bluuebunny/crossref_metadata_2025 huggingface dataset:
The Host-Pathogen Interactions and Epicellular Lifestyle of Neisseria meningitidis
Authors: Mikucki August , McCluskey Nicolie R. , Kahler Charlene M.
Published: April 2022

Neisseria meningitidisis a gram-negative diplococcus and a transient commensal of the human nasopharynx. It shares and competes for this niche with a number of otherNeisseriaspecies includingN. lactamica, N. cinereaandN. mucosa. Unlike these other members of the genus,N. meningitidismay become invasive, crossing the epithelium of the nasopharynx and entering the bloodstream, where it rapidly proliferates causing a syndrome known as Invasive Meningococcal Disease (IMD). IMD progresses rapidly to cause septic shock and meningitis and is often fatal despite aggressive antibiotic therapy. While many of the ways in which meningococci survive in the host environment have been well studied, recent insights into the interactions betweenN. meningitidisand the epithelial, serum, and endothelial environments have expanded our understanding of how IMD develops. This review seeks to incorporate recent work into the established model of pathogenesis. In particular, we focus on the competition thatN. meningitidisfaces in the nasopharynx from otherNeisseriaspecies, and how the genetic diversity of the meningococcus contributes to the wide range of inflammatory and pathogenic potentials observed among different lineages.
Presence of Phylloquinone in the Intraerythrocytic Stages of Plasmodium falciparum
Authors: Sussmann Rodrigo A. C. , Gabriel Heloisa B. , Ríos Alejandro García , Menchaca Vega Danielle S. , Yamaguchi Lydia F. , Doménech-Carbó Antonio , Cebrián-Torrejón Gerardo , Kimura Emilia A. , Kato Massuo J. , Bofill Verdaguer Ignasi , Crispim Marcell , Katzin Alejandro M.
Published: April 2022

Malaria is one of the most widespread parasitic diseases, especially in Africa, Southeast Asia and South America. One of the greatest problems for control of the disease is the emergence of drug resistance, which leads to a need for the development of new antimalarial compounds. The biosynthesis of isoprenoids has been investigated as part of a strategy to identify new targets to obtain new antimalarial drugs. Several isoprenoid quinones, including menaquinone-4 (MK-4/vitamin K2), α- and γ-tocopherol and ubiquinone (UQ) homologs UQ-8 and UQ-9, were previously detected in in vitro cultures of Plasmodium falciparum in asexual stages. Herein, we described for the first time the presence of phylloquinone (PK/vitamin K1) in P. falciparum and discuss the possible origins of this prenylquinone. While our results in metabolic labeling experiments suggest a biosynthesis of PK prenylation via phytyl pyrophosphate (phytyl-PP) with phytol being phosphorylated, on the other hand, exogenous PK attenuated atovaquone effects on parasitic growth and respiration, showing that this metabolite can be transported from extracellular environment and that the mitochondrial electron transport system (ETS) of P. falciparum is capable to interact with PK. Although the natural role and origin of PK remains elusive, this work highlights the PK importance in plasmodial metabolism and future studies will be important to elucidate in seeking new targets for antimalarial drugs.
Acute Fulminant Myocarditis After ChAdOx1 nCoV-19 Vaccine: A Case Report and Literature Review
Authors: Wu Chia-Tung , Chin Shy-Chyi , Chu Pao-Hsien
Published: April 2022

According to recent literatures, myocarditis is an uncommon side effect of mRNA vaccines against COVID-19. On the other hand, myocarditis after adenovirus based vaccine is rarely reported. Here we report a middle-aged healthy female who had acute fulminant perimyocarditis onset 2 days after the first dose of ChAdOx1 vaccine (AstraZeneca) without any other identified etiology. Detailed clinical presentation, serial ECGs, cardiac MRI, and laboratory data were included in the report. Possible mechanisms of acute myocarditis after adenoviral vaccine was reviewed and discussed. To our knowledge, a few cases of myocarditis after Ad26.COV2.S vaccine were reported, and this is the first case report after ChAdOx1 vaccine.
Anatomy and Topography of Coronary Sinus and Mitral Valve Annulus in Functional Mitral Regurgitation
Authors: Rottländer Dennis , Saal Martin , Ögütcü Alev , Degen Hubertus , Haude Michael
Published: April 2022

Background

We aimed to investigate the anatomical relationship of the coronary sinus (CS) and the mitral valve annulus (MVA) in patients with or without functional mitral regurgitation (FMR) using a multislice CT (MSCT) software to determine (a) the distance and angle of both CS and MVA plane and (b) the mitral annulus geometry.

Methods

A total of 215 patients with MSCT and CS to MVA topography evaluation were enrolled in this retrospective study.

Results

This patient cohort included 145 patients without FMR (67.4%, FMR ≤ 1+) and 70 patients (32.6%) with clinically relevant FMR (FMR ≥ 2+). Distance and angulation of CS to MVA planes were highly variable. In all groups, no significant correlation was documented between the distance or angle of CS to MVA planes and left ventricular ejection fraction, left ventricular end-diastolic diameter, or left atrial volume. A significant increase in total CS length could be found in patients with FMR ≥ 2+ compared to the FMR ≤ 1+ group. MVA diameter, area, and perimeter were significantly increased in FMR ≥ 2+ compared to FMR ≤ 1+. In the FMR ≥ 2+ cohort 61% showed a distance of CS to MVA plane <7.8 mm and 58% revealed an angle of CS to MVA plane <14.2°.

