bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency
Authors: Durin Zoé , Houdou Marine , Morelle Willy , Barré Lydia , Layotte Aurore , Legrand Dominique , Ouzzine Mohamed , Foulquier François
Published: May 2022

Glycosylation is a ubiquitous and universal cellular process in all domains of life. In eukaryotes, many glycosylation pathways occur simultaneously onto proteins and lipids for generating a complex diversity of glycan structures. In humans, severe genetic diseases called Congenital Disorders of Glycosylation (CDG), resulting from glycosylation defects, demonstrate the functional relevance of these processes. No real cure exists so far, but oral administration of specific monosaccharides to bypass the metabolic defects has been used in few CDG, then constituting the simplest and safest treatments. Oral D-Galactose (Gal) therapy was seen as a promising tailored treatment for specific CDG and peculiarly for TMEM165-CDG patients. TMEM165 deficiency not only affects the N-glycosylation process but all the other Golgi-related glycosylation types, then contributing to the singularity of this defect. Our previous results established a link between TMEM165 deficiency and altered Golgi manganese (Mn2+) homeostasis. Besides the fascinating power of MnCl2 supplementation to rescue N-glycosylation in TMEM165-deficient cells, D-Gal supplementation has also been shown to be promising in suppressing the observed N-glycosylation defects. Its effect on the other Golgi glycosylation types, most especially O-glycosylation and glycosaminoglycan (GAG) synthesis, was however unknown. In the present study, we demonstrate the differential impact of D-Gal or MnCl2 supplementation effects on the Golgi glycosylation defects caused by TMEM165 deficiency. Whereas MnCl2 supplementation unambiguously fully rescues the N- and O-linked as well as GAG glycosylations in TMEM165-deficient cells, D-Gal supplementation only rescues the N-linked glycosylation, without any effects on the other Golgi-related glycosylation types. According to these results, we would recommend the use of MnCl2 for TMEM165-CDG therapy.
Loss of YY1, a Regulator of Metabolism in Melanoma, Drives Melanoma Cell Invasiveness and Metastasis Formation
Authors: Guendisch Ulf , Loos Benjamin , Cheng Phil F. , Dummer Reinhard , Levesque Mitchell P. , Varum Sandra , Sommer Lukas
Published: May 2022

Deregulation of cellular metabolism through metabolic rewiring and translational reprogramming are considered hallmark traits of tumor development and malignant progression. The transcription factor YY1 is a master regulator of metabolism that we have previously shown to orchestrate a metabolic program required for melanoma formation. In this study, we demonstrate that YY1, while being essential for primary melanoma formation, suppresses metastatic spreading. Its downregulation or loss resulted in the induction of an invasiveness gene program and sensitized melanoma cells for pro-invasive signaling molecules, such as TGF-β. In addition, NGFR, a key effector in melanoma invasion and phenotype switching, was among the most upregulated genes after YY1 knockdown. High levels of NGFR were also associated with other metabolic stress inducers, further indicating that YY1 knockdown mimics a metabolic stress program associated with an increased invasion potential in melanoma. Accordingly, while counteracting tumor growth, loss of YY1 strongly promoted melanoma cell invasiveness in vitro and metastasis formation in melanoma mouse models in vivo. Thus, our findings show that the metabolic regulator YY1 controls phenotype switching in melanoma.
Predictive Value of Plasma Big Endothelin-1 in Adverse Events of Patients With Coronary Artery Restenosis and Diabetes Mellitus: Beyond Traditional and Angiographic Risk Factors
Authors: Ma Yue , Tian Tao , Wang Tianjie , Wang Juan , Guan Hao , Yuan Jiansong , Song Lei , Yang Weixian , Qiao Shubin
Published: May 2022

Background

Patients with diabetes are a high-risk group for coronary in-stent restenosis (ISR), so it would be valuable to identify biomarkers to predict their prognosis. The plasma big endothelin-1 (big ET-1) level is closely related to cardiovascular adverse events; however, for patients with ISR and diabetes who undergo percutaneous coronary intervention (PCI), whether big ET-1 is independently correlated with prognosis is still uncertain.

Methods

Patients with drug-eluting stent (DES) restenosis who underwent successful re-PCI from January 2017 to December 2018 at the Chinese Academy of Medical Sciences Fuwai Hospital were enrolled and followed up for 3 years. The patients were divided into the tertiles of baseline big ET-1. The primary end points were major adverse cardiovascular events (MACEs): cardiac death, non-fatal myocardial infarction (MI), target lesion revascularization (TLR), and stroke. A Cox multivariate proportional hazard model and the C-statistic were used to evaluate the potential predictive value of big ET-1 beyond traditional and angiographic risk factors.

Results

A total of 1,574 patients with ISR were included in this study, of whom 795 were diabetic. In patients with ISR and diabetes, after an average follow-up of 2.96 ± 0.56 years, with the first tertile of big ET-1 as a reference, the hazard ratio [HR] (95% CI) of MACEs after adjustment for traditional and angiographic risk factors was 1.24 (0.51–3.05) for the second tertile and 2.60 (1.16–5.81) for the third. Big ET-1 improved the predictive value for MACEs over traditional risk factors (C-statistic: 0.64 vs. 0.60, p = 0.03). Big ET-1 was not significantly associated with the risk of MACEs in patients without diabetes.

