bluuebunny/crossref_metadata_2025 huggingface dataset:
The Bidirectional Link Between RNA Cleavage and Polyadenylation and Genome Stability: Recent Insights From a Systematic Screen
Authors: Spada Stefano , Luke Brian , Danckwardt Sven
Published: April 2022

The integrity of the genome is governed by multiple processes to ensure optimal survival and to prevent the inheritance of deleterious traits. While significant progress has been made to characterize components involved in the DNA Damage Response (DDR), little is known about the interplay between RNA processing and the maintenance of genome stability. Here, we describe the emerging picture of an intricate bidirectional coupling between RNA processing and genome integrity in an integrative manner. By employing insights from a recent large-scale RNAi screening involving the depletion of more than 170 components that direct (alternative) polyadenylation, we provide evidence of bidirectional crosstalk between co-transcriptional RNA 3′end processing and the DDR in a manner that optimizes genomic integrity. We provide instructive examples illustrating the wiring between the two processes and show how perturbations at one end are either compensated by buffering mechanisms at the other end, or even propel the initial insult and thereby become disease-eliciting as evidenced by various disorders.
Genome-Wide Identification, Phylogeny, and Expression Profile of the Dmrt (Doublesex and Mab-3 Related Transcription Factor) Gene Family in Channel Catfish (Ictalurus punctatus)
Authors: Xu Siqi , Zhang Shiyong , Zhang Wenping , Liu Hongyan , Wang Minghua , Zhong Liqiang , Bian Wenji , Chen Xiaohui
Published: April 2022

The Dmrt (Doublesex and Mab-3 related transcription factor) gene family is a class of crucial transcription factors characterized by a conserved DM domain related to sex determination and differentiation, which has been systematically described in various teleost fish, but less in channel catfish (Ictalurus punctatus), an important global aquaculture species in the US and China. In this study, seven Dmrt genes from channel catfish genome were identified and analyzed using bioinformatics methods. Seven IpDmrt genes were distributed unevenly across five chromosomes. Synteny analysis revealed that Dmrt1, Dmrt2a, Dmrt2b, Dmrt3, Dmrt4, and Dmrt5 were relatively conserved in teleost fish. Tissue distribution analysis showed that IpDmrt1, IpDmrt2b, IpDmrt5, and IpDmrt6 exhibited sexually dimorphic expression patterns and, among them, IpDmrt1 and IpDmrt6 had high expression levels in the testes, while IpDmrt2b and IpDmrt5 had more significant expression levels in the ovaries than in other tissues. After 17β-estradiol treatment, IpDmrt2b and IpDmrt5 were significantly up regulated, while the expression of IpDmrt1 and IpDmrt6 was significantly repressed in XY channel catfish ovaries compared with XX channel catfish ovaries. The present study provides a comprehensive insight into the Dmrt gene family of channel catfish. The results suggest that IpDmrt1 and IpDmrt6 may play an important role in testis differentiation/development, while IpDmrt2b and IpDmrt5 are critical in ovary development in this species.
Overcoming Immune Resistance With Radiation Therapy in Prostate Cancer
Authors: Mulvey Arthur , Muggeo-Bertin Emilien , Berthold Dominik R. , Herrera Fernanda G.
Published: April 2022

Prostate cancer is the second most common cancer in men and represents a significant healthcare burden worldwide. Therapeutic options in the metastatic castration-resistant setting remain limited, despite advances in androgen deprivation therapy, precision medicine and targeted therapies. In this review, we summarize the role of immunotherapy in prostate cancer and offer perspectives on opportunities for future development, based on current knowledge of the immunosuppressive tumor microenvironment. Furthermore, we discuss the potential for synergistic therapeutic strategies with modern radiotherapy, through modulation of the tumor microenvironment. Emerging clinical and pre-clinical data suggest that radiation can convert immune desert tumors into an inflamed immunological hub, potentially sensitive to immunotherapy.
Autoimmunity, Infections, and the Risk of Monoclonal Gammopathy of Undetermined Significance
Authors: Sigurbergsdóttir Aðalbjörg Ýr , Love Thorvardur Jon , Kristinsson Sigurður Yngvi
Published: April 2022

Various epidemiological studies, including case reports and -series in addition to larger, population-based studies, have reported an increased prevalence of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma in individuals with a prior history of immune-related conditions. This is believed to support the role of chronic antigen stimulation in the pathogenesis of these conditions. In this short review, we summarize some of the largest population-based studies researching autoimmune diseases, infections, and the subsequent risk of MGUS, and discuss our understanding on its etiology and pathogenesis. Furthermore, we highlight important methodological limitations of previous studies in the field, but almost all studies on MGUS have been based on clinical, possibly biased, cohorts. Finally, we discuss future directions in researching the associations of MGUS and other disorders, including immune-related conditions, where screening studies play an important role.
CAR-T Cell Performance: How to Improve Their Persistence?
Authors: López-Cantillo Gina , Urueña Claudia , Camacho Bernardo Armando , Ramírez-Segura Cesar
Published: April 2022

