bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Report: Novel MFSD8 Variants in a Chinese Family With Neuronal Ceroid Lipofuscinoses 7
Authors: Qiao Yimeng , Gu Yang , Cheng Ye , Su Yu , Lv Nan , Shang Qing , Xing Qinghe
Published: January 2022

Neuronal ceroid lipofuscinoses (NCLs) are among the most common progressive encephalopathies of childhood. Neuronal ceroid lipofuscinosis 7 (CLN7), one of the late infantile-onset NCLs, is an autosomal recessive disorder caused by mutations in the MFSD8 gene on chromosome 4q28. Almost all reported mutations of MFSD8 in CLN7 patients were SNVs. However, we report a 4-year-old boy with CLN7 harboring compound heterozygous mutations in the MFSD8 gene, including one novel two-nucleotide deletion c.136_137delAT (p. M46Vfs*22) and one whole gene deletion of MFSD8 confirmed by Sanger sequencing, genomic quantitative PCR and CNV-seq. Therefore, for nonconsanguineous CLN7 patients with homozygous mutations in the MFSD8 gene, genetic counseling staff should focus on the possibility of whole gene deletion. This is one case report describing a whole gene deletion in a Chinese patient with CLN7, suggesting the diagnosis of CLN7 should be based on clinical suspicion and genetic testing.
The Roles of Solute Carriers in Auditory Function
Authors: Qian Fuping , Jiang Xiaoge , Chai Renjie , Liu Dong
Published: January 2022

Solute carriers (SLCs) are important transmembrane transporters with members organized into 65 families. They play crucial roles in transporting many important molecules, such as ions and some metabolites, across the membrane, maintaining cellular homeostasis. SLCs also play important roles in hearing. It has been found that mutations in some SLC members are associated with hearing loss. In this review, we summarize SLC family genes related with hearing dysfunction to reveal the vital roles of these transporters in auditory function. This summary could help us understand the auditory physiology and the mechanisms of hearing loss and further guide future studies of deafness gene identification.
The One That Got Away: How Macrophage-Derived IL-1β Escapes the Mycolactone-Dependent Sec61 Blockade in Buruli Ulcer
Authors: Hall Belinda S. , Hsieh Louise Tzung-Harn , Sacre Sandra , Simmonds Rachel E.
Published: January 2022

Buruli ulcer (BU), caused byMycobacterium ulcerans, is a devastating necrotizing skin disease. Key to its pathogenesis is mycolactone, the exotoxin virulence factor that is both immunosuppressive and cytotoxic. The discovery that the essential Sec61 translocon is the major cellular target of mycolactone explains much of the disease pathology, including the immune blockade. Sec61 inhibition leads to a loss in production of nearly all cytokines from monocytes, macrophages, dendritic cells and T cells, as well as antigen presentation pathway proteins and costimulatory molecules. However, there has long been evidence that the immune system is not completely incapable of responding toM. ulceransinfection. In particular, IL-1β was recently shown to be present in BU lesions, and to be induced fromM. ulcerans-exposed macrophages in a mycolactone-dependent manner. This has important implications for our understanding of BU, showing that mycolactone can act as the “second signal” for IL-1β production without inhibiting the pathways of unconventional secretion it uses for cellular release. In this Perspective article, we validate and discuss this recent advance, which is entirely in-line with our understanding of mycolactone’s inhibition of the Sec61 translocon. However, we also show that the IL-1 receptor, which uses the conventional secretory pathway, is sensitive to mycolactone blockade at Sec61. Hence, a more complete understanding of the mechanisms regulating IL-1β function in skin tissue, including the transient intra-macrophage stage ofM. ulceransinfection, is urgently needed to uncover the double-edged sword of IL-1β in BU pathogenesis, treatment and wound healing.
Examining the Effect of Kindlin-3 Binding Site Mutation on LFA-1-ICAM-1 Bonds by Force Measuring Optical Tweezers
Authors: McDonald Craig , Morrison Vicky L. , McGloin David , Fagerholm Susanna Carola
Published: January 2022

Integrins in effector T cells are crucial for cell adhesion and play a central role in cell-mediated immunity. Leukocyte adhesion deficiency (LAD) type III, a genetic condition that can cause death in early childhood, highlights the importance of integrin/kindlin interactions for immune system function. A TTT/AAA mutation in the cytoplasmic domain of the β2 integrin significantly reduces kindlin-3 binding to the β2 tail, abolishes leukocyte adhesion to intercellular adhesion molecule 1 (ICAM-1), and decreases T cell trafficking in vivo. However, how kindlin-3 affects integrin function in T cells remains incompletely understood. We present an examination of LFA-1/ICAM-1 bonds in both wild-type effector T cells and those with a kindlin-3 binding site mutation. Adhesion assays show that effector T cells carrying the kindlin-3 binding site mutation display significantly reduced adhesion to the integrin ligand ICAM-1. Using optical trapping, combined with back focal plane interferometry, we measured a bond rupture force of 17.85 ±0.63 pN at a force loading rate of 30.21 ± 4.35 pN/s, for single integrins expressed on wild-type cells. Interestingly, a significant drop in rupture force of bonds was found for TTT/AAA-mutant cells, with a measured rupture force of 10.08 ± 0.88pN at the same pulling rate. Therefore, kindlin-3 binding to the cytoplasmic tail of the β2-tail directly affects catch bond formation and bond strength of integrin–ligand bonds. As a consequence of this reduced binding, CD8+ T cell activation in vitro is also significantly reduced.
Identification and Tracking of Alloreactive T Cell Clones in Rhesus Macaques Through the RM-scTCR-Seq Platform
Authors: Gerdemann Ulrike , Fleming Ryan A. , Kaminski James , McGuckin Connor , Rui Xianliang , Lane Jennifer F. , Keskula Paula , Cagnin Lorenzo , Shalek Alex K. , Tkachev Victor , Kean Leslie S.
Published: January 2022