Conclusion

Increased plasma big ET-1 was associated with a higher risk of adverse cardiovascular prognosis independent of traditional and angiographic risk factors, and therefore, it might be used as a predictive biomarker, in patients with ISR and diabetes.
Diabetes Is the Strongest Predictor of Limited Exercise Capacity in Chronic Heart Failure and Preserved Ejection Fraction (HFpEF)
Authors: Berisha-Muharremi Venera , Henein Michael Y. , Dini Frank L. , Haliti Edmond , Bytyçi Ibadete , Ibrahimi Pranvera , Poniku Afrim , Batalli Arlind , Tafarshiku Rina , Elezi Shpend , Bajraktari Gani
Published: May 2022

Background and Aim

Type 2 diabetes mellitus (T2DM) is a known risk factor in patients with heart failure (HF), but its impact on phenotypic presentations remains unclear. This study aimed to prospectively examine the relationship between T2DM and functional exercise capacity, assessed by the 6-min walk test (6-MWT) in chronic HF.

Methods

We studied 344 chronic patients with HF (mean age 61 ± 10 years, 54% female) in whom clinical, biochemical, and anthropometric data were available and all patients underwent an echo-Doppler study and a 6-MWT on the same day. The 6-MWT distance divided the cohort into; Group I: those who managed ≤ 300 m and Group II: those who managed >300 m. Additionally, left ventricular (LV) ejection fraction (EF), estimated using the modified Simpson's method, classified patients into HF with preserved EF (HFpEF) and HF with reduced EF (HFrEF).

Results

The results showed that 111/344 (32%) patients had T2DM, who had a higher prevalence of arterial hypertension (p = 0.004), higher waist/hips ratio (p = 0.041), higher creatinine (p = 0.008) and urea (p = 0.003), lower hemoglobin (p = 0.001), and they achieved shorter 6-MWT distance (p < 0.001) compared with those with no T2DM. Patients with limited exercise (<300 m) had higher prevalence of T2DM (p < 0.001), arterial hypertension (p = 0.004), and atrial fibrillation (p = 0.001), higher waist/hips ratio (p = 0.041), higher glucose level (p < 0.001), lower hemoglobin (p < 0.001), larger left atrium (LA) (p = 0.002), lower lateral mitral annular plane systolic excursion (MAPSE) (p = 0.032), septal MAPSE (p < 0.001), and tricuspid annular plane systolic excursion (TAPSE) (p < 0.001), compared with those performing >300 m. In the cohort as a whole, multivariate analysis, T2DM (p < 0.001), low hemoglobin (p = 0.008), atrial fibrillation (p = 0.014), and reduced septal MAPSE (p = 0.021) independently predicted the limited 6-MWT distance.

In patients with HFpEF, diabetes [6.083 (2.613–14.160), p < 0.001], atrial fibrillation [6.092 (1.769–20.979), p = 0.002], and septal MAPSE [0.063 (0.027–0.184), p = 0.002], independently predicted the reduced 6-MWT, whereas hemoglobin [0.786 (0.624–0.998), p = 0.049] and TAPSE [0.462 (0.214–0.988), p = 0.041] predicted it in patients with HFrEF.

Conclusion

Predictors of exercise intolerance in patients with chronic HF differ according to LV systolic function, demonstrated as EF. T2DM seems the most powerful predictor of limited exercise capacity in patients with HFpEF.
Evidences of Bedrock Forcing on Glacier Morphodynamics: A Case Study in Italian Alps
Authors: Dematteis Niccolò , Giordan Daniele , Perret Paolo , Grab Melchior , Maurer Hansruedi , Troilo Fabrizio
Published: May 2022

In mountain glaciers, the influence of bedrock geometry on glacier surface morphology is often assumed; quantitative evidence, however, is rare. In our research, we measured the ice thickness of the Planpincieux Glacier (North-west Italy) and detected the bedrock topography using ground-penetrating radar. Additionally, we investigated the glacier surface morphology using structure from motion and the glacier kinematics using digital image correlation of terrestrial images. A digital terrain analysis showed evidence of recurrent crevasses whose position corresponded to bedrock steps. On average, since 2014, their positions varied between 6 and 14 m and were 40 ± 8 m downstream of the bedrock steps. Bedrock and glacier topography presented out-of-phase correlated undulations that approximately fit a sinusoidal function of different amplitude. Moreover, we show the morphological evolution of an unstable sector whose thickness at the end of the ablation seasons has remained approximately constant since 2014. Contrarily, the ice melting during the 2020 ablation season caused a volume loss of >30%. Since, in general, the damages provoked by a potential ice avalanche depend primarily on the involved volume, this finding demonstrates that frequent morphology monitoring is essential for correct glacial hazard assessment.
Energy Evolution Characteristics of Rock Under Different Confining Conditions
Authors: Zhang Bi-Wen , Fang Kai , Wang Chen , Zhao Tong-Bin , Zhang Xiu-Feng
Published: May 2022

