bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship Between Growth Trajectories and Functional Traits for Woody Trees in a Secondary Tropical Forest
Authors: Scalon Marina Corrêa , Bohn Amabily , Coelho Geraldo Ceni , Meister Luana , Alves Rangel de Freitas , Secco Rubia Tatiana , Zwiener Victor P. , Marcilio-Silva Vinicius , Trindade Weverton C. F. , Marques Marcia C. M.
Published: January 2022

Absolute growth rates change with tree size and age, shifting throughout species ontogeny. The study on interspecific variation in plant traits has generated important insights into the life-history strategies and their consequences for ecosystem functioning. However, it remains unknown to what extent – and even if – species’ functional traits are related to the variation in their growth trajectories. We set out to model growth trajectories of 45 woody species from the Brazilian Atlantic Forest in a secondary subtropical forest under regeneration, aiming to understand if species can be grouped by their growth patterns throughout ontogeny and if these groups could be classified in distinct ecological strategies based on key plant traits. We used a maximum likelihood estimation approach to predict growth trajectories using three ecologically relevant parameters [maximum growth rate (Gmax), diameter at maximum growth rate (Dopt), and the ontogenetic variability in growth rate (K)] followed by multivariate analyses to detect associations among phylogenetic relationships, plant traits, and growth parameters and classify species into growth pattern groups. Across species, growth trajectory parameters varied widely. The cluster analysis identified three distinct groups based on growth trajectories parameters, which were not functionally or ecologically well defined. Our findings supports the idea that traits describing plant size and tree shape, such as maximum height, canopy volume and height to diameter ratio, were generally the best predictors of species growth parameters throughout ontogeny, even though traits representing resource-use and reproductive strategies also played a significant role. Growth-trait framework can be understood as a continuum of multi-trait combinations where, at one end of the gradient, we find trees with higher growth rate and larger diameters supporting a voluminous canopy combined with lower investment in leaf tissue and smaller diaspore; at the other end, taller trees supporting a smaller canopy with higher investment in leaf tissue and longer diaspore. Ultimately, we have shown that tree architecture, leaf and reproductive traits significantly influence growth trajectory along tree ontogeny, which may be the reason why objectively grouping species based on growth-trajectories parameters is ineffective, at least in highly diverse secondary subtropical forests undergoing regeneration.
C4BPA: A Novel Co-Regulator of Immunity and Fat Metabolism in the Bovine Mammary Epithelial Cells
Authors: Iqbal Ambreen , Ziyi Pan , Yu Haibin , Jialing Li , Haochen Wu , Jing Fan , Ping Jiang , Zhihui Zhao
Published: January 2022

The C4b binding protein alpha (C4BPA) chain primarily engages in critical inflammatory and coagulation processes. The previous transcriptomic analysis showed that C4BPA is a differentially expressed gene in lower and higher fat content mammary gland cell lines from Chinese Holstein. This study aimed to investigate the effects of C4BPA on the inflammation and milk fat synthesis in bMECs by C4BPA knockdown and overexpression. The results highlighted that knockdown of C4BPA in bMECs could suppress the mRNA and protein expression of IL-6, IL-8, IL-12, and the TLR-4/NF-κB pathway-related genes and promote the expression of complement and coagulation cascade pathways related genes as well as TNF-α. Moreover, knockdown of C4BPA expression in bMECs reduced the content of triglyceride (TG) and cholesterol (CHOL) in bMECs, increased NEFA content, reduced mRNA and protein expression of ACSL1 and PPARA, and increased the mRNA and protein expression of ELOVL6, FADS1, and LPL. The bMECs, with the overexpression of C4BPA, showed the enhanced expression of TLR-4/NF-κB linked genes, IL-6, IL-8, IL-12, and mRNA and protein level while reduced mRNA expression of TNF-α, compliment, and coagulation cascade related genes was observed. In bMECs, overexpression of C4BPA enhanced the content of TG and CHOL while reducing NEFA and stimulated the mRNA and protein expression of ACSL1, PPARA, and PPARG genes while inhibiting the mRNA and protein expression of FADS1 and LPL genes. Our results show that C4BPA not only regulates the lipid metabolism through the PPAR signaling pathway in bMECs but also contributes to the inflammatory response through TLR-4/NF-κB and the complement and coagulation cascade pathways. This study, for the first time, provides the primary basis for understanding the role of C4BPA in immunity and fat metabolism, which enables the researchers for innovative direction to investigate genes associated with fat metabolism and immunity. This study also advocates that the breeders must pay attention to such type of genes with multiple functions during animal breeding.
Self-Assured and Sober: The Relationship Between Maternal Parenting Sense of Competence, Stress, and Alcohol Use
Authors: Johnson Erin , Fellowes Rebecca , Cant Kelsie , Hunt Sally
Published: January 2022