Conclusion

Distance and angulation of CS to MVA topography using an MSCT approach are similar between patients with or without FMR, while CS length, MVA area, MVA perimeter, anterior-posterior diameter, and intercommissural diameter are significantly increased in all FMR subgroups. However, ~60% of FMR ≥ 2+ patients showed favorable CS to MVA topography for indirect mitral annuloplasty.
Geographical Distribution and Driving Meteorological Forces of Facial Expressions of Visitors in Urban Wetland Parks in Eastern China
Authors: Li Hongyan , Wang Xuege , Wei Hongxu , Xia Tingting , Liu Mengnan , Ai Shengshu
Published: April 2022

Interacting with aquatic environments in blue spaces is believed to benefit mental well-being. Relevant understanding is limited to regional pilot studies using self-reported emotions on questionnaires. We assessed emotional response by rating facial expressions on a large geographical scale with the purpose of detecting a relationship to microclimates. A total of 920 facial photographs were collected from Sina Weibo from 20 wetland parks in 14 eastern cities of China during 2020. Daily average air temperature, rainfall, average relative humidity (RH), and wind velocity were also recorded from the days when photographs were posted online. We found that happy expressions were higher in wetlands of eastern cities than in northern and inland cities. Sad expressions varied statistically among wetland locations. Weather records differed between temperate and subtropical climatic zones and were highly varied among cities. Happy and sad scores were driven by the change in average air temperature. Combined multivariable regression and binomial correlation suggested that increasing air temperature would not evoke positive emotions unless higher than 11.5°C, and an air temperature range of 17.5–22.3°C will be optimum to induce the presentation of a smiling face. Air humidity generally imposed a negative effect on expressions of positive emotions. Further verification of our findings is suggested on a larger geographical scale using more powerful big-data to obtain more robust conclusions.
The Link Between Parent–Child Relationship and Learning Engagement Among Adolescents: The Chain Mediating Roles of Learning Motivation and Academic Self-Efficacy
Authors: Shao Yanhong , Kang Shumin
Published: April 2022

Previous studies have indicated that parent–child relationship as well as learning motivation and academic self-efficacy is an influential factor of learning engagement, but the impact mechanism of the relevant factors needs to be explored. The purpose of the current study is to investigate how parent–child relationship is related to learning engagement via the mediating roles of learning motivation and academic self-efficacy. Structural equation modeling (SEM) was adopted for the analysis of 280 participants from China. Results showed that parent–child relationship was directly correlated with adolescents’ learning engagement. Results also showed that parent–child relationship indirectly predicted adolescents’ learning engagement via learning motivation and academic self-efficacy respectively and sequentially. More importantly, it was revealed that the direct effect was much lower than the total indirect effects which include the indirect effect of learning motivation, the indirect effect of academic self-efficacy, and the indirect effect of learning motivation and academic self-efficacy. Among the three indirect effects, the indirect effect of learning motivation and academic self-efficacy was the greatest. Major findings were discussed with implications and limitations in the study.
Fibroblast Growth Factor 21 Levels Exhibit the Association With Renal Outcomes in Subjects With Type 2 Diabetes Mellitus
Authors: Chang Li-Hsin , Chu Chia-Huei , Huang Chin-Chou , Lin Liang-Yu
Published: April 2022

Background

Whether microalbuminuria predicts renal outcomes in patients with type 2 diabetes mellitus (T2DM) is argued. Fibroblast growth factor 21 (FGF-21) levels were elevated by the pathogenic process of diabetic kidney disease. The purpose of the study was to evaluate the associations of FGF-21 and renal outcomes in subjects with T2DM.

Methods

Chinese patients with T2DM were enrolled and then observed prospectively, and FGF-21 levels at baseline were measured. The associations of FGF-21 levels and renal composite events, defined by a drop > 30% of eGFR or worsening category of albuminuria, were evaluated using Cox analysis. The appropriate cut-off value of FGF-21 was mapped by the receiver operating characteristic (ROC) curve.

Results

Among 312 subjects, higher FGF-21 levels were associated with higher risks of renal events in Cox analysis. The area under the curve of FGF-21 levels in the ROC curve was optimal (0.67, p < 0.001), and the cut-off value of 1.40 pg/dl exhibited the best sensitivity (76.2%) and specificity (53.5%). The frequency of renal composite events was higher in subjects with FGF-21 ≥ 1.40 pg/dl than in others (30% vs. 10%, p<0.001 by the log-rank test). The worse renal outcomes predicted by FGF-21 ≥ 1.40 pg/dl were confirmed using the adjustments of Cox sequential models (hazard ratio 2.28, 95% confidence interval 1.23–4.24, p=0.009) and consistent across subjects with different status of baseline characteristics and renal risks.

Conclusion

FGF-21 levels were proportional to the risks of renal events in broad- spectrum Chinese T2DM subjects, making it a potential biomarker to predict the renal outcomes of T2DM.
Neuroendocrine Regulation of Plasma Cortisol Levels During Smoltification and Seawater Acclimation of Atlantic Salmon
Authors: Culbert Brett M. , Regish Amy M. , Hall Daniel J. , McCormick Stephen D. , Bernier Nicholas J.
Published: April 2022