Constant stiffness confining condition seems more reasonable than constant stress confining condition to simulate the actual confining stress environment of in situ rock which varies with the lateral strain. Compression tests of sandstone samples with two different confining conditions were conducted to study the energy evolution characteristics of rock under constant stress confining condition and constant stiffness confining condition. Except for the conventional triaxial compression tests, CFRP-confined rock samples were also used to simulate the constant stiffness confinement of the rock specimen in the laboratory. The stress–strain curve and failure mode of the samples under different confining conditions were compared. The influence of confining condition on the characteristics of rock energy evolution was investigated. The results show that the stress–strain curves under the confining conditions of constant stress and constant stiffness exhibited strain softening and strain hardening, respectively. Under constant stress confining condition, the specimen failed in the ductile mode while the specimen exhibited a sudden and brittle failure behavior under constant stiffness confining condition. The evolution trend of the elastic strain energy was greatly affected by the magnitude of confining stiffness. The elastic strain energy of the specimen under low stiffness confining condition decreased slightly after reaching its peak. As the confining stiffness increased, the elastic strain energy would not decrease but continued to increase until the failure of the specimen. The maximum elastic strain energy under the confining condition of the high confining stiffness is greater than that of constant stress. Considering the influence of confining stiffness on the storage and release of the strain energy, to obtain the true mechanical behavior of the rock mass under confining conditions, stiffness confining conditions should be taken into consideration in the laboratory.
Insights Into the Roles of GATA Factors in Mammalian Testis Development and the Control of Fetal Testis Gene Expression
Authors: Viger Robert S. , de Mattos Karine , Tremblay Jacques J.
Published: May 2022

Defining how genes get turned on and off in a correct spatiotemporal manner is integral to our understanding of the development, differentiation, and function of different cell types in both health and disease. Testis development and subsequent male sex differentiation of the XY fetus are well-orchestrated processes that require an intricate network of cell-cell communication and hormonal signals that must be properly interpreted at the genomic level. Transcription factors are at the forefront for translating these signals into a coordinated genomic response. The GATA family of transcriptional regulators were first described as essential regulators of hematopoietic cell differentiation and heart morphogenesis but are now known to impact the development and function of a multitude of tissues and cell types. The mammalian testis is no exception where GATA factors play essential roles in directing the expression of genes crucial not only for testis differentiation but also testis function in the developing male fetus and later in adulthood. This minireview provides an overview of the current state of knowledge of GATA factors in the male gonad with a particular emphasis on their mechanisms of action in the control of testis development, gene expression in the fetal testis, testicular disease, and XY sex differentiation in humans.
Adaptive Neuro-Fuzzy Approach for Solar Radiation Forecasting in Cyclone Ravaged Indian Cities: A Review
Authors: Mohanty S. , Patra P. K. , Mohanty A. , Harrag A. , Rezk Hegazy
Published: May 2022

The measurement of solar radiation and its forecasting at any particular location is a difficult task as it depends on various input parameters. So, intelligent modeling approaches with advanced techniques are always necessary for this challenging activity. Adaptive neuro-fuzzy inference system (ANFIS) based on modeling plays a vital role in the selection of relevant input parameters for undertaking precise solar radiation prediction. Numerous literature works focusing on ANFIS-based techniques have been reviewed during the estimation of solar energy incidents in the eastern part of India. During solar forecasting, the input parameters considered for this model are the duration of the sunshine, temperature, and humidity whereas the clearness index value has been considered as an output parameter for calculation. For designing the model, practical data sets have been prepared for some specified locations. Finally, the outcome is compared with several other techniques. During this course of analysis, several studies have been reviewed for a comprehensive literature survey work.
Research on State Monitoring System of Intelligent Disconnecting Switch Based on Sensing Technology
Authors: Chen Jinhong , Wu Guibin , Jian Xingzhan , Cai Liujun , Chen Shaoyong , Chen Rixin
Published: May 2022

The intelligentization, informationization, and internalization of power system infrastructure equipment are the key technologies to achieve the low-carbon transformation of the power system. To tackle the low degree of intelligence and the internet in the monitoring and early warning of mechanical faults of the disconnecting switch, this paper designs an intelligent monitoring system for the disconnecting switch operation status based on sensing technology. Torque sensors, angle encoders, micro-switches, attitude sensors, and temperature and humidity sensor technology are used to monitor the operation status of the disconnecting switch, and an advanced RISC machine (ARM) embedded terminal system is used as the disconnecting switch status monitoring center. The intelligent monitoring system aims to accurately monitor the temperature and humidity environment in the disconnector operating mechanism box, the opening and closing position state of the disconnector, and the torque angle variation characteristics of the disconnector according to the operating parameters collected by the sensor, while achieving remote real-time state monitoring of the disconnecting switch. The function tests and field tests show that the system performance is stable, and the state information collection, intelligent analysis, and remote monitoring meet the actual needs, which can improve the efficiency of disconnecting switch operation, maintenance, and overhaul, thereby reducing the risk of power grid outages.
Coordinated Singing in Coppery Titi Monkeys (Plecturocebus cupreus): Resource or Mate Defense?
Authors: Dolotovskaya Sofya , Heymann Eckhard W.
Published: May 2022

Coordinated singing, performed as duets by mated pairs and often joined by offspring to form choruses, is a distinctive behavioral attribute of the social system of pair-living and pair-bonded Neotropical titi monkeys. Duets and choruses are presumed to be associated with mate or territorial defense, but no consensus has yet been reached regarding their function. Here, we examined temporal and spatial patterns of coordinated singing in eight wild groups of coppery titi monkeys, Plecturocebus cupreus, in Peruvian Amazonia to test predictions of the joint resource and mate defense. We investigated singing rates in relation to female reproductive state, fruit consumption and demographic context using a dataset based on 227 observation days and analyzed temporal and spatial distribution of songs using a dataset based on 150 songs, collected between June 2017 and September 2021. Titi monkeys sang least frequently when females were likely to be sexually receptive and most frequently when females were likely to be pregnant. Groups also sang slightly more often when fruits were consumed more intensively, although this association did not reach statistical significance. The duration of songs was not associated with female reproductive state or fruit consumption, but songs were longer during inter-group encounters compared to non-encounter contexts. Songs were not concentrated in the core areas of home ranges; rather, they were distributed throughout the home ranges in concordance with its use. Finally, songs were concentrated around dawn. Our results provide support for a function in joint resource defense and inter-group communication of coordinated songs in coppery titi monkeys. The function of coordinated songs for mate defense in the form of paternity guarding, on the other hand, was not supported by our findings.
Using Long-Term Follow-Up Data to Classify Genetic Variants in Newborn Screened Conditions
Authors: Wilhelm Kevin , Edick Mathew J. , Berry Susan A. , Hartnett Michael , Brower Amy
Published: May 2022

