bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide Identification of Long Non-Coding RNAs and Their Potential Functions in Poplar Growth and Phenylalanine Biosynthesis
Authors: Zhang Lei , Ge Xiaolan , Du Jiujun , Cheng Xingqi , Peng Xiaopeng , Hu Jianjun
Published: November 2021

Poplar is an important bioenergy tree species. lncRNAs play important roles in various biological regulatory processes, and their expression pattern is more tissue-specific than mRNAs. In this study, P. deltoides “Danhong” (Pd) and P. simonii “Tongliao1” (Ps) with different growth rates and wood quality were used as experimental materials, and the transcriptomes of their shoot apical meristem, xylem, and phloem were sequenced. Furthermore, high-throughput RNA sequencing analysis revealed that the expression patterns of genes and lncRNAs are different between the two genotypes. 6,355 lncRNAs were identified. Based on target prediction, lncRNAs and target genes were involved in ADP binding, oxidoreductase activity, phenylpropanoid biosynthesis, and cyanoamino acid metabolism. The DElncRNAs in two poplars were co-expressed with transcription factors and structural genes of lignin and flavonoid pathways. In addition, we found the potential target lncRNAs of miRNA. This result provides basic evidence for a better understanding of the regulatory role of lncRNAs in regulating phenylalanine molecular pathways and wood formation.
Comprehensive Transcriptomic Profiling of Murine Osteoclast Differentiation Reveals Novel Differentially Expressed Genes and LncRNAs
Authors: Toor Salman M. , Wani Sachin , Albagha Omar M. E.
Published: November 2021

Osteoclasts are the sole bone resorbing cells, which undertake opposing roles to osteoblasts to affect skeletal mass and structure. However, unraveling the comprehensive molecular mechanisms behind osteoclast differentiation is necessitated to overcome limitations and scarcity of available data, particularly in relation with the emerging roles of long non-coding RNAs (LncRNAs) in gene expression. In this study, we performed comprehensive and progressive analyses of the dynamic transcriptomes of murine osteoclasts, generated in vitro. We compared the total RNA-based transcriptomes of murine bone marrow derived cells with differentiated osteoclasts, while focusing on potentially novel genes and LncRNAs, to uncover critical genes and their associated pathways, which are differentially regulated during osteoclast differentiation. We found 4,214 differentially regulated genes during osteoclast differentiation, which included various types of LncRNAs. Among the upregulated protein coding genes not previously associated with osteoclast are Pheta1, Hagh, Gfpt1 and Nol4, while downregulated genes included Plau, Ltf, Sell and Zfp831. Notably, we report Nol4 as a novel gene related to osteoclast activity since Nol4 knockout mice Nol4em1(International Mouse Phenotyping Consortium)J exhibit increased bone mineral density. Moreover, the differentially expressed LncRNAs included antisense and long intergenic non-coding RNAs, among others. Overall, immune-related and metabolism-related genes were downregulated, while anatomical morphogenesis and remodeling-related genes were upregulated in early-differentiated osteoclasts with sustained downregulation of immune-related genes in mature osteoclasts. The gene signatures and the comprehensive transcriptome of osteoclast differentiation provided herein can serve as an invaluable resource for deciphering gene dysregulation in osteoclast-related pathologic conditions.
Structural Abnormalities of Spermatozoa in Triploid Gynogenetic Crucian Carp (Carassius auratus)
Authors: He Wangchao , Sun Yu , Qiang Jiaxu , Luo Xinyue , Zhang Hui , Yang Conghui , Luo Kaikun , Zhao Rurong , Qin Qinbo , Zhang Chun , Liu Shaojun
Published: November 2021

The spermatozoa of triploid gynogenetic crucian carp (Carassius auratus) (3nDTCC) possess a spermatogenesis process with a normal genetic background. However, the genetic materials of these spermatozoa do not completely inherit gynogenetic progeny in general. Understanding the intrinsic mechanism may be helpful for developing breeding strategies of gynogenetic fishes. In this study, the spermatozoa ultrastructure was systematically studied in diploid red crucian carp and 3nDTCC to demonstrate their cytological structural differences. In addition, the artificial breeding tests of 3nDTCC(♀) with different ploidy spermatozoa were performed to verify the contributions of genetic materials from 3nDTCC spermatozoa to the gynogenesis progeny. Furthermore, the mRNA expression of centriole-related genes (i.e.,cep57,cetn1,rootletin, andnek2) involved in spermatozoa packaging was also determined by quantitative real-time PCR (qPCR) to illustrate the molecular expression characteristics of the spermatozoa packaging process in 3nDTCC. The results reveal the adaptive features of spermatozoa in 3nDTCC, including the loose midpiece structure, abnormal head structure, and abnormal expression of centriole-related genes, which may influence the motility of spermatozoa and make it not involved normally in the genetic composition of the gynogenesis offspring.
Addressing Challenges in Endometriosis Pain Communication Between Patients and Doctors: The Role of Language
Authors: Bullo Stella , Weckesser Annalise
Published: November 2021

Introduction: In the context of the complex medical, social, and economic factors that contribute to endometriosis diagnosis delay and its consequent impact on quality of life, this report focuses on patient-practitioner pain communication and examines the role of language in doctor-patient communication. Our study explored what patients and doctors consider challenging and effective in endometriosis pain communication. It further examined what commonly used metaphors by patients could be suggestive, or not, of endometriosis to doctors.

