bluuebunny/crossref_metadata_2025 huggingface dataset:
Groping in the Fog: Soaring Migrants Exhibit Wider Scatter in Flight Directions and Respond Differently to Wind Under Low Visibility Conditions
Authors: Becciu Paolo , Panuccio Michele , Dell’Omo Giacomo , Sapir Nir
Published: October 2021

Atmospheric conditions are known to affect flight propensity, behaviour during flight, and migration route in birds. Yet, the effects of fog have only rarely been studied although they could disrupt orientation and hamper flight. Fog could limit the visibility of migrating birds such that they might not be able to detect landmarks that guide them during their journey. Soaring migrants modulate their flight speed and direction in relation to the wind vector to optimise the cost of transport. Consequently, landmark-based orientation, as well as adjustments of flight speed and direction in relation to wind conditions, could be jeopardised when flying in fog. Using a radar system operated in a migration bottleneck (Strait of Messina, Italy), we studied the behaviour of soaring birds under variable wind and fog conditions over two consecutive springs (2016 and 2017), discovering that migrating birds exhibited a wider scatter of flight directions and responded differently to wind under fog conditions. Birds flying through fog deviated more from the mean migration direction and increased their speed with increasing crosswinds. In addition, airspeed and groundspeed increased in the direction of the crosswind, causing the individuals to drift laterally. Our findings represent the first quantitative empirical evidence of flight behaviour changes when birds migrate through fog and explain why low visibility conditions could risk their migration journey.
Remote Delivery of Motor Function Assessment and Training for Clinical Trials in Neuromuscular Disease: A Response to the COVID-19 Global Pandemic
Authors: James Meredith K. , Rose Kristy , Alfano Lindsay N. , Reash Natalie F. , Eagle Michelle , Lowes Linda P.
Published: October 2021

Clinical outcome assessments of function or strength, assessed by physical therapists, are commonly used as primary endpoints in clinical trials, natural history studies and within clinics for individuals with neuromuscular disorders. These evaluations not only inform the efficacy of investigational agents in clinical trials, but also importantly track disease trajectory to prospectively advise need for equipment, home and work modifications, and other assistive devices. The COVID-19 pandemic had a global impact on the safety and feasibility of in-person visits and assessments, necessitating rapid development of mitigation strategies to ensure ongoing collection of key clinical trial endpoints and access to expert clinical care despite travel restrictions. Physical therapists who are expert in neuromuscular disorders working across clinics, countries, and clinical trials developed initial guidelines and methods for the suitability and feasibility of performing remote evaluations. A number of Sponsors introduced amendments to their study protocols to enable remote evaluations, supported by live video streaming of the assessment to their local clinical evaluators. Similarly, application of these techniques to clinical telemedicine enabled objective evaluations for use in payer discussions, equipment procurement, and general access to expert physical therapy services. Here we report on our methodology for adapting current practices to remote testing and considerations for remote evaluations.
MicroRNA Variants and HLA-miRNA Interactions are Novel Rheumatoid Arthritis Susceptibility Factors
Authors: Guo Shicheng , Jin Yehua , Zhou Jieru , Zhu Qi , Jiang Ting , Bian Yanqin , Zhang Runrun , Chang Cen , Xu Lingxia , Shen Jie , Zheng Xinchun , Shen Yi , Qin Yingying , Chen Jihong , Tang Xiaorong , Cheng Peng , Ding Qin , Zhang Yuanyuan , Liu Jia , Cheng Qingqing , Guo Mengru , Liu Zhaoyi , Qiu Weifang , Qian Yi , Sun Yang , Shen Yu , Nie Hong , Schrodi Steven J. , He Dongyi
Published: October 2021

Genome-wide association studies have identified >100 genetic risk factors for rheumatoid arthritis. However, the reported genetic variants could only explain less than 40% heritability of rheumatoid arthritis. The majority of the heritability is still missing and needs to be identified with more studies with different approaches and populations. In order to identify novel function SNPs to explain missing heritability and reveal novel mechanism pathogenesis of rheumatoid arthritis, 4 HLA SNPs (HLA-DRB1, HLA-DRB9, HLA-DQB1, and TNFAIP3) and 225 common SNPs located in miRNA, which might influence the miRNA target binding or pre-miRNA stability, were genotyped in 1,607 rheumatoid arthritis and 1,580 matched normal individuals. We identified 2 novel SNPs as significantly associated with rheumatoid arthritis including rs1414273 (miR-548ac, OR = 0.84, p = 8.26 × 10−4) and rs2620381 (miR-627, OR = 0.77, p = 2.55 × 10−3). We also identified that rs5997893 (miR-3928) showed significant epistasis effect with rs4947332 (HLA-DRB1, OR = 4.23, p = 0.04) and rs2967897 (miR-5695) with rs7752903 (TNFAIP3, OR = 4.43, p = 0.03). In addition, we found that individuals who carried 8 risk alleles showed 15.38 (95%CI: 4.69–50.49, p < 1.0 × 10−6) times more risk of being affected by RA. Finally, we demonstrated that the targets of the significant miRNAs showed enrichment in immune related genes (p = 2.0 × 10−5) and FDA approved drug target genes (p = 0.014). Overall, 6 novel miRNA SNPs including rs1414273 (miR-548ac, p = 8.26 × 10−4), rs2620381 (miR-627, p = 2.55 × 10−3), rs4285314 (miR-3135b, p = 1.10 × 10−13), rs28477407 (miR-4308, p = 3.44 × 10−5), rs5997893 (miR-3928, p = 5.9 × 10−3) and rs45596840 (miR-4482, p = 6.6 × 10−3) were confirmed to be significantly associated with RA in a Chinese population. Our study suggests that miRNAs might be interesting targets to accelerate understanding of the pathogenesis and drug development for rheumatoid arthritis.
Regional Differences in Various Risk Factors for Postpartum Depression: Applying Mixed Models to the PRAMS Dataset
Authors: Gifford Janace J. , Pluchino Jenna R. , Della Valle Rebecca , Schwarz Jaclyn M.
Published: October 2021

Purpose: The purpose of this study was to assess the association between various risk factors with postpartum depression severity using a large dataset that included variables such as previous mental health status, social factors, societal factors, health care access, and other state-wide or region-specific variables.