Diadromous fishes undergo dramatic changes in osmoregulatory capacity in preparation for migration between freshwater and seawater. One of the primary hormones involved in coordinating these changes is the glucocorticoid hormone, cortisol. In Atlantic salmon (Salmo salar), cortisol levels increase during the spring smoltification period prior to seawater migration; however, the neuroendocrine factors responsible for regulating the hypothalamic-pituitary-interrenal (HPI) axis and plasma cortisol levels during smoltification remain unclear. Therefore, we evaluated seasonal changes in circulating levels of cortisol and its primary secretagogue—adrenocorticotropic hormone (ACTH)—as well as transcript abundance of the major regulators of HPI axis activity in the preoptic area, hypothalamus, and pituitary between migratory smolts and pre-migratory parr. Smolts exhibited higher plasma cortisol levels compared to parr across all timepoints but circulating ACTH levels were only elevated in May. Transcript abundance of preoptic area corticotropin-releasing factor b1 and arginine vasotocin were ~2-fold higher in smolts compared to parr in February through May. Smolts also had ~7-fold greater hypothalamic transcript abundance of urotensin 1 (uts-1a) compared to parr in May through July. When transferred to seawater during peak smolting in May smolts rapidly upregulated hypothalamic uts-1a transcript levels within 24 h, while parr only transiently upregulated uts-1a 96 h post-transfer. In situ hybridization revealed that uts-1a is highly abundant in the lateral tuberal nucleus (NLT) of the hypothalamus, consistent with a role in regulating the HPI axis. Overall, our results highlight the complex, multifactorial regulation of cortisol and provide novel insight into the neuroendocrine mechanisms controlling osmoregulation in teleosts.
High Follicle-Stimulating Hormone Level Associated With Risk of Rheumatoid Arthritis and Disease Activity
Authors: Zhang Xianhui , Qiao Pengyan , Guo Qianyu , Liang Zixie , Pan Jie , Wu Fengping , Wang Xuexue , Zhang Liyun
Published: April 2022

Background

The prevalence of rheumatoid arthritis (RA) has significant gender and age difference. The peak age of RA is consistent with the age of menopause, which is accompanied by a sharp increase in serum follicle-stimulating hormone (FSH) level. This study aims to identify the FSH levels in female RA patients and the relationship with diseases activity.

Methods

In total, 79 female RA patients and 50 age-matched controls were included in our study. Serum sex hormones levels were measured using chemiluminescence. RA patients were grouped by FSH quartile. Disease activity and inflammatory marks were analyzed among groups.

Results

Lower sex hormones and higher gonadotropin were found in RA patients. Serum FSH level was significantly higher in RA patients than in the age-match controls (57.58 ± 15.94 vs. 43.11 ± 19.46, p=0.025). Even after adjusting for age (OR: 1.071; 95%CI: 1.006-1.139; p = 0.031), luteinizing hormone (LH), estradiol (E), and testosterone (T) OR: 1.066; 95%CI: 1.003-1.133; p = 0.039), the OR were still more than one. RA patients in the higher quartiles had higher ESR, DAS28-ESR and DAS28-CRP (p<0.05) than the lowest quartile. Besides, menopause age was significantly related with onset age in post-menopause RA patients (r = 0.432, p =0.008).

Conclusion

High FSH appears to be a risk factor for RA and is positively associated with their disease activity. Early menopause might be an essential factor of RA.
Toward Marrow Adipocytes: Adipogenic Trajectory of the Bone Marrow Stromal Cell Lineage
Authors: Matsushita Yuki , Ono Wanida , Ono Noriaki
Published: April 2022

Bone marrow contains precursor cells for osteoblasts and adipocytes in the stromal compartment. Bone marrow adipose tissue (BMAT) is an important constituent of the bone marrow that is particularly abundant in adults. BMAT is composed of the proximal “regulated” BMAT containing individual adipocytes interspersed within actively hematopoietic marrow, and the distal “constitutive” BMAT containing large adipocytes in the area of low hematopoiesis. Historically, bone marrow adipocytes were regarded as one of the terminal states of skeletal stem cells, which stand at the pinnacle of the lineage and possess trilineage differentiation potential into osteoblasts, chondrocytes and adipocytes. Recent single-cell RNA-sequencing studies uncover a discrete group of preadipocyte-like cells among bone marrow stromal cells (BMSCs), and recent mouse genetic lineage-tracing studies reveal that these adipocyte precursor cells possess diverse functions in homeostasis and regeneration. These adipogenic subsets of BMSCs are abundant in the central marrow space and can directly convert not only into lipid-laden adipocytes but also into skeletal stem cell-like cells and osteoblasts under regenerative conditions. It remains determined whether there are distinct adipocyte precursor cell types contributing to two types of BMATs. In this short review, we discuss the functions of the recently identified subsets of BMSCs and their trajectory toward marrow adipocytes, which is influenced by multiple modes of cell-autonomous and non-cell autonomous regulations.
Think Fast!: Vervet Monkeys Assess the Risk of Being Displaced by a Dominant Competitor When Making Foraging Decisions
Authors: Arseneau-Robar T. Jean M. , Anderson Karyn A. , Vasey Eric N. , Sicotte Pascale , Teichroeb Julie A.
Published: April 2022