Method: A United Kingdom-based qualitative (open-ended question) survey with women with endometriosis (n131) and semi-structured telephone interviews with general practitioners (GPs) (n11). Survey and interview data were analyzed thematically.

Results: Both women and GPs reported the Numeric Rating Scale (NRS) to be insufficient as a standalone tool for communicating endometriosis related pain. Both also found descriptions of the quality, location, and impact on daily life of pain to more effective means of communicating pain symptoms. When presented with common metaphorical expressions surveyed women used to describe their pain, not all GPs recognized such metaphors as indicative of possible endometriosis. Further, some GPs reported some of the expressions to be indicative of other pathologies.

Conclusion: Findings reveal the importance of language in pain communication and the need for additional tools to help women and doctors find the most effective way to communicate the experience and elicit appropriate investigative care. They also show the need for further investigation into how metaphor can be effectively used to improve patient-practitioner communication of endometriosis related pain.
Stigmatization in Patients With Psoriasis: A Mini Review
Authors: Zhang Hanlin , Yang Zihan , Tang Keyun , Sun Qiuning , Jin Hongzhong
Published: November 2021

Psoriasis is a chronic and recurrent immune-related skin disease that often causes disfigurement and disability. Due to the visibility of lesions in patients and inadequate understanding of dermatology knowledge in the general public, patients with psoriasis often suffer from stigma in their daily lives, which has adverse effects on their mental health, quality of life, and therapeutic responses. This review summarized the frequently used questionnaires and scales to evaluate stigmatization in patients with psoriasis, and recent advances on this topic. Feelings of Stigmatization Questionnaire, Questionnaire on Experience with Skin Complaints, and 6-item Stigmatization Scale have been commonly used. The relationship between sociodemographic characteristics, disease-related variables, psychiatric disorders, quality of life, and stigmatization in patients with psoriasis has been thoroughly investigated with these questionnaires. Managing the stigmatization in patients with psoriasis needs cooperation among policymakers, dermatologists, psychologists, psychiatrists, researchers, and patients. Further studies can concentrate more on these existing topics, as well as other topics, including predictors of perceived stigmatization, stigmatization from non-patient groups, influence of biologics on stigmatization, and methods of coping with stigmatization.
Acute Phase Proteins Are Baseline Predictors of Tuberculosis Treatment Failure
Authors: Kumar Nathella Pavan , Moideen Kadar , Nancy Arul , Viswanathan Vijay , Thiruvengadam Kannan , Sivakumar Shanmugam , Hissar Syed , Kornfeld Hardy , Babu Subash
Published: November 2021

Systemic inflammation is a characteristic feature of pulmonary tuberculosis (PTB). Whether systemic inflammation is associated with treatment failure in PTB is not known. Participants, who were newly diagnosed, sputum smear and culture positive individuals with drug-sensitive PTB, were treated with standard anti-tuberculosis treatment and classified as having treatment failure or microbiological cure. The plasma levels of acute phase proteins were assessed at baseline (pre-treatment). Baseline levels of C-reactive protein (CRP), alpha-2 macroglobulin (a2M), Haptoglobin and serum amyloid P (SAP) were significantly higher in treatment failure compared to cured individuals. ROC curve analysis demonstrated the utility of these individual markers in discriminating treatment failure from cure. Finally, combined ROC analysis revealed high sensitivity and specificity of 3 marker signatures comprising of CRP, a2M and SAP in distinguishing treatment failure from cured individuals with a sensitivity of 100%, specificity of 100% and area under the curve of 1. Therefore, acute phase proteins are very accurate baseline predictors of PTB treatment failure. If validated in larger cohorts, these markers hold promise for a rapid prognostic testing for adverse treatment outcomes in PTB.
Therapeutic Potential of a Novel Bifidobacterium Identified Through Microbiome Profiling of RA Patients With Different RF Levels
Authors: Jeong Yunju , Jhun JooYeon , Lee Seon-Yeong , Na Hyun Sik , Choi JeongWon , Cho Keun-Hyung , Lee Seung Yoon , Lee A Ram , Park Sang-Jun , You Hyun Ju , Kim Ji-Won , Park Myeong Soo , Kwon Bin , Cho Mi-La , Ji Geun Eog , Park Sung-Hwan
Published: November 2021

The potential therapeutic effects of probiotic bacteria in rheumatoid arthritis (RA) remain controversial. Thus, this study aimed to discover potential therapeutic bacteria based on the relationship between the gut microbiome and rheumatoid factor (RF) in RA. Bacterial genomic DNA was extracted from the fecal samples of 93 RA patients and 16 healthy subjects. Microbiota profiling was conducted through 16S rRNA sequencing and bioinformatics analyses. The effects of Bifidobacterium strains on human peripheral blood mononuclear cells and collagen-induced arthritis (CIA) mice were assessed. Significant differences in gut microbiota composition were observed in patients with different RF levels. The relative abundance of Bifidobacterium and Collinsella was lower in RF-high than in RF-low and RF-negative RA patients, while the relative abundance of Clostridium of Ruminococcaceae family was higher in RF-high than in RF-low and RF-negative patients. Among 10 differentially abundant Bifidobacterium, B. longum RAPO exhibited the strongest ability to inhibit IL-17 secretion. Oral administration of B. longum RAPO in CIA mice, obese CIA, and humanized avatar model significantly reduced RA incidence, arthritis score, inflammation, bone damage, cartilage damage, Th17 cells, and inflammatory cytokine secretion. Additionally, B. longum RAPO significantly inhibited Th17 cells and Th17-related genes—IL-17A, IRF4, RORC, IL-21, and IL-23R—in the PBMCs of rheumatoid arthritis patients. Our findings suggest that B. longum RAPO may alleviate RA by inhibiting the production of IL-17 and other proinflammatory mediators. The safety and efficacy of B. longum RAPO in patients with RA and other autoimmune disorders merit further investigation.
The Roles of Exosomes in Immunoregulation and Autoimmune Thyroid Diseases
Authors: Zou Junli , Peng Huiyong , Liu Yingzhao
Published: November 2021