Alcohol misuse is widespread, creating serious health and parenting harms. It is important to explore the motivations behind why people drink and the modifiable factors determining severity of the behavior. While alcohol-related research has historically focused on men, the closing gender gap in alcohol consumption highlights a need for targeted research on women. Parenting stress is a commonly reported motivation for maternal drinking. Likewise, parenting stress is associated with parenting sense of competence. However, there is no research connecting parenting sense of competence with alcohol use directly, nor indirectly via moderation of the alcohol and parenting stress relationship. The current study explored these associations and investigated the potential moderation through a questionnaire completed by a sample of 406 mothers. There were significant correlations between all factors, however, parenting sense of competence was not a significant moderator of the parenting stress and alcohol use relationship. Specifically, as a mother's parenting stress increases, her confidence in the parenting role tends to decline and she is more likely to misuse alcohol. Despite this, variation in parenting sense of competence among women was not significantly correlated with one's likelihood to drink when coping with stress. Further exploration of these relationships is required, with replication of the current study following the COVID-19 pandemic.
Single-Cell Technologies for the Study of Antibody-Secreting Cells
Authors: Broketa Matteo , Bruhns Pierre
Published: January 2022

Antibody-secreting cells (ASC), plasmablasts and plasma cells, are terminally differentiated B cells responsible for large-scale production and secretion of antibodies. ASC are derived from activated B cells, which may differentiate extrafollicularly or form germinal center (GC) reactions within secondary lymphoid organs. ASC therefore consist of short-lived, poorly matured plasmablasts that generally secrete lower-affinity antibodies, or long-lived, highly matured plasma cells that generally secrete higher-affinity antibodies. The ASC population is responsible for producing an immediate humoral B cell response, the polyclonal antibody repertoire, as well as in parallel building effective humoral memory and immunity, or potentially driving pathology in the case of autoimmunity. ASC are phenotypically and transcriptionally distinct from other B cells and further distinguishable by morphology, varied lifespans, and anatomical localization. Single cell analyses are required to interrogate the functional and transcriptional diversity of ASC and their secreted antibody repertoire and understand the contribution of individual ASC responses to the polyclonal humoral response. Here we summarize the current and emerging functional and molecular techniques for high-throughput characterization of ASC with single cell resolution, including flow and mass cytometry, spot-based and microfluidic-based assays, focusing on functional approaches of the secreted antibodies: specificity, affinity, and secretion rate.
Safety of Neoadjuvant Immunotherapy in Resectable Cancers: A Meta-Analysis
Authors: Xu Jiawei , Wu Yongfeng , Xu Yuedan , Qiu Yuan , Li Xiaobo , Song Yumeng , Zhang Ling
Published: January 2022

Background

Neoadjuvant immunotherapy has preliminarily been effective in multiple resectable cancers. However, its safety is still largely unknown.

Methods

A systematic literature search was conducted in PubMed, Embase, Web of Science, and Cochrane Library up to February 28th, 2021. Pooled incidence and risk ratio (RR) of adverse events were calculated using the R software.

Results

Twenty-eight studies involving 2863 patients were included. First, the incidence for all-grade treatment-related adverse events (trAEs) was 94% (95% CI, 81%-98%), with 43% (95% CI, 24%-64%) for high-grade trAEs. For different treatment groups, neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy was associated with a higher incidence of all-grade [99% (95% CI, 98%-99%) vs. 76% (95% CI 47%-92%); P < 0.001] and high-grade [80% (58%-92%) vs. 15% (9%-24%); P < 0.001] trAEs compared with neoadjuvant ICIs alone. The most common high-grade trAEs were lipase increased (5%; 95% CI, 2%-10%), colitis (3%; 95% CI, 0-7%) and transaminitis (3%; 95% CI, 0-7%) for neoadjuvant ICIs, and neutropenia (53%; 95% CI, 31%-74%), anemia (8%; 95% CI, 3%-15%) and AST increased (4%; 95% CI, 2%-7%) for neoadjuvant ICIs plus chemotherapy. Furthermore, the incidence rates of progressive disease while on treatment, treatment-related surgical delays and deaths were 6% (95% CI, 4%-10%), 3.2% (12 of 377 patients) and 0.47% (5 of 1075 patients), respectively.

Conclusion

Compared with neoadjuvant ICIs alone, neoadjuvant ICIs plus chemotherapy had a higher incidence of trAEs. In addition, neoadjuvant immunotherapy had a low rate of progressive diseases, surgical delays and deaths.
Targeting Tryptophan Catabolism in Cancer Immunotherapy Era: Challenges and Perspectives
Authors: Peyraud Florent , Guegan Jean-Philippe , Bodet Dominique , Cousin Sophie , Bessede Alban , Italiano Antoine
Published: January 2022

Metabolism of tryptophan (Trp), an essential amino acid, represent a major metabolic pathway that both promotes tumor cell intrinsic malignant properties as well as restricts antitumour immunity, thus emerging as a drug development target for cancer immunotherapy. Three cytosolic enzymes, namely indoleamine 2,3-dioxygenase 1 (IDO1), IDO2 and tryptophan 2,3-dioxygenase (TDO2), catalyzes the first-rate limiting step of the degradation of Trp to kynurenine (Kyn) and modulates immunity toward immunosuppression mainly through the aryl hydrocarbon receptor (AhR) activation in numerous types of cancer. By restoring antitumor immune responses and synergizing with other immunotherapies, the encouraging preclinical data of IDO1 inhibitors has dramatically failed to translate into clinical success when combined with immune checkpoints inhibitors, reigniting the debate of combinatorial approach. In this review, we i) provide comprehensive evidences on immunomodulatory role of the Trp catabolism metabolites that highlight this pathway as relevant target in immuno-oncology, ii)ii) discuss underwhelming results from clinical trials investigating efficacy of IDO1 inhibitors and underlying mechanisms that might have contributed to this failure, and finally, iii) discuss the current state-of-art surrounding alternative approaches of innovative antitumor immunotherapies that target molecules of Trp catabolism as well as challenges and perspectives in the era of immunotherapy.
Knowledge Mapping of Immunotherapy for Hepatocellular Carcinoma: A Bibliometric Study
Authors: Shen Jianming , Shen Hui , Ke Lixin , Chen Jialin , Dang Xi , Liu Baoxian , Hua Yunpeng
Published: January 2022

