bluuebunny/crossref_metadata_2025 huggingface dataset:
IMPDH1, a prognostic biomarker and immunotherapy target that correlates with tumor immune microenvironment in pan-cancer and hepatocellular carcinoma
Authors: Liu Chengdong , Zhang Wanli , Zhou Xiaohan , Liu Li
Published: December 2022

Backgrounds

IMPDH1, a rate-limiting enzyme in de novos synthesis of guanine nucleotides, plays an essential role in the growth and progression of certain tumors. However, there is still a lack of study on IMPDH1 evaluating its role in the tumor immune microenvironment, the potential mechanisms, and its potential as a promising tumor therapeutic target.

Methods

The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Genotype-Tissue Expression (GTEx), TIMER2.0, KM-Plotter, University of Alabama at Birmingham Cancer data analysis Portal (UALCAN), cbioportal, The Human Protein Atlas (HPA), and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) were used to perform the systematic analysis of IMPDH1, including mRNA expression, protein expression, prognostic value, Enrichment analysis, DNA methylation, immune cell infiltration in pan-cancer, Then, we conducted qRT-PCR and immunohistochemistry to analyze the expression level of IMPDH1 in cancer tissues and non-cancer tissues of patients with primary hepatocellular carcinoma (HCC), and performed the same verification at cellular level.

Results

We discovered that IMPDH1 was highly expressed in a variety of tumors and was associated with poor prognosis. IMPDH1 not only had the potential as a tumor prognostic marker and therapeutic target, but also was closely related to immune cells, immune checkpoints and immune-related genes and pathways in the tumor immune microenvironment (TIME). Meanwhile, IMPDH1 expression influenced the efficacy and prognosis of tumor patients treated with immune checkpoint inhibitors.

Conclusions

IMPDH1 may be as a potential combined target of immunotherapy.
Distinguishing venomous jellyfish species via high resolution melting analysis
Authors: Osathanunkul Maslin , Sawongta Nipitpong , Sathirapongsasuti Nuankanya , Poonsawat Thunyaporn , Detsri Usawadee , Aungtonya Charatsee , Suwannapoom Chatmongkon
Published: December 2022

Accurate species identification is critical for highly venomous jellyfish studies particularly for evaluation of their distribution as it is important not only for understanding population dynamics but also predicting risk to locals and tourists. Hazardous jellyfish species have been determined using methods such as comparative morphology and chemistry, which are less useful and practical in some cases. A few molecular methods have been developed in aiding hazardous jellyfish species identification. However, no studies have focused on designing and developing high resolution melting (HRM) assays to distinguish jellyfish species from each other. This is despite several studies showing the potential of HRM in effectively distinguishing plants and animals. In this study, we developed an HRM method to differentiate jellyfish species in five box jellyfish families (Carukiidae, Chirodropidae, Chiropsalmidae, Chiropsellidae, and Tripedaliidae) and Physaliidae found in Thai waters. All jellyfish samples (10 species) were able to be distinguished by the HRM with 16S rRNA primers. Even closely related species in the same genus could be clearly discriminated by their melting profiles. The melting curves of the 10 species were then used as references. By comparing the normalized melting curves of twenty-two jellyfish specimens with the reference curves, the tested specimens were assigned into species. In addition, HRM results of all jellyfish specimens tested in this study were similar to those of morphological based identification by experts. This is the first attempt of using HRM analysis to determine species of jellyfish collected from Thai waters.
Generation of high-frequency topographic Rossby waves in the Gulf of Mexico
Authors: Johnson Exley Alexis , Donohue Kathleen A. , Watts D. Randolph , Tracey Karen L. , Kennelly Maureen A.
Published: December 2022

The Loop Current Eddy (LCE) separation cycle energizes deep circulation in the eastern Gulf of Mexico, transferring energy from the surface intensified Loop Current (LC) to the typically quiescent lower layers. To document the generation and radiation of deep energy during this cycle, an array of 24 current and pressure recording inverted echo sounders (CPIES) is deployed in the region 89°W to 86°W, 25°N to 27.5°N with the intent to capture circulation near bathymetric features thought to be important for current-topographic interactions: Campeche Bank, Mississippi Fan, and West Florida Shelf. During the nearly two-year deployment, June 2019 to May 2021, three LCE separation events are observed, during which energy injected into the deep Gulf organizes into two distinct frequency bands (1/100 – 1/20 days–1 and 1/20 – 1/10 days–1). High-frequency variability dominates the array’s northwest corner in the vicinity of the Mississippi Fan. Wave properties are consistent with topographic Rossby Waves (TRWs) with wavelengths of 150 – 300 km. Their generation coincides with each LCE separation and is attributed to an upper-lower layer resonant coupling between surface meanders and the sloping topography of the Mississippi Fan. TRWs captured by the CPIES array will likely intensify as wavelengths shorten in steeper topography along propagation pathways towards the Sigsbee Escarpment, generating hazardous currents with the potential to disrupt oil and gas operations in the region.
Xanthophyll cycle-related non-photochemical quenching protects Sargassum thunbergii from high light-induced photoinhibition
Authors: Nan Guo-Ning , Zhou Xiao-Qun , Zhang Xiu-Mei , Zhang Quan-Sheng , Hu Zi-Min , Huang Rui-Ping , Zhang Di
Published: December 2022