Exosomes are extracellular microvesicles (30-150 nm) released from cells that contain proteins, lipids, RNA and DNA. They can deliver bioactive molecules and serve as carriers facilitating cell-cell communication, such as antigen presentation, inflammatory activation, autoimmune diseases (AIDs) and tumor metastasis. Recently, much attention has been attracted to the biology and functions of exosomes in immune regulation and AIDs, including autoimmune thyroid diseases (AITDs). Some studies have shown that exosomes are involved in the occurrence and development of AITDs, but they are still in the preliminary stage of exploration. This review mainly introduces the association of exosomes with immune regulation and emphasizes the potential role of exosomes in AITDs, aiming to provide new research strategies and directions for the pathogenesis and early diagnosis of AITDs.
From DNA Damage to Cancer Progression: Potential Effects of Cytolethal Distending Toxin
Authors: Lai Yi-Ru , Chang Yu-Fang , Ma Jason , Chiu Cheng-Hsun , Kuo Ming-Ling , Lai Chih-Ho
Published: November 2021

Cytolethal distending toxin (CDT), one of the most important genotoxins, is produced by several gram-negative bacteria and is involved in bacterial pathogenesis. Recent studies have shown that bacteria producing this peculiar genotoxin target host DNA, which potentially contributes to development of cancer. In this review, we highlighted the recent studies focusing on the idea that CDT leads to DNA damage, and the cells with inappropriately repaired DNA continue cycling, resulting in cancer development. Understanding the detailed mechanisms of genotoxins that cause DNA damage might be useful for targeting potential markers that drive cancer progression and help to discover new therapeutic strategies to prevent diseases caused by pathogens.
Epithelial Aryl Hydrocarbon Receptor Protects From Mucus Production by Inhibiting ROS-Triggered NLRP3 Inflammasome in Asthma
Authors: Hu Xinyue , Shen Yingchun , Zhao Yilin , Wang Ji , Zhang Xin , Tu Wei , Kaufman William , Feng Juntao , Gao Peisong
Published: November 2021

Background

Despite long-standing recognition in the significance of mucus overproduction in asthma, its etiology remains poorly understood. Muc5ac is a secretory mucin that has been associated with reduced pulmonary function and asthma exacerbations.

Objectives

We sought to investigate the immunological pathway that controls Muc5ac expression and allergic airway inflammation in asthma.

Methods

Cockroach allergen-induced Muc5ac expression and aryl hydrocarbon receptor (AhR) signaling activation was examined in the human bronchial epithelial cells (HBECs) and mouse model of asthma. AhR regulation of Muc5ac expression, mitochondrial ROS (Mito-ROS) generation, and NLRP3 inflammasome was determined by AhR knockdown, the antagonist CH223191, and AhR-/- mice. The role of NLRP3 inflammasome in Muc5ac expression and airway inflammation was also investigated.

Results

Cockroach allergen induced Muc5ac overexpression in HBECs and airways of asthma mouse model. Increased expression of AhR and its downstream genes CYP1A1 and CYP1B1 was also observed. Mice with AhR deletion showed increased allergic airway inflammation and MUC5AC expression. Moreover, cockroach allergen induced epithelial NLRP3 inflammasome activation (e.g., NLRP3, Caspase-1, and IL-1β), which was enhanced by AhR knockdown or the antagonist CH223191. Furthermore, AhR deletion in HBECs led to enhanced ROS generation, particularly Mito-ROS, and inhibition of ROS or Mito-ROS subsequently suppressed the inflammasome activation. Importantly, inhibition of the inflammasome with MCC950, a NLRP3-specifc inhibitor, attenuated allergic airway inflammation and Muc5ac expression. IL-1β generated by the activated inflammasomes mediated cockroach allergen-induced Muc5ac expression in HBECs.

Conclusions

These results reveal a previously unidentified functional axis of AhR-ROS-NLRP3 inflammasome in regulating Muc5ac expression and airway inflammation.
Understanding the Connection Between Common Stroke Comorbidities, Their Associated Inflammation, and the Course of the Cerebral Ischemia/Reperfusion Cascade
Authors: Przykaza Łukasz
Published: November 2021

Despite the enormous progress in the understanding of the course of the ischemic stroke over the last few decades, a therapy that effectively protects neurovascular units (NVUs) and significantly improves neurological functions in stroke patients has still not been achieved. The reasons for this state are unclear, but it is obvious that the cerebral ischemia and reperfusion cascade is a highly complex phenomenon, which includes the intense neuroinflammatory processes, and comorbid stroke risk factors strongly worsen stroke outcomes and likely make a substantial contribution to the pathophysiology of the ischemia/reperfusion, enhancing difficulties in searching of successful treatment. Common concomitant stroke risk factors (arterial hypertension, diabetes mellitus and hyperlipidemia) strongly drive inflammatory processes during cerebral ischemia/reperfusion; because these factors are often present for a long time before a stroke, causing low-grade background inflammation in the brain, and already initially disrupting the proper functions of NVUs. Broad consideration of this situation in basic research may prove to be crucial for the success of future clinical trials of neuroprotection, vasculoprotection and immunomodulation in stroke. This review focuses on the mechanism by which coexisting common risk factors for stroke intertwine in cerebral ischemic/reperfusion cascade and the dysfunction and disintegration of NVUs through inflammatory processes, principally activation of pattern recognition receptors, alterations in the expression of adhesion molecules and the subsequent pathophysiological consequences.
Intramuscular Vaccination With the HSV-1(VC2) Live-Attenuated Vaccine Strain Confers Protection Against Viral Ocular Immunopathogenesis Associated With γδT Cell Intracorneal Infiltration
Authors: Nabi Rafiq , Lewin Andrew C. , Collantes Therese M. , Chouljenko Vladimir N. , Kousoulas Konstantin G.
Published: November 2021