Methods: We obtained the most recently available (2016–2017) dataset from the Pregnancy Risk Assessment Monitoring System (PRAMS), which is a dataset compiled by the Centers for Disease Control (CDC) that collects state-specific, population-based data on maternal attitudes and experiences before, during, and shortly after pregnancy from over 73,000 women in 39 states. We utilized a hierarchical linear model to analyze the data across various levels, with a symptom severity scale (0–8) as the dependent variable.

Results: Of the 21 variables included in the final model, nine variables were statistically significant predictors of symptom severity. Statistically significant predictors of increased postpartum depression symptom severity included previous depression diagnosis and depression symptoms during pregnancy, baby not residing with mother, unintentional pregnancy, women with less than a high school degree and more than a college degree, Women Infants Children (WIC) enrollment, and married women. In contrast to these other factors, attendance at a postpartum follow up appointment was associated with significantly increased symptom severity. Age revealed an inverted curve in predicting postpartum symptom severity.

Conclusions: There was no significant difference in symptom severity scores across the 39 participating states. Most notably, postpartum depression symptom severity was associated with previous depression diagnosis and previous symptom severity, but our results also reveal novel social and education factors that contribute to the support and well-being of the mother and child.
The Dynamic Immunological Parameter Landscape in Coronavirus Disease 2019 Patients With Different Outcomes
Authors: Tang Guoxing , Huang Min , Luo Ying , Liu Wei , Lin Qun , Mao Liyan , Wu Shiji , Xiong Zhigang , Hou Hongyan , Sun Ziyong , Wang Feng
Published: October 2021

Objectives

The longitudinal and systematic evaluation of immunity in coronavirus disease 2019 (COVID-19) patients is rarely reported.

Methods

Parameters involved in innate, adaptive, and humoral immunity were continuously monitored in COVID-19 patients from onset of illness until 45 days after symptom onset.

Results

This study enrolled 27 mild, 47 severe, and 46 deceased COVID-19 patients. Generally, deceased patients demonstrated a gradual increase of neutrophils and IL-6 but a decrease of lymphocytes and platelets after the onset of illness. Specifically, sustained low numbers of CD8+T cells, NK cells, and dendritic cells were noted in deceased patients, while these cells gradually restored in mild and severe patients. Furthermore, deceased patients displayed a rapid increase of HLA-DR expression on CD4+T cells in the early phase, but with a low level of overall CD45RO and HLA-DR expressions on CD4+and CD8+T cells, respectively. Notably, in the early phase, deceased patients showed a lower level of plasma cells and antigen-specific IgG, but higher expansion of CD16+CD14+proinflammatory monocytes and HLA-DR−CD14+monocytic-myeloid-derived suppressor cells (M-MDSCs) than mild or severe patients. Among these immunological parameters, M-MDSCs showed the best performance in predicting COVID-19 mortality, when using a cutoff value of ≥10%. Cluster analysis found a typical immunological pattern in deceased patients on day 9 after onset, which was characterized as the increase of inflammatory markers (M-MDSCs, neutrophils, CD16+CD14+monocytes, and IL-6) but a decrease of host immunity markers.

Conclusions

This study systemically characterizes the kinetics of immunity of COVID-19, highlighting the importance of immunity in patient prognosis.
Immunotherapy With 5, 15-DPP Mediates Macrophage M1 Polarization and Modulates Subsequent Mycobacterium tuberculosis Infectivity in rBCG30 Immunized Mice
Authors: Ahmad Faraz , Umar Mohd. Saad , Khan Nazoora , Jamal Fauzia , Gupta Pushpa , Zubair Swaleha , Gupta Umesh Datta , Owais Mohammad
Published: October 2021

Tuberculosis (TB) is a significant and continuing problem worldwide, with a death toll of around 1.5 million human lives annually. BCG, the only vaccine against TB, offers a varied degree of protection among human subjects in different regions and races of the world. The majority of the population living near the tropics carries a varying degree of tolerance against BCG due to the widespread prevalence of non-tuberculous mycobacteria (NTM). Interestingly, ≈90% of the Mycobacterium tuberculosis (Mtb) infected population restrain the bacilli on its own, which strengthens the notion of empowering the host immune system to advance the protective efficacy of existing mycobacterial vaccines. In general, Mtb modulates IL-10/STAT3 signaling to skew host mononuclear phagocytes toward an alternatively activated, anti-inflammatory state that helps it thrive against hostile immune advances. We hypothesized that modulating the IL-10/STAT3 driven anti-inflammatory effects in mononuclear cells may improve the prophylactic ability of TB vaccines. This study investigated the immunotherapeutic ability of a porphyrin based small molecule inhibitor of IL-10/STAT3 axis, 5, 15-diphenyl porphyrin (DPP), in improving anti-TB immunity offered by second generation recombinant BCG30 (rBCG30-ARMF-II®) vaccine in mice. The DPP therapy potentiated vaccine induced anti-TB immunity by down-modulating anti-inflammatory responses, while simultaneously up-regulating pro-inflammatory immune effector responses in the immunized host. The employed DPP based immunotherapy led to the predominant activation/proliferation of pro-inflammatory monocytes/macrophages/DCs, the concerted expansion of CD4+/CD8+ effector and central memory T cells, alongside balanced Th17 and Treg cell amplification, and conferred augmented resistance to aerosol Mtb challenge in rBCG30 immunized BALB/c mice.
Gamma Delta T Cells and Their Involvement in COVID-19 Virus Infections
Authors: von Massow Georg , Oh Steve , Lam Alan , Gustafsson Kenth
Published: October 2021