Foraging animals need to quickly assess the costs and benefits of different foraging decisions, including resource quantity, quality, preference, ease of access, dispersion, distance, and predation risk. Social animals also need to take social context into account and adapt foraging strategies that maximize net resource intake and minimize contest competition with conspecifics. We used an experimental approach to investigate how social context impacts wild vervet monkey (Chlorocebus pygerythrus) foraging decisions in a multi-destination pentagon array. We baited four platforms with less-preferred corn and one platform with a larger, preferred resource (half banana) that required handling time. We ran over 1,000 trials and found that when monkeys foraged alone, they usually took the path that minimized travel distance but prioritized the preferred-food platform when in competition. However, the foraging strategy chosen by low-ranking individuals depended on the handling skill of the decision maker (i.e., time it would take them to retrieve the banana), the relative rank of their audience members (i.e., who has priority-of-access to resources), and the distance audience members were from the experiment site (i.e., their travel time). When the risk of being displaced by a dominant competitor was low (because they were far away and/or because the decision-maker was skilled in retrieving the banana), low-ranking individuals chose a route that minimized travel costs. Conversely, when the risk of losing food to a dominant competitor was high, decision-makers rushed for the preferred-food platform at the onset of the trial. When the risk of displacement was moderate because a dominant audience member was at least 50 m away, low-ranking individuals partly prioritized the preferred-food platform but took the time to stop for one platform of corn on the way. This strategy increased the total amount of food obtained during the trial. These findings suggest that lower-ranking individuals, who experienced high contest competition at the foraging experiment, calculated the risk of being displaced by a dominant competitor when making foraging decisions. This experiment demonstrates that vervets go through a complex decision-making process that simultaneously considers the profitability of different foraging decisions and their social context.
Clocks Ticking in the Dark: A Review of Biological Rhythms in Subterranean African Mole-Rats
Authors: Oosthuizen Maria K. , Bennett Nigel C.
Published: April 2022

Biological rhythms are rhythmic fluctuations of biological functions that occur in almost all organisms and on several time scales. These rhythms are generated endogenously and entail the coordination of physiological and behavioural processes to predictable, external environmental rhythms. The light-dark cycle is usually the most prominent environmental cue to which animals synchronise their rhythms. Biological rhythms are believed to provide an adaptive advantage to organisms. In the present review, we will examine the occurrence of circadian and seasonal rhythms in African mole-rats (family Bathyergidae). African mole-rats are strictly subterranean, they very rarely emerge aboveground and therefore, do not have regular access to environmental light. A key adaptation to their specialised habitat is a reduction in the visual system. Mole-rats exhibit both daily and seasonal rhythmicity in a range of behaviours and physiological variables, albeit to different degrees and with large variability. We review previous research on the entire circadian system of African mole-rats and discuss output rhythms in detail. Laboratory experiments imply that light remains the strongestzeitgeberfor entrainment but in the absence of light, animals can entrain to ambient temperature rhythms. Field studies report that rhythmic daily and seasonal behaviour is displayed in their natural habitat. We suggest that ambient temperature and rainfall play an important role in the timing of rhythmic behaviour in mole-rats, and that they likely respond directly to thesezeitgebersin the field rather than exhibit robust endogenous rhythms. In the light of climate change, these subterranean animals are buffered from the direct and immediate effects of changes in temperature and rainfall, partly because they do not have robust circadian rhythms, however, on a longer term they are vulnerable to changes in their food sources and dispersal abilities.
β2-Integrins – Regulatory and Executive Bridges in the Signaling Network Controlling Leukocyte Trafficking and Migration
Authors: Guenther Carla
Published: April 2022

Leukocyte trafficking is an essential process of immunity, occurring as leukocytes travel within the bloodstream and as leukocyte migration within tissues. While it is now established that leukocytes can utilize the mesenchymal migration mode or amoeboid migration mode, differences in the migratory behavior of leukocyte subclasses and how these are realized on a molecular level in each subclass is not fully understood. To outline these differences, first migration modes and their dependence on parameters of the extracellular environments will be explained, as well as the intracellular molecular machinery that powers migration in general. Extracellular parameters are detected by adhesion receptors such as integrins. β2-integrins are surface receptors exclusively expressed on leukocytes and are essential for leukocytes exiting the bloodstream, as well as in mesenchymal migration modes, however, integrins are dispensable for the amoeboid migration mode. Additionally, the balance of different RhoGTPases – which are downstream of surface receptor signaling, including integrins – mediate formation of membrane structures as well as actin dynamics. Individual leukocyte subpopulations have been shown to express distinct RhoGTPase profiles along with their differences in migration behavior, which will be outlined. Emerging aspects of leukocyte migration include signal transduction from integrinsviaactin to the nucleus that regulates DNA status, gene expression profiles and ultimately leukocyte migratory phenotypes, as well as altered leukocyte migration in tumors, which will be touched upon.
Intranasal Lentiviral Vector-Mediated Antibody Delivery Confers Reduction of SARS-CoV-2 Infection in Elderly and Immunocompromised Mice
Authors: Du Yue , Zhang Shengnan , Zhang Zhaoyong , Miah Kamran M. , Wei Peilan , Zhang Lu , Zhu Yuhui , Li Zhengtu , Ye Feng , Gill Deborah R. , Hyde Stephen C. , Wang Yanqun , Zhao Jincun
Published: April 2022