With the rapid increase in publicly available sequencing data, healthcare professionals are tasked with understanding how genetic variation informs diagnosis and affects patient health outcomes. Understanding the impact of a genetic variant in disease could be used to predict susceptibility/protection and to help build a personalized medicine profile. In the United States, over 3.8 million newborns are screened for several rare genetic diseases each year, and the follow-up testing of screen-positive newborns often involves sequencing and the identification of variants. This presents the opportunity to use longitudinal health information from these newborns to inform the impact of variants identified in the course of diagnosis. To test this, we performed secondary analysis of a 10-year natural history study of individuals diagnosed with metabolic disorders included in newborn screening (NBS). We found 564 genetic variants with accompanying phenotypic data and identified that 161 of the 564 variants (29%) were not included in ClinVar. We were able to classify 139 of the 161 variants (86%) as pathogenic or likely pathogenic. This work demonstrates that secondary analysis of longitudinal data collected as part of NBS finds unreported genetic variants and the accompanying clinical information can inform the relationship between genotype and phenotype.
SpatialMap: Spatial Mapping of Unmeasured Gene Expression Profiles in Spatial Transcriptomic Data Using Generalized Linear Spatial Models
Authors: Gao Dalong , Ning Jin , Liu Gang , Sun Shiquan , Dang Xiaoqian
Published: May 2022

Recent advances in various single-cell RNA sequencing (scRNA-seq) technologies have enabled profiling the gene expression level with the whole transcriptome at a single-cell resolution. However, it lacks the spatial context of tissues. The image-based transcriptomics in situ studies (e.g., MERFISH and seqFISH) maintain the cell spatial context at individual cell levels but can only measure a limited number of genes or transcripts (up to roughly 1,000 genes). Therefore, integrating scRNA-seq data and image-based transcriptomics data can potentially gain the complementary benefits of both. Here, we develop a computational method, SpatialMap, to bridge the gap, which primarily facilitates spatial mapping of unmeasured gene profiles in spatial transcriptomic data via integrating with scRNA-seq data from the same tissue. SpatialMap directly models the count nature of spatial gene expression data through generalized linear spatial models, which accounts for the spatial correlation among spatial locations using conditional autoregressive (CAR) prior. With a newly developed computationally efficient penalized quasi-likelihood (PQL)-based algorithm, SpatialMap can scale up to performing large-scale spatial mapping analysis. Finally, we applied the SpatialMap to four publicly available tissue-paired studies (i.e., scRNA-seq studies and image-based transcriptomics studies). The results demonstrate that the proposed method can accurately predict unmeasured gene expression profiles across various spatial and scRNA-seq dataset pairs of different species and technologies.
Identification of Immune-Related Genes for Risk Stratification in Multiple Myeloma Based on Whole Bone Marrow Gene Expression Profiling
Authors: Wang Qiang-Sheng , Shi Qi-Qin , Meng Ye , Chen Meng-Ping , Hou Jian
Published: May 2022

Background: Multiple myeloma (MM) is characterized by abnormal proliferation of bone marrow clonal plasma cells. Tumor immunotherapy, a new therapy that has emerged in recent years, offers hope to patients, and studying the expression characteristics of immune-related genes (IRGs) based on whole bone marrow gene expression profiling (GEP) in MM patients can help guide personalized immunotherapy.

Methods: In this study, we explored the potential prognostic value of IRGs in MM by combining GEP and clinical data from the GEO database. We identified hub IRGs and transcription factors (TFs) associated with disease progression by Weighted Gene Co-expression Network Analysis (WGCNA), and modeled immune-related prognostic signature by univariate and multivariate Cox and least absolute shrinkage and selection operator (LASSO) regression analysis. Subsequently, the prognostic ability of signature was verified by multiple statistical methods. Moreover, ssGSEA and GSEA algorithm reveled different immunological characteristics and biological function variation in different risk groups. We mapped the hub IRGs by protein-protein interaction network (PPI) and extracted the top 10 ranked genes. Finally, we conducted vitro assays on two alternative IRGs.

Results: Our study identified a total of 14 TFs and 88 IRGs associated with International Staging System (ISS). Ten IRGs were identified by Cox -LASSO regression analysis, and used to develop optimal prognostic signature for overall survival (OS) in MM patients. The 10-IRGs were BDNF, CETP, CD70, LMBR, LTBP1, NENF, NR1D1, NR1H2, PTK2B and SEMA4. In different groups, risk signatures showed excellent survival prediction ability, and MM patients also could be stratified at survival risk. In addition, IRF7 and SHC1 were hub IRGs in PPI network, and the vitro assays proved that they could promote tumor progression. Notably, ssGSEA and GSEA results confirmed that different risk groups could accurately indicate the status of tumor microenvironment (TME) and activation of biological pathways.

