chromosome was observed and resulted in decreased ciprofloxacin susceptibility; this also correlated with increased fitness and a stable resistance phenotype. The overexpression of AcrAB-TolC played an important role in isolates with small decreases in susceptibility and expression was upregulated by MarA more often than by RamA. This study increases our understanding of the relative importance of several resistance mechanisms in the development of fluoroquinolone resistance in Salmonella from the food chain.
The New Antibacterial Properties of the Plants: Quo vadis Studies of Anti-virulence Phytochemicals?
Authors: Díaz-Nuñez José Luis , García-Contreras Rodolfo , Castillo-Juárez Israel
Published: May 2021

The recent increase in bacterial resistance to antibiotics has motivated the resurgence of the study of natural antimicrobial products. For centuries, plants have been recognized for their bactericidal properties. However, in the last two decades, it has been reported that several plant derived metabolites at growth subinhibitory concentrations also tend to have anti-virulence properties, since they reduce the expression of factors that cause damage and the establishment of pathogenic bacteria. In this area of study, plants have been positioned as one of the main natural sources of anti-virulence molecules, but only a small portion of the plant species that exist have been investigated. Also, anti-virulence studies have been primarily focused on analyzing the ability of extracts and compounds to inhibit quorum sensing and biofilms formation in vitro. This mini-review discusses the current panorama, the trends in the study of anti-virulence phytochemicals, as well as their potential for the development of antibacterial therapies.
Deep Soil Layers of Drought-Exposed Forests Harbor Poorly Known Bacterial and Fungal Communities
Authors: Frey Beat , Walthert Lorenz , Perez-Mon Carla , Stierli Beat , Köchli Roger , Dharmarajah Alexander , Brunner Ivano
Published: May 2021

Soil microorganisms such as bacteria and fungi play important roles in the biogeochemical cycling of soil nutrients, because they act as decomposers or are mutualistic or antagonistic symbionts, thereby influencing plant growth and health. In the present study, we investigated the vertical distribution of the soil microbiome to a depth of 2 m in Swiss drought-exposed forests of European beech and oaks on calcareous bedrock. We aimed to disentangle the effects of soil depth, tree (beech, oak), and substrate (soil, roots) on microbial abundance, diversity, and community structure. With increasing soil depth, organic carbon, nitrogen, and clay content decreased significantly. Similarly, fine root biomass, microbial biomass (DNA content, fungal abundance), and microbial alpha-diversity decreased and were consequently significantly related to these physicochemical parameters. In contrast, bacterial abundance tended to increase with soil depth, and the bacteria to fungi ratio increased significantly with greater depth. Tree species was only significantly related to the fungal Shannon index but not to the bacterial Shannon index. Microbial community analyses revealed that bacterial and fungal communities varied significantly across the soil layers, more strongly for bacteria than for fungi. Both communities were also significantly affected by tree species and substrate. In deep soil layers, poorly known bacterial taxa fromNitrospirae, Chloroflexi, Rokubacteria, Gemmatimonadetes,Firmicutesand GAL 15 were overrepresented. Furthermore, archaeal phyla such asThaumarchaeotaandEuryarchaeotawere more abundant in subsoils than topsoils. Fungal taxa that were predominantly found in deep soil layers belong to the ectomycorrhizalBoletus luridusandHydnum vesterholtii. Both taxa are reported for the first time in such deep soil layers. Saprotrophic fungal taxa predominantly recorded in deep soil layers were unknown species ofXylaria. Finally, our results show that the microbial community structure found in fine roots was well represented in the bulk soil. Overall, we recorded poorly known bacterial and archaeal phyla, as well as ectomycorrhizal fungi that were not previously known to colonize deep soil layers. Our study contributes to an integrated perspective on the vertical distribution of the soil microbiome at a fine spatial scale in drought-exposed forests.
Identification of a Hypoxia-Related Signature for Predicting Prognosis and the Immune Microenvironment in Bladder Cancer
Authors: Jiang Minxiao , Ren Liangliang , Chen Yuanlei , Wang Huan , Wu Haiyang , Cheng Sheng , Li Gonghui , Yu Shicheng
Published: May 2021