Vaccines for COVID-19 are now a crucial public health need, but the degree of protection provided by conventional vaccinations for individuals with compromised immune systems is unclear. The use of viral vectors to express neutralizing monoclonal antibodies (mAbs) in the lung is an alternative approach that does not wholly depend on individuals having intact immune systems and responses. Here, we identified an anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibody, NC0321, which can efficiently neutralize a range of SARS-CoV-2 variants, including alpha, beta, delta, and eta. Both prophylactic and therapeutic NC0321 treatments effectively protected mice from SARS-CoV-2 infection. Notably, we adopted viral vector-mediated delivery of NC0321 IgG1 as an attractive approach to prevent SARS-CoV-2 infection. The NC0321 IgG1 expression in the proximal airway, expressed by a single direct in-vivo intranasal (I.N.) administration of a self-inactivating and recombinant lentiviral vector (rSIV.F/HN-NC0321), can protect young, elderly, and immunocompromised mice against mouse-adapted SARS-CoV-2 surrogate challenge. Long-term monitoring indicated that rSIV.F/HN-NC0321 mediated robust IgG expression throughout the airway of young and SCID mice, importantly, no statistical difference in the NC0321 expression between young and SCID mice was observed. A single I.N. dose of rSIV.F/HN-NC0321 30 or 180 days prior to SARS-CoV-2 challenge significantly reduced lung SARS-CoV-2 titers in an Ad5-hACE2-transduced mouse model, reconfirming that this vectored immunoprophylaxis strategy could be useful, especially for those individuals who cannot gain effective immunity from existing vaccines, and could potentially prevent clinical sequelae.
STING Is Required in Conventional Dendritic Cells for DNA Vaccine Induction of Type I T Helper Cell- Dependent Antibody Responses
Authors: Ulrich-Lewis Justin Theophilus , Draves Kevin E. , Roe Kelsey , O’Connor Megan A. , Clark Edward A. , Fuller Deborah Heydenburg
Published: April 2022

DNA vaccines elicit antibody, T helper cell responses and CD8+T cell responses. Currently, little is known about the mechanism that DNA vaccines employ to induce adaptive immune responses. Prior studies have demonstrated thatstimulator of interferon genes(STING) and conventional dendritic cells (cDCs) play critical roles in DNA vaccine induced antibody and T cell responses.STINGactivation by double stranded (dsDNA) sensing proteins initiate the production of type I interferon (IFN),but the DC-intrinsic effect ofSTINGsignaling is still unclear. Here, we investigated the role ofSTINGwithin cDCs on DNA vaccine induction of antibody and T cell responses.STINGknockout (STING-/-) and conditional knockout mice that lackSTINGin cDCs (cDC STING cKO), were immunized intramuscularly with a DNA vaccine that expressed influenza A nucleoprotein (pNP). BothSTING-/-andcDC STING cKOmice had significantly lower type I T helper (Th1) type antibody (anti-NP IgG2C) responses and lower frequencies of Th1 associated T cells (NP-specific IFN-γ+CD4+T cells) post-immunization than wild type (WT) andcDC STING littermate controlmice. In contrast, all mice had similar Th2-type NP-specific (IgG1) antibody titers.STING-/-mice developed significantly lower polyfunctional CD8+T cells than WT,cDC STING cKOandcDC STING littermate controlmice. These findings suggest thatSTINGwithin cDCs mediates DNA vaccine induction of type I T helper responses including IFN-γ+CD4+T cells, and Th1-type IgG2Cantibody responses. The induction of CD8+effector cell responses also requireSTING, but not within cDCs. These findings are the first to show thatSTINGis required within cDCs to mediate DNA vaccine induced Th1 immune responses and provide new insight into the mechanism whereby DNA vaccines induce Th1 responses.
Low Level of Serum Immunoglobulin G Is Beneficial to Clinical Cure Obtained With Pegylated Interferon Therapy in Inactive Surface Antigen Carriers
Authors: Li Hong , Lin Xiao , Liu Lili , Qin Ling , Zheng Yanhong , Liu Xiaohui , Wei Xinhuan , Liang Shan , Liu Yali , Zhang Jing , Chen Xinyue , Cao Zhenhuan
Published: April 2022

Purpose

Our recent study showed a high rate of HBsAg clearance in inactive HBsAg carriers (IHCs) treated with pegylated IFN (PEG-IFN). To better understand the immune-mediated component of HBsAg clearance, this study investigated the role of serum immunoglobulin G (IgG) and its subclasses in predicting HBsAg clearance in IHCs with PEG-IFN therapy.

Methods

In this study, IHCs received PEG-IFN for 96 weeks. Subjects who achieved clearance of HBsAg were considered responders (R group), and those in whom HBsAg was not cleared were considered non-responders (NR group). The HBsAg, ALT, and serum lgG subtypes (lgG1, IgG2, IgG3, lgG4) were tested at baseline, and at 12 and 24 weeks of treatment. To evaluate the factors in predicting HBsAg clearance, univariate and multivariate logistic regression analyses were performed. The receiver operator characteristic curves and the area under the receiver operator characteristic curve (AUROC) were used to evaluate prognostic values.

Results

Our results showed that 39 cases obtained HBsAg clearance (group R), while 21 cases did not (group NR). There was no significant difference in age, ALT, and AST levels between the two groups. The serum levels of IgG1, lgG2, lgG3 and lgG4 at baseline, and at 12 and 24 weeks were significantly lower in IHC with HBsAg clearance than in the NR group. Univariate logistic regression analysis showed that serum IgG1, IgG2, IgG3, and IgG4 levels at baseline, and at 12, and 24 weeks were all strong predictors of HBsAg clearance. In all indicators, lgG2 had the highest AUROC at baseline and lgG3 the highest AUROC at week 12. A multifactor logistic analysis was performed with y=33.933-0.001*BaselinelgG1-0.002*BaselinelgG2. The area under the curve was 0.941 with 100% sensitivity and 76.19% specificity.