As a common macroalga living in the intertidal zone, Sargassum thunbergii (Sargassaceae, Phaeophyta) is often exposed to drastic changes in solar photosynthetically active radiation during a diurnal cycle; thus, the potential photosynthetic adaptation processes deserve attention. In this work, we examined the photosynthetic performance and xanthophyll cycle activity of this alga in response to high light (1,200 μmol photons m–2 s–1, the average in-situ light intensity at noon) by using chlorophyll fluorescence and high-performance liquid chromatography (HPLC). On exposure to high light, a rapid decrease in the effective quantum yield of photosystem II (PSII) (Y(II)) occurred, indicating down-regulation of PSII activity; a corresponding increase in non-photochemical quenching (NPQ) indicated the existence of energy-dissipating cycles. After turning off the light, Y(II) gradually increased to 0.7, accompanied by a decrease in NPQ. However, no complete recovery of NPQ was observed, and its value remained at ≈4, even after an 80-min dark treatment. The size of the xanthophyll cycle pigments pool was quantified using HPLC and was found to be ≈16 mol mol−1 Chl a × 100. The activity of the xanthophyll cycle, characterized by a de-epoxidation state (DPS), could reach up to ≈0.5. Such a large pigments pool and rapid accumulation of zeaxanthin may allow S. thunbergii to induce high values of NPQ (≈10). These results were further complemented by inhibitor (dithiothreitol, DTT) and pre-illumination experiments showing that (1) both NPQ and the xanthophyll cycle could be inhibited by DTT, and there was always a strong positive correlation between NPQ and DPS; (2) the previously formed antheraxanthin exhibited a long retention time and a slow epoxidation; and (3) the long retention of antheraxanthin contributed to a rapid accumulation of zeaxanthin. In conclusion, our present study demonstrated that xanthophyll cycle-induced NPQ can significantly protect S. thunbergii from light fluctuations in the intertidal zone.
Cardio-cerebrovascular complications in COVID-19 patients: A retrospective cohort study
Authors: Hong Kwan , Kisiju Trishna , Kim Jeehyun , Chun Byung Chul
Published: December 2022

Background

Recent studies have highlighted the cardio-cerebrovascular manifestations of coronavirus disease 2019 (COVID-19).

Objective

This study aimed to analyze the likelihood of cardiovascular and cerebrovascular manifestations among patients with COVID-19-positive individuals in South Korea.

Methods

A cohort database for COVID-19 from the National Health Insurance Service was used which included patients diagnosed with COVID-19 between January 1 and June 4, 2020. Individuals who tested COVID-19 positive, notwithstanding the severity of the disease, were designated as cases. COVID-19- negative individuals were used as controls for the study. The exclusion criteria included people who had a history of cardiovascular and cerebrovascular diseases between 2015 and 2019. A new diagnosis of cardiovascular and cerebrovascular complications was considered the primary endpoint. The adjusted incidence rate ratio (IRR) of development of complications was estimated using log-link Poisson regression. The model was adjusted at two levels, the first one included age and sex while the second included age, sex, residence area, and level of income. The hazard ratio (HR) was estimated using Cox-proportional hazard regression analysis while adjusting for all demographic variables and covariates.

Results

Significant results were obtained for acute conditions, such as ischemic heart disease and cerebral hemorrhage. The IRR of COVID-19- positive individuals compared with that of controls for the diagnosis of ischemic heart disease was 1.78 (1.57–2.02; 95% confidence interval [CI]) when adjusted for age and sex. HR was calculated as 3.02 (2.19–4.17; 95% CI) after adjusting for the covariates. In case of cerebral hemorrhage, the adjusted IRR was 2.06 (1.25–3.40; 95% CI) and the adjusted HR was 4.08 (0.90–19.19; 95% CI).

Conclusion

The findings of our study suggest that COVID-19 infection can be a significant risk factor for acute cardiovascular complications, such as ischemic heart disease and acute cerebrovascular complications, such as cerebral infarction, after properly adjusting for covariates.
Effectiveness and safety of tetanus vaccine administration by intramuscular vs. subcutaneous route in anticoagulated patients: Randomized clinical trial in primary care
Authors: Lago-Deibe Fernando Isidro , Valladares-Cabaleiro Mercedes , Fernández-Domínguez María José , Fernández-Fernández Isabel , Clavería Ana , Rodríguez-Pastoriza Sara , Roca-Pardinas Javier , Martín-Miguel María Victoria
Published: December 2022

Design

Prospective, double-blind clinical trial comparing tetanus-diphtheria vaccine administration routes, intramuscular (IM) vs. subcutaneous (SC) injection, in patients with oral anticoagulants. ISRCTN69942081.

Study population

Patients treated with oral anticoagulants, 15 health centers, Vigo (Spain). Sample size, 117 in each group.

Outcome variables

Safety analysis: systemic reactions and, at the vaccine administration site, erythematic, swelling, hematoma, granuloma, pain.

Effectiveness analysis: differences in tetanus toxoid antibody titers.

Independent variables: route, sex, age, baseline serology, number of doses administered.

Analysis

Following the CONSORT guidelines, we performed an intention-to-treat analysis. We conducted a descriptive study of the variables included in both groups (117 in each group) and a bivariate analysis. Fewer than 5% of missing values. Imputation in baseline and final serology with the median was performed. Lost values were assumed to be values missing at random. We conducted a descriptive study of the variables and compared routes. For safety, multivariate logistic regression was applied, with each safety criterion as outcome and the independent variables. Odds ratios (ORs) were calculated. For effectiveness, a generalized additive mixed model, with the difference between final and initial antibody titers as outcome. Due to the bimodal distribution of the outcome, the normal mixture fitting with gamlssMX was used. All statistical analyses were performed with the gamlss.mx and texreg packages of the R free software environment.