Adoptive cell therapy with T cells reprogrammed to express chimeric antigen receptors (CAR-T cells) has been highly successful in patients with hematological neoplasms. However, its therapeutic benefits have been limited in solid tumor cases. Even those patients who respond to this immunotherapy remain at risk of relapse due to the short-term persistence or non-expansion of CAR-T cells; moreover, the hostile tumor microenvironment (TME) leads to the dysfunction of these cells after reinfusion. Some research has shown that, in adoptive T-cell therapies, the presence of less differentiated T-cell subsets within the infusion product is associated with better clinical outcomes. Naive and memory T cells persist longer and exhibit greater antitumor activity than effector T cells. Therefore, new methods are being studied to overcome the limitations of this therapy to generate CAR-T cells with these ideal phenotypes. In this paper, we review the characteristics of T-cell subsets and their implications in the clinical outcomes of adoptive therapy with CAR-T cells. In addition, we describe some strategies developed to overcome the reduced persistence of CAR T-cells and alternatives to improve this therapy by increasing the expansion ability and longevity of modified T cells. These methods include cell culture optimization, incorporating homeostatic cytokines during the expansion phase of manufacturing, modulation of CAR-T cell metabolism, manipulating signaling pathways involved in T-cell differentiation, and strategies related to CAR construct designs.
Prognostic Role of NLR, PLR and MHR in Patients With Idiopathic Pulmonary Fibrosis
Authors: Chen Yiran , Cai Jingya , Zhang Mengmeng , Yan Xin
Published: April 2022

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with low survival time. Since the pathophysiological progression of IPF is closely associated with immunological and inflammatory responses, immune biomarkers, including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-high density lipoprotein ratio (MHR), have the potential to predict overall survival in IPF patients.

Methods

A total of 278 patients with IPF were finally enrolled. The demographic and clinical characteristics of the patients at baseline were recorded. Multivariable Cox regression analysis was used to evaluate the association between the three biomarkers and overall survival in both the total cohort and acute exacerbation subgroup.

Results

The median follow-up was 5.84 months. After adjusting for confounders, we found that only elevated NLR was associated with worse overall survival (OR = 1.019, 95% CI 1.001-1.037, P =0.041) by using multivariable Cox regression analysis. In 116 acute exacerbation IPF patients, the results of the Cox multiple regression model also indicated that the NLR was a significant prognostic factor (OR= 1.022, 95% CI 1.001-1.044, P =0.036). The NLR before death was also significantly higher than that at admission in nonsurvival acute exacerbation IPF patients (P=0.014). No significant differences were found in PLR (P=0.739) or MHR changes (P=0.478).

Conclusions

Our results indicated that elevated NLR expression is associated with shorter overall survival in IPF patients, which is independent of other prognostic factors. The NLR may be regarded as a reliable prognostic biomarker for IPF patients.
EU-Funded Telemedicine Projects – Assessment of, and Lessons Learned From, in the Light of the SARS-CoV-2 Pandemic
Authors: Paleari Laura , Malini Virginia , Paoli Gabriella , Scillieri Stefano , Bighin Claudia , Blobel Bernd , Giacomini Mauro
Published: April 2022

The SARS-CoV-2 health emergency has demonstrated the need for developing structured telemedicine systems to protect citizens from the spread of the virus. Thereby, their importance and the necessity to tailor their diffusion at large scale for providing services both at a distance and in time has been shown. For these reasons, the European Union advocates the digital transition of health systems for the next 5 years. The main aim of this work is to revisit the telemedicine research projects financed by European Community during the period 2000-2020 with particular respect to the results derived from their application. The analysis showed that some integration of tele-care and tele-health could be obtained with tele-monitoring systems and the implementation of Electronic Personal Record (EPR). Furthermore, telemedicine allows enhancing health care in critical environments, to protect health and life of the most vulnerable patients, and to encourage cross-border dialogue. The criteria of “from distance” and “timely delivered” are granted, but the effectiveness of the overall offered services highly depends on the availability and the quality of the input data. Unfortunately, this remains a relevant problem in the SARS-CoV-2 pandemic.
Trichoderma longibrachiatum-Associated Skin Inflammation and Atypical Hyperplasia in Mouse
Authors: Zhang Gongjie , Li Dongming
Published: April 2022

Background

The relationship between infection and tumors has attracted increasing attention. Trichoderma spp. are often isolated from tumors. However, their potential role remains unclear. We recently reported the isolation of Trichoderma longibrachiatum from a patient with pulmonary spindle cell carcinoma that was confirmed as primary infection by application of laser capture microdissection and polymerase chain reaction. To explore whether the strain is pathogenic and whether it can cause atypical cell proliferation and infiltration of NK cells and T cells, we designed a mouse infection experiment.

Methods

Twelve ICR mice were randomly separated into three groups. Cyclophosphamide was used to inhibit the immunity of mice. A mouse model of Trichoderma infection was successfully established by intracutaneous injection on the back skin with a suspension of strain PKUT180420015. The pathological manifestations of Trichoderma infection and the interaction between immune cells and fungi were observed by histopathology, immunohistochemistry and intensive fungal staining. Reisolation of the fungus was observed by infected tissue culture. The inoculated sites exhibited swelling 3 days after inoculation, and ulcers developed at approximately 14 days. Skin specimens were obtained and then cultured at 3, 7, and 14 days after inoculation. We selected mice 14 days after inoculation in Group 3, whose ulcers were the most typical, for histological analysis.

Results

Inflammation, angioinvasion and necrosis were observed. Immunohistochemistry showed positive markers of Ki67, CD3, CD56, GZMB, and PRF. Periodic acid-Schiff staining, periodic acid-silver methenamine staining, and Calcofluor staining showed fungal spores in the vascular lumen, vascular walls and around the blood vessels.