T cell receptor (TCR) clonotype tracking is a powerful tool for interrogating T cell mediated immune processes. New methods to pair a single cell’s transcriptional program with its TCR identity allow monitoring of T cell clonotype-specific transcriptional dynamics. While these technologies have been available for human and mouse T cells studies, they have not been developed for Rhesus Macaques (RM), a critical translational organism for autoimmune diseases, vaccine development and transplantation. We describe a new pipeline, ‘RM-scTCR-Seq’, which, for the first time, enables RM specific single cell TCR amplification, reconstruction and pairing of RM TCR’s with their transcriptional profiles. We apply this method to a RM model of GVHD, and identify and track in vitro detected alloreactive clonotypes in GVHD target organs and explore their GVHD driven cytotoxic T cell signature. This novel, state-of-the-art platform fundamentally advances the utility of RM to study protective and pathogenic T cell responses.
The Role of Immunometabolism in the Pathogenesis of Systemic Lupus Erythematosus
Authors: Robinson George Anthony , Wilkinson Meredyth G. Ll. , Wincup Chris
Published: January 2022

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder in which pathogenic abnormalities within both the innate and adaptive immune response have been described. In order to activated, proliferate and maintain this immunological response a drastic upregulation in energy metabolism is required. Recently, a greater understanding of these changes in cellular bioenergetics have provided new insight into the links between immune response and the pathogenesis of a number of diseases, ranging from cancer to diabetes and multiple sclerosis. In this review, we highlight the latest understanding of the role of immunometabolism in SLE with particular focus on the role of abnormal mitochondrial function, lipid metabolism, and mTOR signaling in the immunological phenomenon observed in the SLE. We also consider what implications this has for future therapeutic options in the management of the disease in future.
The Non-N6-Methyladenosine Epitranscriptome Patterns and Characteristics of Tumor Microenvironment Infiltration and Mesenchymal Transition in Glioblastoma
Authors: Xu Jianye , Gao Zijie , Liu Kaining , Fan Yang , Zhang Zongpu , Xue Hao , Guo Xing , Zhang Ping , Deng Lin , Wang Shaobo , Wang Huizhi , Wang Qingtong , Zhao Rongrong , Li Gang
Published: January 2022

Background

An increasing number of RNA modification types other than N6-methyladenosine (m6A) modification have been detected. Nonetheless, the probable functions of RNA modifications beyond m6A in the tumor microenvironment (TME), mesenchymal (MES) transition, immunotherapy, and drug sensitivity remain unclear.

Methods

We analyzed the characteristics of 32 non-m6A RNA modification regulators in 539 glioblastoma (GBM) patients and the TME cell infiltration and MES transition patterns. Using principal component analysis, a non-m6A epitranscriptome regulator score (RM score) model was established. We estimated the association between RM score and clinical characteristics, TME status, GBM subtypes, and drug and immunotherapy response.

Results

Three definite non-m6A RNA modification patterns associated with diverse biological pathways and clinical characteristics were identified. The high RM score group was characterized by a poor prognosis, enhanced immune infiltration, and MES subtype. Further analysis indicated that the high RM score group had a lower tumor mutation burden as well as a weaker response to immunotherapy. The higher RM score group may benefit more from drugs targeting the EGFR and WNT signaling pathways.

Conclusion

Our study exposed the potential relationship of non-m6A RNA modification regulators with clinical features, TME status, and GBM subtype and clarified its therapeutic value.
Modulation of Macrophage Immunometabolism: A New Approach to Fight Infections
Authors: Gauthier Thierry , Chen Wanjun
Published: January 2022

Macrophages are essential innate immune cells that contribute to host defense during infection. An important feature of macrophages is their ability to respond to extracellular cues and to adopt different phenotypes and functions in response to these stimuli. The evidence accumulated in the last decade has highlighted the crucial role of metabolic reprogramming during macrophage activation in infectious context. Thus, understanding and manipulation of macrophage immunometabolism during infection could be of interest to develop therapeutic strategies. In this review, we focus on 5 major metabolic pathways including glycolysis, pentose phosphate pathway, fatty acid oxidation and synthesis, tricarboxylic acid cycle and amino acid metabolism and discuss how they sustain and regulate macrophage immune function in response to parasitic, bacterial and viral infections as well as trained immunity. At the end, we assess whether some drugs including those used in clinic and in development can target macrophage immunometabolism for potential therapy during infection with an emphasis on SARS-CoV2 infection.
Complete Protection Against Yersinia pestis in BALB/c Mouse Model Elicited by Immunization With Inhalable Formulations of rF1-V10 Fusion Protein via Aerosolized Intratracheal Inoculation
Authors: Zhang Wei , Song Xiaolin , Zhai Lina , Guo Jianshu , Zheng Xinying , Zhang Lili , Lv Meng , Hu Lingfei , Zhou Dongsheng , Xiong Xiaolu , Yang Wenhui
Published: January 2022