Conclusion

Together, our findings suggest that serum IgG has a higher predictive value compared to the convention predictors of HBsAg and ALT for HBsAg clearance and thus may be a better clinical predictor of HBsAg clearance in IHCs.
Comorbidities in the UK Primary Sjögren’s Syndrome Registry
Authors: Tarn Jessica , Lendrem Dennis , Barnes Michael , Casement John , Ng Wan-Fai
Published: April 2022

Introduction

Primary Sjögren’s Syndrome (PSS) is a chronic disease characterised by symptoms of oral and ocular dryness, pain, fatigue, anxiety and depression. PSS patients can be subclassified by the pattern of severity of these five key symptoms using the Newcastle Sjögren’s Stratification Tool (NSST). Although PSS is often associated with one or more comorbidities, the relationship between comorbidities, polypharmacy, and PSS symptom burden is unclear. Using data from the UK Primary Sjögren’s Syndrome Registry (UKPSSR) we describe the landscape of polypharmacy and comorbidities in PSS.

Methods

The UKPSSR is research biobank of clinically well-defined PSS patients where clinical, demographic, comorbidities and concomitant medications data are recorded. Patients were subclassified into the four NSST subgroups: Low Symptom Burden (LSB), High Symptom Burden (HSB), Dryness Dominated Fatigue (DDF) and Pain Dominated Fatigue (PDF). Group analyses of comorbid conditions and polypharmacy scores were performed. Comorbidity and Polypharmacy Scores (CPS) were modelled as a function of age, sex, symptom duration, body mass index (BMI), current immunosuppressant and hydroxychloroquine prescriptions and NSST subgroup.

Results

There were marked differences in the number and the nature of comorbidities associated with the NSST subgroups. LSB and DDF patients were characterized by fewer comorbidities and medications. In contrast, HSB and PDF patients were associated with more comorbidities and were more likely to be prescribed multiple medications. Group analysis shows that HSB patients are more closely associated with peripheral vascular disease and infection whereas the PDF patients were associated with cardiovascular disease and gastrointestinal comorbidities. Comorbidity and polypharmacy scores increase with age and BMI regardless of symptom subgroup and symptom duration. In addition, the longer the reported symptom duration the higher the associated comorbidities and polypharmacy scores.

Conclusion

Comorbid conditions are more prevalent in some subgroups of the PSS cohort but increase with age and BMI across the entire cohort. It is unclear from these data whether specific comorbid conditions are a consequence of PSS or represent shared aetiology or pathogenetic susceptibility. Regardless, these findings may have implications for disease management and clinical trial design.
Long Non-Coding RNAs in the Cell Fate Determination of Neoplastic Thymic Epithelial Cells
Authors: Iaiza Alessia , Tito Claudia , Ganci Federica , Sacconi Andrea , Gallo Enzo , Masciarelli Silvia , Fontemaggi Giulia , Fatica Alessandro , Melis Enrico , Petrozza Vincenzo , Venuta Federico , Marino Mirella , Blandino Giovanni , Fazi Francesco
Published: April 2022

Thymic Epithelial Tumors (TETs) arise from epithelial cells of the thymus and are very rare neoplasms comprising Thymoma, Thymic carcinoma, and Thymic Neuroendocrine tumors that still require in-depth molecular characterization. Long non-coding RNAs (lncRNAs) are emerging as relevant gene expression modulators involved in the deregulation of several networks in almost all types of human cancer, including TETs. LncRNAs act at different control levels in the regulation of gene expression, from transcription to translation, and modulate several pathways relevant to cell fate determination under normal and pathological conditions. The activity of lncRNAs is strongly dependent on their expression, localization, and post-transcriptional modifications. Starting from our recently published studies, this review focuses on the involvement of lncRNAs in the acquisition of malignant traits by neoplastic thymic epithelial cells, and describes the possible use of these molecules as targets for the design of novel therapeutic approaches specific for TET. Furthermore, the involvement of lncRNAs in myasthenia gravis (MG)-related thymoma, which is still under investigation, is discussed.
Epigenetic Regulation of Host Defense Peptide Synthesis: Synergy Between Histone Deacetylase Inhibitors and DNA/Histone Methyltransferase Inhibitors
Authors: Whitmore Melanie A. , Li Hong , Lyu Wentao , Khanam Sharmily , Zhang Guolong
Published: April 2022

Host defense peptides (HDPs) are an integral part of the innate immune system acting as the first line of defense. Modulation of HDP synthesis has emerged as a promising host-directed approach to fight against infections. Inhibition of histone deacetylation or DNA methylation is known to enhance HDP gene expression. In this study, we explored a possible synergy in HDP gene induction between histone deacetylase inhibitors (HDACi) and DNA/histone methyltransferase inhibitors (DNMTi/HMTi). Two chicken macrophage cell lines were treated with structurally distinct HDACi, HMTi, or DNMTi individually or in combinations, followed by HDP gene expression analysis. Each epigenetic compound was found to be capable of inducing HDP expression. To our surprise, a combination of HDACi and HMTi or HDACi and DNMTi showed a strong synergy to induce the expressions of most HDP genes. The HDP-inducing synergy between butyrate, an HDACi, and BIX01294, an HMTi, were further verified in chicken peripheral blood mononuclear cells. Furthermore, tight junction proteins such as claudin 1 were also synergistically induced by HDACi and HMTi. Overall, we conclude that HDP genes are regulated by epigenetic modifications. Strategies to increase histone acetylation while reducing DNA or histone methylation exert a synergistic effect on HDP induction and, therefore, have potential for the control and prevention of infectious diseases.
Metabolomic Study on Tridacna maxima Giant Clams Reveals Metabolic Fingerprint of Environmental Pollutants
Authors: Almulhim Fatimah , Rossbach Susann , Emwas Abdul-Hamid , Kharbatia Najeh M. , Jaremko Lukasz , Jaremko Mariusz , Duarte Carlos M.
Published: April 2022