Herpes simplex virus type-1 (HSV-1) ocular infection is one of the leading causes of infectious blindness in developed countries. The resultant herpetic keratitis (HK) is caused by an exacerbated reaction of the adaptive immune response that persists beyond virus clearance causing substantial damage to the cornea. Intramuscular immunization of mice with the HSV-1(VC2) live-attenuated vaccine strain has been shown to protect mice against lethal ocular challenge. Herein, we show that following ocular challenge, VC2 vaccinated animals control ocular immunopathogenesis in the absence of neutralizing antibodies on ocular surfaces. Ocular protection is associated with enhanced intracorneal infiltration of γδ T cells compared to mock-vaccinated animals. The observed γδ T cellular infiltration was inversely proportional to the infiltration of neutrophils, the latter associated with exacerbated tissue damage. Inhibition of T cell migration into ocular tissues by the S1P receptors agonist FTY720 produced significant ocular disease in vaccinated mice and marked increase in neutrophil infiltration. These results indicate that ocular challenge of mice immunized with the VC2 vaccine induce a unique ocular mucosal response that leads into the infiltration of γδ T cells resulting in the amelioration of infection-associated immunopathogenesis.
A Serum Biomarker Panel of exomiR-451a, exomiR-25-3p and Soluble TWEAK for Early Diagnosis of Rheumatoid Arthritis
Authors: Rodríguez-Muguruza Samantha , Altuna-Coy Antonio , Castro-Oreiro Sonia , Poveda-Elices Maria José , Fontova-Garrofé Ramon , Chacón Matilde R.
Published: November 2021

Background

The etiology of rheumatoid arthritis (RA) remains poorly understood. Early and accurate diagnosis still difficult to achieve. Inflammatory related molecules released into the circulation such cytokines and exosome-derived microRNAs (exomiRNAs) could be good candidates for early diagnosis of autoimmune diseases. We sought to discover a serum biomarker panel for the early detection of RA based on exomiRNAs and inflammatory markers.

Methods

A 179 miRNAs-microarray panel was analyzed in a pilot study (4 early RA and 4 controls). Validation of deregulated exomiRNAs was performed in a larger cohort (24 patients with early RA and 24 controls). miRNet software was used to predict exomiRNA gene-targets interactions. Potentially altered pathways were analyzed by Reactome pathway database search. STRING database was used to predict protein-protein interaction networks. Enzyme-linked immunosorbent assay was used to measure serum levels of sTWEAK and sCD163. Signature biomarker candidates were statistical analyzed.

Results

We detected 11 differentially expressed exomiRNAs in early RA pilot study. Validation analysis revealed that 6/11 exomiRNAs showed strong agreement with the pilot microarray data (exomiR-144-3p, -25-3p, -15a-5p, -451a, -107 and -185-5p). sTWEAK and sCD163 biomarkers were significantly elevated in the serum of patients with early RA. Receiver operating characteristic (ROC) analysis showed that the best panel to diagnose early RA contained exomiR-451a, exomiR-25-3p and sTWEAK, and could correctly classify 95.6% of patients, with an area under the ROC curve of 0.983 and with 100% specificity and 85.7% sensitivity. The YWHAB gene was identified as a common target of the putative miRNA-regulated pathways.

Conclusion

A novel serum biomarker panel composed of exomiR-451a, exomiR-25-3p and serum levels of sTWEAK may have use in the early clinical diagnosis of RA. A new predicted exomiRNA-target gene YHWAB has been identified and may have a relevant role in the development of RA.
Early Warning of Harmful Algal Bloom Risk Using Satellite Ocean Color and Lagrangian Particle Trajectories
Authors: Lin Junfang , Miller Peter I. , Jönsson Bror F. , Bedington Michael
Published: November 2021

Combining Lagrangian trajectories and satellite observations provides a novel basis for monitoring changes in water properties with high temporal and spatial resolution. In this study, a prediction scheme was developed for synthesizing satellite observations and Lagrangian model data for better interpretation of harmful algal bloom (HAB) risk. The algorithm can not only predict variations in chlorophyll-a concentration but also changes in spectral properties of the water, which are important for discrimination of different algal species from satellite ocean color. The prediction scheme was applied to regions along the coast of England to verify its applicability. It was shown that the Lagrangian methodology can significantly improve the coverage of satellite products, and the unique animations are effective for interpretation of the development of HABs. A comparison between chlorophyll-a predictions and satellite observations further demonstrated the effectiveness of this approach: r2 = 0.81 and a low mean absolute percentage error of 36.9%. Although uncertainties from modeling and the methodology affect the accuracy of predictions, this approach offers a powerful tool for monitoring the marine ecosystem and for supporting the aquaculture industry with improved early warning of potential HABs.
Vertical Transmission of Diverse Cultivation-Recalcitrant Endophytic Bacteria Elucidated Using Watermelon Seed Embryos
Authors: Thomas Pious , Sahu Pramod Kumar
Published: November 2021