The global outbreak of the SARS-Cov-2 virus in 2020 has killed millions of people worldwide and forced large parts of the world into lockdowns. While multiple vaccine programs are starting to immunize the global population, there is no direct cure for COVID-19, the disease caused by the SARS-Cov-2 infection. A common symptom in patients is a decrease in T cells, called lymphopenia. It is as of yet unclear what the exact role of T cells are in the immune response to COVID-19. The research so far has mainly focused on the involvement of classical αβ T cells. However, another subset of T cells called γδ T cells could have an important role to play. As part of the innate immune system, γδ T cells respond to inflammation and stressed or infected cells. The γδ T cell subset appears to be particularly affected by lymphopenia in COVID-19 patients and commonly express activation and exhaustion markers. Particularly in children, this subset of T cells seems to be most affected. This is interesting and relevant because γδ T cells are more prominent and active in early life. Their specific involvement in this group of patients could indicate a significant role for γδ T cells in this disease. Furthermore, they seem to be involved in other viral infections and were able to kill SARS infected cellsin vitro. γδ T cells can take up, process and present antigens from microbes and human cells. Ase.g.tumour-associated antigens are presented by MHC on γδ T cells to classical T-cells, we argue here that it stands to reason that also viral antigens, such as SARS-Cov-2-derived peptides, can be presented in the same way. γδ T cells are already used for medical purposes in oncology and have potential in cancer therapy. As γδ T cells are not necessarily able to distinguish between a transformed and a virally infected cell it could therefore be of great interest to investigate further the relationship between COVID-19 and γδ T cells.
HLA-G: An Important Mediator of Maternal-Fetal Immune-Tolerance
Authors: Zhuang Baimei , Shang Jin , Yao Yuanqing
Published: October 2021

Maternal-fetal immune-tolerance occurs throughout the whole gestational trimester, thus a mother can accept a genetically distinct fetus without immunological aggressive behavior. HLA-G, one of the non-classical HLA class I molecules, is restricted-expression at extravillous trophoblast. It can concordantly interact with various kinds of receptors mounted on maternally immune cells residing in the uterus (e.g. CD4+ T cells, CD8+ T cells, natural killer cells, macrophages, and dendritic cells) for maintaining immune homeostasis of the maternal-fetus interface. HLA-G is widely regarded as the pivotal protective factor for successful pregnancies. In the past 20 years, researches associated with HLA-G have been continually published. Indeed, HLA-G plays a mysterious role in the mechanism of maternal-fetal immune-tolerance. It can also be ectopically expressed on tumor cells, infected sites and other pathologic microenvironments to confer a significant local tolerance. Understanding the characteristics of HLA-G in immunologic tolerance is not only beneficial for pathological pregnancy, but also helpful to the therapy of other immune-related diseases, such as organ transplant rejection, tumor migration, and autoimmune disease. In this review, we describe the biological properties of HLA-G, then summarize our understanding of the mechanisms of fetomaternal immunologic tolerance and the difference from transplant tolerance. Furthermore, we will discuss how HLA-G contributes to the tolerogenic microenvironment during pregnancy. Finally, we hope to find some new aspects of HLA-G in fundamental research or clinical application for the future.
Case Report: A Case of Hereditary Gingival Fibromatosis With a High Level of Human β Defensins in Gingival Epithelium
Authors: Gao Ge , Tian Qing , Han Anpeng , Yang Rongxia , Shi Fan , Chen Dong
Published: October 2021

Hereditary gingival fibromatosis [HGF, (MIM 135300)], a rare benign oral condition, has several adverse consequences such as aesthetic changes, malocclusion, speech impediments, and abnormal dentition. However, relatively few studies have addressed the beneficial effects of thick gingival tissues in resisting external stimuli. In this report, we present a unique case of a family affected by HGF that manifests as a ‘healthy’ gingiva. Human β-defensins (hBDs) are known to play a pivotal role in the clearance and killing of various microbes, and contribute to maintaining a healthy oral environment, which is currently emerging research area. However, the expression pattern and localisation of hBDs in patients with HGF have not yet been reported. hBD-2 and hBD-3 in the pedigree we collected had relatively elevated expression. High hBD levels in the gingival tissue of patients from the family may be beneficial in protecting oral tissue from external stimuli and promoting periodontal regeneration, but their role and the mechanisms underlying HGF need to be clarified.
Variability of the Sea Surface Microlayer Across a Filament’s Edge and Potential Influences on Gas Exchange
Authors: Barthelmeß Theresa , Schütte Florian , Engel Anja
Published: October 2021