Conclusions

Our studies showed that a T. longibrachiatum strain (PKUT180420015) isolated from a biopsy specimen in a patient with pulmonary spindle cell carcinoma could induce atypical hyperplasia, with the expression of Ki67, CD3, CD56, GZMB, and PRF in mice. These data indicate that the fungus may be involved in inducing atypical hyperplasia or tumorigenesis.
A New Vaccination Method Based on Phage NgoΦ6 and Its Phagemid Derivatives
Authors: Piekarowicz Andrzej , Kłyż Aneta , Stein Daniel C.
Published: April 2022

Phagemid particles based on the Neisseria gonorrhoeae filamentous phage NgoΦ6 were used as a vaccine delivery system. We demonstrate that the host proteins incorporated into/associated with these particles can be encoded by chromosomal genes of the host bacterium or from plasmids able to replicate as an autonomous entity in the phagemid host. Phagemid particles were prepared from three types of cells, namely, Salmonella enterica ser. Typhimurium [pBSKS::Φ6fm(ST)] containing phagemid genome as an autonomous plasmid, Haemophilus influenzae Rd containing phagemid [pBSKS::Φ6fm(Hin)] integrated into the chromosome, and S. enterica ser. Typhimurium [pMPMT6::Φ6fm(ST)] containing an additional plasmid, pE1 HCV, encoding the Hepatitis C virus envelope glycoprotein E1. Approximately 200 μg of purified phage particles was used to immunize rabbits. The phagemid particles prepared from these three strains all elicited a large amount of IgG antibodies that were able to recognize bacterial host cells and proteins, as determined by ELISA and FACS analysis. The amount of specific anti-S. enterica ser. Typhimurium, anti-H. influenzae, and anti-E1 HCV antibodies elicited by vaccination was 170 μg/ml for anti-Salmonella, 80 μg/ml for anti-H. influenzae, and 65 μg/ml for anti-E1 HCV. Taken in toto, these data suggest that classical phage display methods have underestimated the potential for filamentous phage as a novel immunogen delivery system.
Variation of Soil Microbial Community and Sterilization to Fusarium oxysporum f. sp. niveum Play Roles in Slightly Acidic Electrolyzed Water-Alleviated Watermelon Continuous Cropping Obstacle
Authors: Wu Xue , Wu Cuinan , Lu Daipeng , Wu Yiwen , Ye Zhangying , Xia Liru , Sun Yudong , Bao Encai , Ye Lin , Tang Yuxin , Cao Kai
Published: April 2022

It is critical to exploit technologies for alleviating watermelon continuous cropping obstacle which frequently occurs and results in the limiting production and economic losses of watermelon. This study aimed to explore the effects of slightly acidic electrolyzed water (SAEW) on watermelon continuous cropping obstacles. The results showed that SAEW significantly improved the growth of watermelon seedlings cultivated in continuous cropping soil and caused a mass of changes to the diversity of the soil microbial community. Compared with Con, SAEW decreased the diversity index of bacteria by 2%, 0.48%, and 3.16%, while it increased the diversity index of fungus by 5.68%, 10.78%, and 7.54% in Shannon, Chao1, and ACE index, respectively. Besides, the enrichment level of Fusarium oxysporum f. sp. niveum (FON) was remarkably downregulated by 50.2% at 14 days of SAEW treatment, which could decrease the incidence of Fusarium wilt disease. The wet and dry weights of FON mycelia in the fluid medium were depressed more than 93%, and the number of FON colonies in continuous cropping soil was reduced by 83.56% with SAEW treatment. Additionally, a strong correlation between watermelon, FON, and SAEW was presented by correlation analysis. Furthermore, the content of endogenous reactive oxygen species (ROS) was over quadruply increased by SAEW, which may contribute to the sterilizing effect of SAEW on FON. Taken together, our findings demonstrated that exogenous SAEW could alter the soil microbial diversity and decrease the accumulation of FON, which improved the growth of watermelon seedlings and finally alleviated continuous cropping obstacles of watermelon.
Bacterial Transformation and Processing of Diatom-Derived Organic Matter: A Case Study for Skeletonema dohrnii
Authors: Liu Yang , Wang Xueru , Sun Jun
Published: April 2022

Bacterial transformation and processing of phytoplankton-derived organic matter are extremely important for the formation of ubiquitous organic matter (OM) in aquatic ecosystems. Heterotrophic bacteria convert OM into biomass and recycle inorganic components, contributing to the production of microbial food webs. While phytoplankton-derived organic matter is commonly studied, the transformation and processing of dissolved OM (DOM) and lysate OM (LOM) by culturable epiphytic bacteria remains poorly understood. In this study, cultivable epiphytic bacteria from the marine diatom, Skeletonema dohrnii, were isolated, purified, and identified. Three bacteria, Roseobacteria sp., Marinobacter sp., and Bacillus sp., were selected to study the transformation and processing of S. dohrnii-derived DOM and LOM using excitation-emission matrix (EEM) fluorescence methods, and bacterial abundance, dissolved organic carbon (DOC) concentration, and transparent exopolymer particle (TEP) content were measured. Meanwhile, the bacterial transformation of DOM and LOM was further evaluated by the fluorescence index, biological index, β/α, and humification index. The primary fluorophores, peak A (humic-like), peak C (humic-like), peak M (humic-like), peak B (protein-like), and peak T (tryptophan-like), were present in the sample. The fluorescence of DOM and LOM was dominated by protein-like signal that became increasingly humic-like over time, suggesting that more complex molecules (e.g., recalcitrant OM) are being produced. The fluorescence of DOM and LOM was dominated by a protein-like signal that became increasingly humic-like over time, suggesting that epiphytic bacteria produced more complex molecules. Results showed that the bacteria utilized LOM more rapidly than DOM. While the three bacteria transformed OM to different degrees, all were able to facilitate microbial reprocessing of OM into refractory OM.
The Potential of Pre-fermented Juice or Lactobacillus Inoculants to Improve the Fermentation Quality of Mixed Silage of Agro-Residue and Lucerne
Authors: Mu Lin , Wang Qinglan , Cao Xin , Li Hui , Zhang Zhifei
Published: April 2022