Pneumonic plague, caused by Yersinia pestis, is an infectious disease with high mortality rates unless treated early with antibiotics. Currently, no FDA-approved vaccine against plague is available for human use. The capsular antigen F1, the low-calcium-response V antigen (LcrV), and the recombinant fusion protein (rF1-LcrV) of Y. pestis are leading subunit vaccine candidates under intense investigation; however, the inability of recombinant antigens to provide complete protection against pneumonic plague in animal models remains a significant concern. In this study, we compared immunoprotection against pneumonic plague provided by rF1, rV10 (a truncation of LcrV), and rF1-V10, and vaccinations delivered via aerosolized intratracheal (i.t.) inoculation or subcutaneous (s.c.) injection. We further considered three vaccine formulations: conventional liquid, dry powder produced by spray freeze drying, or dry powder reconstituted in PBS. The main findings are: (i) rF1-V10 immunization with any formulation via i.t. or s.c. routes conferred 100% protection against Y. pestis i.t. infection; (ii) rF1 or rV10 immunization using i.t. delivery provided significantly stronger protection than rF1 or rV10 immunization via s.c. delivery; and (iii) powder formulations of subunit vaccines induced immune responses and provided protection equivalent to those elicited by unprocessed liquid formulations of vaccines. Our data indicate that immunization with a powder formulation of rF1-V10 vaccines via an i.t. route may be a promising vaccination strategy for providing protective immunity against pneumonic plague.
No Genetic Causal Association Between Periodontitis and Arthritis: A Bidirectional Two-Sample Mendelian Randomization Analysis
Authors: Yin Kang-Jia , Huang Ji-Xiang , Wang Peng , Yang Xiao-Ke , Tao Sha-Sha , Li Hong-Miao , Ni Jing , Pan Hai-Feng
Published: January 2022

Objectives

Periodontitis (PD) has been linked to arthritis in previous epidemiological observational studies; however, the results are inconclusive. It remains unclear whether the association between PD and arthritis is causal. The purpose of this study was to investigate the causal association of PD with arthritis, including rheumatoid arthritis (RA) and osteoarthritis (OA).

Methods

We performed a two-sample bidirectional Mendelian randomization (MR) analysis using publicly released genome-wide association studies (GWAS) statistics. The inverse-variance weighted (IVW) method was used as the primary analysis. We applied four complementary methods, including weighted median, weighted mode, MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) to detect and correct for the effect of horizontal pleiotropy.

Results

Genetically determined PD did not have a causal effect on OA (OR = 1.06, 95% CI: 0.99-1.15, P = 0.09) and RA (OR = 0.99, 95% CI: 0.87-1.13, P = 0.89). Furthermore, we did not find a significant causal effect of arthritis on PD in the reverse MR analysis. The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. Horizontal pleiotropy was unlikely to distort the causal estimates according to the sensitivity analysis.

Conclusions

Our MR analysis reveals non-causal association of PD with arthritis, despite observational studies reporting an association between PD and arthritis.
Hydroxyapatite Growth on Poly(Dimethylsiloxane-Block-ε-Caprolactone)/Tricalcium Phosphate Coatings Obtained by Electrophoretic Deposition
Authors: Redondo Franco Leonardo , Giaroli María Carolina , Ciolino Andrés Eduardo , Ninago Mario Daniel
Published: January 2022

For the first time, composite coatings based on poly(dimethylsiloxane-block-ε-caprolactone) copolymer and tricalcium phosphate were obtained on stainless steel plates by using the electrophoretic deposition technique. The effect of different deposition times on the final characteristics of the resulting coatings was also studied. Block copolymers were obtained through a combination of anionic and ring-opening polymerization, with good homogeneity and chemical composition (Ð < 1.3 and wPCL = 0.39). The composites obtained at different electrophoretic deposition times revealed a linear dependence between the deposited weight and time during assays. When immersing in simulated body fluid, a higher amount of residual solids ( ∼ 20 %) were observed by thermogravimetric analysis after 7 days of immersion. Scanning electron microscopy micrographs revealed a porous microstructure over the metallic substrate and the absence of micro-cracks, and X-ray diffraction patterns exhibited diffraction peaks associated with a hydroxyapatite layer. Finally, energy-dispersive X-ray analysis revealed values of the Ca/P ratio between 1.40 and 1.50 in samples, which are closer to the stoichiometric hydroxyapatite values reported in hard tissues. The results obtained in this article confirm the usefulness of poly(dimethylsiloxane-block-ε-caprolactone) copolymer and cheaper tricalcium phosphate as precursors of compact and homogenous coatings obtained by electrophoretic deposition, which yields useful substrates for hydroxyapatite growth.
Eco-Friendly Anticorrosion Superhydrophobic Al2O3@PDMS Coating With Salt Deliquescence Self-Coalescence Behaviors Under High Atmospheric Humidity
Authors: Zhang Binbin , Yan Jiayang , Xu Weichen , Yu Teng , Chen Zhuoyuan , Duan Jizhou
Published: January 2022