Major uncertainties in air-sea gas flux parameterizations may arise from a yet unpredictable sea surface microlayer (SML). Its influence on gas exchange is twofold as organic matter, in particular surfactants, on one side and organisms enriched in the SML on the other can alter air-sea gas fluxes. However, spatial heterogeneity of the SML and its potential consequences for gas exchange are not well understood. This study examines the SML’s surfactant pool and the dynamics of microbial enrichment across the sharp hydrological front of a newly upwelled filament off Mauritania. The front was marked by a distinct decrease in temperature and salinity compared to the stratified water column outside the filament. Distinct chemical and microbial SML properties were observed and associated with the filament. Overall, organic matter in the SML was significantly higher concentrated inside the filament and in equivalence to the underlying water. Degradation indices derived from total amino acids (TAA) composition indicated production of fresh organic matter inside and increased degradation outside the filament. Moreover, a shift in the microbial community was observed, for instance Synechococcus spp. prevailed outside the filament. Autotrophic and heterotrophic microorganisms preferably colonized the SML outside the filament. Organic matter enrichment in the SML depended largely on the chemical nature of biomolecules. Total organic carbon (TOC), total nitrogen and total combined carbohydrates were only slightly enriched while glucose, TAA and surfactants were considerably enriched in the SML. Surfactant concentration was positively correlated to TAA, in particular to arginine and glutamic acid, indicating that fresh organic matter components enhanced surface activity. Further, TOC and surfactant concentration correlated significantly (r2 = 0.47, p-value < 0.001). The lower limit of this linear correlation hits approximately the lowest TOC concentration expected within the global surface ocean. This suggests that surfactants are primarily derived from autochthonous production and most refractory components are excluded. Using a previously established relationship between surfactants and CO2 gas exchange (Pereira et al., 2018), we estimated that surfactants suppressed gas exchange by 12% inside the filament. This could be of relevance for freshly upwelled filaments, which are often supersaturated in greenhouse gases.
Feasibility of Using the Hollow Glass Microsphere to Develop Lightweight CAC-GGBFS-Blended Strain-Hardening Cementitious Composites
Authors: Fan Wei , Zhuge Yan , Ma Xing , Chow Christopher W.K. , Gorjian Nima , Liu Yue
Published: October 2021

Strain hardening cementitious composites (SHCCs) with superior tensile strength and ductility have been utilized as an effective repair material. A corrosion-resistant binder, calcium aluminate cement (CAC)–ground granulated blast-furnace slag (GGBFS) blends, has been introduced into SHCC to expand its application in the concrete sewage network rehabilitation. As a repair material, the lightweight property is particularly favorable as it can broaden its functionality. This article presents a study on developing a novel lightweight CAC-GGBFS-blended SHCC using hollow glass microsphere (HGM), namely, HGMLW-SHCCs. The fine silica sand content was substituted with HGM at 25, 50, 75, and 100 vol% in HGMLW-SHCC. We examined flowability, density, uniaxial compressive behavior, direct tensile behavior, and pseudo strain-hardening indices. Microstructure analysis was also conducted to understand the meso-scale behavior of this new lightweight composite. The newly developed HGMLW-SHCC had a 28-day density of only 1756 kg/m3. Compressive and tensile strengths were determined in the range of 62.80–49.39 MPa and 5.81–4.19 MPa, respectively. All mixtures exhibited significant strain-hardening behavior. Even though the increased HGM content negatively affected the tensile strength of HGMLW-SHCC, it had a positive effect on its ductility. In addition, HGM can reduce crack width and tensile stress fluctuations significantly. The results showed that HGM was a promising material for producing strong and lightweight corrosion-resistant SHCCs to be used as a retrofitting material in the wastewater industry.
Human CLA+ Memory T Cell and Cytokines in Psoriasis
Authors: de Jesús-Gil Carmen , Sans-de San Nicolàs Lídia , García-Jiménez Irene , Ferran Marta , Pujol Ramon M. , Santamaria-Babí Luis F.
Published: October 2021

Psoriasis is a common inflammatory skin condition resulting from the interplay between epidermal keratinocytes and immunological cellular components. This sustained inflammation is essentially driven by pro-inflammatory cytokines with the IL-23/IL-17 axis playing a critical central role, as proved by the clinical efficacy of their blockade in patients. Among all the CD45R0+memory T cell subsets, those with special tropism for cutaneous tissues are identified by the expression of the Cutaneous Lymphocyte-associated Antigen (CLA) carbohydrate on their surface, that is induced during T cell maturation particularly in the skin-draining lymph nodes. Because of their ability to recirculate between the skin and blood, circulating CLA+memory T cells reflect the immune abnormalities found in different human cutaneous conditions, such as psoriasis. Based on this premise, studying the effect of different environmental microbial triggers and psoriatic lesional cytokines on CLA+memory T cells, in the presence of autologous epidermal cells from patients, revealed important IL-17 cytokines responses that are likely to enhance the pro-inflammatory loop underlying the development of psoriatic lesions. The goal of this mini-review is to present latest data regarding cytokines implicated in plaque and guttate psoriasis immunopathogenesis from the prism of CLA+memory T cells, that are specifically related to the cutaneous immune system.
Endotoxin Mass Concentration in Plasma Is Associated With Mortality in a Multicentric Cohort of Peritonitis-Induced Shock
Authors: Payen Didier , Dupuis Claire , Deckert Valérie , Pais de Barros Jean-Paul , Rérole Anne-Laure , Lukaszewicz Anne-Claire , Coudroy Remi , Robert René , Lagrost Laurent
Published: October 2021

Objectives: To investigate the association of plasma LPS mass with mortality and inflammation in patients with peritonitis-induced septic shock (SS).