Conclusion: Our study suggested that immune-related signature could be used as prognostic markers in MM patients.
Prevalence of Pregnancy Associated Malaria in India
Authors: Jain Khushi , Gupta Palak , Balodhi Ashutosh , Deeba Farah , Salam Nasir
Published: May 2022

Malaria in pregnancy is a major public health concern. It results in impaired maternal health and adversely effects fetal and perinatal outcomes. The present systematic review was conducted to assess the prevalence, distribution and adverse pregnancy outcomes in malaria infected females in India. A comprehensive search and review of PubMed and Web of Science based on PRISMA guidelines was carried out to find articles reporting prevalence of malaria in pregnant women from India. Data from 16 studies were analyzed and prevalence of malaria among pregnant women in India was found to be 11.4 % (95 % CI: 7.3, 16.3). Prevalence of malaria among asymptomatic and symptomatic pregnant women was found to be 10.62% (95% CI: 6.05, 16.23) and 13.13% (95% CI: 7.2, 20.52), respectively. P. falciparum and P. vivax were both reported with in the same population. The geospatial distribution of malaria in pregnancy spanned over nine very populous states of India. The review also reported severe maternal and perinatal outcomes. Given the seriousness of malaria in pregnant women and its effects on the fetus and new-born, a stringent district wise guideline for early detection and prophylaxis in regions identified in this review will help in its better control.
The Association Between Adverse Childhood Experiences and Postpartum Depression
Authors: Prentice Danielle M. , Otaibi Banan W. , Stetter Christy , Kunselman Allen R. , Ural Serdar H.
Published: May 2022

Objective

Adverse childhood experiences (ACEs) are linked to worsening overall health outcomes and psychological diagnoses. Routine screening, particularly in patients with postpartum depression (PPD), would identify patients who could benefit from interventions to prevent the perpetuation of ACEs and establish a system of preventative care to mitigate the risks of adverse health outcomes associated with high ACE scores. The purpose of this study is to explore the link between ACEs and PPD to advocate for the use of the ACE questionnaire as a routine screening tool in all pregnant patients diagnosed with PPD. We hypothesize that a cohort of patients with PPD will be more likely to have high-risk ACE scores than the general female population.

Study Design

Our IRB approved, retrospective cohort study identified all patients diagnosed with PPD at an academic medical center between January 2015 and December 2019. The subjects were identified using retrospective chart review. Subjects were recruited via telephone and asked to complete an ACE questionnaire. Questionnaires were sent via RedCap. ACE scores were calculated, categorized as 0, 1, 2, 3, or 4 or more ACEs, and compared to the prevalence in the original Kaiser-CDC ACE study female cohort using a chi-square goodness-of-fit test.

Results

There were 132/251 surveys completed (53% response rate). In our PPD population, 19.3% had 0 ACEs, 17.0% had 1 ACE, 13.1% had 2 ACEs, 16.5% had 3 ACEs, and 34.1% had 4 or more ACEs. These percentages were significantly different from the Kaiser-CDC ACE Study percentages of 34.5, 24.5, 15.5, 10.3, and 15.2%, respectively (p < 0.001).

Conclusion

Our unique study showed that women with PPD are more likely to have high-risk ACE scores than the general female population. This finding has important implications in regards to counseling, intervening to prevent perpetual ACEs, and establishing important provider-patient relationships for life-long preventative care.

Non-gendered language is used when possible throughout. However, the wording from studies cited in this paper was preserved.
Profiles of Proinflammatory Cytokines and T Cells in Patients With Tourette Syndrome: A Meta-Analysis
Authors: Li Ying , Wang Xiaolin , Yang Hanxue , Li Yanlin , Gui Jingang , Cui Yonghua
Published: May 2022

Background

Tic disorder is a neurodevelopmental disorder characterized by motor and phonic tic symptoms. Tourette syndrome (TS) is a subtype of tic disorder that shows more persistent tic symptoms. The etiological mechanism of TS concerning immune dysfunction remains unclear due to limited evidence, especially for pediatric TS patients.

Method

In the present study, a meta-analysis was performed to confirm the identified changes in proinflammatory cytokines and T cells of pediatric TS patients. A total of five databases, including PubMed, Web of Science, PsycINFO, Google Scholar and the China National Knowledge Infrastructure (CNKI), were used for the literature search. The standardized mean difference (SMD) and mean difference (MD) with a 95% confidence interval (CI) were used to present the effect size of each type of proinflammatory cytokine and T cell. Sensitivity analysis, subgroup analysis and meta-regression analysis were used to explore the heterogeneity of the meta-analysis. This meta-analysis was registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols (number: INPLASY2021110079).

Results

In the 25 studies included in this meta-analysis, thirteen studies focused on the levels of T cells, and twelve studies focused on the levels of proinflammatory cytokines. Based on the random-effects model, the pooled MDs are -1.45 (95% CI: -3.44, 0.54) for CD3 cells, -4.44 (95% CI: -6.80, -2.08) for CD4 cells, and 1.94 (95% CI: -0.08, 3.97) for CD8 cells. The pooled SMDs are1.36 for IL-6 (95% CI: 0.00, 2.72) and 2.39 for tumor necrosis factor alpha (TNF-α) (95% CI: 0.93, 3.84).