Bio-inspired superhydrophobic coatings have been demonstrated to be promising anticorrosion materials. However, developing robust superhydrophobic coatings through simple one-step fluorine-free procedures to meet various functional requirements remains a major challenge. In this study, we fabricated an eco-friendly superhydrophobic Al2O3@PDMS composite coating with mechanical robustness based on Al2O3 NPs, PDMS, and spray coating technique. To characterize surface morphologies, chemical compositions, surface wettability, and anticorrosion properties, FE-SEM, EDS, XPS, contact angle meter, electrochemical impendence spectroscopy, and potentiodynamic polarization techniques were employed. The electrochemical results show that |Z|0.01 Hz and Rct values of the superhydrophobic Al2O3@PDMS coating were four orders of magnitude higher than bare Q235 carbon steel, indicating a significant improvement in corrosion resistance. Furthermore, the deliquescence behaviors of NaCl salt particles and the instantaneous self-coalescence phenomenon were recorded under high atmospheric humidity to suggest that a superhydrophobic surface with Cassie–Baxter interfacial contacts can serve as an efficient barrier to suppress the formation of saline liquid thin films and protect the underlying substrate from corrosion. This robust superhydrophobic Al2O3@PDMS coating is expected to be easily applied to a variety of substrates and to find potential applications for liquid repellency, self-cleaning, corrosion resistance, and other properties.
Dramatic Therapeutic Response to Dabrafenib Plus Trametinib in BRAF V600E Mutated Papillary Craniopharyngiomas: A Case Report and Literature Review
Authors: Fasano Morena , Della Corte Carminia Maria , Caterino Marianna , Pirozzi Mario , Rauso Raffaele , Troiani Teresa , Martini Giulia , Napolitano Stefania , Morgillo Floriana , Ciardiello Fortunato
Published: January 2022

Background

Craniopharyngioma is a rare intracranial tumor, with a high morbidity rate due to its common refractiveness to conventional treatments. BRAF V600E mutation has recently been identified as the principal oncogenic molecular driver of papillary craniopharyngiomas (PCP), one of the two main variants of craniopharyngioma.

Case Presentation

A 49-year-old man with recurrent craniopharyngioma, harboring BRAF V600E mutation, has been treated with targeted therapy based on a combination of a BRAF-inhibitor, dabrafenib (150 mg, orally two times daily), and a MEK-inhibitor, trametinib (2 mg, orally two times daily). Before starting treatment, the patient was symptomatic: he lamented confusion, dysphasia, and intense fatigue, that did not allow him to work normally. After just one cycle of treatment, the patient showed an important clinical improvement, reporting a progressive regression of the basal symptoms, hinting at a rapid and dramatic response, which was confirmed at the first radiological assessment. Thus, treatment was continued and at the time of writing, the treatment is still ongoing (total duration of treatment: 14 months) and it is well tolerated, with very good quality of life: the patient has no limitations in daily activities and he has even been able to restart to work.

Conclusion

The use of targeted therapies—as a clinical practice or in clinical trials—represents an important therapeutic alternative and a great evolution for patients' prognosis vs. the standard of care, historically represented by unselected chemotherapies. The discovery of the BRAF V600E mutation in patients with PCP is very rare, resulting in a lack of data on the efficacy of the combination of dabrafenib and trametinib.
Reconstructing the Effectiveness of Policy Measures to Avoid Next-Wave COVID-19 Infections and Deaths Using a Dynamic Simulation Model: Implications for Health Technology Assessment
Authors: Hagens Arnold , Cordova-Pozo Kathya , Postma Maarten , Wilschut Jan , Zino Lorenzo , van der Schans Jurjen
Published: January 2022

Objective

The goal of this study was to dynamically model next-wave scenarios to observe the impact of different lockdown measures on the infection rates (IR) and mortality for two different prototype countries, mimicking the 1st year of the COVID-19 pandemic in Europe.

Methods

A dynamic simulation SIRD model was designed to assess the effectiveness of policy measures on four next-wave scenarios, each preceded by two different lockdowns. The four scenarios were (1) no-measures, (2) uniform measures, (3) differential measures based on isolating > 60 years of age group, and (4) differential measures with additional contact reduction measures for the 20–60 years of age group. The dynamic simulation model was prepared for two prototype European countries, Northwestern (NW) and Southern (S) country. Both prototype countries were characterized based on age composition and contact matrix.

Results

The results show that the outcomes of the next-wave scenarios depend on number of infections of previous lockdowns. All scenarios reduce the incremental deaths compared with a no-measures scenario. Differential measures show lower number of deaths despite an increase of infections. Additionally, prototype S shows overall more deaths compared with prototype NW due to a higher share of older citizens.

Conclusion

This study shows that differential measures are a worthwhile option for controlling the COVID-19 epidemic. This may also be the case in situations where relevant parts of the population have taken up vaccination. Additionally, the effectiveness of interventions strongly depends on the number of previously infected individuals. The results of this study may be useful when planning and forecasting the impact of non-pharmacological interventions and vaccination campaigns.
Different Circulation Pattern of Multiple Respiratory Viruses in Southern China During the COVID-19 Pandemic
Authors: Zeng Zhiqi , Guan Wenda , Liu Yong , Lin Zhengshi , Liang Wenhua , Liang Jingyi , Chen Bingqian , Wu Tong , Wang Yutao , Yang Chunguang , Wu Qiubao , Mai Zhitong , Zhou Jinchao , Zhou Junhou , Wang Zhoulang , Lin Zhijie , Hu Chaohui , Wu Chunqiu , Zhu Pengyuan , Chen Canxiong , Zhong Nanshan , Lau Eric H. Y. , Hon Chitin , Liang Yaoming , Yang Zifeng , He Jianxing
Published: January 2022