Design: Longitudinal endotoxin and inflammatory parameters in a multicentric cohort of SS.

Patients: Protocolized post-operative parameters of 187 SS patients collected at T1 (12 h max post-surgery) and T4 (24 h after T1).

Intervention:Post-hoc analysis of ABDOMIX trial.

Measurements and Results: Plasma concentration of LPS mass as determined by HPLC-MS/MS analysis of 3-hydroxymyristate, activity of phospholipid transfer protein (PLTP), lipids, lipoproteins, IL-6, and IL-10. Cohort was divided in low (LLPS) and high (HLPS) LPS levels. The predictive value for mortality was tested by multivariate analysis. HLPS and LLPS had similar SAPSII (58 [48.5; 67]) and SOFA (8 [6.5; 9]), but HLPS showed higher death and LPS to PLTP ratio (p < 0.01). LPS was stable in HLPS, but it increased in LLPS with a greater decrease in IL-6 (p < 0.01). Dead patients had a higher T1 LPS (p = 0.02), IL-6 (<0.01), IL-10 (=0.01), and day 3 SOFA score (p = 0.01) than survivors. In the group of SAPSII > median, the risk of death in HLPS (38%) was higher than in LLPS (24%; p < 0.01). The 28-day death was associated only with SAPSII (OR 1.06 [1.02; 1.09]) and HLPS (OR 2.47 [1; 6.11]) in the multivariate model. In HLPS group, high PLTP was associated with lower plasma levels of IL-6 (p = 0.02) and IL-10 (p = 0.05).

Conclusions: Combination of high LPS mass concentration and high SAPS II is associated with elevated mortality in peritonitis-induced SS patients.
Sargassum Differentially Shapes the Microbiota Composition and Diversity at Coastal Tide Sites and Inland Storage Sites on Caribbean Islands
Authors: Hervé Vincent , Lambourdière Josie , René-Trouillefou Malika , Devault Damien Alain , Lopez Pascal Jean
Published: October 2021

Rafts of drifting pelagicSargassumthat are circulating across the Atlantic Ocean are complex ecosystems composed of a large number of associated species. Upon massive stranding, they lead to various socio-environmental issues including the inflow of contaminants and human health concerns. In this study, we used metabarcoding approaches to examine the differences in both the eukaryotic- and prokaryotic-associated communities fromSargassumpresent in two islands of the Lesser Antilles, namely Guadeloupe and Martinique. We detected significant differences in microbial community structure and composition between landingSargassum, the surrounding seawater, andSargassumfrom inland storage sites. In total we identified 22,214 prokaryotic and 17,679 eukaryotic OTUs. Among them, functional prediction analyses revealed a number of prokaryotes that might contribute to organic matter decomposition, nitrogen cycling and gas production, including sulfate-reducing bacteria at coastal landing sites, and methanogenic archaea at inland storage sites. We also found that Metazoan was the most abundant group inSargassumsamples, with nematode clades that presented exclusive or specific richness and abundance patterns depending on theirSargassumsubstrate. Together, these molecular inventories of the micro- and meiofauna communities provide baseline information for further characterization of trophic interactions, algal organic matter decomposition and nutrient transfers at coastal and inland storage sites.
Comparison of Physicochemical Changes and Water Migration of Acinetobacter johnsonii, Shewanella putrefaciens, and Cocultures From Spoiled Bigeye Tuna (Thunnus obesus) During Cold Storage
Authors: Wang Xin-Yun , Xie Jing
Published: October 2021

This study investigates the physicochemical changes and water migration of Acinetobacter johnsonii (A), Shewanella putrefaciens (S), and cocultured A. johnsonii and S. putrefaciens (AS) inoculated into bigeye tuna during cold storage. The physicochemical indexes [fluorescence ratio (FR), total volatile base nitrogen (TVB-N), thiobarbituric acid (TBA), trimethylamine (TMA), peroxide value (POV), and pH] of bigeye tuna increased cold storage. A significant decrease in trapped water was found in the AS samples, and direct monitoring of the water dynamics was provided by low-field nuclear magnetic resonance. Samples inoculated with A. johnsonii and S. putrefaciens also induced the degradation of myofibrillar proteins and weakness of some Z-lines and M-lines. Higher values of physicochemical indexes and water dynamics were shown in the coculture of S. putrefaciens and A. johnsonii than in the other groups. Therefore, this paper reveals that the coculture of A. johnsonii and S. putrefaciens resulted in a bigeye tuna that was more easily spoiled when compared to the single culture. This study provides insight into the spoilage potential of A. johnsonii and S. putrefaciens during cold storage, which further assists in the application of appropriate technologies to keep the freshness of aquatic foods.
Structural and Functional Insights Into Skl and Pal Endolysins, Two Cysteine-Amidases With Anti-pneumococcal Activity. Dithiothreitol (DTT) Effect on Lytic Activity
Authors: Gallego-Páramo Cristina , Hernández-Ortiz Noelia , Buey Rubén M. , Rico-Lastres Palma , García Guadalupe , Díaz J. Fernando , García Pedro , Menéndez Margarita
Published: October 2021