Seed transmission of endophytic microorganisms is a growing research area in plant biology and microbiology. We employed cultivation versus cultivation-independent approaches on excised embryos from watermelon seeds (6–12 months in storage) and on embryo-derived in vitro seedlings (EIVS) to assess the vertical transmission of endophytic bacteria. Surface-disinfected watermelon seeds bore abundant residual bacteria in the testa and perisperm tissues, predominantly Bacillus spp. propounding the essentiality of excluding all non-embryonic tissues for vertical transmission studies. Tissue homogenates from re-disinfected seed embryos displayed no cultivable bacteria during the 1-week monitoring. Bright-field live microscopy revealed abundant bacteria in tissue homogenates and in embryo sections as intracellular motile particles. Confocal imaging on embryo sections after SYTO-9 staining and eubacterial fluorescent in situ hybridization (FISH) endorsed enormous bacterial colonization. Quantitative Insights Into Microbial Ecology (QIIME)-based 16S rRNA V3–V4 taxonomic profiling excluding the preponderant chloroplast and mitochondrial sequences revealed a high bacterial diversity in watermelon seed embryos mainly Firmicutes barring spore formers followed by Proteobacteria, Bacteroidetes, and Actinobacteria, and other minor phyla. Embryo-base (comprising the radicle plus plumule parts) and embryo-cotyledon parts differed in bacterial profiles with the abundance of Firmicutes in the former and Proteobacteria dominance in the latter. EIVS displayed a higher bacterial diversity over seed embryos indicating the activation from the dormant stage of more organisms in seedlings or their better amenability to DNA techniques. It also indicated embryo-to-seedling bacterial transmission, varying taxonomic abundances for seed embryos and seedlings, and differing phylogenic profiles for root, hypocotyl, and cotyledon/shoot-tip tissues. Investigations on different watermelon cultivars confirmed the embryo transmission of diverse cultivation recalcitrant endophytic bacteria. Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes formed the core phyla across different cultivars with 80–90% similarity at genus to phylum levels. Conversely, freshly harvested seeds displayed a dominance of Proteobacteria. The findings revealed that dicot seeds such as in different watermelon cultivars come packaged with abundant and diverse vertical and seedling-transmissible cultivation recalcitrant endophytic bacteria with significant implications for plant biology.
Microbiome of Field Grown Hemp Reveals Potential Microbial Interactions With Root and Rhizosphere Soil
Authors: Ahmed Bulbul , Smart Lawrence B. , Hijri Mohamed
Published: November 2021

Hemp (Cannabis sativa L.) is a crop bred and grown for the production of fiber, grain, and floral extracts that contribute to health and wellness. Hemp plants interact with a myriad of microbiota inhabiting the phyllosphere, endosphere, rhizoplane, and rhizosphere. These microbes offer many ecological services, particularly those of below ground biotopes which are involved in nutrient cycling, uptake, and alleviating biotic and abiotic stress. The microbiota communities of the hemp rhizosphere in the field are not well documented. To discover core microbiota associated with field grown hemp, we cultivated single C. sativa cultivar, “TJ’s CBD,” in six different fields in New York and sampled hemp roots and their rhizospheric soil. We used Illumina MiSeq amplicon sequencing targeting 16S ribosomal DNA of bacteria and ITS of fungi to study microbial community structure of hemp roots and rhizospheres. We found that Planctobacteria and Ascomycota dominated the taxonomic composition of hemp associated microbial community. We identified potential core microbiota in each community (bacteria: eight bacterial amplicon sequence variant – ASV, identified as Gimesia maris, Pirellula sp. Lacipirellula limnantheis, Gemmata sp. and unclassified Planctobacteria; fungi: three ASVs identified as Fusarium oxysporum, Gibellulopsis piscis, and Mortierella minutissima). We found 14 ASVs as hub taxa [eight bacterial ASVs (BASV) in the root, and four bacterial and two fungal ASVs in the rhizosphere soil], and 10 BASV connected the root and rhizosphere soil microbiota to form an extended microbial communication in hemp. The only hub taxa detected in both the root and rhizosphere soil microbiota was ASV37 (Caulifigura coniformis), a bacterial taxon. The core microbiota and Network hub taxa can be studied further for biocontrol activities and functional investigations in the formulation of hemp bioinoculants. This study documented the microbial diversity and community structure of hemp grown in six fields, which could contribute toward the development of bioinoculants for hemp that could be used in organic farming.
Deep Learning Classification of Lake Zooplankton
Authors: Kyathanahally Sreenath P. , Hardeman Thomas , Merz Ewa , Bulas Thea , Reyes Marta , Isles Peter , Pomati Francesco , Baity-Jesi Marco
Published: November 2021