China implemented stringent non-pharmaceutical interventions (NPIs) in spring 2020, which has effectively suppressed SARS-CoV-2. In this study, we utilized data from routine respiratory virus testing requests from physicians and examined circulation of 11 other respiratory viruses in Southern China, from January 1, 2018 to December 31, 2020. A total of 58,169 throat swabs from patients with acute respiratory tract infections (ARTIs) were collected and tested. We found that while the overall activity of respiratory viruses was lower during the period with stringent NPIs, virus activity rebounded shortly after the NPIs were relaxed and social activities resumed. Only influenza was effectively suppressed with very low circulation which extended to the end of 2020. Circulation of other respiratory viruses in the community was maintained even during the period of stringent interventions, especially for rhinovirus. Our study shows that NPIs against COVID-19 have different impacts on respiratory viruses.
Nitrogen Advanced Treatment of Urban Sewage by Denitrification Deep-Bed Filter: Removal Performance and Metabolic Pathway
Authors: Huang Xiao , Xing Yixiao , Wang Hongjie , Dai Zhongyi , Chen Tiantian
Published: January 2022

This study aimed to explore the performance of denitrification deep-bed filter (DN-DBF) to treat municipal sewage for meeting a more stringent discharge standard of total nitrogen (TN) (10.0 mg L–1). A lab-scale DN-DBF was conducted to optimize operation parameters and reveal the microbiological mechanism for TN removal. The results showed that more than 12.7% TN removal was obtained by adding methanol compared with sodium acetate. The effluent TN concentration reached 6.0–7.0 mg L–1 with the optimal influent carbon and nitrogen ratio (C/N) and hydraulic retention time (HRT) (3:1 and 0.25 h). For the nitrogen removal mechanism, Blastocatellaceae_Subgroup_4 and norank_o_JG30-KF-CM45 were dominant denitrification floras with an abundance of 6–10%. Though large TN was removed at the top layer of DN-DBF, microbial richness and diversity at the middle layer were higher than both ends. However, the relative abundance of nitrite reductase enzymes (EC1.7.2.1) gradually increases as the depth increases; conversely, the relative abundance of nitrous oxide reductase gradually decreased.
Lactic Acid Bacteria as Biopreservation Against Spoilage Molds in Dairy Products – A Review
Authors: Shi Ce , Maktabdar Maryam
Published: January 2022

Mold spoilage of dairy products such as yogurt is a concern in dairy industry. Not only does it lead to substantial food waste, economic losses, and even brand image damage, but it may also cause public health concern due to the potential production of mycotoxin. Good hygiene practices are necessary to prevent contamination, but contamination may nevertheless occur at the production site and, not least, at the site of the consumer. In recent years, there has been a growing interest from consumers for “clean label” food products, which are natural, less-processed, and free of added, chemical preservatives, and a wish for shelf lives of considerable length in order to minimize food waste. This has sparked an interest in using lactic acid bacteria (LAB) or their metabolites as biopreservatives as a way to limit the growth of spoilage organisms in dairy products. A range of compounds produced by LAB with potential antifungal activity have been described as contributing factors to the inhibitory effect of LAB. More recently, growth inhibition effects caused by specific competitive exclusion have been elucidated. It has also become clear that the sensitivity toward both individual antifungal compounds and competition mechanisms differ among molds. In this review, the main spoilage molds encountered in dairy products are introduced, and an overview of the antifungal activity of LAB against different spoilage molds is presented including the main antifungal compounds derived from LAB cultures and the sensitivity of the spoilage molds observed toward these compounds. The recent findings of the role of competitive exclusion with emphasis on manganese depletion and the possible implications of this for biopreservation are described. Finally, some of the knowledge gaps, future challenges, and trends in the application of LAB biopreservation in dairy products are discussed.
Distinct Co-occurrence Relationships and Assembly Processes of Active Methane-Oxidizing Bacterial Communities Between Paddy and Natural Wetlands of Northeast China
Authors: Liu Xu , Shi Yu , Yang Teng , Gao Gui-Feng , Zhang Liyan , Xu Ruoyu , Li Chenxin , Liu Ruiyang , Liu Junjie , Chu Haiyan
Published: January 2022

Studies of methane-oxidizing bacteria are updating our views of their composition and function in paddy and natural wetlands. However, few studies have characterized differences in the methane-oxidizing bacterial communities between paddy and natural wetlands. Here, we conducted a 13C stable isotope-probing experiment and high-throughput sequencing to determine the structure profiling, co-occurrence relationships, and assembly processes of methanotrophic communities in four wetlands of Northeast China. There was a clear difference in community structure between paddy and natural wetlands. LEfSe analyses revealed that Methylobacter, FWs, and Methylosinus were enriched in natural wetlands, while Methylosarcina were prevailing in paddy, all identified as indicative methanotrophs. We observed distinct co-occurrence relationships between paddy and natural wetlands: more robust and complex connections in natural wetlands than paddy wetlands. Furthermore, the relative importance of stochastic processes was greater than that of deterministic processes, as stochastic processes explained >50% of the variation in communities. These results demonstrated that the co-occurrence relationships and assembly processes of active methanotrophic communities in paddy and natural wetlands were distinct. Overall, the results of this study enhance our understanding of the communities of methane-oxidizing bacteria in paddy and natural wetlands of Northeast China.
Global Phosphoproteomics Analysis of IBRS-2 Cells Infected With Senecavirus A
Authors: Li Jieyi , Zhang Zhongwang , Lv Jianliang , Ma Zhongyuan , Pan Li , Zhang Yongguang
Published: January 2022