We have structurally and functionally characterized Skl and Pal endolysins, the latter being the first endolysin shown to kill effectively Streptococcus pneumoniae, a leading cause of deathly diseases. We have proved that Skl and Pal are cysteine-amidases whose catalytic domains, from CHAP and Amidase_5 families, respectively, share an α3β6-fold with papain-like topology. Catalytic triads are identified (for the first time in Amidase_5 family), and residues relevant for substrate binding and catalysis inferred from in silico models, including a calcium-binding site accounting for Skl dependence on this cation for activity. Both endolysins contain a choline-binding domain (CBD) with a β-solenoid fold (homology modeled) and six conserved choline-binding loci whose saturation induced dimerization. Remarkably, Pal and Skl dimers display a common overall architecture, preserved in choline-bound dimers of pneumococcal lysins with other catalytic domains and bond specificities, as disclosed using small angle X-ray scattering (SAXS). Additionally, Skl is proved to be an efficient anti-pneumococcal agent that kills multi-resistant strains and clinical emergent-serotype isolates. Interestingly, Skl and Pal time-courses of pneumococcal lysis were sigmoidal, which might denote a limited access of both endolysins to target bonds at first stages of lysis. Furthermore, their DTT-mediated activation, of relevance for other cysteine-peptidases, cannot be solely ascribed to reversal of catalytic-cysteine oxidation.
Unique Features of Mycobacterium abscessus Biofilms Formed in Synthetic Cystic Fibrosis Medium
Authors: Belardinelli Juan M. , Li Wei , Avanzi Charlotte , Angala Shiva K. , Lian Elena , Wiersma Crystal J. , Palčeková Zuzana , Martin Kevin H. , Angala Bhanupriya , de Moura Vinicius C. N. , Kerns Callan , Jones Victoria , Gonzalez-Juarrero Mercedes , Davidson Rebecca M. , Nick Jerry A. , Borlee Bradley R. , Jackson Mary
Published: October 2021

Characterizing Mycobacterium abscessus complex (MABSC) biofilms under host-relevant conditions is essential to the design of informed therapeutic strategies targeted to this persistent, drug-tolerant, population of extracellular bacilli. Using synthetic cystic fibrosis medium (SCFM) which we previously reported to closely mimic the conditions encountered by MABSC in actual cystic fibrosis (CF) sputum and a new model of biofilm formation, we show that MABSC biofilms formed under these conditions are substantially different from previously reported biofilms grown in standard laboratory media in terms of their composition, gene expression profile and stress response. Extracellular DNA (eDNA), mannose-and glucose-containing glycans and phospholipids, rather than proteins and mycolic acids, were revealed as key extracellular matrix (ECM) constituents holding clusters of bacilli together. None of the environmental cues previously reported to impact biofilm development had any significant effect on SCFM-grown biofilms, most likely reflecting the fact that SCFM is a nutrient-rich environment in which MABSC finds a variety of ways of coping with stresses. Finally, molecular determinants were identified that may represent attractive new targets for the development of adjunct therapeutics targeting MABSC biofilms in persons with CF.
Polymerase Chain Reaction-Assisted Evaluation of the Efficacy of Seed-Treatment Prevention of Sporisorium reilianum Infection in Sorghum Seedlings
Authors: Zhang Zhi , Fan Juan , Feng Mucai , Qiu Hongbo , Hu Anlong
Published: October 2021

Head smut, caused by Sporisorium reilianum [(Kuhn) Langdon and Fullerton], is a major disease of sorghum. Seed treatment is considered to be the most effective way to control the disease; however, the pathogen can infect at the seedling stage and the infected plant will not display symptoms until the reproductive stage is reached. The evaluation of the efficacy of seed treatments is time consuming and is dependent upon visible symptoms. Polymerase chain reaction (PCR) methods have the ability to identify pathogens and diagnose their presence at an early stage of infection. In this study, the S. reilianum-specific primer SR3 was used for PCR detection pathogen. We optimized temperature, humidity, and spore quantity test conditions and were able to achieve >88% infection incidence in sorghum seedlings. Sorghum seeds were soaked in various concentrations of tebuconazole and planted for 7 days in soil containing 0.2% teliospores. The efficacy of tebuconazole against S. reilianum was evaluated by PCR and recorded as disease incidence. Results indicated that the reduction in disease incidence after exposure to 0.15, 0.30, 0.45, 0.60, and 0.75 μg/mL tebuconazole was 6.24, 37.48, 67.74, 81.24, and 93.74%, respectively. Significant differences between the concentrations of tebuconazole were observed. The PCR assay represents a valuable tool for evaluating the efficacy of fungicide seed treatments for the control of S. reilianum in sorghum under laboratory conditions.
Lactobacillus Biofilms Influence Anti-Candida Activity
Authors: Parolin Carola , Croatti Vanessa , Laghi Luca , Giordani Barbara , Tondi Maria Rosaria , De Gregorio Priscilla Romina , Foschi Claudio , Vitali Beatrice
Published: October 2021