Conclusion

We provided evidence of immune dysfunction in pediatric TS patients, with elevated levels of particular proinflammatory cytokines and disproportionate changes in T-cell subpopulations. Small to large effect sizes were identified for increased IL-6 levels as well as a reduced number of T helper cells, while a large effect size was identified for increased TNF-α levels. These results indicate a close association between peripheral immune activation and TS. However, the most direct and meaningful interaction between peripheral immune status and microglial activation in the central nervous system in TS patients requires further exploration.
Inflammation and Interferon Signatures in Peripheral B-Lymphocytes and Sera of Individuals With Fibromyalgia
Authors: Fineschi Serena , Klar Joakim , Gustafsson Kristin Ayoola , Jonsson Kent , Karlsson Bo , Dahl Niklas
Published: May 2022

Fibromyalgia (FM) is an idiopathic chronic disease characterized by widespread musculoskeletal pain, hyperalgesia and allodynia, often accompanied by fatigue, cognitive dysfunction and other symptoms. Autoimmunity and neuroinflammatory mechanisms have been suggested to play important roles in the pathophysiology of FM supported by recently identified interferon signatures in affected individuals. However, the contribution of different components in the immune system, such as the B-lymphocytes, in the progression to FM are yet unknown. Furthermore, there is a great need for biomarkers that may improve diagnostics of FM. Herein, we investigated the gene expression profile in peripheral B-cells, as well as a panel of inflammatory serum proteins, in 30 FM patients and 23 healthy matched control individuals. RNA sequence analysis revealed 60 differentially expressed genes when comparing the two groups. The group of FM patients showed increased expression of twenty-five interferon-regulated genes, such as S100A8 and S100A9, VCAM, CD163, SERPINA1, ANXA1, and an increased interferon score. Furthermore, FM was associated with elevated levels of 19 inflammatory serum proteins, such as IL8, AXIN1, SIRT2 and STAMBP, that correlated with the FM severity score. Together, the results shows that FM is associated with an interferon signature in B-cells and increased levels of a set of inflammatory serum proteins. Our findings bring further support for immune activation in the pathogenesis of FM and highlight candidate biomarkers for diagnosis and intervention in the management of FM.
Tubulin Isotypes: Emerging Roles in Defining Cancer Stem Cell Niche
Authors: Maliekal Tessy Thomas , Dharmapal Dhrishya , Sengupta Suparna
Published: May 2022

Although the role of microtubule dynamics in cancer progression is well-established, the roles of tubulin isotypes, their cargos and their specific function in the induction and sustenance of cancer stem cells (CSCs) were poorly explored. But emerging reports urge to focus on the transport function of tubulin isotypes in defining orchestrated expression of functionally critical molecules in establishing a stem cell niche, which is the key for CSC regulation. In this review, we summarize the role of specific tubulin isotypes in the transport of functional molecules that regulate metabolic reprogramming, which leads to the induction of CSCs and immune evasion. Recently, the surface expression of GLUT1 and GRP78 as well as voltage-dependent anion channel (VDAC) permeability, regulated by specific isotypes of β-tubulins have been shown to impart CSC properties to cancer cells, by implementing a metabolic reprogramming. Moreover, βIVb tubulin is shown to be critical in modulating EphrinB1signaling to sustain CSCs in oral carcinoma. These tubulin-interacting molecules, Ephrins, GLUT1 and GRP78, are also important regulators of immune evasion, by evoking PD-L1 mediated T-cell suppression. Thus, the recent advances in the field implicate that tubulins play a role in the controlled transport of molecules involved in CSC niche. The indication of tubulin isotypes in the regulation of CSCs offers a strategy to specifically target those tubulin isotypes to eliminate CSCs, rather than the general inhibition of microtubules, which usually leads to therapy resistance.
A SARS–CoV-2 Spike Receptor Binding Motif Peptide Induces Anti-Spike Antibodies in Mice andIs Recognized by COVID-19 Patients
Authors: Pratesi Federico , Errante Fosca , Pacini Lorenzo , Peña-Moreno Irina Charlot , Quiceno Sebastian , Carotenuto Alfonso , Balam Saidou , Konaté Drissa , Diakité Mahamadou M. , Arévalo-Herrera Myriam , Kajava Andrey V. , Rovero Paolo , Corradin Giampietro , Migliorini Paola , Papini Anna M. , Herrera Sócrates
Published: May 2022

The currently devastating pandemic of severe acute respiratory syndrome known as coronavirus disease 2019 or COVID-19 is caused by the coronavirus SARS-CoV-2. Both the virus and the disease have been extensively studied worldwide. A trimeric spike (S) protein expressed on the virus outer bilayer leaflet has been identified as a ligand that allows the virus to penetrate human host cells and cause infection. Its receptor-binding domain (RBD) interacts with the angiotensin-converting enzyme 2 (ACE2), the host-cell viral receptor, and is, therefore, the subject of intense research for the development of virus control means, particularly vaccines. In this work, we search for smaller fragments of the S protein able to elicit virus-neutralizing antibodies, suitable for production by peptide synthesis technology. Based on the analysis of available data, we selected a 72 aa long receptor binding motif (RBM436-507) of RBD. We used ELISA to study the antibody response to each of the three antigens (S protein, its RBD domain and the RBM436-507 synthetic peptide) in humans exposed to the infection and in immunized mice. The seroreactivity analysis showed that anti-RBM antibodies are produced in COVID-19 patients and immunized mice and may exert neutralizing function, although with a frequency lower than anti-S and -RBD. These results provide a basis for further studies towards the development of vaccines or treatments focused on specific regions of the S virus protein, which can benefit from the absence of folding problems, conformational constraints and other advantages of the peptide synthesis production.
γδ T Cells in Brain Homeostasis and Diseases
Authors: Park Jang Hyun , Kang In , Lee Heung Kyu
Published: May 2022