Phosphorylation is a widespread posttranslational modification that regulates numerous biological processes. Viruses can alter the physiological activities of host cells to promote virus particle replication, and manipulating phosphorylation is one of the mechanisms. Senecavirus A (SVA) is the causative agent of porcine idiopathic vesicular disease. Although numerous studies on SVA have been performed, comprehensive phosphoproteomics analysis of SVA infection is lacking. The present study performed a quantitative mass spectrometry-based phosphoproteomics survey of SVA infection in Instituto Biologico-Rim Suino-2 (IBRS-2) cells. Three parallel experiments were performed, and 4,520 phosphosites were quantified on 2,084 proteins. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that many phosphorylated proteins were involved in apoptosis and spliceosome pathways, and subcellular structure localization analysis revealed that more than half were located in the nucleus. Motif analysis of proteins with differentially regulated phosphosites showed that proline, aspartic acid, and glutamic acid were the most abundant residues in the serine motif, while proline and arginine were the most abundant in the threonine motif. Forty phosphosites on 27 proteins were validated by parallel reaction monitoring (PRM) phosphoproteomics, and 30 phosphosites in 21 proteins were verified. Nine proteins with significantly altered phosphosites were further discussed, and eight [SRRM2, CDK13, DDX20, DDX21, BAD, ELAVL1, PDZ-binding kinase (PBK), and STAT3] may play a role in SVA infection. Finally, kinase activity prediction showed 10 kinases’ activity was reversed following SVA infection. It is the first phosphoproteomics analysis of SVA infection of IBRS-2 cells, and the results greatly expand our knowledge of SVA infection. The findings provide a basis for studying the interactions of other picornaviruses and their mammalian host cells.
Brain Morphometry and Cognitive Performance in Normal Brain Aging: Age- and Sex-Related Structural and Functional Changes
Authors: Statsenko Yauhen , Habuza Tetiana , Smetanina Darya , Simiyu Gillian Lylian , Uzianbaeva Liaisan , Neidl-Van Gorkom Klaus , Zaki Nazar , Charykova Inna , Al Koteesh Jamal , Almansoori Taleb M. , Belghali Maroua , Ljubisavljevic Milos
Published: January 2022

Background

The human brain structure undergoes considerable changes throughout life. Cognitive function can be affected either negatively or positively. It is challenging to segregate normal brain aging from the accelerated one.

Objective

To work out a descriptive model of brain structural and functional changes in normal aging.

Materials and Methods

By using voxel-based morphometry and lesion segmentation along with linear statistics and machine learning (ML), we analyzed the structural changes in the major brain compartments and modeled the dynamics of neurofunctional performance throughout life. We studied sex differences in lifelong dynamics of brain volumetric data with Mann-Whitney U-test. We tested the hypothesis that performance in some cognitive domains might decline as a linear function of age while other domains might have a non-linear dependence on it. We compared the volumetric changes in the major brain compartments with the dynamics of psychophysiological performance in 4 age groups. Then, we tested linear models of structural and functional decline for significant differences between the slopes in age groups with the T-test.

Results

White matter hyperintensities (WMH) are not the major structural determinant of the brain normal aging. They should be viewed as signs of a disease. There is a sex difference in the speed and/or in the onset of the gray matter atrophy. It either starts earlier or goes faster in males. Marked sex difference in the proportion of total cerebrospinal fluid (CSF) and intraventricular CSF (iCSF) justifies that elderly men are more prone to age-related brain atrophy than women of the same age.

Conclusion

The article gives an overview and description of the conceptual structural changes in the brain compartments. The obtained data justify distinct patterns of age-related changes in the cognitive functions. Cross-life slowing of decision-making may follow the linear tendency of enlargement of the interhemispheric fissure because the center of task switching and inhibitory control is allocated within the medial wall of the frontal cortex, and its atrophy accounts for the expansion of the fissure. Free online tool at https://med-predict.com illustrates the tests and study results.
Unique Phenotypes With Corresponding Pathology in Late-Onset Hereditary Transthyretin Amyloidosis of A97S vs. V30M
Authors: Hsueh Hsueh-Wen , Chao Chi-Chao , Chang Koping , Jeng Yung-Ming , Katsuno Masahisa , Koike Haruki , Hsieh Sung-Tsang
Published: January 2022

Objective

Hereditary transthyretin amyloidosis (ATTRv) encompasses different phenotypes among various genotypes. The analysis of the natural history and risk factors of faster progression in different genotypes would refine the treatment strategy.

Methods

The clinical manifestations of ATTRv from A97S (p.A117S) of Taiwanese and late-onset V30M (p.V50M) of Japanese were compared. An autopsy study of A97S was performed.

Results

There existed three unique features in the A97S cohort compared to the V30M cohort: (1) dysphagia, (2) carpal tunnel syndrome (CTS), and (3) onset age. First, dysphagia was common in A97S (53.4%) but not in V30M and served as a contributor to fast disease progression. All phases of swallowing were affected. In the autopsy pathology, there were extensive amyloid deposits in the viscera and nerves of the tongue, larynx, and esophagus. In A97S, 45 patients (43.3%) had a history of CTS before the onset of length-dependent symptoms by 3 years. The amyloid deposition was more prominent in the median nerve than that in the transverse carpal ligament. The onset age at different stages was younger in the A97S cohort than the V30M cohort by 4–5 years.