Lactobacilli are the dominant members of the healthy human vaginal microbiota and represent the first defense line from pathogen infection, including vulvovaginal candidiasis. Biofilm is the predominant microbial growth form in nature, and the formation of biofilms inside the human body has important implications in health and disease. In particular, the formation of biofilm by members of the human resident microbiota is desirable, as it can improve microbial persistence and influence functionality. In the present study, we investigated the capability of 16 vaginal Lactobacillus strains (belonging to Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus vaginalis, and Lactobacillus plantarum species) to form biofilms, and we correlated their mode of growth to anti-Candida activity. L. plantarum strains were the best biofilm producers, and high variability was registered in the level of biofilm formation among L. crispatus and L. gasseri strains. Culture supernatants derived from Lactobacillus biofilm and planktonic growth were tested toward a panel of Candida clinical isolates (Candida albicans, Candida glabrata, Candida lusitaniae, Candida tropicalis, Candida krusei, and Candida parapsilosis) and their metabolome assessed by 1H-NMR. L. crispatus and L. plantarum strains exhibited the best fungistatic profile, and biofilms enhanced their anti-Candida activity; on the contrary, L. gasseri strains were more effective when grown in a planktonic mode. Biofilm/planktonic mode of growth also affects Lactobacillus metabolism, mainly influencing nitrogen and amino acid pathways, and anti-Candida activity is instead strictly related to carbohydrate metabolism. The present study underlined the strict interdependence between microbial mode of growth, metabolism, and functional properties. Biofilm formation by members of the healthy human microbiota represents a crucial issue in the field of microbial physiology and host–microbiota interactions, beyond supporting the development of new antimycotic strategies based on probiotics grown in adherence.
Innate Immunity Evasion Strategies of Highly Pathogenic Coronaviruses: SARS-CoV, MERS-CoV, and SARS-CoV-2
Authors: Li Jin-Yan , Zhou Zhi-Jian , Wang Qiong , He Qing-Nan , Zhao Ming-Yi , Qiu Ye , Ge Xing-Yi
Published: October 2021

In the past two decades, coronavirus (CoV) has emerged frequently in the population. Three CoVs (SARS-CoV, MERS-CoV, SARS-CoV-2) have been identified as highly pathogenic human coronaviruses (HP-hCoVs). Particularly, the ongoing COVID-19 pandemic caused by SARS-CoV-2 warns that HP-hCoVs present a high risk to human health. Like other viruses, HP-hCoVs interact with their host cells in sophisticated manners for infection and pathogenesis. Here, we reviewed the current knowledge about the interference of HP-hCoVs in multiple cellular processes and their impacts on viral infection. HP-hCoVs employed various strategies to suppress and evade from immune response, including shielding viral RNA from recognition by pattern recognition receptors (PRRs), impairing IFN-I production, blocking the downstream pathways of IFN-I, and other evasion strategies. This summary provides a comprehensive view of the interplay between HP-hCoVs and the host cells, which is helpful to understand the mechanism of viral pathogenesis and develop antiviral therapies.
Rhizosphere Microbiome: The Emerging Barrier in Plant-Pathogen Interactions
Authors: Li Jingtao , Wang Chenyang , Liang Wenxing , Liu Sihui
Published: October 2021

In the ecosystem, microbiome widely exists in soil, animals, and plants. With the rapid development of computational biology, sequencing technology and omics analysis, the important role of soil beneficial microbial community is being revealed. In this review, we mainly summarized the roles of rhizosphere microbiome, revealing its complex and pervasive nature contributing to the largely invisible interaction with plants. The manipulated beneficial microorganisms function as an indirect layer of the plant immune system by acting as a barrier to pathogen invasion or inducing plant systemic resistance. Specifically, plant could change and recruit beneficial microbial communities through root-type-specific metabolic properties, and positively shape their rhizosphere microorganisms in response to pathogen invasion. Meanwhile, plants and beneficial microbes exhibit the abilities to avoid excessive immune responses for their reciprocal symbiosis. Substantial lines of evidence show pathogens might utilize secreting proteins/effectors to overcome the emerging peripheral barrier for their advantage in turn. Overall, beneficial microbial communities in rhizosphere are involved in plant–pathogen interactions, and its power and potential are being explored and explained with the aim to effectively increase plant growth and productivity.
Recent Advances in Lectin-Based Affinity Sorbents for Protein Glycosylation Studies
Authors: Goumenou Anastasia , Delaunay Nathalie , Pichon Valérie
Published: October 2021

Glycosylation is one of the most significant post-translational modifications occurring to proteins, since it affects some of their basic properties, such as their half-life or biological activity. The developments in analytical methodologies has greatly contributed to a more comprehensive understanding of the quantitative and qualitative characteristics of the glycosylation state of proteins. Despite those advances, the difficulty of a full characterization of glycosylation still remains, mainly due to the complexity of the glycoprotein and/or glycopeptide mixture especially when they are present in complex biological samples. For this reason, various techniques that allow a prior selective enrichment of exclusively glycosylated proteins or glycopeptides have been developed in the past and are coupled either on- or off- line with separation and detection methods. One of the most commonly implemented enrichment methods includes the use of lectin proteins immobilized on various solid supports. Lectins are a group of different, naturally occurring proteins that share a common characteristic, which concerns their affinity for specific sugar moieties of glycoproteins. This review presents the different formats and conditions for the use of lectins in affinity chromatography and in solid phase extraction, including their use in dispersive mode, along with the recent progress made on either commercial or home-made lectin-based affinity sorbents, which can lead to a fast and automated glycosylation analysis.
Tubulin and Tubulin Posttranslational Modifications in Alzheimer’s Disease and Vascular Dementia
Authors: Santiago-Mujika Estibaliz , Luthi-Carter Ruth , Giorgini Flaviano , Kalaria Raj N. , Mukaetova-Ladinska Elizabeta B.
Published: October 2021