Results

A previously published protocol was used across the 6-year study period. The breakdown by sex and route showed: 102 women and 132 men; and 117 IM and 117 SC, with one dose administered in over 80% of participants. There were no differences between groups in any independent variable. The second and third doses administered were not analyzed, due to the low number of cases. In terms of safety, there were no severe general reactions. Locally, significant adjusted differences were observed: in pain, by sex (male, OR: 0.39) and route (SC, OR: 0.55); in erythema, by sex (male, OR: 0.34) and route (SC, OR: 5.21); and in swelling, by sex (male, OR: 0.37) and route (SC, OR: 2.75). In terms of effectiveness, the model selected was the one adjusted for baseline serology.
Burden, satisfaction caregiving, and family relations in informal caregivers of older adults
Authors: Marinho Jéssica da Silva , Batista Ilaise Brilhante , Nobre Rute Alessandra da Silva , Guimarães Maria Sortênia Alves , Santos-Orlandi Ariene Angelini dos , Brito Tábatta Renata Pereira , Pagotto Valéria , Saidel Maria Giovana Borges , Fusco Suzimar de Fátima Benato , Maia Flavia de Oliveira Motta , Corona Ligiana Pires , Nunes Daniella Pires
Published: December 2022

Introduction

Family caregivers of older persons devote much of their time and energy to caring for another person. This exposure may burden caregivers and compromise their health and quality of life.

Objective

To investigate the relationship between burden, sociodemographic, caregiving, and health characteristics of informal caregivers of dependent older adults.

Methods

Cross-sectional and analytical study carried out in Palmas, Tocantins, Brazil, with 52 informal caregivers of older persons who need full-time help for basic living activities. Caregivers' burden was assessed by Zarit Burden Interview (ZBI). Data were analyzed using a T-test, Pearson's correlation, and Multiple Linear Regression.

Results

The ZBI mean score of caregivers was 26.3 points (SD = 14.6; min = 0; max = 68). Burden scores were higher among caregivers who did not receive help from other people in care (p = 0.016), reported family dysfunction (p = 0.001), and had depression symptoms (p = 0.007). A correlation was found between the scores of burdens and satisfaction with care (r = 0.76; p < 0.001) and perceived material support (r = −0.30; p = 0.40). Satisfaction with care (β: 0.61; p < 0.001) and family dysfunction (β: 8.07; p = 0.033) were significantly associated with the burden score.

Conclusion

Caregivers with dysfunctional families and satisfaction with the care presented the highest-burden scores. The findings reveal the need for strategies to facilitate mediation and reduce caregiver burden by strengthening the family network support or providing professional assistance.
Addressing quality and safety in anatomic pathology in low- and middle-income countries
Authors: Smith Stephen M. , Eadara Amrik , Parkash Vinita
Published: December 2022

The World Health Organization (WHO) has created a sustainable development goal of reducing preventable mortality from cancer in low- and middle-income countries (LMICs) by 30% by 2030. Central to achieving this goal is the creation and maintenance of quality anatomic pathology services (APS). Within the last decade, quality assurance programs and patient safety measures have become a major focus of research for upper middle- and high-income countries (UMHICs), which has led to marked documented improvement in the quality of services provided by laboratories, as well as a decrease in patient safety events. We propose that as APS are developed in LMICs, the lessons learned by UMHICs are necessary to incorporate to produce quality and safe services toward obtaining the aforementioned goal. Furthermore, data suggests that Quality Improvement work requires change at the macrosystems and microsystems levels to achieve these goals. Here, we propose five “microsystems” strategies for professional organizations, healthcare institutions in LMICs and UMHICs that would accelerate quality improvement programs/systems implementation in APS in LMICs.
Selected renal cells harbor nephrogenic potential
Authors: Narayan Prakash , Bruce Andrew T. , Rivera Elias A. , Bertram Timothy A. , Jain Deepak
Published: December 2022

Selected renal cells (SRCs), a renal epithelial cell-enriched platform, are being advanced as an autologous cell-based therapy for the treatment of chronic kidney disease. However, the mechanism underlying its renal reparative and restorative effects remains to be fully elucidated. In this study, we coupled knowledgebase data with empirical findings to demonstrate that genes differentially expressed by SRCs form interactomes within tubules and glomeruli and mediate a suite of renal developmental activities including epithelial cell differentiation, renal vasculature development, and glomerular and nephron development. In culture, SRCs form organoids which self-assemble into tubules in the presence of a scaffold. Implanted into the kidneys of subtotally nephrectomized rats, SRCs are associated with comma- and S-shaped body cell formation and glomerular development, and improvement in renal filtration indices and renal microarchitecture. These data suggest that SRCs harbor nephrogenic potential, which may explain, at least in part, their therapeutic activity.
What factors are associated with functional impairment among the oldest old?
Authors: Hajek André , König Hans-Helmut
Published: December 2022

Purpose

Most of the existing studies did not explicitly focus on the oldest old who are at high risk of functional impairment. Moreover, some potential risk factors (such as financial poverty) of functional impairment have been neglected so far. Thus, our aim was to clarify the determinants (with a particular emphasis on financial poverty) of functional impairment exclusively among the oldest old.