Background

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and many patients are diagnosed with advanced disease. The treatment of advanced liver cancer has made significant strides in recent years, owing to the practice of immunotherapy drugs. Numerous studies have been published on immunotherapy for HCC; however, no relevant bibliometric study has been published. This study aims to gain a better understanding of the current situation and to identify potential new research directions by conducting a bibliometric analysis on immunotherapy for HCC.

Methods

We searched the Web of Science Core Collection (WoSCC) for articles related to immunotherapy for HCC. Three software (VOSviewer, CiteSpace, and python) were primarily used to assess the contribution and co-occurrence relationships of various countries/regions, institutes, journals, and, authors as well as to identify research hotspots and promising future trends in this research field.

Results

A total of 1,641 English articles published between 2011 and 2020 were collected, with the number of articles increasing nearly every year. The majority of publications originated from China (n = 893, 54.42%), followed by the United States and Japan. The Sun Yat-sen University contributed the most publications (n = 97, 5.91%). Nakatsura Tetsuya (n = 26) and Llovet JM (n = 366) were ranked first in the top ten authors and co-cited authors. Cancer Immunology Immunotherapy was the most productive academic journal on immunotherapy for HCC [n = 46, 2.80%; impact factor (IF) 2020 = 6.9679]. Aggregation and identification of critical nodes in the co-cited network demonstrated a shift in the field of HCC immunotherapy. Initially, the hotspots were predominantly “glypican-3”, “cytokine-induced killer cells”, and “ny-eso-1”, while the emphasis has shifted in recent years to “landscape”, “camrelizumab”, “combination therapy”, and “immune score”.

Conclusion

Increased attention has been paid to HCC with the advancement of immunotherapy. At the moment, the most active frontiers are focused on better understanding the immunological landscape of liver cancer, screening the population that can benefit from immunotherapy, and the clinical application of immune checkpoint inhibitors, particularly in combination with other therapeutic options (such as local therapy and targeted therapy).
Structural Basis for Unusual TCR CDR3β Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule
Authors: Liu Yang , Lei Jun , San Dan , Yang Yi , Paek Chonil , Xia Zixiong , Chen Yongshun , Yin Lei
Published: January 2022

In HIV infection, some closely associated human leukocyte antigen (HLA) alleles are correlated with distinct clinical outcomes although presenting the same HIV epitopes. The mechanism that underpins this observation is still unknown, but may be due to the essential features of HLA alleles or T cell receptors (TCR). In this study, we investigate how T18A TCR, which is beneficial for a long-term control of HIV in clinic, recognizes immunodominant Gag epitope TL9 (TPQDLTML180-188) from HIV in the context of the antigen presenting molecule HLA-B*81:01. We found that T18A TCR exhibits differential recognition for TL9 restricted by HLA-B*81:01. Furthermore, via structural and biophysical approaches, we observed that TL9 complexes with HLA-B*81:01 undergoes no conformational change after TCR engagement. Remarkably, the CDR3β in T18A complexes does not contact with TL9 at all but with intensive contacts to HLA-B*81:01. The binding kinetic data of T18A TCR revealed that this TCR can recognize TL9 epitope and several mutant versions, which might explain the correlation of T18A TCR with better clinic outcomes despite the relative high mutation rate of HIV. Collectively, we provided a portrait of how CD8+ T cells engage in HIV-mediated T cell response.
The Beginner’s Guide to O-GlcNAc: From Nutrient Sensitive Pathway Regulation to Its Impact on the Immune System
Authors: Mannino Michael P. , Hart Gerald W.
Published: January 2022

The addition of N-acetyl glucosamine (GlcNAc) on the hydroxy group of serine/threonine residues is known asO-GlcNAcylation (OGN). The dynamic cycling of this monosaccharide on and off substrates occursvia O-linked β-N-acetylglucosamine transferase (OGT) andO-linked β-N-acetylglucosaminase (OGA) respectively. These enzymes are found ubiquitously in eukaryotes and genetic knock outs of theogtgene has been found to be lethal in embryonic mice. The substrate scope of these enzymes is vast, over 15,000 proteins across 43 species have been identified withO-GlcNAc. OGN has been known to play a key role in several cellular processes such as: transcription, translation, cell signaling, nutrient sensing, immune cell development and various steps of the cell cycle. However, its dysregulation is present in various diseases: cancer, neurodegenerative diseases, diabetes.O-GlcNAc is heavily involved in cross talk with other post-translational modifications (PTM), such as phosphorylation, acetylation, and ubiquitination, by regulating each other’s cycling enzymes or directly competing addition on the same substrate. This crosstalk between PTMs can affect gene expression, protein localization, and protein stability; therefore, regulating a multitude of cell signaling pathways. In this review the roles of OGN will be discussed. The effectO-GlcNAc exerts over protein-protein interactions, the various forms of crosstalk with other PTMs, and its role as a nutrient sensor will be highlighted. A summary of how theseO-GlcNAc driven processes effect the immune system will also be included.
Neutralizing Antibody Responses to SARS-CoV-2 in Recovered COVID-19 Patients Are Variable and Correlate With Disease Severity and Receptor-Binding Domain Recognition
Authors: Maciola Agnieszka Katarzyna , La Raja Massimo , Pacenti Monia , Salata Cristiano , De Silvestro Giustina , Rosato Antonio , Pasqual Giulia
Published: January 2022