Accumulating evidence indicates that hypoxia is highly associated with bladder cancer genesis, progression, and immune microenvironment. Nevertheless, few studies have identified the role of hypoxia-related genes as a prognostic signature in bladder cancer. This study aimed to establish a hypoxia-related signature with high accuracy for prognosis and immune microenvironment prediction in bladder cancer. We obtained expression profiles and clinical information from Gene Expression Omnibus and The Cancer Genome Atlas. Then the univariate Cox regression, random survival forest algorithm, and multivariate Cox regression analysis were conducted to identify the core genes and four hypoxia-related genes (ANXA2, GALK1, COL5A1, and HS3ST1) were selected to construct the signature. Kaplan-Meier survival analysis demonstrated that patients with a low-risk score had a higher disease-specific survival rate (p < 0.0001). The areas under the curve of the signature were 0.829 at 1 year, 0.869 at 3 years, and 0.848 at 5 years, respectively. Additionally, we found this hypoxia-related signature was highly correlated with tumor immune microenvironment and had the potential to predict the efficacy of immunotherapy. In summary, our study developed a hypoxia-related signature, which had high accuracy for prognosis prediction and the potential to guide the immunotherapy for bladder cancer patients.
Neuroprotective Effects of Danshen Chuanxiongqin Injection Against Ischemic Stroke: Metabolomic Insights by UHPLC-Q-Orbitrap HRMS Analysis
Authors: Zhou Peipei , Zhou Lin , Shi Yingying , Li Zhuolun , Liu Liwei , Zuo Lihua , Zhang Jun , Liang Shuhong , Kang Jian , Du Shuzhang , Yang Jing , Sun Zhi , Zhang Xiaojian
Published: May 2021

The incidence of cerebral ischemic stroke characterized by high mortality is increasing every year. Danshen Chuanxiongqin Injection (DSCXQ), a traditional Chinese medicine (TCM) preparation, is often applied to treat cerebral apoplexy and its related sequelae. However, there is a lack of systematic research on how DSCXQ mediates its protective effects against cerebral ischemia stroke. Metabolomic analysis based on UHPLC-Q-Orbitrap HRMS was employed to explore the potential mechanisms of DSCXQ on ischemic stroke induced by transient middle cerebral artery occlusion (MCAO). Pattern analysis and metabolomic profiling, combined by multivariate analysis disclosed that 55 differential metabolites were identified between Sham group and Model group, involving sphingolipid metabolism, glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, primary bile acid biosynthesis, pantothenate and CoA synthesis and valine, leucine and isoleucine biosynthesis pathways. DSCXQ could reverse brain metabolic deviations in stroke by significantly upregulating the levels of L-tryptophan, Lyso (18:0/0:0), LPC (18:2), Indole-3-methyl acetate, and downregulating the levels of sphinganine 1-phosphate, L-threonic acid, glutaconic acid and N6,N6,N6-Trimethyl-L-lysine. In our study, we focused on the neuroprotective effects of DSCXQ against neuroinflammatory responses and neuronal apoptosis on a stroke model based on sphingolipid metabolism. The expressions of Sphk1, S1PR1, CD62P, Bcl-2, Bax, and cleaved Caspase-3 in brain tissue were evaluated. The neurological deficit, cerebral infarct size and behavioral abnormality were estimated. Results showed that DSCXQ intervention significantly reduced cerebral infarct size, ameliorated behavioral abnormality, inhibited the expression of Sphk1, S1PR1, CD62P, Bax, Cleaved Caspase-3, while increased the level of Bcl-2, and prevented neuronal apoptosis. The limitations are that our study mainly focused on the verification of sphingolipid metabolism pathway in stroke, and while other metabolic pathways left unverified. Our study indicates that SphK1-SIP axis may potentiate neuroinflammatory responses and mediate brain damage through neuronal apoptosis, and DSCXQ could suppress the activity of SphK1-SIP axis to protect brain tissue in cerebral ischemia. In conclusion, this study facilitates our understanding of metabolic changes in ischemia stroke and the underlying mechanisms related to the clinical application of DSCXQ.
Oxaliplatin-Induced Neuropathy: Genetic and Epigenetic Profile to Better Understand How to Ameliorate This Side Effect
Authors: Branca Jacopo Junio Valerio , Carrino Donatello , Gulisano Massimo , Ghelardini Carla , Di Cesare Mannelli Lorenzo , Pacini Alessandra
Published: May 2021

In the most recent decades, oxaliplatin has been used as a chemotherapeutic agent for colorectal cancer and other malignancies as well. Oxaliplatin interferes with tumor growth predominantly exerting its action in DNA synthesis inhibition by the formation of DNA-platinum adducts that, in turn, leads to cancer cell death. On the other hand, unfortunately, this interaction leads to a plethora of systemic side effects, including those affecting the peripheral and central nervous system. Oxaliplatin therapy has been associated with acute and chronic neuropathic pain that induces physicians to reduce the dose of medication or discontinue treatment. Recently, the capability of oxaliplatin to alter the genetic and epigenetic profiles of the nervous cells has been documented, and the understanding of gene expression and transcriptional changes may help to find new putative treatments for neuropathy. The present article is aimed to review the effects of oxaliplatin on genetic and epigenetic mechanisms to better understand how to ameliorate neuropathic pain in order to enhance the anti-cancer potential and improve patients’ quality of life.
Transcriptional and Post-transcriptional Control of the Nitrate Respiration in Bacteria
Authors: Durand Sylvain , Guillier Maude
Published: May 2021