Methods

Data were taken from the “Survey on quality of life and subjective well-being of the very old in North Rhine-Westphalia (NRW80+)” – a representative sample of individuals ≥80 years (community-dwelling and in institutionalized settings) in North Rhine-Westphalia (n = 1,863, average age was 86.5 years, ranging from 80 to 102 years). Common tools were used to quantify functional impairment. In regression analysis, these determinants were included: sex, age, marital status, educational level, income poverty, asset poverty, depressive symptoms, cognitive impairment, and the number of chronic conditions.

Results

Multiple linear regressions showed that higher functional impairment was associated with being female (ADL, β = 0.06, p < 0.01; IADL, β = 0.09, p < 0.01), higher age (ADL, β = 0.02, p < 0.001; IADL, β = 0.04, p < 0.001), low education (compared to high education: IADL, β = −0.10, p < 0.05), the presence of income poverty (ADL, β = 0.09, p < 0.05; IADL, β = 0.16, p < 0.01), more depressive symptoms (ADL, β = 0.12, p < 0.001; IADL, β = 0.14, p < 0.001), higher cognitive impairment (ADL, β = −0.03, p < 0.001; IADL, β = −0.06, p < 0.001), and a higher number of chronic conditions (ADL, β = 0.03, p < 0.001; IADL, β = 0.05, p < 0.001).

Conclusion

Several determinants of functional impairment among the oldest old have been identified (i.e., being female, higher age, low education, presence of income poverty, more depressive symptoms, higher cognitive impairment, and more chronic conditions). Such knowledge (e.g., regarding the association between income poverty and functional impairment) may assist in characterizing individuals aged 80 years and over at high risk for functional impairment. Ultimately, such knowledge may help to design specific interventions for high risk groups. Moreover, such knowledge may enrich the research areas addressing inequalities.
Characterization of the RpoN regulon reveals the regulation of motility, T6SS2 and metabolism in Vibrio parahaemolyticus
Authors: Gu Dan , Zhang Youkun , Wang Kangru , Li Mingzhu , Jiao Xinan
Published: December 2022

Vibrio parahaemolyticus is a foodborne pathogen that can colonize the small intestine of the host and cause diarrhea. The alternative sigma factor RpoN plays a vital role in regulating motility, carbon utilization and affects host colonization in V. parahaemolyticus RIMD2210633. In this study, transcriptome and phenotypic analysis further expanded our understanding of the RpoN regulon in V. parahaemolyticus. A deletion mutant of rpoN (ΔrpoN) was subjected to RNA-seq for systemic identification of the RpoN-controlled genes. Compared with the wild-type (WT), 399 genes were differentially expressed in the ΔrpoN strain. Moreover, 264 genes were down-regulated in the ΔrpoN strain, including those associated with nitrogen utilization (VP0118), glutamine synthetase (VP0121), formate dehydrogenase (VP1511 and VP1513-VP1515), quorum sensing (opaR and luxZ), polar flagellar systems, and type VI secretion system 2 (T6SS2). Quantitative real-time reverse transcription PCR (qRT-PCR) and electrophoretic mobility shift assay (EMSA) further confirmed that RpoN could directly bind to the promoters of these genes associated with polar flagellar systems (flgB and fliE), lateral flagellar systems (flgB2 and lafA), T6SS2 (hcp2 and VPA1044) and glutamine synthetase (VP0121), and then positively regulate the expression of these systems. A RpoN-binding motif was identified in V. parahaemolyticus using the MEME suite and verified by the EMSA. Besides, the deletion of rpoN caused a significant decrease in hemolytic activity, adhesion, and cytotoxicity. Our results provide new cues to better understand the regulatory networks of RpoN protein to motility, T6SS2, and metabolism in V. parahaemolyticus.
Epichloë endophyte interacts with saline-alkali stress to alter root phosphorus-solubilizing fungal and bacterial communities in tall fescue
Authors: Liu Hui , Tang Huimin , Ni Xiaozhen , Zhang Jiazhen , Zhang Xi
Published: December 2022

Epichloëendophytes, present in aboveground tissues, modify belowground microbial community. This study was conducted to investigate endophyte (Epichloë coenophialum) associated with tall fescue (Lolium arundinaceum) interacted with an altered saline-alkali stress (0, 200 and 400 mmol/l) to affect the belowground phosphorus solubilizing microorganisms including phosphorus solubilizing fungi (PSF) and bacteria (PSB). We found that a significant interaction betweenE. coenophialumand saline-alkali stress occurred in the diversity and composition of PSF in tall fescue roots. Under saline-alkali stress conditions (200 and 400 mmol/l),E. coenophialumsignificantly increased the PSF diversity and altered its composition in the roots, decreasing the relative abundance of dominantCladosporiumand increasing the relative abundance ofFusarium.However, there was no significant interaction betweenE. coenophialumand saline-alkali stress on the PSB diversity in tall fescue roots.E. coenophialumsignificantly reduced the diversity of PSB in the roots, andE. coenophialumeffects did not depend on the saline-alkali stress treatment. Structural equation modeling (SEM) showed thatE. coenophialumpresence increased soil available phosphorus concentration under saline-alkali stress primarily by affecting PSF diversity instead of the diversity and composition of PSB.
Effect of Lactobacillus plantarum KSFY01 on the exercise capacity of D-galactose-induced oxidative stress-aged mice
Authors: Chen Qiuping , Liu Chuannan , Zhang Yinglong , Wang Shuai , Li Fang
Published: December 2022

Objectives

Aging is a process that involves comprehensive physiological changes throughout the body, and improvements in the exercise capacity of individuals may delay aging and relieve fatigue. Probiotics are subject to ongoing research to investigate their antioxidant properties. The purpose of this study was to investigate the effect of the probiotic Lactobacillus plantarum KSFY01 (L. plantarum KSFY01) on exercise tolerance in mice induced into a state of accelerated physiological aging by oxidative stress.