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) caused outbreaks of the pandemic starting from the end of 2019 and, despite ongoing vaccination campaigns, still influences health services and economic factors globally. Understanding immune protection elicited by natural infection is of critical importance for public health policy. This knowledge is instrumental to set scientific parameters for the release of “immunity pass” adopted with different criteria across Europe and other countries and to provide guidelines for the vaccination of COVID-19 recovered patients. Here, we characterized the humoral response triggered by SARS-CoV-2 natural infection by analyzing serum samples from 94 COVID-19 convalescent patients with three serological platforms, including live virus neutralization, pseudovirus neutralization, and ELISA. We found that neutralization potency varies greatly across individuals, is significantly higher in severe patients compared with mild ones, and correlates with both Spike and receptor-binding domain (RBD) recognition. We also show that RBD-targeting antibodies consistently represent only a modest proportion of Spike-specific IgG, suggesting broad specificity of the humoral response in naturally infected individuals. Collectively, this study contributes to the characterization of the humoral immune response in the context of natural SARS-CoV-2 infection, highlighting its variability in terms of neutralization activity, with implications for immune protection in COVID-19 recovered patients.
Brain Antigens Stimulate Proliferation of T Lymphocytes With a Pathogenic Phenotype in Multiple Sclerosis Patients
Authors: Gottlieb Assaf , Pham Hoai Phuong T. , Lindsey John William
Published: January 2022

A method to stimulate T lymphocytes with a broad range of brain antigens would facilitate identification of the autoantigens for multiple sclerosis and enable definition of the pathogenic mechanisms important for multiple sclerosis. In a previous work, we found that the obvious approach of culturing leukocytes with homogenized brain tissue does not work because the brain homogenate suppresses antigen-specific lymphocyte proliferation. We now report a method that substantially reduces the suppressive activity. We used this non-suppressive brain homogenate to stimulate leukocytes from multiple sclerosis patients and controls. We also stimulated with common viruses for comparison. We measured proliferation, selected the responding CD3+ cells with flow cytometry, and sequenced their transcriptomes for mRNA and T-cell receptor sequences. The mRNA expression suggested that the brain-responding cells from MS patients are potentially pathogenic. The T-cell receptor repertoire of the brain-responding cells was clonal with minimal overlap with virus antigens.
Evidence for Size-Selective Predation by Antarctic Humpback Whales
Authors: Cade David E. , Kahane-Rapport Shirel R. , Wallis Ben , Goldbogen Jeremy A. , Friedlaender Ari S.
Published: January 2022

Animals aggregate around resource hotspots, but what makes one resource more appealing than another can be difficult to determine. In March 2020 the Antarctic fjord Charlotte Bay included >5× as many humpback whales as neighboring Wilhelmina Bay, a site previously known for super aggregations of whales and their prey, Antarctic krill. We used suction-cup attached bio-logging tags and active acoustic prey mapping to test the hypothesis that whale abundance in Charlotte Bay would be associated with higher prey biomass density, and that whale foraging effort would be concentrated in regions of Charlotte Bay with the highest biomass. Here we show, however, that patch size and krill length at the depth of foraging were more likely predictors of foraging effort than biomass. Tagged whales spent >80% of the night foraging, and whales in both bays demonstrated similar nighttime feeding rates (48.1 ± 4.0 vs. 50.8 ± 16.4 lunges/h). However, whales in Charlotte Bay foraged for 58% of their daylight hours, compared to 22% in Wilhelmina Bay, utilizing deep (280–450 m) foraging dives in addition to surface feeding strategies like bubble-netting. Selective foraging on larger krill by humpback whales has not been previously established, but suggests that whales may be sensitive to differences in individual prey quality. The utilization of disparate foraging strategies in different parts of the water column allows humpback whales to target the most desirable parts of their foraging environments.
Investigating the Environmental Survival of Marteilia refringens, a Marine Protozoan Parasite of the Flat Oyster Ostrea edulis, Through an Environmental DNA and Microscopy-Based Approach
Authors: Mérou Nicolas , Lecadet Cyrielle , Billon Tom , Chollet Bruno , Pouvreau Stéphane , Arzul Isabelle
Published: January 2022