The objective of this study was to determine the effect of pre-fermented juice, Lactobacillus plantarum, and L. buchneri on chemical composition, fermentation, aerobic stability, dynamics of microbial community, and metabolic pathway of a mixture of lucerne, wheat bran (WB), and rice straw (RS). All mixtures were ensiled for 1, 3, 5, 7, 15, 30, and 45 days after treatment with uninoculated (control, C); L. plantarum [LP, 1 × 106 cfu/g of fresh weight (FW)]; L. buchneri (LB, 1 × 106 cfu/g of FW); LP + LB (LPB, 1 × 106 cfu/g of FW of each inoculant); and pre-fermented juice (J; 2 × 106 cfu/g of FW). Four lactic acid bacteria (LAB) species from three genera were cultured from the pre-fermented juice, with W. cibaria being dominant. The inoculants increased lactic acid (LA), decreased pH and ammonia nitrogen (AN) compared to C silage at earlier stages of ensiling, and high dry matter (DM) and water-soluble carbohydrate (WSC) content in inoculated silages. Adding LPB increased the abundance of L. plantarum, L. paralimentarius, and L. nodensis, resulting in the lowest pH. Pre-fermented juice enriched W. cibaria, L. sakei, L. parabrevis, Pseudomonas putida, and Stenotrophomonas maltophilia, mainly enhanced accumulation of acetic acid (AA) and LA, and decreased pH, crude protein losses, AN, and hemicellulose contents. L. buchneri and L. brevis had a high abundance in LB-treated and J silages, respectively, inhibited undesirable bacteria, and improved aerobic stability with more than 16 days. In addition, the metabolic pathways changed with time and L. buchneri inoculants promoted global metabolism. In conclusion, inoculations altered bacterial succession and metabolic pathways in silage; LB and pre-fermented juice enhanced ensiling by promoting pH reductions, enhancing concentrations of LA and AA, and extending aerobic stability more than 16 days.
Changes to the Bacterial Microbiome in the Rhizosphere and Root Endosphere of Persea americana (Avocado) Treated With Organic Mulch and a Silicate-Based Mulch or Phosphite, and Infested With Phytophthora cinnamomi
Authors: Farooq Qurrat Ul Ain , Hardy Giles Edward St. John , McComb Jen A. , Thomson Peter Campbell , Burgess Treena Isobel
Published: April 2022

Plant growth and responses of the microbial profile of the rhizosphere soil and root endosphere were investigated for avocado plants infested or not infested with Phytophthora cinnamomi and the changes were compared in plants grown with various soil additives or by spraying plants with phosphite. Soil treatments were organic mulches or silica-based mineral mulch. Reduction of root growth and visible root damage was least in the infested plants treated with phosphite or mineral mulch applied to the soil. Rhizosphere soils and root endospheres were analyzed for bacterial communities using metabarcoding. Bacterial abundance and diversity were reduced in infested rhizospheres and root endospheres. The presence or absence of mineral mulch resulted in greater diversity and larger differences in rhizosphere community composition between infested and non-infested pots than any other treatment. Some rhizosphere bacterial groups, especially Actinobacteria and Proteobacteria, had significantly higher relative abundance in the presence of Phytophthora. The bacterial communities of root endospheres were lower in abundance than rhizosphere communities and not affected by soil treatments or phosphite but increased in abundance after infection with P. cinnamomi. These findings suggested that the addition of silicate-based mineral mulch protects against Phytophthora root rot, which may be partly mediated through changes in rhizosphere bacterial community composition. However, the changes to the microbiome induced by spraying plants with phosphite are different from those resulting from the application of mineral mulch to the soil.
Characteristics of Bacterial Microbiota in Different Intestinal Segments of Aohan Fine-Wool Sheep
Authors: Ma Yuhao , Deng Xiaotian , Yang Xue , Wang Jiankui , Li Tun , Hua Guoying , Han Deping , Da Lai , Li Rui , Rong Weiheng , Deng Xuemei
Published: April 2022