Plankton are effective indicators of environmental change and ecosystem health in freshwater habitats, but collection of plankton data using manual microscopic methods is extremely labor-intensive and expensive. Automated plankton imaging offers a promising way forward to monitor plankton communities with high frequency and accuracy in real-time. Yet, manual annotation of millions of images proposes a serious challenge to taxonomists. Deep learning classifiers have been successfully applied in various fields and provided encouraging results when used to categorize marine plankton images. Here, we present a set of deep learning models developed for the identification of lake plankton, and study several strategies to obtain optimal performances, which lead to operational prescriptions for users. To this aim, we annotated into 35 classes over 17900 images of zooplankton and large phytoplankton colonies, detected in Lake Greifensee (Switzerland) with the Dual Scripps Plankton Camera. Our best models were based on transfer learning and ensembling, which classified plankton images with 98% accuracy and 93% F1 score. When tested on freely available plankton datasets produced by other automated imaging tools (ZooScan, Imaging FlowCytobot, and ISIIS), our models performed better than previously used models. Our annotated data, code and classification models are freely available online.
High-Quality Genome-Scale Reconstruction of Corynebacterium glutamicum ATCC 13032
Authors: Feierabend Martina , Renz Alina , Zelle Elisabeth , Nöh Katharina , Wiechert Wolfgang , Dräger Andreas
Published: November 2021

Corynebacterium glutamicum belongs to the microbes of enormous biotechnological relevance. In particular, its strain ATCC 13032 is a widely used producer of L-amino acids at an industrial scale. Its apparent robustness also turns it into a favorable platform host for a wide range of further compounds, mainly because of emerging bio-based economies. A deep understanding of the biochemical processes in C. glutamicum is essential for a sustainable enhancement of the microbe's productivity. Computational systems biology has the potential to provide a valuable basis for driving metabolic engineering and biotechnological advances, such as increased yields of healthy producer strains based on genome-scale metabolic models (GEMs). Advanced reconstruction pipelines are now available that facilitate the reconstruction of GEMs and support their manual curation. This article presents iCGB21FR, an updated and unified GEM of C. glutamicum ATCC 13032 with high quality regarding comprehensiveness and data standards, built with the latest modeling techniques and advanced reconstruction pipelines. It comprises 1042 metabolites, 1539 reactions, and 805 genes with detailed annotations and database cross-references. The model validation took place using different media and resulted in realistic growth rate predictions under aerobic and anaerobic conditions. The new GEM produces all canonical amino acids, and its phenotypic predictions are consistent with laboratory data. The in silico model proved fruitful in adding knowledge to the metabolism of C. glutamicum: iCGB21FR still produces L-glutamate with the knock-out of the enzyme pyruvate carboxylase, despite the common belief to be relevant for the amino acid's production. We conclude that integrating high standards into the reconstruction of GEMs facilitates replicating validated knowledge, closing knowledge gaps, and making it a useful basis for metabolic engineering. The model is freely available from BioModels Database under identifier MODEL2102050001.
The Acquisition of the scr Gene Cluster Encoding Sucrose Metabolization Enzymes Enables Strains of Vibrio parahaemolyticus and Vibrio vulnificus to Utilize Sucrose as Carbon Source
Authors: Hammerl Jens Andre , Göllner Cornelia , Jäckel Claudia , Swidan Fatima , Gutmann Helena , Strauch Eckhard
Published: November 2021

Most strains of Vibrio parahaemolyticus are unable to utilize sucrose as carbon source, though few exceptions exist. We investigated a sucrose-positive V. parahaemolyticus strain by whole-genome sequencing (WGS) and confirmed the presences of a genomic island containing sucrose utilization genes. A 4.7 kb DNA cluster consisting of three genes: scrA encoding a sucrose uptake protein, scrK encoding a fructokinase, and scrB coding for a sucrose-6-phosphate hydrolase, was PCR amplified and inserted into the Vibrio/Escherichia coli shuttle vector pVv3. Two recombinant plasmids, only differing in the orientation of the insert with respect to the pVv3-lacZα-fragment, conferred the E. coli K12 transformants the ability to utilize sucrose. The introduction of the two plasmids into sucrose-negative V. parahaemolyticus and V. vulnificus strains also results in a change of the sucrose utilization phenotype from negative to positive. By performing a multiplex PCR targeting scrA, scrK, and scrB, 43 scr-positive V. parahaemolyticus isolates from our collection of retail strains were detected and confirmed to be able to use sucrose as carbon source. Strains unable to utilize the disaccharide were negative by PCR for the scr genes. For in-depth characterization, 17 sucrose-positive V. parahaemolyticus were subjected to WGS. A genomic island with a nucleotide identity of >95% containing scrA, scrB, scrK and three additional coding sequences (CDS) were identified in all strains. The additional genes were predicted as a gene coding for a transcriptional regulator (scrR), a porin encoding gene and a CDS of unknown function. Sequence comparison indicated that the genomic island was located in the same region of the chromosome II in all analyzed V. parahaemolyticus strains. Structural comparison of the genomes with sequences of the sucrose utilizing species V. alginolyticus revealed the same genomic island, which indicates a possible distribution of this genetic structure by horizontal gene transfer. The comparison of all genome sequences based on SNP differences reveals that the presence of sucrose utilizing genes is found in genetically diverse V. parahaemolyticus strains and is not restricted to a subset of closely related strains.
Effects of Dietary Modified Bazhen on Reproductive Performance, Immunity, Breast Milk Microbes, and Metabolome Characterization of Sows
Authors: Geng Jian , Jin Weicheng , Hao Jingyou , Huo Mohan , Zhang Yuefeng , Xie Chunmei , Zhao Baokai , Li Yanhua
Published: November 2021