Conclusion

These phenotypic characteristics together with autopsy pathology in A97S are distinct from V30M. Early dysphagia in A97S correlated with fast progression. In A97S, median neuropathy leading to CTS might be in a continuous spectrum of ATTRv course rather than an independent disease entity. Such observations may serve as a foundation to explore and analyze unique phenotypes among various genotypes.
Regulation of Hippocampal Gamma Oscillations by Modulation of Intrinsic Neuronal Excitability
Authors: Klemz Alexander , Wildner Florian , Tütüncü Ecem , Gerevich Zoltan
Published: January 2022

Ion channels activated around the subthreshold membrane potential determine the likelihood of neuronal firing in response to synaptic inputs, a process described as intrinsic neuronal excitability. Long-term plasticity of chemical synaptic transmission is traditionally considered the main cellular mechanism of information storage in the brain; however, voltage- and calcium-activated channels modulating the inputs or outputs of neurons are also subjects of plastic changes and play a major role in learning and memory formation. Gamma oscillations are associated with numerous higher cognitive functions such as learning and memory, but our knowledge of their dependence on intrinsic plasticity is by far limited. Here we investigated the roles of potassium and calcium channels activated at near subthreshold membrane potentials in cholinergically induced persistent gamma oscillations measured in the CA3 area of rat hippocampal slices. Among potassium channels, which are responsible for the afterhyperpolarization in CA3 pyramidal cells, we found that blockers of SK (KCa2) and KV7.2/7.3 (KCNQ2/3), but not the BK (KCa1.1) and IK (KCa3.1) channels, increased the power of gamma oscillations. On the contrary, activators of these channels had an attenuating effect without affecting the frequency. Pharmacological blockade of the low voltage-activated T-type calcium channels (CaV3.1–3.3) reduced gamma power and increased the oscillation peak frequency. Enhancement of these channels also inhibited the peak power without altering the frequency of the oscillations. The presented data suggest that voltage- and calcium-activated ion channels involved in intrinsic excitability strongly regulate the power of hippocampal gamma oscillations. Targeting these channels could represent a valuable pharmacological strategy against cognitive impairment.
Circadian Strain, Light Exposure, and Depressive Symptoms in Rural Communities of Southern Brazil
Authors: Pilz Luísa K. , Xavier Nicóli B. , Levandovski Rosa , Oliveira Melissa A. B. , Tonon André C. , Constantino Débora B. , Machado Valdomiro , Roenneberg Till , Hidalgo Maria Paz
Published: January 2022

Irregular light–dark cycles and circadian/sleep disturbances have been suggested as risk or co-occurring factors in depression. Among a set of metrics developed to quantify strain on the circadian system, social jetlag (SJL) has been put forward as a measure of the discrepancy between biological and social clocks. Here, we approached the question on whether light exposure and SJL would also be associated with depressive symptoms in Quilombola communities in Southern Brazil. These rural communities are void of potential confounders of modern lifestyles and show low levels of SJL. 210 Quilombolas (age range 16–92; 56% women) were asked about their sleep times and light exposure using the Munich ChronoType Questionnaire (MCTQ). The Beck Depression Inventory (BDI) was used to assess depressive symptoms. Additionally, we analyzed 7-day actimetry recordings in 124 subjects. BDI scores higher than 10 (having clinically significant depressive symptoms; controlled for age and sex in the multivariate analysis) were positively associated with SJL >1 h and negatively associated with median light exposure during the day, especially in the morning from 8:00 to 10:00. Our results suggest that low light exposure during the day, and higher levels of SJL are associated with depressive symptoms; longitudinal and experimental studies are needed to understand the underlying mechanisms. Nevertheless, we highlight the potential of treatment strategies aimed at decreasing circadian strain and insufficient light exposure, which are suggested as areas of further research in Psychiatry.
Neurogenic Dysphagia in Subdural Hematoma
Authors: Won Sae-Yeon , Krieger Simon , Dubinski Daniel , Gessler Florian , Behmanesh Bedjan , Freiman Thomas M. , Konczalla Juergen , Seifert Volker , Lapa Sriramya
Published: January 2022

Introduction

Dysphagia is a common and severe symptom of traumatic brain injury (TBI) affecting up to 78% of patients. It is associated with pneumonia, increased morbidity, and mortality. Although subdural hematoma (SDH) accounts for over 50% of TBI, the occurrence of dysphagia in this subtype has not been investigated yet.

Methods

All patients with SDH admitted to the author's institution between the years 2007 and 2020 were included in the study. Patients with SDH and clinical suspicion for dysphagia received a clinical swallowing assessment by a speech and language pathologist (SLP). Furthermore, the severity of dysphagia was rated according to swallowing disorder scale. Functional outcome was evaluated by the Glasgow outcome scale (GOS).

Results

Out of 545 patients with SDH, 71 patients had dysphagia (13%). The prevalence of dysphagia was significantly lower in the surgical arm compared to the conservative arm (11.8 vs. 21.8%; OR 0.23; p = 0.02). Independent predictors for dysphagia were GCS <13 at admission (OR 4.17; p < 0.001), cardiovascular disease (OR 2.29; p = 0.002), and pneumonia (OR 2.88; p = 0.002), whereas the operation was a protective factor (OR 0.2; p < 0.001). In a subgroup analysis, right-sided SDH was an additional predictor for dysphagia (OR 2.7; p < 0.001). Overall, patients with dysphagia improved significantly under the SLP treatment from the initial diagnosis to hospital discharge (p < 0.01). However, a subgroup of patients with the most severe grade of dysphagia showed no significant improvement. Patients with dysphagia had significantly worse outcomes (GOS 1–3) compared to those without dysphagia (48.8 vs. 26.4%; p < 0.001).