The microbial community performs vital functions in the intestinal system of animals. Modulation of the gut microbiota structure can indirectly or directly affect gut health and host metabolism. Aohan fine-wool sheep grow in semi-desert grasslands in China and show excellent stress tolerance. In this study, we amplified 16S rRNA gene to investigate the dynamic distribution and adaptability of the gut microbiome in the duodenum, jejunum, ileum, cecum, colon, and rectum of seven Aohan fine-wool sheep at 12 months. The results showed that the microbial composition and diversity of the ileum and the large intestine (collectively termed the hindgut) were close together, and the genetic distance and functional projections between them were similar. Meanwhile, the diversity index results revealed that the bacterial richness and diversity of the hindgut were significantly higher than those of the foregut. We found that from the foregut to the hindgut, the dominant bacteria changed from Proteobacteria to Bacteroidetes. In LEfSe analysis, Succiniclasticum was found to be significantly abundant bacteria in the foregut and was involved in succinic acid metabolism. Ruminococcaceae and Caldicoprobacteraceae were significantly abundant in hindgut, which can degrade cellulose polysaccharides in the large intestine and produce beneficial metabolites. Moreover, Coriobacteriaceae and Eggthellaceae are involved in flavonoid metabolism and polyphenol production. Interestingly, these unique bacteria have not been reported in Mongolian sheep or other sheep breeds. Collectively, the gut microbiota of Aohan fine-wool sheep is one of the keys to adapting to the semi-desert grassland environment. Our results provide new insights into the role of gut microbiota in improving stress tolerance and gut health in sheep.
The Fis Nucleoid Protein Negatively Regulates the Phase Variation fimS Switch of the Type 1 Pilus Operon in Enteropathogenic Escherichia coli
Authors: Saldaña-Ahuactzi Zeus , Soria-Bustos Jorge , Martínez-Santos Verónica I. , Yañez-Santos Jorge A. , Martínez-Laguna Ygnacio , Cedillo-Ramirez María Lilia , Puente José L. , Girón Jorge A.
Published: April 2022

In Escherichia coli the expression of type 1 pili (T1P) is determined by the site-specific inversion of the fimS ON–OFF switch located immediately upstream of major fimbrial subunit gene fimA. Here we investigated the role of virulence (Ler, GrlR, and GrlA) and global regulators (H-NS, IHF, and Fis) in the regulation of the fimS switch in the human enteropathogenic E. coli (EPEC) O127:H6 strain E2348/69. This strain does not produce detectable T1P and PCR analysis of the fimS switch confirmed that it is locked in the OFF orientation. Among the regulator mutants analyzed, only the ∆fis mutant produced significantly high levels of T1P on its surface and yielded high titers of agglutination of guinea pig erythrocytes. Expression analysis of the fimA, fimB, and fimE promoters using lacZ transcriptional fusions indicated that only PfimA activity is enhanced in the absence of Fis. Collectively, these data demonstrate that Fis is a negative regulator of T1P expression in EPEC and suggest that it is required for the FimE-dependent inversion of the fimS switch from the ON-to-OFF direction. It is possible that a similar mechanism of T1P regulation exists in other intestinal and extra-intestinal pathogenic classes of E. coli.
Development and Preliminary Application of a Triplex Real-Time Quantitative PCR Assay for the Simultaneous Detection of Entamoeba histolytica, Giardia lamblia, and Cryptosporidium parvum
Authors: Zhang Yaoguang , Chen Jian , Pan Hao , Ma Xiaojiang , Jiang Li , Zhu Qian , Wu Huanyu , Wang Zhenyu
Published: April 2022

Background

The protozoan parasites including Entamoeba histolytica, Giardia lamblia, and Cryptosporidium parvum can infect the human intestinal tract and cause serious diseases. In this study, we aimed to develop a triplex real-time quantitative PCR (qPCR) for the simultaneous differential detection of these three intestinal protozoa.

Methods

Specific primers and TaqMan probes were designed for the 16S-like SSU rRNA sequence of E. histolytica, the gdh sequence of G. lamblia, and the 18srRNA sequence of C. parvum. A triplex qPCR assay was developed based on single-duplicate experiments to evaluate its limit of detection (LOD), specificity, stability, and reproducibility. Additionally, 163 fecal samples from patients with diarrhea who tested positive for copro-antigen were tested to verify the practicality of the assay.

Results

The triplex qPCR assay could specifically detect E. histolytica, G. lamblia, and C. parvum without cross-reactivity amongst the target-specific TaqMan probes of these three intestinal protozoan parasites and did not produce amplification curves for any other non-target species, and had good specificity. Amplification of serial dilutions showed that the triplex qPCR detected as little as 500 copies/μL of standard plasmid DNA. The standard curve displayed good linearity between 5 × 102 and 5 × 108 copies/μL; qPCR assays were performed with an efficiency of more than 95% and R2 values were greater than 0.99. The triplex qPCR assay had good repeatability with intra- and inter-assay coefficients of variation less than 1.92%. Among the 163 fecal samples, four samples were confirmed to be positive for C. parvum using the triplex qPCR assay.