Outside-host parasite survival is a key parameter to better understand disease mechanisms, especially for marine pathogens transmitted from one host to another through an environmental stage. For non-cultivable micro-parasites like Marteilia refringens, a protozoan parasite infecting the flat oyster Ostrea edulis, investigating this parameter requires innovative approaches. In the present study, we have developed an Environmental DNA (eDNA)-based method allowing detecting and quantifying up to 25 and 10 parasites DNA in seawater and sediment, respectively. This method was used in combination with light and transmission electron microscopy (TEM) to study experimentally parasite survival in seawater and flat oyster faeces after its release from naturally infected oysters. M. refringens DNA could be detected up to 20 days, in both seawater and oyster faeces with a more stable detection over time in the latter. Light and transmission microscopy confirm that parasites leaving flat oysters are sporangia. We also observed a membrane dissolution of the sporangia over time that could indicate the release of parasite spore. This study not only improves our understanding of M. refringens ecology but also highlights the interest to combine molecular and microscopical analysis to study non-cultivable micro-parasites life cycle outside their host.
Publication Trends of Research on Polypoidal Choroidal Vasculopathy During 2001–2020: A 20-Year Bibliometric Study
Authors: Wang Yimin , Xie Minyue , Zhang Min , Zhao Xiaohuan , Zhu Xinyue , Wang Yuwei , Chen Yuhong , Chen Jieqiong , Sun Xiaodong
Published: January 2022

Introduction

Polypoidal choroidal vasculopathy (PCV) is a special subtype of AMD, which is one of the leading threats to vision health worldwide. At this time, many aspects of PCV, from how it works to potential treatments, remain a mystery. In this study, we explored the frontier researches and revealed the study trends within the study of PCV.

Methods

We collected all the publications in this field from 2001 to 2020, analyzed trends within them, and defined the contributions of various countries/regions, institutions, authors, and journals. Additionally, VOSviewer software was used to define the hot keywords in this field.

Results

A total of 1,190 publications were ultimately examined; We found that PCV is becoming an increasingly relevant topic of research, and that Japan has contributed the most publications (428), the most citations (14,504 in total), and the highest H-index value (62) to the field. Our keywords analysis was classified into four clusters to show the hotspots within the study of PCV, namely mechanism-related, imaging-related, prognosis-related, and therapy-related topics. The average years in which the keywords appeared the most were also calculated, and we identified anti-VEGF therapy, anti-complement therapy and angiography as having been the main focus in recent years.

Conclusions

These results helped clarify the comprehensive research progress that has been made as well as the future trends in the study of PCV, which can assist and guide future research.
Transporter Genes and fosA Associated With Fosfomycin Resistance in Carbapenem-Resistant Klebsiella pneumoniae
Authors: Wang Yu-Ping , Chen Yen-Hao , Hung I-Cheng , Chu Po-Hsun , Chang Yu-Han , Lin Yi-Tsung , Yang Hung-Chih , Wang Jin-Town
Published: January 2022

Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) are of significant clinical concern worldwide. Fosfomycin is one of the limited treatment options for CRKP. However, resistance to fosfomycin in CRKP has been observed. In this study, we aimed to investigate the fosfomycin resistance mechanism of CRKP. Fosfomycin-resistant Klebsiella pneumoniae isolates were collected from four medical centers in Taiwan from 2010 to 2018. The genes that contributed to fosfomycin resistance were amplified and sequenced. Carbohydrate utilization assays and mutagenesis studies were performed to determine the mechanisms underlying fosfomycin resistance. Forty fosfomycin-resistant CRKP strains were collected and used for further analysis. Fourteen strains exhibited low-level resistance (MIC = 256–512 mg/dl), while 26 strains showed high-level resistance (MIC ≥ 1,024 mg/dl). Chromosomal fosAKP I91V was detected in 39/40 fosfomycin-resistant CRKP strains. We observed that amino acid substitution of chromosomal fosAKP I91V increased the MIC of fosfomycin by approximately eight folds, and this was the only mechanism elucidated for low-level fosfomycin resistance. Among the 26 high-level resistance strains, fosAKP I91V combined with transporter deficiencies (18/26, 69.2%) was the most common resistant mechanism, and one strain showed transporter deficiency only. Plasmid-borne fosA3 accounted for 27.0% (7/26) of high-level resistance. Various G3P and G6P transporter gene mutations, including three novel single amino acid mutations (glpT E299D, glpT D274V, and uhpC A393V) were detected in 19 strains. No murA mutation was found in this study. Our study highlights the need for new therapeutic agents for CRKP infections in Taiwan.
CRISPR Cas13-Based Tools to Track and Manipulate Endogenous Telomeric Repeat-Containing RNAs in Live Cells
Authors: Xu Meng , Chigumira Tafadzwa , Chen Ziheng , Tones Jason , Zhao Rongwei , Dahl Kris Noel , Chenoweth David M. , Zhang Huaiying
Published: January 2022