γδ T cells are a distinct subset of T cells expressing γδ T cell receptor (TCR) rather than αβTCR. Since their discovery, the critical roles of γδ T cells in multiple physiological systems and diseases have been investigated. γδ T cells are preferentially located at mucosal surfaces, such as the gut, although a small subset of γδ T cells can circulate the blood. Additionally, a subset of γδ T cells reside in the meninges in the central nervous system. Recent findings suggest γδ T cells in the meninges have critical roles in brain function and homeostasis. In addition, several lines of evidence have shown γδ T cells can infiltrate the brain parenchyma and regulate inflammatory responses in multiple diseases, including neurodegenerative diseases. Although the importance of γδ T cells in the brain is well established, their roles are still incompletely understood due to the complexity of their biology. Because γδ T cells rapidly respond to changes in brain status and regulate disease progression, understanding the role of γδ T cells in the brain will provide critical information that is essential for interpreting neuroimmune modulation. In this review, we summarize the complex role of γδ T cells in the brain and discuss future directions for research.
Immunogenicity and Reactogenicity in Q Fever Vaccine Development
Authors: Fratzke Alycia P. , van Schaik Erin J. , Samuel James E.
Published: May 2022

Coxiella burnetiiis an obligate intracellular bacterium which, in humans, causes the disease Q fever. Although Q fever is most often a mild, self-limiting respiratory disease, it can cause a range of severe syndromes including hepatitis, myocarditis, spontaneous abortion, chronic valvular endocarditis, and Q fever fatigue syndrome. This agent is endemic worldwide, except for New Zealand and Antarctica, transmittedviaaerosols, persists in the environment for long periods, and is maintained through persistent infections in domestic livestock. Because of this, elimination of this bacterium is extremely challenging and vaccination is considered the best strategy for prevention of infection in humans. Many vaccines againstC. burnetiihave been developed, however, only a formalin-inactivated, whole cell vaccine derived from virulentC. burnetiiis currently licensed for use in humans. Unfortunately, widespread use of this whole cell vaccine is impaired due to the severity of reactogenic responses associated with it. This reactogenicity continues to be a major barrier to access to preventative vaccines againstC. burnetiiand the pathogenesis of this remains only partially understood. This review provides an overview of past and current research onC. burnetiivaccines, our knowledge of immunogenicity and reactogenicity inC. burnetiivaccines, and future strategies to improve the safety of vaccines againstC. burnetii.
Differential Effects of Alarmins on Human and Mouse Basophils
Authors: Gambardella Adriana R. , Poto Remo , Tirelli Valentina , Schroeder John T. , Marone Gianni , Mattei Fabrizio , Varricchi Gilda , Schiavoni Giovanna
Published: May 2022

Epithelial-derived alarmins (IL-33, TSLP, and IL-25) play an upstream role in the pathogenesis of asthma. Basophil-derived cytokines are a pivotal component of allergic inflammation. We evaluated thein vitroeffects of IL-33, TSLP, and IL-25, alone and in combination with IL-3 on purified peripheral blood human basophils (hBaso) and bone marrow-derived mouse basophils (mBaso) in modulating the production of IL-4, IL-13, CXCL8 or the mouse CXCL8 equivalents CXCL1 and CXCL2. IL-3 and IL-33, but not TSLP and IL-25, concentration-dependently induced IL-4, IL-13, and CXCL8 release from hBaso. IL-3 synergistically potentiated the release of cytokines induced by IL-33 from hBaso. In mBaso, IL-3 and IL-33 rapidly induced IL-4 and IL-13 mRNA expression and protein release. IL-33, but not IL-3, induced CXCL2 and CXCL1 from mBaso. Differently from hBaso, TSLP induced IL-4, IL-13, CXCL1 and CXCL2 mRNA expression and protein release from mBaso. IL-25 had no effect on IL-4, IL-13, and CXCL1/CXCL2 mRNA expression and protein release even in the presence of IL-3. No synergism was observed between IL-3 and either IL-25 or TSLP. IL-3 inhibited both TSLP- and IL-33-induced CXCL1 and CXCL2 release from mBaso. Our results highlight some similarities and marked differences between the effects of IL-3 and alarmins on the release of cytokines from human and mouse basophils.
PLGA Nanospheres as Delivery Platforms for Eimeria mitis 1a Protein: A Novel Strategy to Improve Specific Immunity
Authors: Xu Lixin , Yu Zhengqing , He Ke , Wen Zhaohai , Aleem Muhammad Tahir , Yan Ruofeng , Song Xiaokai , Lu Mingmin , Li XiangRui
Published: May 2022