Methods

A mouse model of accelerated aging was established using D-galactose to induce oxidative stress. The bacteria L. plantarum KSFY01 was isolated from fermented yak yogurt. The effect of L. plantarum KSFY01 on the improvement of exercise capacity in aging-accelerated mice was evaluated by measuring their running time until exhaustion, histopathological sections, related biochemical indicators, and underlying gene expression.

Results

The oral administration of L. plantarum KSFY01 prolonged the running time of mice and reduced their creatine kinase (CK), alanine aminotransferase (ALT), and aspartate aminotransferasem (AST) levels. From this study, we observed that L. plantarum KSFY01 significantly improved the exercise capacity of mice and alleviated liver damage. Treatment with L. plantarum KSFY01 reduced the blood urea nitrogen (BUN), lactic acid (LD) accumulation, and lactate dehydrogenase (LDH) elevations produced by the accelerated aging state, and also reversed the changes in muscle glycogen (MG). Overall, L. plantarum KSFY01 could effectively improve metabolite accumulation, thereby relieving fatigue in exercised mice. The results of the antioxidant indices in vivo showed that L. plantarum KSFY01 intervention increased the activity of antioxidant enzymes, decreased the level of malondialdehyde (MDA), and restored the balance between the oxidative and antioxidant systems in fatigued mice. By investigating the underlying molecular mechanism, our results showed that L. plantarum KSFY01 intervention significantly reversed the decline in the expression levels of nuclear factor-erythroid 2 related factor 2 (Nrf2) signaling pathway-related factors and improved the body’s antioxidant capacity. We determined that the underlying molecular mechanism responsible for the antioxidant effect of L. plantarum KSFY01 mainly involves the activation of the Nrf2 pathway. The effect of L. plantarum KSFY01 was dose-dependent, and the expression level of Nrf2 increased with increasing dosage of the probiotic.

Conclusion

This study demonstrated that the probiotic L. plantarum KSFY01 exerts antioxidant effects and improved the athletic ability of mice. These findings are of significance to the development and utilization of probiotic resources.
Decreased precipitation reduced the complexity and stability of bacterial co-occurrence patterns in a semiarid grassland
Authors: Wang Jinlong , Wang Chunjuan , Zhang Jinwei , Wu Xuefeng , Hou Yu , Zhao Guiyun , Sun Haiming
Published: December 2022

Introduction

Grasslands harbor complex bacterial communities, whose dynamic interactions are considered critical for organic matter and nutrient cycling. However, less is known about how changes in precipitation impact bacterial interactions.

Methods

We conducted precipitation manipulation experiments in the Eastern Eurasian Steppe in China and constructed co-occurrence networks for bacterial communities.

Results

The network topological features of the bacterial communities exhibited considerable differences among increased precipitation, control, and decreased precipitation gradients. The bacterial co-occurrence pattern in the increased precipitation gradient was the most complex and stable, with a large network size, followed by those of the control and decreased precipitation gradients. Soil moisture (SM) was the primary factor influencing the complexity, size, and stability of bacterial networks across different precipitation gradients, followed by total nitrogen (TN), belowground biomass, aboveground biomass, and total carbon (TC).

Discussion

Our results indicate that drought conditions reduce the complexity and stability of the bacterial community, and future changes in precipitation will greatly reshape bacterial interactions in semiarid grasslands. Overall, these findings could enhance our understanding of how microbes respond to changing precipitation patterns by regulating their interactions in water-limited ecosystems and will improve our ability to predict the impacts of precipitation regime change on ecosystem nutrient cycling and feedback between ecosystem processes and global climate change.
Genomic landscape of the SARS-CoV-2 pandemic in Brazil suggests an external P.1 variant origin
Authors: Perico Camila P. , De Pierri Camilla R. , Neto Giuseppe Pasqualato , Fernandes Danrley R. , Pedrosa Fabio O. , de Souza Emanuel M. , Raittz Roberto T.
Published: December 2022

Brazil was the epicenter of worldwide pandemics at the peak of its second wave. The genomic/proteomic perspective of the COVID-19 pandemic in Brazil could provide insights to understand the global pandemics behavior. In this study, we track SARS-CoV-2 molecular information in Brazil using real-time bioinformatics and data science strategies to provide a comparative and evolutive panorama of the lineages in the country. SWeeP vectors represented the Brazilian and worldwide genomic/proteomic data from Global Initiative on Sharing Avian Influenza Data (GISAID) between February 2020 and August 2021. Clusters were analyzed and compared with PANGO lineages. Hierarchical clustering provided phylogenetic and evolutionary analyses of the lineages, and we tracked the P.1 (Gamma) variant origin. The genomic diversity based on Chao's estimation allowed us to compare richness and coverage among Brazilian states and other representative countries. We found that epidemics in Brazil occurred in two moments with different genetic profiles. The P.1 lineages emerged in the second wave, which was more aggressive. We could not trace the origin of P.1 from the variants present in Brazil. Instead, we found evidence pointing to its external source and a possible recombinant event that may relate P.1 to a B.1.1.28 variant subset. We discussed the potential application of the pipeline for emerging variants detection and the PANGO terminology stability over time. The diversity analysis showed that the low coverage and unbalanced sequencing among states in Brazil could have allowed the silent entry and dissemination of P.1 and other dangerous variants. This study may help to understand the development and consequences of variants of concern (VOC) entry.
Epidemiological investigations of diarrhea in children in Praia city, Cape Verde
Authors: Colito Denise Andrade , Dorta-Guerra Roberto , Da Costa Lima Hailton Spencer , Pina Carine , Gonçalves Deisy , Valladares Basilio , Foronda Pilar
Published: December 2022