TERRA, TElomeric Repeat-containing RNA, is a long non-coding RNA transcribed from telomeres. Emerging evidence indicates that TERRA regulates telomere maintenance and chromosome end protection in normal and cancerous cells. However, the mechanism of how TERRA contributes to telomere functions is still unclear, partially owing to the shortage of approaches to track and manipulate endogenous TERRA molecules in live cells. Here, we developed a method to visualize TERRA in live cells via a combination of CRISPR Cas13 RNA labeling and SunTag technology. Single-particle tracking reveals that TERRA foci undergo anomalous diffusion in a manner that depends on the timescale and telomeric localization. Furthermore, we used a chemically-induced protein dimerization system to manipulate TERRA subcellular localization in live cells. Overall, our approaches to monitor and control TERRA locations in live cells provide powerful tools to better understand its roles in telomere maintenance and genomic integrity.
Comprehensive Analysis of Circular RNA Expression in ceRNA Networks and Identification of the Effects of hsa_circ_0006867 in Keloid Dermal Fibroblasts
Authors: Pang Qianqian , Lin Xiaohu , Sun Jiaqi , Hu Jie , Dai Siya , Shen Yichen , Xu Mingyuan , Xu Jinghong
Published: January 2022

Circular RNAs (circRNAs) play a crucial role in the pathogenesis of various fibrotic diseases, but the potential biological function and expression profile of circRNAs in keloids remain unknown. Herein, microarray technology was applied to detect circRNA expression in four patient-derived keloid dermal fibroblasts (KDFs) and normal dermal fibroblasts (NDFs). A total of 327 differentially expressed (DE) circRNAs (fold change > 1.5, p < 0.05) were identified with 195 upregulated and 132 downregulated circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the upregulated circRNAs were mainly enriched in the cytoskeleton and tight junctions, while the downregulated circRNAs were related to morphogenesis of the epithelium and axonal guidance. To explore the function of DE circRNAs, a circRNA-miRNA-mRNA network, including five circRNAs, nine miRNAs, and 235 correlated mRNAs, was constructed using bioinformatics analyses. The expression of five DE circRNAs was validated by qRT–PCR in 18 pairs of KDFs and NDFs, and hsa_circ_0006867 showed promising regulatory function in keloids in vitro. Silencing hsa_circ_00006867 suppressed the proliferation, migration, and invasion of keloid fibroblasts. RNA-binding protein immunoprecipitation (RIP) assays indicated that hsa_circ_00006867 may serve as a platform for miRNA binding to Argonaute (AGO) 2. In addition, hsa-miR-29a-5p may be a potential target miRNA of hsa_circ_00006867. Taken together, our research provided multiple novel clues to understand the pathophysiologic mechanism of keloids and identified hsa_circ_0006867 as a biomarker of keloids.
Prognostic and Predictive Factors in Elderly Patients With Glioblastoma: A Single-Center Retrospective Study
Authors: Liu Jinghui , Li Chen , Wang Yuan , Ji Peigang , Guo Shaochun , Zhai Yulong , Wang Na , Lou Miao , Xu Meng , Chao Min , Jiao Yang , Zhao Wenjian , Feng Fuqiang , Qu Yan , Ge Shunnan , Wang Liang
Published: January 2022

Glioblastoma (GBM) is the most common primary malignant intracranial tumor and the median age at diagnosis is 65 years. However, elderly patients are usually excluded from clinical studies and age is considered as an independent negative prognostic factor for patients with GBM. Therefore, the best treatment method for GBM in elderly patients has remained controversial. Elderly GBM patients (≥ 60 years old) treated between January 2015 and December 2019 were enrolled in this study. Medical records were reviewed retrospectively, and clinicopathological characteristics, treatments, and outcomes were analyzed. A total of 68 patients were included, with a median age of 65.5 years (range: 60–79). The median preoperative Karnofsky performance scale (KPS) score was 90 (range 40–100) and median postoperative KPS score was 80 (range 0–90). Univariate analysis results showed that age, gender, comorbidities, preoperative KPS < 90 and MGMT promoter methylation were not significantly associated with PFS and OS. On the other hand, total resection, postoperative KPS ≥ 80, Ki67 > 25%, and Stupp-protocol treatment were significantly associated with prolonged PFS and OS. Moreover, multivariate analysis found that postoperative KPS ≥ 80, total resection, and Stupp-protocol treatment were prognostic factors for PFS and OS. The findings of this study have suggested that, on the premise of protecting function as much as possible, the more aggressive treatment regimens may prolong survival for elderly patients with GBM. However, further studies, particularly prospective randomized clinical trials, should be conducted to provide more definitive data on the appropriate management of elderly patients, especially for patients with MGMT promoter methylation.
Widowhood Impairs Emotional Cognition Among Elderly
Authors: Bi Taiyong , Kou Hui , Kong Yanshu , Shao Boyao
Published: January 2022

Background

The negative impacts of spousal bereavement on the emotional health of the elderly (e.g., depression and anxiety) have been revealed. However, whether widowhood impairs emotional cognition among the elderly is less known. The purpose of this study is to reveal the emotional cognitive deficits among the widowed elderly.

Methods

In this study, we recruited 44 widowed elderly (WE) and 44 elder couples (non-widowed elderly, NWE) and examined their emotional cognition including attention and visual working memory, which were measured by the visual search task and delayed-match-to-sample task, respectively. Three kinds of emotional faces (i.e., sad, angry, and happy) were adopted as the attentional or mnemonic targets.

Results

It revealed that WE had a general deficit in search efficiency across emotional types, while they showed mnemonic deficits in negative faces but not positive faces. Furthermore, the modeling analysis revealed that the level of depression or state anxiety of the elderly moderated the effects of widowhood on the deficits of mnemonic processing, i.e., the deficits were only evident among WE with the high level of depression or state anxiety.