Bazhen is a classic prescription used for the prevention of qi and blood deficiency. The present study aimed to investigate the effects of dietary supplementation with modified Bazhen powder (MBP) on sows during lactation. Forty pure-bred Yorkshire sows on day 100 of gestation were randomly fed a standard diet supplemented with 20 g MBP per sow per day (MBP group) or without (control group) during -14 to 7 days relative to parturition. Results showed that the serum levels of interleukin 2 (IL-2), immunoglobulin A (IgA), and IgG were higher, whereas IL-10 level was lower in sows fed with MBP diet than in controls on day 7 postpartum. A significantly elevated proportion of serum CD4+ T cells and a slight increase in the ratio of CD4+ to CD8+ T cells in the MBP group were also observed. Furthermore, MBP supplementation improved gastrointestinal function of postpartum sows, evidenced by increased levels of motilin, gastrin, and nitric oxide. Ultra high-performance liquid chromatography combined with a quadrupole time of flight and tandem mass spectrometer identified a total of 21 absorbed milk components. 16S rRNA gene amplicon sequencing data revealed that the microbiota diversity of the colostrum and transitional milk in the MBP group was increased. At the genus level, relative abundances of Enterococcus and Anaerostipes were significantly lower in the MBP group on day 0 of lactation. Metabolomic analysis showed that 38 metabolites were upregulated, and 41 metabolites were downregulated in the transitional milk; 31 metabolites were upregulated and 8 metabolites were downregulated in the colostrum in response to MBP. Metabolic pathways, protein digestion and absorption, and biosynthesis of amino acids were enriched in the colostrum and transitional milk. Our findings provide new insights into the beneficial effects of MBP, highlighted by the changes to the microbiota and metabolomic profile of breast milk from sows fed with an MBP-supplemented diet. Thus, MBP should be considered as a potential dietary supplement for lactating sows in pork production.
Identification of CRF66_BF, a New HIV-1 Circulating Recombinant Form of South American Origin
Authors: Bacqué Joan , Delgado Elena , Benito Sonia , Moreno-Lorenzo María , Montero Vanessa , Gil Horacio , Sánchez Mónica , Nieto-Toboso María Carmen , Muñoz Josefa , Zubero-Sulibarria Miren Z. , Ugalde Estíbaliz , García-Bodas Elena , Cañada Javier E. , del Romero Jorge , Rodríguez Carmen , Rodríguez-Avial Iciar , Elorduy-Otazua Luis , Portu José J. , García-Costa Juan , Ocampo Antonio , Cabrera Jorge J. , Thomson Michael M.
Published: November 2021

Circulating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Among 110 reported in the literature, 17 are BF1 intersubtype recombinant, most of which are of South American origin. Among these, all 5 identified in the Southern Cone and neighboring countries, except Brazil, derive from a common recombinant ancestor related to CRF12_BF, which circulates widely in Argentina, as deduced from coincident breakpoints and clustering in phylogenetic trees. In a HIV-1 molecular epidemiological study in Spain, we identified a phylogenetic cluster of 20 samples from 3 separate regions which were of F1 subsubtype, related to the Brazilian strain, in protease-reverse transcriptase (Pr-RT) and of subtype B in integrase. Remarkably, 14 individuals from this cluster (designated BF9) were Paraguayans and only 4 were native Spaniards. HIV-1 transmission was predominantly heterosexual, except for a subcluster of 6 individuals, 5 of which were men who have sex with men. Ten additional database sequences, from Argentina (n = 4), Spain (n = 3), Paraguay (n = 1), Brazil (n = 1), and Italy (n = 1), branched within the BF9 cluster. To determine whether it represents a new CRF, near full-length genome (NFLG) sequences were obtained for 6 viruses from 3 Spanish regions. Bootscan analyses showed a coincident BF1 recombinant structure, with 5 breakpoints, located in p17gag, integrase, gp120, gp41-rev overlap, and nef, which was identical to that of two BF1 recombinant viruses from Paraguay previously sequenced in NFLGs. Interestingly, none of the breakpoints coincided with those of CRF12_BF. In a maximum likelihood phylogenetic tree, all 8 NFLG sequences grouped in a strongly supported clade segregating from previously identified CRFs and from the CRF12_BF “family” clade. These results allow us to identify a new HIV-1 CRF, designated CRF66_BF. Through a Bayesian coalescent analysis, the most recent common ancestor of CRF66_BF was estimated around 1984 in South America, either in Paraguay or Argentina. Among Pr-RT sequences obtained by us from HIV-1-infected Paraguayans living in Spain, 14 (20.9%) of 67 were of CRF66_BF, suggesting that CRF66_BF may be one of the major HIV-1 genetic forms circulating in Paraguay. CRF66_BF is the first reported non-Brazilian South American HIV-1 CRF_BF unrelated to CRF12_BF.
Longitudinal Cognitive Performance of Older Adults With ADHD Presenting to a Cognitive Neurology Clinic: A Case Series of Change Up to 21 Years
Authors: Callahan Brandy L. , Shammi Prathiba , Taylor Rebecca , Ramakrishnan Nayani , Black Sandra E.
Published: November 2021

Background: The neuropsychological features of older adults with ADHD are largely unknown. This retrospective chart review aims to elucidate their cognitive trajectories using a case series of six older adults with ADHD presenting with memory complaints to a cognitive neurology clinic, whom we argue are a particularly relevant group to study due to their potential to mimic neurodegenerative syndromes.

Methods: Participants were included if they were age 40 or older at intake, had ADHD based on DSM-5 criteria, and had cognitive data collected prior to 2014 with follow-up at least 5 years later.

Results: Five men and one woman were included (M = 53.8 years at intake) and had an average of 135.0 months of follow-up data available. Despite notable between- and within-subject variability, cognition generally improved or remained stable across visits. Two participants experienced notable memory decline, but a global consideration of their performance in other domains suggests these deficits may be frontally-mediated.