Conclusion

Dysphagia is a frequent symptom in SDH, and the early identification of dysphagia is crucial regarding the initiation of treatment and functional outcome. Surgery is effective in preventing dysphagia and should be considered in high-risked patients.
An fNIRS Study of Brain Lateralization During Observation and Execution of a Fine Motor Task
Authors: Khaksari Kosar , Smith Elizabeth G. , Miguel Helga O. , Zeytinoglu Selin , Fox Nathan , Gandjbakhche Amir H.
Published: January 2022

Brain activity in the action observation network (AON) is lateralized during action execution, with greater activation in the contralateral hemisphere to the side of the body used to perform the task. However, it is unknown whether the AON is also lateralized when watching another person perform an action. In this study, we use fNIRS to measure brain activity over the left and right cortex while participants completed actions with their left and right hands and watched an actor complete action with their left and right hands. We show that while activation is lateralized when the participants themselves are moving, brain lateralization is not affected by the side of the body when the participant is observing another person’s action. In addition, we demonstrate that individual differences in hand preference and dexterity between the right and left hands are related to brain lateralization patterns.
Breast Milk: A Meal Worth Having
Authors: Duale Anoud , Singh Parul , Al Khodor Souhaila
Published: January 2022

A mother is gifted with breast milk, the natural source of nutrition for her infant. In addition to the wealth of macro and micro-nutrients, human milk also contains many microorganisms, few of which originate from the mother, while others are acquired from the mouth of the infant and the surroundings. Among these microbes, the most commonly residing bacteria are Staphylococci, Streptococci, Lactobacilli and Bifidobacteria. These microorganisms initiate and help the development of the milk microbiota as well as the microbiota of the gastrointestinal tract in infants, and contribute to developing immune regulatory factors such as cytokines, growth factors, lactoferrin among others. These factors play an important role in reducing the risk of developing chronic diseases like type 2 diabetes, asthma and others later in life. In this review, we will summarize the known benefits of breastfeeding and highlight the role of the breast milk microbiota and its cross-talk with the immune system in breastfed babies during the early years of life.
Prevotella histicola Mitigated Estrogen Deficiency-Induced Depression via Gut Microbiota-Dependent Modulation of Inflammation in Ovariectomized Mice
Authors: Huang Furong , Liu Xiujie , Xu Sheng , Hu Sitao , Wang Sisi , Shi Dibang , Wang Kaicheng , Wang Zhongxiang , Lin Qiongqiong , Li Shan , Zhao Siyuan , Jin KeKe , Wang Chuang , Chen Lei , Wang Fangyan
Published: January 2022

Background

Estrogen deficiency-induced depression is closely associated with an imbalance in intestinal microbiota and inflammation. Prevotella histicola (P. histicola), an emerging probiotic, apparently improves inflammatory responses. This study aims to verify the antidepressant-like effects of P. histicola and clarify its potential mechanisms.

Methods

Mice were treated with P. histicola and cohousing after ovariectomy (OVX). The changes in depression-like behaviors among mice were examined by behavioral tasks, and alterations in the microbiota were detected through 16S rRNA sequencing. Changes in neuronal injury, protein synthesis, inflammatory factors, intestinal permeability, and nerve proliferation were observed by H&E, Nissl staining, qRT-PCR, western blotting, and immunofluorescence.

Results

P. histicola significantly reduces depression-like behaviors and neuronal damage induced by estrogen deficiency. Additionally, P. histicola significantly increases the abundance of intestinal flora, especially Lactobacillus and Akkermansia. Meanwhile, the cohoused mice also had a better emotional state and neutral structure compared with OVX mice. P. histicola was also found to upregulate tight junction proteins ZO-1, occludin, claudin-1, and MUC2 in the ileum and colon and reduce the levels of inflammatory factors VCAM, MCP-1, IL-6, IL-8, and TNF-α, mainly in the ileum, colon, and decrease the expression of COX-2, TLR4, Myd88, JNK, MCP-1, IL-6, IL-8, and TNF-α in the hippocampus. Moreover, significant downregulation of apoptosis (caspase-3 and caspase-8) and upregulation of neurotrophic factors (BDNF and Ki-67) were observed after P. histicola treatment.

Conclusion

Our data show that P. histicola significantly mitigates depression of OVX mice through improvement in intestinal microbiota to repair intestinal leakage and inhibit central inflammation to promote the expression of BDNF for hippocampal neurogenesis. P. histicola may be therapeutically beneficial for PMD.
Recent Progress in Understanding the Action of Natural Compounds at Novel Therapeutic Drug Targets for the Treatment of Liver Cancer
Authors: Zheng Yannan , Zhang Wenhui , Xu Lin , Zhou Hua , Yuan Man , Xu Hongxi
Published: January 2022

Liver cancer is the third most common cause of cancer-related death following lung and stomach cancers. As a highly lethal disease, liver cancer is diagnosed frequently in less developed countries. Natural compounds extracted from herbs, animals and natural materials have been adopted by traditional Chinese medicine (TCM) practices and reported to be effective in the development of new medications for the treatment of diseases. It is important to focus on the mechanisms of action of natural compounds against hepatocellular carcinoma (HCC), particularly in terms of cell cycle regulation, apoptosis induction, autophagy mediation and cell migration and invasion. In this review, we characterize novel representative natural compounds according to their pharmacologic effects based on recently published studies. The aim of this review is to summarize and explore novel therapeutic drug targets of natural compounds, which could accelerate the discovery of new anticancer drugs.