Alzheimer’s disease (AD) and vascular dementia (VaD) are the two most common forms of dementia in older people. Although these two dementia types differ in their etiology, they share many pathophysiological and morphological features, including neuronal loss, which is associated with the microtubule (MT) destabilization. Stabilization of MTs is achieved in different ways: through interactions with MT binding proteins (MTBP) or by posttranslational modifications (PTMs) of tubulin. Polyglutamylation and tyrosination are two foremost PTMs that regulate the interaction between MTs and MTBPs, and play, therefore, a role in neurodegeneration. In this review, we summarize key information on tubulin PTMs in relation to AD and VaD and address the importance of studying further the tubulin code to reveal sites of potential intervention in development of novel and effective dementia therapy.
Long-Term Use of Metformin Is Associated With Reduced Risk of Cognitive Impairment With Alleviation of Cerebral Small Vessel Disease Burden in Patients With Type 2 Diabetes
Authors: Teng Zhenjie , Feng Jing , Qi Qianqian , Dong Yanhong , Xiao Yining , Xie Xiaohua , Meng Nan , Chen Huifang , Zhang Wenhui , Lv Peiyuan
Published: October 2021

Objective: Type 2 diabetes (T2D) is a risk factor for cognitive impairment and cerebral small vessel disease (CSVD). The relation of metformin use and cognitive impairment or CSVD is not clear. The objective of this study was to investigate the cross-sectional effects of long-term use of metformin on total CSVD burden and cognitive function in patients with T2D.

Methods: A total of 234 participants with T2D from the memory clinic in Hebei General Hospital were enrolled in this retrospective study. Duration of metformin use and dosage were recorded. Along with cerebral magnetic resonance imaging (MRI) examination, Mini-Mental State Examination (MMSE) was also performed to assess their cognitive status. We determined the validated total CSVD score (ranging from 0–4) by combining four markers of CSVD that were visually rated. We used binary logistic regression analysis, ordinal logistic regression analysis and mediation analysis to assess the relation of long-term use of metformin with CSVD burden and cognitive function.

Results: Binary logistic regression analysis showed long-term use of metformin was associated with reducing the risk of cognitive impairment (OR: 0.446; 95% Confidence Interval (CI): 0.249 to 0.800; P = 0.007), after adjustment of potential confounders, such as total CSVD burden score, age, HbA1c, hypertension, history of stroke, homocysteine, body mass index, TG and HDL-C. Ordinal logistic regression analysis suggested that long-term use of metformin was associated with alleviation of total CSVD burden score (OR: 0.583; 95% CI: 0.359 to 0.943; P = 0.027), after adjusting for age, HbA1c, hypertension, history of stroke, homocysteine, body mass index, TG and HDL-C. Mediation analysis showed significant mediation by the presence of severe CSVD burden score for long-term use of metformin in relation to cognitive impairment.

Conclusion: Long-term use of metformin was associated with lower rates of cognitive impairment and lower total CSVD burden score in patients with T2D. A proportion of the relation between long-term use of metformin and cognitive impairment may be attributable to alleviation of CSVD burden.
Reward-Related Decision-Making in Current and Past Disordered Gambling: Implications for Impulsive Choice and Risk Preference in the Maintenance of Gambling Disorder
Authors: Schluter Magdalen G. , Hodgins David C.
Published: October 2021

Impulsive reward-related decision-making (RRDM) is robustly associated with gambling disorder (GD), although its role in the development and perpetuation of GD is still being investigated. This project sought to examine the possible roles of impulsive and risky choice, two aspects of RRDM, in the perpetuation of GD. Additionally, the potential moderating role of comorbid substance misuse was considered. A total of 434 participants with symptoms of current GD and symptoms of concurrent substance use disorder (SUD; n = 105), current GD with past SUD (n = 98), past GD with current SUD (n = 53), or past GD with past substance use disorder (SUD; n = 92), and 96 healthy controls were recruited through MTurk. Participants completed a randomly adjusting delay discounting (a measure of impulsive choice) and probabilistic discounting (a measure of risky choice) task and self-report questionnaires of gambling participation, GD and SUD symptomology, and trait impulsivity. Although control participants showed significantly greater delay discounting compared to individuals with a current or history of GD, no significant group differences emerged between individuals with current GD or a history of GD. Individuals with current GD showed significantly less probabilistic discounting compared to individuals with a history of GD and control participants showed the greatest rates of probabilistic discounting. These effects remained after controlling for lifetime gambling symptom severity and trait impulsivity. Overall, these findings suggest a potential maintaining role of risky choice in gambling disorder, but do not support a maintaining role for impulsive choice.
Direction-Specific Iterative Tuning of Motor Commands With Local Generalization During Randomized Reaching Practice Across Movement Directions
Authors: Parmar Pritesh N. , Patton James L.
Published: October 2021

During motor learning, people often practice reaching in variety of movement directions in a randomized sequence. Such training has been shown to enhance retention and transfer capability of the acquired skill compared to the blocked repetition of the same movement direction. The learning system must accommodate such randomized order either by having a memory for each movement direction, or by being able to generalize what was learned in one movement direction to the controls of nearby directions. While our preliminary study used a comprehensive dataset from visuomotor learning experiments and evaluated the first-order model candidates that considered the memory of error and generalization across movement directions, here we expanded our list of candidate models that considered the higher-order effects and error-dependent learning rates. We also employed cross-validation to select the leading models. We found that the first-order model with a constant learning rate was the best at predicting learning curves. This model revealed an interaction between the learning and forgetting processes using the direction-specific memory of error. As expected, learning effects were observed at the practiced movement direction on a given trial. Forgetting effects (error increasing) were observed at the unpracticed movement directions with learning effects from generalization from the practiced movement direction. Our study provides insights that guide optimal training using the machine-learning algorithms in areas such as sports coaching, neurorehabilitation, and human-machine interactions.