Metabolite profiling of marine invertebrates, such as bivalve mollusks, may not only provide insights into the health state of an individual holobiont, but also the pollution levels of their environment Here, we combined 1H nuclear magnetic responance (NMR) spectroscopy and mass spectrometry (MS)-based metabolomics techniques to investigate the organ-specific metabolomic profiles of Tridacna maxima giant clams. Clams were collected from across-shelf gradient in the Red Sea, from inshore to off-shore. We unequivocally profiled 306 metabolites and observed that the sampling location had minimal effects on metabolite composition. However, we observed significant differences in metabolite profiles among different organs (i.e., gills, mantle organ, and digestive system). Importantly, in addition to endogenous metabolites, we detected the presence of terephthalic acid and isophthalic acid, which likely originate from marine plastic ingestion. Collectively, our study opens opportunities for a deeper understanding of Tridacna maxima physiology through metabolomics, and illustrates the power of invertebrate metabolite profiling for monitoring plastic-related aquatic pollutants.
Symbiotic Dinoflagellates of the Giant Clam, Tridacna squamosa, Express Ammonium Transporter 2 at the Plasma Membrane and Increase Its Expression Levels During Illumination
Authors: Pang Caryn Z. , Boo Mel V. , Ip Yuen K. , Chew Shit F.
Published: April 2022

Giant clams harbor dinoflagellates generally of the three genera (Symbiodinium, Cladocopium, and Durusdinium) of phototrophic Symbiodiniaceae. Coccoid dinoflagellates (alias zooxanthellae) are found mainly inside zooxanthellal tubules located in the colorful outer mantle. The symbionts need to obtain carbon, nitrogen and phosphorus from the host for growth and metabolism. The host can absorb exogenous ammonia through the ctenidium and assimilate it into glutamine. Although the host does not normally excrete ammonia, its hemolymph contains only low concentrations of ammonia, indicating that the symbionts can absorb and recycle the ammonia produced metabolically by the host. In this study, we had obtained from the outer mantle of the giant clam, Tridacna squamosa, three major ammonium transporter 2 (AMT2) sequences, one each for Symbiodinium spp. (Symb-AMT2), Cladocopium spp. (Clad-AMT2), and Durusdinium spp. (Duru-AMT2), which comprised 1341 bp, 1308 bp, and 1296 bp, respectively. The respective deduced amino acid sequences contained 447 (~ 46.5 kDa), 436 (~ 45.5 kDa), and 432 (~ 45.0 kDa) residues. Phenogramic and sequence similarity analyses confirmed that these sequences were derived from dinoflagellates. Zooxanthellae-AMT2 (Zoox-AMT2), which represented comprehensively AMT2 of Symbiodinium spp., Cladocopium spp., and Durusdinium spp. was localized at the dinoflagellates’ plasma membranes, indicating that it could partake in the absorption of ammonia from the luminal fluid of the zooxanthellal tubules. Zoox-AMT2 expression was detected in the outer mantle, inner mantle, foot muscle, hepatopancreas and ctenidium of T. squamosa, indicating that the coccoid dinoflagellates residing in all five organs had the potential of ammonia absorption. The outer mantle had the highest transcript level of Zoox-AMT2, and illumination upregulated the protein abundance of Zoox-AMT2 therein. Therefore, it can be deduced that the coccoid dinoflagellates residing in the outer mantle could augment the potential of ammonia absorption in alignment with photosynthesis as the assimilation of ammonia required an increased supply of carbon chains.
Genome-Wide SNP Markers Based on SLAF-Seq Uncover Genetic Diversity of Saccharina Cultivars in Shandong, China
Authors: Wang Xiangyu , Wang Wenjun , Zhan Dongmei , Ge Shanshan , Tang Liuqing
Published: April 2022

China has an abundance of Saccharina cultivars. Most of them are in Shandong Province. These cultivars have been used for many years, and their genetic structure is likely to change. In this study, 13 Saccharina cultivars that are widely applicated in China were collected from Rongcheng and Changdao and sequenced using SLAF-seq technology. A total of 277.27M reads were obtained with a 12.98× sequencing depth, a mean 87.84% Q30 ratio, and a mean 48.49% GC content. A subset of >300,000 SNPs associated with minor allele frequency (MAF) > 0.05 and integrity > 0.5 was obtained. A phylogenetic tree and a population structure analysis based on the high-confidence SNP data showed that the 13 Saccharina cultivars could be divided into 2 groups. The average nucleic acid diversity (Pi), heterozygosity (Ho), and expected heterozygosity (He) of SNP markers in the populations were 4.38×10-5, 0.249, and 0.265, respectively. The average inbreeding coefficient is 0.198, which is high. The results could provide scientific basis for heterosis in Saccharina breeding and germplasm utilization.
Hypothermal Effects on Energy Supply for Ionocytes in Gills of Freshwater- and Seawater-Acclimated Milkfish, Chanos chanos
Authors: Chang Chia-Hao , Liu Chia-Jui , Lu Wei-Jie , Wu Li-Yang , Lai Kuang-Jie , Lin Yu-Ting , Lee Tsung-Han
Published: April 2022