Conclusion

The triplex qPCR established in this study not only provides a rapid, sensitive, specific tool for the simultaneous detection of E. histolytica, G. lamblia, and C. parvum, but also has good practical application value.
Targeting Selective Autophagy as a Therapeutic Strategy for Viral Infectious Diseases
Authors: Liu Yishan , Zhou Tao , Hu Jiajia , Jin Shouheng , Wu Jianfeng , Guan Xiangdong , Wu Yaoxing , Cui Jun
Published: April 2022

Autophagy is an evolutionarily conserved lysosomal degradation system which can recycle multiple cytoplasmic components under both physiological and stressful conditions. Autophagy could be highly selective to deliver different cargoes or substrates, including protein aggregates, pathogenic proteins or superfluous organelles to lysosome using a series of cargo receptor proteins. During viral invasion, cargo receptors selectively target pathogenic components to autolysosome to defense against infection. However, viruses not only evolve different strategies to counteract and escape selective autophagy, but also utilize selective autophagy to restrict antiviral responses to expedite viral replication. Furthermore, several viruses could activate certain forms of selective autophagy, including mitophagy, lipophagy, aggrephagy, and ferritinophagy, for more effective infection and replication. The complicated relationship between selective autophagy and viral infection indicates that selective autophagy may provide potential therapeutic targets for human infectious diseases. In this review, we will summarize the recent progress on the interplay between selective autophagy and host antiviral defense, aiming to arouse the importance of modulating selective autophagy as future therapies toward viral infectious diseases.
Neural Indices of Emotion Regulatory Implementation Correlate With Behavioral Regulatory Selection: Proof-of-Concept Investigation
Authors: Fine Naomi B. , Schwartz Naama , Hendler Talma , Gonen Tal , Sheppes Gal
Published: April 2022

“Do what you do best” conveys an intuition about the association between ability and preference. In the field of emotion regulation, ability and preference are manifested in two central stages, namely, implementation and selection of regulatory strategies, which to date have been mainly studied separately. Accordingly, the present proof-of-concept study wished to provide preliminary evidence for an association between neural indices of implementation ability and behavioral selection preferences. In this pilot study, participants performed a classic neuroimaging regulatory implementation task that examined their ability (neurally reflected in the degree of amygdala modulation) to execute two central regulatory strategies, namely, attentional distraction and cognitive reappraisal while viewing negative images. Then participants performed a separate, classic behavioral selection task that examined their choice preferences for using distraction and reappraisal while viewing negative images. Confirming our conceptual framework, we found that exclusively for distraction, which has been associated with robust amygdala modulation, a decrease in amygdala activity during implementation (i.e., enhanced ability) was associated with enhanced preference to behaviorally select distraction [r(15) = −0.69, p = 0.004]. These preliminary findings link between two central emotion regulatory stages, suggesting a clue of the adaptive association between neural ability and behavioral preference for particular regulatory strategies.
The Anterior Piriform Cortex and Predator Odor Responses: Modulation by Inhibitory Circuits
Authors: Matsukawa Mutsumi , Yoshikawa Masaaki , Katsuyama Narumi , Aizawa Shin , Sato Takaaki
Published: April 2022

Rodents acquire more information from the sense of smell than humans because they have a nearly fourfold greater variety of olfactory receptors. They use olfactory information not only for obtaining food, but also for detecting environmental dangers. Predator-derived odor compounds provoke instinctive fear and stress reactions in animals. Inbred lines of experimental animals react in an innate stereotypical manner to predators even without prior exposure. Predator odors have also been used in models of various neuropsychiatric disorders, including post-traumatic stress disorder following a life-threatening event. Although several brain regions have been reported to be involved in predator odor-induced stress responses, in this mini review, we focus on the functional role of inhibitory neural circuits, especially in the anterior piriform cortex (APC). We also discuss the changes in these neural circuits following innate reactions to odor exposure. Furthermore, based on the three types of modulation of the stress response observed by our group using the synthetic fox odorant 2,5-dihydro-2,4,5-trimethylthiazoline, we describe how the APC interacts with other brain regions to regulate the stress response. Finally, we discuss the potential therapeutic application of odors in the treatment of stress-related disorders. A clearer understanding of the odor–stress response is needed to allow targeted modulation of the monoaminergic system and of the intracerebral inhibitory networks. It would be improved the quality of life of those who have stress-related conditions.
Purkinje Cell Activity in the Medial and Lateral Cerebellum During Suppression of Voluntary Eye Movements in Rhesus Macaques
Authors: Avila Eric , Flierman Nico A. , Holland Peter J. , Roelfsema Pieter R. , Frens Maarten A. , Badura Aleksandra , De Zeeuw Chris I.
Published: April 2022

Volitional suppression of responses to distracting external stimuli enables us to achieve our goals. This volitional inhibition of a specific behavior is supposed to be mainly mediated by the cerebral cortex. However, recent evidence supports the involvement of the cerebellum in this process. It is currently not known whether different parts of the cerebellar cortex play differential or synergistic roles in the planning and execution of this behavior. Here, we measured Purkinje cell (PC) responses in the medial and lateral cerebellum in two rhesus macaques during pro- and anti-saccade tasks. During an antisaccade trial, non-human primates (NHPs) were instructed to make a saccadic eye movement away from a target, rather than toward it, as in prosaccade trials. Our data show that the cerebellum plays an important role not only during the execution of the saccades but also during the volitional inhibition of eye movements toward the target. Simple spike (SS) modulation during the instruction and execution periods of pro- and anti-saccades was prominent in PCs of both the medial and lateral cerebellum. However, only the SS activity in the lateral cerebellar cortex contained information about stimulus identity and showed a strong reciprocal interaction with complex spikes (CSs). Moreover, the SS activity of different PC groups modulated bidirectionally in both of regions, but the PCs that showed facilitating and suppressive activity were predominantly associated with instruction and execution, respectively. These findings show that different cerebellar regions and PC groups contribute to goal-directed behavior and volitional inhibition, but with different propensities, highlighting the rich repertoire of the cerebellar control in executive functions.
Targeting C–C Chemokine Receptor 5: Key to Opening the Neurorehabilitation Window After Ischemic Stroke
Authors: Feng Yi-Qi , Xu Zhen-Zhen , Wang Yan-Ting , Xiong Yue , Xie Wanli , He Yu-Yao , Chen Lu , Liu Guo-Yang , Li Xia , Liu Jie , Wu Qingping
Published: April 2022