Conclusion: In this small sample, cognition remained generally unchanged across 5–21 years. Isolated impairments likely reflect substantial intra-individual variability across time and measures.
Deletion of Oncomodulin Gives Rise to Early Progressive Cochlear Dysfunction in C57 and CBA Mice
Authors: Climer Leslie K. , Hornak Aubrey J. , Murtha Kaitlin , Yang Yang , Cox Andrew M. , Simpson Preston L. , Le Andy , Simmons Dwayne D.
Published: November 2021

Ca2+ signaling is a major contributor to sensory hair cell function in the cochlea. Oncomodulin (OCM) is a Ca2+ binding protein (CaBP) preferentially expressed in outer hair cells (OHCs) of the cochlea and few other specialized cell types. Here, we expand on our previous reports and show that OCM delays hearing loss in mice of two different genetic backgrounds: CBA/CaJ and C57Bl/6J. In both backgrounds, genetic disruption of Ocm leads to early progressive hearing loss as measured by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). In both strains, loss of Ocm reduced hearing across lifetime (hearing span) by more than 50% relative to wild type (WT). Even though the two WT strains have very different hearing spans, OCM plays a considerable and similar role within their genetic environment to regulate hearing function. The accelerated age-related hearing loss (ARHL) of the Ocm KO illustrates the importance of Ca2+ signaling in maintaining hearing health. Manipulation of OCM and Ca2+ signaling may reveal important clues to the systems of function/dysfunction that lead to ARHL.
Brain Pathogenesis and Potential Therapeutic Strategies in Myotonic Dystrophy Type 1
Authors: Liu Jie , Guo Zhen-Ni , Yan Xiu-Li , Yang Yi , Huang Shuo
Published: November 2021

Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy that affects multiple systems including the muscle and heart. The mutant CTG expansion at the 3′-UTR of the DMPK gene causes the expression of toxic RNA that aggregate as nuclear foci. The foci then interfere with RNA-binding proteins, affecting hundreds of mis-spliced effector genes, leading to aberrant alternative splicing and loss of effector gene product functions, ultimately resulting in systemic disorders. In recent years, increasing clinical, imaging, and pathological evidence have indicated that DM1, though to a lesser extent, could also be recognized as true brain diseases, with more and more researchers dedicating to develop novel therapeutic tools dealing with it. In this review, we summarize the current advances in the pathogenesis and pathology of central nervous system (CNS) deficits in DM1, intervention measures currently being investigated are also highlighted, aiming to promote novel and cutting-edge therapeutic investigations.
Diffusion Tensor Imaging Along the Perivascular Space Index in Different Stages of Parkinson’s Disease
Authors: Ma Xinxin , Li Shuhua , Li Chunmei , Wang Rui , Chen Min , Chen Haibo , Su Wen
Published: November 2021

Background: The aim of this study was to evaluate the glymphatic system activity in patients with Parkinson’s disease (PD) using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) methods.

Methods: In total, 71 patients with idiopathic PD and 36 age- and sex-matched normal controls (NCs) were involved. Patients with PD were divided into early (n = 35) and late (n = 36) subgroups, based on Hoehn and Yahr (HY) stages. We calculated the diffusivity along the perivascular spaces (ALPS), as well as projection fibers and association fibers separately, to acquire the ALPS index. Enlarged perivascular spaces (EPVS) and periventricular white matter hyperintensities were also rated. Differences in ALPS index between the PD group and NCs and between two PD subgroups and NCs were compared. In addition, a multivariate logistic regression analysis was conducted to investigate the association between ALPS index and clinical variables.

Results: Patients with PD revealed lower ALPS index than NCs (p = 0.010). The late PD group exhibited significantly lower ALPS index than NCs (p = 0.006). However, there were no marked differences noticed in ALPS index between NCs and early PD group and between the two PD subgroups. In the early PD group, there was a significantly positive correlation between ALPS index and Mini-Mental State Examination (MMSE) score (β = 0.021, p = 0.029) and a negative correlation between ALPS index and EPVS score (β = −0.050, p = 0.034), after controlling for multiple variables. In the late PD group, ALPS index was inversely associated with age (β = −0.012, p = 0.004).

Conclusion: Impairment of the glymphatic system is involved in PD. DTI-ALPS index could be a promising biomarker of glymphatic system in PD.
Cognitive Influences in Parkinson's Disease Patients and Their Caregivers: Perspectives From an Australian Cohort
Authors: Lubomski Michal , Davis Ryan L. , Sue Carolyn M.
Published: November 2021

Objectives: Cognitive impairment impacts negatively on Parkinson's disease (PD) patient and caregiver quality of life (QoL). We examined cognitive impairment in PD patients and their caregivers to determine if caregiver cognition affected their PD relative.

Methods: Validated cognition and clinical outcome measures were assessed in 103 PD patients and 81 caregivers.

Results: PD patients showed more cognitive impairment than their carers, with 48.6% having possible Mild Cognitive Impairment (MCI) and 16.5% having PD dementia. Increasing age, male gender, lower education level, various non-motor symptoms and certain therapies, associated with poorer cognition in PD. Eighteen and a half percent of caregivers were found to have MCI, in association with a lower physical and mental QoL. This reflected in lower QoL and mood for the respective PD patients.

Conclusion: Impaired cognition and QoL in caregivers was associated with decreased QoL and mood for respective PD patients, suggesting MCI in caregivers is an important consideration for the management of PD.