In oxygen (O2) limiting environments, numerous aerobic bacteria have the ability to shift from aerobic to anaerobic respiration to release energy. This process requires alternative electron acceptor to replace O2 such as nitrate (NO3–), which has the next best reduction potential after O2. Depending on the organism, nitrate respiration involves different enzymes to convert NO3– to ammonium (NH4+) or dinitrogen (N2). The expression of these enzymes is tightly controlled by transcription factors (TFs). More recently, bacterial small regulatory RNAs (sRNAs), which are important regulators of the rapid adaptation of microorganisms to extremely diverse environments, have also been shown to control the expression of genes encoding enzymes or TFs related to nitrate respiration. In turn, these TFs control the synthesis of multiple sRNAs. These results suggest that sRNAs play a central role in the control of these metabolic pathways. Here we review the complex interplay between the transcriptional and the post-transcriptional regulators to efficiently control the respiration on nitrate.
The Role of Mitochondrial Dysfunction in Vascular Disease, Tumorigenesis, and Diabetes
Authors: Zhunina Olga A. , Yabbarov Nikita G. , Grechko Andrey V. , Starodubova Antonina V. , Ivanova Ekaterina , Nikiforov Nikita G. , Orekhov Alexander N.
Published: May 2021

Mitochondrial dysfunction is known to be associated with a wide range of human pathologies, such as cancer, metabolic, and cardiovascular diseases. One of the possible ways of mitochondrial involvement in the cellular damage is excessive production of reactive oxygen and nitrogen species (ROS and RNS) that cannot be effectively neutralized by existing antioxidant systems. In mitochondria, ROS and RNS can contribute to protein and mitochondrial DNA (mtDNA) damage causing failure of enzymatic chains and mutations that can impair mitochondrial function. These processes further lead to abnormal cell signaling, premature cell senescence, initiation of inflammation, and apoptosis. Recent studies have identified numerous mtDNA mutations associated with different human pathologies. Some of them result in imbalanced oxidative phosphorylation, while others affect mitochondrial protein synthesis. In this review, we discuss the role of mtDNA mutations in cancer, diabetes, cardiovascular diseases, and atherosclerosis. We provide a list of currently described mtDNA mutations associated with each pathology and discuss the possible future perspective of the research.
Drug Repurposing on G Protein-Coupled Receptors Using a Computational Profiling Approach
Authors: de Felice Alessandra , Aureli Simone , Limongelli Vittorio
Published: May 2021

G protein-coupled receptors (GPCRs) are the largest human membrane receptor family regulating a wide range of cell signaling. For this reason, GPCRs are highly desirable drug targets, with approximately 40% of prescribed medicines targeting a member of this receptor family. The structural homology of GPCRs and the broad spectrum of applications of GPCR-acting drugs suggest an investigation of the cross-activity of a drug toward different GPCR receptors with the aim of rationalizing drug side effects, designing more selective and less toxic compounds, and possibly proposing off-label therapeutic applications. Herein, we present an originalin silicoapproach named “Computational Profiling for GPCRs” (CPG), which is able to represent, in a one-dimensional (1D) string, the physico-chemical properties of a ligand–GPCR binding interaction and, through a tailored alignment algorithm, repurpose the ligand for a different GPCR. We show three case studies where docking calculations and pharmacological data confirm the drug repurposing findings obtained through CPG on 5-hydroxytryptamine receptor 2B, beta-2 adrenergic receptor, and M2 muscarinic acetylcholine receptor. The CPG code is released as a user-friendly graphical user interface with numerous options that make CPG a powerful tool to assist the drug design of GPCR ligands.
Probiotic Supplementation Facilitates Recovery of 6-OHDA-Induced Motor Deficit via Improving Mitochondrial Function and Energy Metabolism
Authors: Nurrahma Bira Arumndari , Tsao Shu-Ping , Wu Chieh-Hsi , Yeh Tu-Hsueh , Hsieh Pei-Shan , Panunggal Binar , Huang Hui-Yu
Published: May 2021