Stroke is the world’s second major cause of adult death and disability, resulting in the destruction of brain tissue and long-term neurological impairment; induction of neuronal plasticity can promote recovery after stroke. C–C chemokine receptor 5 (CCR5) can direct leukocyte migration and localization and is a co-receptor that can mediate human immunodeficiency virus (HIV) entry into cells. Its role in HIV infection and immune response has been extensively studied. Furthermore, CCR5 is widely expressed in the central nervous system (CNS), is engaged in various physiological activities such as brain development, neuronal differentiation, communication, survival, and learning and memory capabilities, and is also involved in the development of numerous neurological diseases. CCR5 is differentially upregulated in neurons after stroke, and the inhibition of CCR5 in specific regions of the brain promotes motor and cognitive recovery. The mechanism by which CCR5 acts as a therapeutic target to promote neurorehabilitation after stroke has rarely been systematically reported yet. Thus, this review aims to discuss the function of CCR5 in the CNS and the mechanism of its effect on post-stroke recovery by regulating neuroplasticity and the inflammatory response to provide an effective basis for clinical rehabilitation after stroke.
Neuroimaging Parameters Are Not Associated With Chronic Post-stroke Fatigue in Young Stroke Patients
Authors: Boot Esther M. , van de Camp Sanne A. J. H. , Maaijwee Noortje A. , Arntz Renate M. , Kessels Roy P. C. , de Leeuw Frank-Erik , Tuladhar Anil M.
Published: April 2022

Introduction

Post-stroke fatigue is frequently present in young adults, but its underlying mechanism is still unclear. The aim of the study was to investigate the association between lesion location, network efficiency and chronic post-stroke fatigue based on voxel-based lesion-symptom mapping and structural network connectivity analysis.

Patients and Methods

One hundred and thirty five young patients, aged 18–50 years, with a first-ever transient ischemic attack or cerebral infarction from the Follow-Up of Transient ischemic attack and stroke patients and Unelucidated Risk factor Evaluation (FUTURE) study, underwent 1.5T MRI and were assessed for fatigue using the self-report Checklist Individual Strength. Stroke lesions were manually segmented, and structural network efficiency was calculated using the diffusion MRI-based brain networks and graph theory for each patient. Univariate and multivariate analyses was performed to study the associations between MRI parameters and chronic post-stroke fatigue. In addition, we used voxel-based lesion-symptom mapping to analyze the relationship between the lesion location and chronic post-stroke fatigue.

Results

Mean age at index event was 39.0 years (SD ± 8.2), and mean follow-up duration was 11.0 years (SD ± 8.0). 50 patients (37%) had post-stroke fatigue. Voxel-based lesion-symptom mapping showed no significant relation between stroke lesions and the presence of chronic post-stroke fatigue. Furthermore, there were no significant associations between the lesion size or network efficiency, and the presence of chronic post-stroke fatigue.

Discussion

We did not find any association between stroke characteristics (lesion location and size) and chronic post-stroke fatigue (CIS20-R), nor associations between structural brain network connectivity and post-stroke fatigue on the long term in young stroke patients.
Outcome of Endovascular Thrombectomy in Pre-stroke Dependent Patients With Acute Ischemic Stroke: A Systematic Review and Meta-Analysis
Authors: Adamou Antonis , Gkana Androniki , Mavrovounis Georgios , Beltsios Eleftherios T. , Kastrup Andreas , Papanagiotou Panagiotis
Published: April 2022

Introduction

Endovascular thrombectomy (EVT) is a well-established and effective therapeutic option for patients that meet certain criteria. However, this modality is not well studied in patients with pre-existing disability. The aim of the present study was to investigate the impact of mechanical thrombectomy in patients with acute onset ischemic stroke and pre-stroke dependency (PSD) in regard to their clinical outcome and mortality.

Materials and Methods

The MEDLINE, Scopus, and Cochrane Library databases were comprehensively searched with a cut-off date of December 11th, 2021. We performed meta-analysis to investigate the 90-day clinical outcome, the 90-day mortality, and the rate of symptomatic intracerebral hemorrhage (sICH) between the PSD (modified Rankin Scale score ≥ 3) and non-PSD (modified Rankin Scale score = 0–2) groups who underwent EVT for acute onset ischemic stroke.

Results

Six studies were included in the meta-analysis involving 4,543 cases with no PSD and 591 cases with PSD. The non-PSD group showed a statistically significant better clinical outcome at 90 days compared to the PSD group [RR (95% CI) = 1.44 (1.06, 1.85); pz = 0.02]. The non-PSD group demonstrated a statistically significant lower risk of death at 90 days in comparison to the PSD group [RR (95% CI) = 0.45 (0.41, 0.50); pz < 0.01]. Lastly, the rate of sICH was comparable between the two groups [RR (95% CI) = 0.89 (0.64, 1.24); pz = 0.48].