Introduction

Diarrheal disease is a major cause of infant mortality and morbidity in Africa and results primarily from contaminated food and water sources, but its prevalence predictors in Cape Verde are not completely known. For this reason, this study aimed to identify the etiological agents of diarrhea in Cape Verdean children and assess its associated risk factors.

Methods

A survey questionnaire was used, and a total of 105 stool samples from children with diarrhea aged 0–12 years at the Central Hospital of Praia (Santiago, Cape Verde) were analyzed. The analyses were carried out using Biofire FilmArray Gastrointestinal Panels. Possible risk factors for these pathogens were analyzed using logistic regression, chi-square tests, or Fisher’s exact test.

Results

Among the bacteria, enteroaggregative Escherichia coli (45.71%; 95% CI: 36.71–56.70), enteropathogenic E. coli (40%; 95% CI: 30.56–50.02), Shigella/enteroinvasive E. coli (29.52%; 95% CI: 21.02–39.22), E. coli enterotoxigenic (12.38%; 95% CI: 6.76–20.24), Campylobacter sp. (10.48%; 95% CI: 5.35–1.97), Vibrio sp. (4.76%; 95% CI: 1.56–10.76), Clostridioides difficile (3.81%; 95% CI: 1.05–9.47), Vibrio cholerae (2.86%; 0.59–8.12), Shiga-like toxin-producing E. coli (2.86%; 0.59–8.12) and Salmonella sp. (0.95%; 0.02–5.19) were identified; four viruses, Rotavirus A (28.57%; 95% CI: 20.18–38.21), Sapovirus I. II. IV and V (11.43%; 95% CI: 6.05–19.11), Norovirus GI.GII (6.67%; 95% CI: 2.72–13.25) and Adenovirus F 40.41 (6.67%; 95% CI: 2.72–13.25) were also observed. All the pathogens detected in this study were found in coinfections. Significant associations with risk factors were found; specifically, having a bathroom at home reduced the risk of Campylobacter sp., having animals at home increased the risk of Shigella/EIEC infection, and drinking bottled water reduced the risk of Sapovirus infection.

Discussion

From the findings of this study, it can be concluded that, in Cape Verde, there is a high prevalence and diversity of pathogens among children. Our results could help to establish an adequate diagnosis and effective treatments for diarrheal disease.
The clinical characteristics and risk factors for severe COVID-19 in patients with COVID-19 and tuberculosis coinfection
Authors: Wang Yang , Chen Yanping , Gu Lina , Lou Lixin , Zhang Jian , Zhang Kaiyu
Published: December 2022

Background

Under the wave of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) variant Omicron epidemic, the number of infectious cases has increased dramatically in Jilin Province, China since March 2022.The clinical features and severity of SARS-CoV-2 Omicron variant infection in tuberculosis (TB) patients are not yet clear.

Methods

Data were obtained from 153 patients with the Omicron variant and TB coinfection and 153 non-TB COVID-19 patients who had been hospitalized at Changchun Infectious Disease Hospital from March to June 2022.

Results

Among these coinfection patients, 17 patients showed COVID-19-related pneumonia on chest imaging and 11 were diagnosed with severe COVID-19. The median duration of SARS-CoV-2 clearance was 13 days. The negative conversion time was associated with age, COVID-19-related pneumonia and antibody IgG. A higher white blood cell count, a lower lymphocyte percentage, a higher CRP level, and a higher D-dimer level were found in the severe group. Age and increased PCT were individual risk factors for the severity of COVID-19. Compared with the non-TB patients, the coinfection patients had higher severity of COVID-19 and the elder coinfection patients had a longer negative conversion time.

Conclusion

This study found an association between age, pneumonia, antibody IgG and RNA negative conversion time in COVID-19 and TB coinfection patients, and age and increased PCT were risk factors for the severity of COVID-19.
Chemical synthesis of left arm of Chlamydomonas reinhardtii mitochondrial genome and in vivo functional analysis
Authors: Wang Quan , Luo Haolin , Zhuang Jieyi , Li Xinyi , Huang Danqiong , Hu Zhangli , Zhang Guiying
Published: December 2022