Parkinson’s disease (PD) is a neurodegenerative disease associated with progressive impairment of motor and non-motor functions in aging people. Overwhelming evidence indicate that mitochondrial dysfunction is a central factor in PD pathophysiology, which impairs energy metabolism. While, several other studies have shown probiotic supplementations to improve host energy metabolism, alleviate the disease progression, prevent gut microbiota dysbiosis and alter commensal bacterial metabolites. But, whether probiotic and/or prebiotic supplementation can affect energy metabolism and cause the impediment of PD progression remains poorly characterized. Therefore, we investigated 8-weeks supplementation effects of probiotic [Lactobacillus salivarius subsp. salicinius AP-32 (AP-32)], residual medium (RM) obtained from the AP-32 culture medium, and combination of AP-32 and RM (A-RM) on unilateral 6-hydroxydopamine (6-OHDA)-induced PD rats. We found that AP-32, RM and A-RM supplementation induced neuroprotective effects on dopaminergic neurons along with improved motor functions in PD rats. These effects were accompanied by significant increases in mitochondrial activities in the brain and muscle, antioxidative enzymes level in serum, and altered SCFAs profile in fecal samples. Importantly, the AP-32 supplement restored muscle mass along with improved motor function in PD rats, and produced the best results among the supplements. Our results demonstrate that probiotic AP-32 and A-RM supplementations can recover energy metabolism via increasing SCFAs producing and mitochondria function. This restoring of mitochondrial function in the brain and muscles with improved energy metabolism might additionally be potentiated by ROS suppression by the elevated generation of antioxidants, and which finally leads to facilitated recovery of 6-OHDA-induced motor deficit. Taken together, this work demonstrates that probiotic AP-32 supplementation could be a potential candidate for alternate treatment strategy to avert PD progression.
Homeostatic Depression Shows Heightened Sensitivity to Synaptic Calcium
Authors: Yeates Catherine J. , Frank C. Andrew
Published: May 2021

Synapses and circuits rely on homeostatic forms of regulation in order to transmit meaningful information. The Drosophila melanogaster neuromuscular junction (NMJ) is a well-studied synapse that shows robust homeostatic control of function. Most prior studies of homeostatic plasticity at the NMJ have centered on presynaptic homeostatic potentiation (PHP). PHP happens when postsynaptic muscle neurotransmitter receptors are impaired, triggering retrograde signaling that causes an increase in presynaptic neurotransmitter release. As a result, normal levels of evoked excitation are maintained. The counterpart to PHP at the NMJ is presynaptic homeostatic depression (PHD). Overexpression of the Drosophila vesicular glutamate transporter (VGlut) causes an increase in the amplitude of spontaneous events. PHD happens when the synapse responds to the challenge by decreasing quantal content (QC) during evoked neurotransmission—again, resulting in normal levels of postsynaptic excitation. We hypothesized that there may exist a class of molecules that affects both PHP and PHD. Impairment of any such molecule could hurt a synapse’s ability to respond to any significant homeostatic challenge. We conducted an electrophysiology-based screen for blocks of PHD. We did not observe a block of PHD in the genetic conditions screened, but we found loss-of-function conditions that led to a substantial deficit in evoked amplitude when combined with VGlut overexpression. The conditions causing this phenotype included a double heterozygous loss-of-function condition for genes encoding the inositol trisphosphate receptor (IP3R —itpr) and ryanodine receptor (RyR). IP3Rs and RyRs gate calcium release from intracellular stores. Pharmacological agents targeting IP3R and RyR recapitulated the genetic losses of these factors, as did lowering calcium levels from other sources. Our data are consistent with the idea that the homeostatic signaling process underlying PHD is especially sensitive to levels of calcium at the presynapse.
MELAS/LS Overlap Syndrome Associated With Mitochondrial DNA Mutations: Clinical, Genetic, and Radiological Studies
Authors: Wei Yanping , Huang Yan , Yang Yingmai , Qian Min
Published: May 2021

Introduction: Mitochondrial diseases are characterized by considerable clinical and genetic heterogeneity. Mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS) and Leigh syndrome (LS) are both established mitochondrial syndromes; sometimes they can overlap.

Methods: A retrospective observational cohort study was done to analyze the clinical manifestations, biochemical findings, neuroimaging and genetic data, and disease outcomes of 14 patients with identified MELAS/LS overlap syndrome.

Results: A total of 14 patients, 9 males and 5 females, were enrolled. The median age at onset was 14 years, while the average age was 12.6 years. As for clinical features in concordance with MELAS, the top three most common symptoms were seizures, cognitive impairment, and stroke-like episodes (SLE). Brain atrophy was present in seven patients. As for the clinical hallmarks of LS, the top three most common symptoms were ataxia, spastic paraplegia, and bulbar palsy. Patients presented with individual syndrome or overlap syndromes with similar frequency, and the prognosis did not seem to be related to the initial presentation. Thirteen patients were identified with MTND mutations, among which m.13513G>A mutation in the MT-ND5 gene was the most common. Only one patient with m.8344A>G mutation of MTTK gene was found.

Discussion: Our study demonstrated that MTND genes are important mutation hot spots in MELAS/LS overlap syndrome. The follow-up is very important for the final diagnosis of overlap syndrome.