Conclusion

These findings reveal the attentional deficits in sad, angry, and happy faces and the mnemonic deficits in sad and angry faces among elderly who suffer from widowhood and point out the important role of emotional problems such as depression and state anxiety in modulating these emotional cognitive deficits.
Analysis of Brain Structural Connectivity Networks and White Matter Integrity in Patients With Mild Cognitive Impairment
Authors: Bergamino Maurizio , Schiavi Simona , Daducci Alessandro , Walsh Ryan R. , Stokes Ashley M.
Published: January 2022

White matter integrity and structural connectivity may be altered in mild cognitive impairment (MCI), and these changes may closely reflect decline in specific cognitive domains. Multi-shell diffusion data in healthy control (HC, n = 31) and mild cognitive impairment (MCI, n = 19) cohorts were downloaded from the ADNI3 database. The data were analyzed using an advanced approach to assess both white matter microstructural integrity and structural connectivity. Compared with HC, lower intracellular compartment (IC) and higher isotropic (ISO) values were found in MCI. Additionally, significant correlations were found between IC and Montreal Cognitive Assessment (MoCA) scores in the MCI cohort. Network analysis detected structural connectivity differences between the two groups, with lower connectivity in MCI. Additionally, significant differences between HC and MCI were observed for global network efficiency. Our results demonstrate the potential of advanced diffusion MRI biomarkers for understanding brain changes in MCI.
Enacting Plant-Inspired Robotics
Authors: Lee Jonny , Calvo Paco
Published: January 2022

Plants offer a source of bioinspiration for soft robotics. Nevertheless, a gap remains in designing robots based on the fundamental principles of plant intelligence, rooted in a non-centralized, modular architecture and a highly plastic phenotype. We contend that a holistic approach to plant bioinspiration—one that draws more fully on the features of plant intelligence and behavior—evidences the value of an enactivist perspective. This is because enactivism emphasizes not only features of embodiment such as material composition and morphology, but also autonomy as an important aspect of plant intelligence and behavior. The enactivist sense of autonomy concerns the dynamics of self-producing systems (such as plants) that create a distinction between themselves and a domain of interactions that bear on the conditions of viability of the system. This contrasts with the widespread, but diluted notion of autonomy that merely indicates the independent operability of a system for an arbitrary period. Different notions of autonomy are relevant for soft roboticists, for instance, when evaluating limitations on existing growing robots (“growbots”) that take bioinspiration from plants, but depend on a fixed source of energy and material provided by an external agent. More generally, plant-inspired robots serve as a case study for an enactivist approach to intelligence, while, correspondingly, enactivism calls attention to the possibility of non-zoological forms of intelligence embodied in a self-organizing, autonomous system.
Stimulus-Selective Response Plasticity in Primary Visual Cortex: Progress and Puzzles
Authors: Montgomery Daniel P. , Hayden Dustin J. , Chaloner Francesca A. , Cooke Samuel F. , Bear Mark F.
Published: January 2022

Stimulus-selective response plasticity (SRP) is a robust and lasting modification of primary visual cortex (V1) that occurs in response to exposure to novel visual stimuli. It is readily observed as a pronounced increase in the magnitude of visual evoked potentials (VEPs) recorded in response to phase-reversing grating stimuli in neocortical layer 4. The expression of SRP at the individual neuron level is equally robust, but the qualities vary depending on the neuronal type and how activity is measured. This form of plasticity is highly selective for stimulus features such as stimulus orientation, spatial frequency, and contrast. Several key insights into the significance and underlying mechanisms of SRP have recently been made. First, it occurs concomitantly and shares core mechanisms with behavioral habituation, indicating that SRP reflects the formation of long-term familiarity that can support recognition of innocuous stimuli. Second, SRP does not manifest within a recording session but only emerges after an off-line period of several hours that includes sleep. Third, SRP requires not only canonical molecular mechanisms of Hebbian synaptic plasticity within V1, but also the opposing engagement of two key subclasses of cortical inhibitory neuron: the parvalbumin- and somatostatin-expressing GABAergic interneurons. Fourth, pronounced shifts in the power of cortical oscillations from high frequency (gamma) to low frequency (alpha/beta) oscillations provide respective readouts of the engagement of these inhibitory neuronal subtypes following familiarization. In this article we will discuss the implications of these findings and the outstanding questions that remain to gain a deeper understanding of this striking form of experience-dependent plasticity.
Advances in Proteomic and Metabolomic Profiling of Neurodegenerative Diseases
Authors: Schumacher-Schuh Artur , Bieger Andrei , Borelli Wyllians V. , Portley Makayla K. , Awad Paula Saffie , Bandres-Ciga Sara
Published: January 2022