Discussion

We report a higher rate of unfavorable clinical outcome and a higher mortality rate in patients with PSD undergoing EVT compared to those with no previous disability. However, there was a significant proportion of PSD cases who fared well post-procedurally, indicating that PSD patients should not be routinely excluded from mechanical thrombectomy.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021284181, identifier: CRD42021284181.
Neuroscience Education Begins With Good Science: Communication About Phineas Gage (1823–1860), One of Neurology’s Most-Famous Patients, in Scientific Articles
Authors: Schleim Stephan
Published: April 2022

Phineas Gage is one of the most famous neurological patients. His case is still described in psychology textbooks and in scientific journal articles. A controversy has been going on about the possible consequences of his accident, destroying part of his prefrontal cortex, particularly with respect to behavioral and personality changes. Earlier studies investigated the accuracy of descriptions in psychology textbooks. This is, to my knowledge, the first analysis of journal articles in this respect. These were investigated with regard to four criteria: Description of (1) personality changes, (2) psychopathy-like behavior, (3) alternative explanations besides the immediate brain damage, and (4) Gage’s recovery. 92% of articles described personality changes, 52% of a psychopathy-like kind; only 4% mentioned alternative explanations and 16% described Gage’s recovery. The results are discussed in the light of the available historical evidence. The article closes with several suggestions on improving science communication about the famous case.
Effect of Exercise on the Cognitive Function of Older Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis
Authors: Cai Yi-Hui , Wang Zi , Feng Le-Yi , Ni Guo-Xin
Published: April 2022

Background

Aging and type 2 diabetes mellitus (T2DM) are important risk factors for the development of cognitive deterioration and dementia. The objective of this research was to investigate the effects of an exercise intervention on cognitive function in older T2DM patients.

Methods

Eight literature databases (PubMed, EBSCO, Scopus, Embase, The Cochrane Library, Web of Science, Ovid, and ProQuest) were searched from inception to 20 January 2022. The researchers examined randomized controlled trials (RCTs) that evaluated the impact of exercise on the cognitive performance of older T2DM patients. The Cochrane risk-of-bias tool (ROB 2) for RCTs was used to assess each study. The quality of evidence was assessed using the GRADE (grading of recommendations, assessment, development, and evaluations) approach. The mini-mental state examination (MMSE), Modified MMSE (3MSE), and Montreal cognitive assessment (MoCA) were used to evaluate the cognitive outcomes. We performed a subgroup analysis with stratification according to exercise intervention modality, duration, and cognitive impairment.

Results

Five trials were eligible, with a total of 738 T2DM patients. The combined findings revealed that exercise improved global cognitive function significantly (standardized mean difference: 1.34, 95% confidence interval: 0.23–2.44,p< 0.01). The effect of exercise on global cognitive performance was not significantly influenced by intervention modality, intervention duration, or cognitive impairment in the sub-group analysis (p> 0.05). In the studies that were included, no relevant adverse events were reported.

Conclusion

Exercise is beneficial in improving global cognitive function in older adults with T2DM. Studies with bigger sample sizes and higher quality are additionally expected to draw more definite conclusions.

Systematic Review Registration

[https://www.crd.york.ac.uk/PROSPERO/#recordDetails], identifier [CRD42022296049].
Microbiota Composition and Diversity in Weight Loss Population After the Intake of IQP-AE-103 in a Double-Blind, Randomized, Placebo-Controlled Study
Authors: Peng Li Vern , Cooper Jennifer , De Costa Patricia , Chong Pee Win
Published: April 2022

The effect of the novel IQP-AE-103 (proprietary combination of dehydrated okra powder and inulin) on body weight reduction and the association with changes in microbiota composition were investigated in a double-blind, randomized, placebo-controlled trial. A total of seventy-two overweight or moderately obese subjects with a body mass index of ≥25 and <35 kg/m2 were randomly allocated to receive IQP-AE-103 or placebo; each group received two IQP-AE-103 or placebo capsules three times daily, respectively. Body weight, body fat, waist circumference, and hip circumference were measured, and fecal samples were collected at baseline and after 12 weeks of intervention. Using 16S rRNA gene sequencing on the fecal samples, the microbiota dissimilarity, diversity, and differences in relative abundance between or within groups were analyzed. At the end of the study, body weight was significantly reduced in the IQP-AE-103 group compared with the placebo group, 5.16 ± 2.39 kg vs. 0.97 ± 2.09 kg (p < 0.001). Subjects from the IQP-AE-103 group who achieved a reduction of ≥5% of total body weight from baseline (hereafter referred to as 5% responders or IQP5) had a mean body weight reduction of 6.74 ± 1.94 kg, significantly greater than the placebo group (p < 0.001). Using Lefse and statistical analysis, subjects in the IQP-AE-103 group had a significantly lower relative abundance of Firmicutes than the placebo group (p < 0.05) after 12 weeks of intervention. The 5% responders from the IQP-AE-103 group had a remarkable 4.6-fold higher relative abundance of Akkermansia muciniphila than the placebo group (p < 0.05). As the significant differences between groups were only observed post-intervention, the overall differences in microbiota profile suggest that the weight loss in overweight and moderately obese subjects who consumed IQP-AE-103 for 12 weeks is accompanied by a positive change in microbiota composition. These changes might be linked to the beneficial effects of microbiome modulations in alleviating obesity and metabolic syndrome. To the best of our knowledge, we are the first to report over-the-counter (OTC) supplementation that results in both significant changes in weight and favorable shifts on the subject microbiota profile. The trial is registered under ClinicalTrials.gov Identifier no. NCT03058367.