The milkfish, Chanos chanos, is an important aquaculture species that can be cultured in freshwater (FW) and seawater (SW) ponds because of its high euryhalinity. In winter, cold snap leading to high mortality of this tropical species is a critical issue for the aquaculture industry in Taiwan. Under hypothermal stress, however, changes in energy supply for osmoregulation of this euryhaline species is intriguing. In this study, we used an antibody against glycogen phosphorylase (GP) to identify glycogen-rich (GR) cells distributed adjacent to the mitochondria-rich (MR) ionocytes in milkfish gills. Glucose transporter 1 (GLUT1), which plays a major role in energy supply, was also identified and localized in GR cells. Moreover, the expression of indicators of aerobic metabolism and energy production, citrate synthase (CS) and cytochrome c oxidase (COX), were analyzed in gills of FW- and SW-acclimated milkfish to reveal different strategies of energy utilization under hypothermal stress. When exposed to a low-temperature environment, SW individuals used branchial glycogen and lactate to match the energy demands of aerobic metabolism in ionocytes, and elevated aerobic capacity to support and maintain normal functions in gills. However, branchial glycogen mainly localized in the GR cells of FW milkfish was not utilized under hypothermal stress. Meanwhile, a similar level of branchial COX activity and COXIV protein abundance at low temperatures between FW and SW milkfish indicated similar energy requirements in gills. This suggested that another source, but not branchial glycogen, maintained the energy demand in FW milkfish. The present study illustrated differential energy supply strategies in gills between SW- and FW-acclimated milkfish for osmoregulation under low temperatures.
The Role of the Superior Cervical Sympathetic Ganglion in Ischemia Reperfusion-Induced Acute Kidney Injury in Rats
Authors: Zhang Wencui , Li Zhen , Li Zhixiao , Sun Tianning , He Zhigang , Manyande Anne , Xu Weiguo , Xiang Hongbing
Published: April 2022

Acute kidney injury (AKI) has been found to be a serious clinical problem with high morbidity and mortality, and is associated with acute inflammatory response and sympathetic activation that subsequently play an important role in the development of AKI. It is well known that the sympathetic nervous system (SNS) and immune system intensely interact and mutually control each other in order to maintain homeostasis in response to stress or injury. Evidence has shown that the superior cervical sympathetic ganglion (SCG) participates in the bidirectional network between the immune and the SNS, and that the superior cervical ganglionectomy has protective effect on myocardial infarction, however, the role of the SCG in the setting of renal ischemic reperfusion injury has not been studied. Here, we sought to determine whether or not the SCG modulates renal ischemic reperfusion (IR) injury in rats. Our results showed that bilateral superior cervical ganglionectomy (SCGx) 14 days before IR injury markedly reduced the norepinephrine (NE) in plasma, and down-regulated the increased expression of tyrosine hydroxylase (TH) in the kidney and hypothalamus. Sympathetic denervation by SCGx in the AKI group increased the level of blood urea nitrogen (BUN) and kidney injury molecule-1 (KIM-1), and exacerbated renal pathological damage. Sympathetic denervation by SCGx in the AKI group enhanced the expression of pro-inflammatory cytokines in plasma, kidney and hypothalamus, and increased levels of Bax in denervated rats with IR injury. In addition, the levels of purinergic receptors, P2X3R and P2X7R, in the spinal cord were up-regulated in the denervated rats of the IR group. In conclusion, these results demonstrate that the sympathetic denervation by SCGx aggravated IR-induced AKI in rats via enhancing the inflammatory response, thus, the activated purinergic signaling in the spinal cord might be the potential mechanism in the aggravated renal injury.
Community Assembly and Stability in the Root Microbiota During Early Plant Development
Authors: Aleklett Kristin , Rosa Daniel , Pickles Brian John , Hart Miranda M.
Published: April 2022

Little is known about how community composition in the plant microbiome is affected by events in the life of a plant. For example, when the plant is exposed to soil, microbial communities may be an important factor in root community assembly. We conducted two experiments asking whether the composition of the root microbiota in mature plants could be determined by either the timing of root exposure to microbial communities or priority effects by early colonizing microbes. Timing of microbial exposure was manipulated through an inoculation experiment, where plants of different ages were exposed to a common soil inoculum. Priority effects were manipulated by challenging roots with established microbiota with an exogenous microbial community. Results show that even plants with existing microbial root communities were able to acquire new microbial associates, but that timing of soil exposure affected root microbiota composition for both bacterial and fungal communities in mature plants. Plants already colonized were only receptive to colonizers at 1 week post-germination. Our study shows that the timing of soil exposure in the early life stages of a plant is important for the development of the root microbiota in mature plants.
Amyloid and Tau Positron Emission Tomography Imaging in Alzheimer’s Disease and Other Tauopathies
Authors: Maschio Cinzia , Ni Ruiqing
Published: April 2022

The detection and staging of Alzheimer’s disease (AD) using non-invasive imaging biomarkers is of substantial clinical importance. Positron emission tomography (PET) provides readouts to uncover molecular alterations in the brains of AD patients with high sensitivity and specificity. A variety of amyloid-β (Aβ) and tau PET tracers are already available for the clinical diagnosis of AD, but there is still a lack of imaging biomarkers with high affinity and selectivity for tau inclusions in primary tauopathies, such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and Pick’s disease (PiD). This review aims to provide an overview of the existing Aβ and tau PET imaging biomarkers and their binding properties from in silico, in vitro, and in vivo assessment. Imaging biomarkers for pathologic proteins are vital for clinical diagnosis, disease staging and monitoring of the potential therapeutic approaches of AD. Off-target binding of radiolabeled tracers to white matter or other neural structures is one confounding factor when interpreting images. To improve binding properties such as binding affinity and to eliminate off-target binding, second generation of tau PET tracers have been developed. To conclude, we further provide an outlook for imaging tauopathies and other pathological features of AD and primary tauopathies.