Chlamydomonas reinhardtii is a photosynthetic eukaryote showing great industrial potential. The synthesis and in vivo function of the artificial C. reinhardtii genome not only promotes the development of synthetic biology technology but also supports industries that utilize this algae. Mitochondrial genome (MtG) is the smallest and simplest genome of C. reinhardtii that suits synthetic exploration. In this article, we designed and assembled a synthetic mitochondria left arm (syn-LA) genome sharing >92% similarity to the original mitochondria genome (OMtG) left arm, transferred it into the respiratory defect strain cc-2654, screened syn-LA containing transformants from recovered dark-growth defects using PCR amplification, verified internal function of syn-LA via western blot, detected heteroplasmic ratio of syn-LA, tried promoting syn-LA into homoplasmic status with paromomycin stress, and discussed the main limitations and potential solutions for this area of research. This research supports the functionalization of a synthetic mitochondrial genome in living cells. Although further research is needed, this article nevertheless provides valuable guidance for the synthesis of eukaryotic organelle genomes and opens possible directions for future research.
Comparative transcriptomic analysis-based identification of the regulation of foreign proteins with different stabilities expressed in Pichia pastoris
Authors: Niu Tingting , Cui Yi , Shan Xu , Qin Shuzhen , Zhou Xuejie , Wang Rui , Chang Alan , Ma Nan , Jing Jingjing , He Jianwei
Published: December 2022

Introduction

The industrial yeast Pichia pastoris is widely used as a cell factory to produce proteins, chemicals and advanced biofuels. We have previously constructed P. pastoris strains that overexpress protein disulfide isomerase (PDI), which is a kind of molecular chaperone that can improve the expression of an exogenous protein when they are co-expressed. Chicken cystatin (cC) is a highly thermostable cysteine protease inhibitor and a homologous protein of human cystatin C (HCC). Wild-type cC and the two mutants, I66Q and ΔW (a truncated cC lacking the á-helix 2) represent proteins with different degrees of stability.

Methods

Wild-type cC, I66Q and ΔW were each overexpressed in P. pastoris without and with the coexpression of PDI and their extracellular levels were determined and compared. Transcriptomic profiling was performed to compare the changes in the main signaling pathways and cell components (other than endoplasmic reticulum quality control system represented by molecular chaperones) in P. pastoris in response to intracellular folding stress caused by the expression of exogenous proteins with different stabilities. Finally, hub genes hunting was also performed.

Results and discussion

The coexpression of PDI was able to increase the extracellular levels of both wild-type cC and the two mutants, indicating that overexpression of PDI could prevent the misfolding of unstable proteins or promote the degradation of the misfolded proteins to some extent. For P. pastoris cells that expressed the I66Q or ΔW mutant, GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses of the common DEGs in these cells revealed a significant upregulation of the genes involved in protein processing, but a significant downregulation of the genes enriched in the Ribosome, TCA and Glycolysis/Gluconeogenesis pathways. Hub genes hunting indicated that the most downregulated ribosome protein, C4QXU7 in this case, might be an important target protein that could be manipulated to increase the expression of foreign proteins, especially proteins with a certain degree of instability.

Conclusion

These findings should shed new light on our understanding of the regulatory mechanism in yeast cells that responds to intracellular folding stress, providing valuable information for the development of a convenient platform that could improve the efficiency of heterologous protein expression in P. pastoris.
The Neurospora crassa PCL-1 cyclin is a PHO85-1 (PGOV) kinase partner that directs the complex to glycogen metabolism and is involved in calcium metabolism regulation
Authors: Campanella Jonatas Erick Maimoni , Candido Thiago de Souza , Barbosa Luiz Carlos Bertucci , Gomes Antoniel Augusto Severo , Leite Carla Andréa , Higashi Erika Silva , Barbugli Paula Aboud , Fontes Marcos Roberto de Matos , Bertolini Maria Célia
Published: December 2022

Cyclins are a family of proteins characterized by possessing a cyclin box domain that mediates binding to cyclin dependent kinases (CDKs) partners. In this study, the search for a partner cyclin of the PHO85-1 CDK retrieved PCL-1 an ortholog of yeast Pcls (for Pho85 cyclins) that performs functions common to Pcls belonging to different cyclin families. We show here that PCL-1, as a typical cyclin, is involved in cell cycle control and cell progression. In addition, PCL-1 regulates glycogen metabolism; Δpcl-1 cells accumulate higher glycogen levels than wild-type cells and the glycogen synthase (GSN) enzyme is less phosphorylated and, therefore, more active in the mutant cells. Together with PHO85-1, PCL-1 phosphorylates in vitro GSN at the Ser636 amino acid residue. Modeling studies identified PHO85-1 and PCL-1 as a CDK/cyclin complex, with a conserved intermolecular region stabilized by hydrophobic and polar interactions. PCL-1 is also involved in calcium and NaCl stress response. Δpcl-1 cells are sensitive to high NaCl concentration; on the contrary, they grow better and overexpress calcium responsive genes under high calcium chloride concentration compared to the wild-type strain. The expression of the calcium-responsive CRZ-1 transcription factor is modulated by PCL-1, and this transcription factor seems to be less phosphorylated in Δpcl-1 cells since exhibits nuclear location in these cells in the absence of calcium. Our results show that PCL-1 locates at different cell regions suggesting that it may determine its activity by controlling its intracellular location and reveal an interesting functional divergence between yeast and filamentous fungus cyclins.
Cryptochrome-mediated blue-light signal contributes to carotenoids biosynthesis in microalgae
Authors: Zhang Zhongyi , Han Tianli , Sui Jikang , Wang Hui
Published: December 2022