Proteomics and metabolomics are two emerging fields that hold promise to shine light on the molecular mechanisms causing neurodegenerative diseases. Research in this area may reveal and quantify specific metabolites and proteins that can be targeted by therapeutic interventions intended at halting or reversing the neurodegenerative process. This review aims at providing a general overview on the current status of proteomic and metabolomic profiling in neurodegenerative diseases. We focus on the most common neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. We discuss the relevance of state-of-the-art metabolomics and proteomics approaches and their potential for biomarker discovery. We critically review advancements made so far, highlighting how metabolomics and proteomics may have a significant impact in future therapeutic and biomarker development. Finally, we further outline technologies used so far as well as challenges and limitations, placing the current information in a future-facing context.
Identification and Characterization of Influential Factors in Susceptibility to Attention Deficit Hyperactivity Disorder Among Preschool-Aged Children
Authors: Deng Xiangling , Yang Min , Wang Shunan , Zhou Bo , Wang Kundi , Zhang Zhixin , Niu Wenquan
Published: January 2022

Attention deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder. Currently, increasing amounts of attention have been focused on the epidemiologic profiling of ADHD in children, viewed as a continuously distributed risk dimension throughout the whole lifespan. This study aimed to identify and characterize potential influential factors susceptible to ADHD-related symptoms among preschool-aged children. A comprehensive questionnaire was self-designed for both children and their parents or guardians and was distributed to 30 kindergartens from Beijing and Hebei, collecting potential influential factors in susceptibility to ADHD. ADHD was assessed by the Conner’s Abbreviated Symptom Questionnaire (C-ASQ), and 7,938 children were analyzed. Least absolute shrinkage and selection operator (LASSO) regression and hierarchical degree of adjustment were used to control possible covariates. Five factors, namely, children’s secondhand smoking exposure, breastfeeding duration, sleep mode, maternal pregnancy smoking exposure, and parental self-rating for patience, were identified to be independently and significantly associated with ADHD susceptibility. Meanwhile, dose–response relationships were observed between breastfeeding duration, parental self-rating for patience, and ADHD-related symptoms. Finally, a nomogram model was created for predicting ADHD susceptibility based on significant and conventional attributes under each criterion.
MicroRNA-21 Is a Versatile Regulator and Potential Treatment Target in Central Nervous System Disorders
Authors: Bai Xue , Bian Zhigang
Published: January 2022

MicroRNAs (miRNAs) are a class of endogenous, non-coding, single-stranded RNAs with a length of approximately 22 nucleotides that are found in eukaryotes. miRNAs are involved in the regulation of cell differentiation, proliferation, invasion, apoptosis, and metabolism by regulating the expression of their target genes. Emerging studies have suggested that various miRNAs play key roles in the pathogenesis of central nervous system (CNS) disorders and may be viable therapeutic targets. In particular, miR-21 has prominently emerged as a focus of increasing research on the mechanisms of its involvement in CNS disorders. Herein, we reviewed recent studies on the critical roles of miR-21, including its dysregulated expression and target genes, in the regulation of pathophysiological processes of CNS disorders, with a special focus on apoptosis and inflammation. Collectively, miR-21 is a versatile regulator in the progression of CNS disorders and could be a promising biomarker and therapeutic target for these diseases. An in-depth understanding of the mechanisms by which miR-21 affects the pathogenesis of CNS disorders could pave the way for miR-21 to serve as a therapeutic target for these conditions.
AMPA Receptor Function in Hypothalamic Synapses
Authors: Royo Maria , Escolano Beatriz Aznar , Madrigal M. Pilar , Jurado Sandra
Published: January 2022

AMPA receptors (AMPARs) are critical for mediating glutamatergic synaptic transmission and plasticity, thus playing a major role in the molecular machinery underlying cellular substrates of memory and learning. Their expression pattern, transport and regulatory mechanisms have been extensively studied in the hippocampus, but their functional properties in other brain regions remain poorly understood. Interestingly, electrophysiological and molecular evidence has confirmed a prominent role of AMPARs in the regulation of hypothalamic function. This review summarizes the existing evidence on AMPAR-mediated transmission in the hypothalamus, where they are believed to orchestrate the role of glutamatergic transmission in autonomous, neuroendocrine function, body homeostasis, and social behavior.
Investigating Urinary Circular RNA Biomarkers for Improved Detection of Renal Cell Carcinoma
Authors: Peter Madonna R. , Zhao Fang , Jeyapala Renu , Kamdar Shivani , Xu Wei , Hawkins Cynthia , Evans Andrew J. , Fleshner Neil E. , Finelli Antonio , Bapat Bharati
Published: January 2022

Renal cell carcinomas (RCC) are usually asymptomatic until late stages, posing several challenges for early detection of malignant disease. Non-invasive liquid biopsy biomarkers are emerging as an important diagnostic tool which could aid with routine screening of RCCs. Circular RNAs (circRNAs) are novel non-coding RNAs that play diverse roles in carcinogenesis. They are promising biomarkers due to their stability and ease of detection in small quantities from non-invasive sources such as urine. In this study, we analyzed the expression of various circRNAs that were previously identified in RCC tumors (circEGLN3, circABCB10, circSOD2 and circACAD11) in urinary sediment samples from non-neoplastic controls, patients with benign renal tumors, and clear cell RCC (ccRCC) patients. We observed significantly reduced levels of circEGLN3 and circSOD2 in urine from ccRCC patients compared to healthy controls. We also assessed the linear variant of EGLN3 and found differential expression between patients with benign tumors compared to ccRCC patients. These findings highlight the potential of circRNA markers as non-invasive diagnostic tools to detect malignant RCC.