The infections of chicken coccidiosis impact the welfare of chickens and the economical production of poultry.Eimeria mitisis ubiquitous in chicken coccidiosis, andE. mitisinfection can significantly affect the productivity of birds. Up to now, few efficient vaccines againstE. mitishave been reported, whereas the recombinant subunit vaccines delivered by nanomaterials may elicit an encouraging outcome. Thus, in this study, we choseE. mitis1a (Em1a) protein as the candidate antigen to generate Em1a preparations. The recombinant Em1a (rEm1a) protein was encapsulated with poly lactic-co-glycolic acid (PLGA) and chitosan (CS) nanospheres. The physical characterization of the rEm1a-PLGA and rEm1a-CS nanospheres was investigated, and the resulting nanospheres were proven to be nontoxic. The protective efficacy of rEm1a-PLGA and rEm1a-CS preparations was evaluated inE. mitis-challenged birds in comparison with two preparations containing rEm1a antigen emulsified in commercially available adjuvants. ELISA assay, flow cytometry analysis, and quantitative real-time PCR (qPCR) analysis indicated that vaccination with rEm1a-loaded nanospheres significantly upregulated the secretions of antibodies and cytokines and proportions of CD4+and CD8+T lymphocytes. Compared with the other three preparations, rEm1a-PLGA nanosphere was more effective in improving growth performance and inhibiting oocyst output in feces, indicating that the PLGA nanosphere was associated with optimal protection againstE. mitis. Collectively, our results highlighted the advantages of nanovaccine in eliciting protective immunity and may provide a new perspective for developing effective vaccines against chicken coccidiosis.
Avian Leucosis Virus-Host Interaction: The Involvement of Host Factors in Viral Replication
Authors: Tang Shuang , Li Jie , Chang Yung-Fu , Lin Wencheng
Published: May 2022

Avian leukosis virus (ALV) causes various diseases associated with tumor formation and decreased fertility. Moreover, ALV induces severe immunosuppression, increasing susceptibility to other microbial infections and the risk of failure in subsequent vaccination against other diseases. There is growing evidence showing the interaction between ALV and the host. In this review, we will survey the present knowledge of the involvement of host factors in the important molecular events during ALV infection and discuss the futuristic perspectives from this angle.
Residency and Use of an Important Nursery Habitat, Raja Ampat’s Wayag Lagoon, by Juvenile Reef Manta Rays (Mobula alfredi)
Authors: Setyawan Edy , Erdmann Mark V. , Mambrasar Ronald , Hasan Abdi W. , Sianipar Abraham B. , Constantine Rochelle , Stevenson Ben C. , Jaine Fabrice R. A.
Published: May 2022

The behaviour and spatial use patterns of juvenile manta rays within their critical nursery habitats remain largely undocumented. Here, we report on the horizontal movements and residency of juvenile reef manta rays (Mobula alfredi) at a recently discovered nursery site in the Wayag lagoon, Raja Ampat, Indonesia. Using a multi-disciplinary approach, we provide further corroborative evidence that the lagoon serves as an important M. alfredi nursery. A total of 34 juvenile rays were photo-identified from 47 sightings in the sheltered nursery between 2013–2021. Five (14.7%) of these individuals were resighted for at least 486 days (~1.3 years), including two juveniles resighted after 641 and 649 days (~1.7 years), still using the nursery. Visually estimated (n=34) disc widths (DW) of juveniles using the nursery site ranged from 150–240 cm (mean ± SD: 199 ± 19), and the DW of two juveniles measured using drones were 218 and 219 cm. Five juveniles were tracked using GPS-enabled satellite transmitters for 12–69 days (mean ± SD: 37 ± 22) in 2015 and 2017, and nine juveniles were tracked using passive acoustic transmitters for 69–439 days (mean ± SD: 182 ± 109) from May 2019–September 2021. Satellite-tracked individuals exhibited restricted movements within Wayag lagoon. The minimum core activity space (50% Utilisation Distribution-UD) estimated for these five individuals ranged from 1.1–181.8 km2 and the extent of activity space (95% UD) between 5.3–1,195.4 km2 in area. All acoustically tagged individuals displayed high residency within the nursery area, with no acoustic detections recorded outside the lagoon in the broader Raja Ampat region. These juveniles were detected by receivers in the lagoon throughout the 24 h diel cycle, with more detections recorded at night and different patterns of spatial use of the lagoon between day and night. The observed long-term residency of juvenile M. alfredi provides further compelling evidence that the Wayag lagoon is an important nursery area for this globally vulnerable species. These important findings have been used to underpin the formulation of management strategies to specifically protect the Wayag lagoon, which will be instrumental for the survival and recovery of M. alfredi populations in Raja Ampat region.
pH-Responsive Hydrogel Bilayer With Reversible, Bidirectional Bending Behavior
Authors: Shojaeifard Mohammad , Niroumandi Soha , Baghani Mostafa
Published: May 2022

Smart hydrogels are promising materials for shape-shifting structures regarding their large reversible deformation in response to external stimuli in the absence of mechanical loading. Actuators composed of responsive hydrogels have gained significant attention due to their low power consumption, bio-compatibility, fast response, and accessibility. Among these structures, bidirectional hydrogel-based actuators are more fascinating, especially when they have similar reversible bending in both directions. This paper introduces a new design concept of a hydrogel bilayer made of a poly (HEMA-co-DMAEMA) layer and a poly (HEMA-co-AA) hydrogel layer that swells at low and high pH, respectively. This structure is capable of bending in diverse directions while the pH of the aqueous bath alters. The main characteristic of this structure is having reversible bidirectional bending, which has similar behaviors in both directions, unlike previous hydrogel-elastomer bilayers. Then, we develop an analytical method to solve the swelling-induced bidirectional bending of a pH-sensitive hydrogel bilayer. On the other hand, the finite bending of bilayer structure is studied by the finite element method in several cases to demonstrate the validity and accuracy of the proposed analytical solution. Lastly, the impacts of material composition and geometrical factors are investigated to be used for bilayer actuator design and application.