Microalgae are considered as ideal cell factories for producing natural carotenoids which display favorable biological activities. As the most important abiotic factor, light not only provides energy for photosynthetic metabolism, but also regulates numerous biological processes. Blue light is the main wavelength of light that can travel through water. Previous studies have shown that blue light triggered carotenoid accumulation in several microalgae species, but the molecular mechanism remains unclear. Cryptochromes were blue-light-absorbing photoreceptors that have been found in all studied algal genomes. In this study, several different types of cryptochrome genes were cloned from Haematococcus pluvialis and Phaeodactylum tricornutum. Among them, cryptochrome genes HpCRY4 from H. pluvialis and PtCPF1 from P. tricornutum were upregulated under blue light treatment, in correlation with the increase of astaxanthin and fucoxanthin contents. Besides, heterologous expression and gene knockout was performed to verify the function of HpCRY4 and PtCPF1 in regulating carotenoid biosynthesis in microalgae. These results indicate that carotenoid biosynthesis in microalgae promoted by blue light was mediated by cryptochromes as photoreceptors.
Hydrogen sulfide-sensitive Chitosan-SS-Levofloxacin micelles with a high drug content: Facile synthesis and targeted Salmonella infection therapy
Authors: Lu Chunbo , Lu Wenhui , Qin Xiantao , Liang Shuyi , Niu Congmin , Guo Jiayi , Xu Yujie
Published: December 2022

The delivery system of antibiotics plays an important role in increasing the drug efficacy and reducing the risks of off-target toxicities and antibiotic resistance. The pathophysiology of bacterial infections is similar to that of tumor tissues, but only a few delivery systems have been able to target and release antibiotics on demand. Herein, we designed and developed a robust Chitosan-SS-Levofloxacin (CS-SS-LF) micelles for targeted antibiotic delivery, in which disulfide bond can be reduced by hydrogen sulfide (H2S), a typical product of Salmonella, and subsequently released antibiotic to eradicate Salmonella infection. CS-SS-LF micelles showed uniform size and sharp response to H2S. Compared with levofloxacin alone, these micelles possessed a better capacity in disrupting Salmonella biofilms and reducing bacterial burden in organs. The H2S-sensitive CS-SS-LF micelles might enable a new way to address bacterial infections.
Motility increase of adherent invasive Escherichia coli (AIEC) induced by a sub-inhibitory concentration of recombinant endolysin LysPA90
Authors: Hwang Yoon Jung , Jo Jaehak , Kim Eunsuk , Yoon Hyunjin , Hong Hyewon , Kim Min Soo , Myung Heejoon
Published: December 2022

Endolysins are bacteriophage enzymes required for the eruption of phages from inside host bacteria via the degradation of the peptidoglycan cell wall. Recombinant endolysins are increasingly being seen as potential antibacterial candidates, with a number currently undergoing clinical trials. Bacteriophage PBPA90 infecting Pseudomonas aeruginosa harbors a gene encoding an endolysin, lysPA90. Herein, recombinant LysPA90 demonstrated an intrinsic antibacterial activity against Escherichia coli in vitro. It was observed that a sub-inhibitory concentration of the recombinant protein induced the upregulation of genes related to flagella biosynthesis in a commensal E. coli strain. Increases in the number of bacterial flagella, and in motility, were experimentally substantiated. The treatment caused membrane stress, leading to the upregulation of genes rpoE, rpoH, dnaK, dnaJ, and flhC, which are upstream regulators of flagella biosynthesis. When adherent invasive Escherichia coli (AIEC) strains were treated with subinhibitory concentrations of the endolysin, bacterial adhesion and invasion into intestinal epithelial Caco-2 cells was seen to visibly increase under microscopic examination. Bacterial counting further corroborated this adhesion and invasion of AIEC strains into Caco-2 cells, with a resultant slight decrease in the viability of Caco-2 cells then being observed. Additionally, genes related to flagella expression were also upregulated in the AIEC strains. Finally, the enhanced expression of the proinflammatory cytokine genes TNF-α, IL-6, IL-8, and MCP1 in Caco-2 cells was noted after the increased invasion of the AIEC strains. While novel treatments involving endolysins offer great promise, these results highlight the need for the further exploration of possible unanticipated and unintended effects.
Escherichia coli protein synthesis is limited by mRNA availability rather than ribosomal capacity during phosphate starvation
Authors: Espinosa Rocio , Sørensen Michael Askvad , Svenningsen Sine Lo
Published: December 2022

Protein synthesis is the most energetically costly process in the cell. Consequently, it is a tightly regulated process, and regulation of the resources allocated to the protein synthesis machinery is at the heart of bacterial growth optimization theory. However, the molecular mechanisms that result in dynamic downregulation of protein synthesis in response to nutrient starvation are not well described. Here, we first quantify the Escherichia coli response to phosphate starvation at the level of accumulation rates for protein, RNA and DNA. Escherichia coli maintains a low level of protein synthesis for hours after the removal of phosphate while the RNA contents decrease, primarily as a consequence of ribosomal RNA degradation combined with a reduced RNA synthesis rate. To understand the molecular basis for the low protein synthesis rate of phosphate-starved cells, template mRNA for translation was overproduced in the form of a highly induced long-lived mRNA. Remarkably, starved cells increased the rate of protein synthesis and reduced the rate of ribosomal RNA degradation upon mRNA induction. These observations suggest that protein synthesis in phosphate-starved cells is primarily limited by the availability of template, and does not operate at the maximum capacity of the ribosomes. We suggest that mRNA limitation is an adaptive response to phosphate starvation that prevents the deleterious consequences of overcommitting resources to protein synthesis. Moreover, our results support the model that degradation of ribosomal RNA occurs as a consequence of the availability of idle ribosomal subunits.