bluuebunny/crossref_metadata_2025 huggingface dataset:
Drosophila Adducin facilitates phase separation and function of a conserved spindle orientation complex
Authors: Parra Amalia S. , Moezzi Cameron A. , Johnston Christopher A.
Published: August 2023

Asymmetric cell division (ACD) allows stem cells to generate differentiating progeny while simultaneously maintaining their own pluripotent state. ACD involves coupling mitotic spindle orientation with cortical polarity cues to direct unequal segregation of cell fate determinants. In Drosophila neural stem cells (neuroblasts; NBs), spindles orient along an apical-basal polarity axis through a conserved complex of Partner of Inscuteable (Pins; human LGN) and Mushroom body defect (Mud; human NuMA). While many details of its function are well known, the molecular mechanics that drive assembly of the cortical Pins/Mud complex remain unclear, particularly with respect to the mutually exclusive Pins complex formed with the apical scaffold protein Inscuteable (Insc). Here we identify Hu li tai shao (Hts; human Adducin) as a direct Mud-binding protein, using an aldolase fold within its head domain (HtsHEAD) to bind a short Mud coiled-coil domain (MudCC) that is adjacent to the Pins-binding domain (MudPBD). Hts is expressed throughout the larval central brain and apically polarizes in mitotic NBs where it is required for Mud-dependent spindle orientation. In vitro analyses reveal that Pins undergoes liquid-liquid phase separation with Mud, but not with Insc, suggesting a potential molecular basis for differential assembly mechanics between these two competing apical protein complexes. Furthermore, we find that Hts binds an intact Pins/Mud complex, reduces the concentration threshold for its phase separation, and alters the liquid-like property of the resulting phase separated droplets. Domain mapping and mutational analyses implicate critical roles for both multivalent interactions (via MudCC oligomerization) and protein disorder (via an intrinsically disordered region in Hts; HtsIDR) in phase separation of the Hts/Mud/Pins complex. Our study identifies a new component of the spindle positioning machinery in NBs and suggests that phase separation of specific protein complexes might regulate ordered assembly within the apical domain to ensure proper signaling output.
Proton pump inhibitors induced fungal dysbiosis in patients with gastroesophageal reflux disease
Authors: Shi Yichao , Li Jianfeng , Cai Shuntian , Zhao Hong , Zhao Huijun , Sun Gang , Yang Yunsheng
Published: August 2023

Gut mycobiota inhabits human gastrointestinal lumen and plays a role in human health and disease. We investigated the influence of proton pump inhibitors (PPIs) on gastric mucosal and fecal mycobiota in patients with gastroesophageal reflux diseases (GERD) by using Internal Transcribed Spacer 1 sequencing. A total of 65 participants were included, consisting of the healthy control (HC) group, GERD patients who did not use PPIs (nt-GERD), and GERD patients who used PPIs, which were further divided into short-term (s-PPI) and long-term PPI user (l-PPI) groups based on the duration of PPI use. The alpha diversity and beta diversity of gastric mucosal mycobiota in GERD patients with PPI use were significantly different from HCs, but there were no differences between s-PPI and l-PPI groups. LEfSe analysis identified Candida at the genus level as a biomarker for the s-PPI group when compared to the nt-GERD group. Meanwhile, Candida, Nothojafnea, Rhizodermea, Ambispora, and Saccharicola were more abundant in the l-PPI group than in the nt-GERD group. Furthermore, colonization of Candida in gastric mucosa was significantly increased after PPI treatment. However, there was no significant difference in Candida colonization between patients with endoscopic esophageal mucosal breaks and those without. There were significant differences in the fecal mycobiota composition between HCs and GERD patients regardless whether or not they used PPI. As compared to nt-GERD patient samples, there was a high abundance of Alternaria, Aspergillus, Mycenella, Exserohilum, and Clitopilus in the s-PPI group. In addition, there was a significantly higher abundance of Alternaria, Aspergillus, Podospora, Phallus, and Monographella in the l-PPI group than nt-GERD patients. In conclusion, our study indicates that dysbiosis of mycobiota was presented in GERD patients in both gastric mucosal and fecal mycobiota. PPI treatment may increase the colonization of Candida in the gastric mucosa in GERD patients.
Antibacterial activity of the novel oxazolidinone contezolid (MRX-I) against Mycobacterium abscessus
Authors: Gao Shan. , Nie Wenjuan. , Liu Lina. , Su Lei. , You Yingxia. , Geng Ruixue. , Chu Naihui
Published: August 2023

Objective

To evaluate contezolid (MRX-I) antibacterial activity against Mycobacterium abscessus in vitro and in vivo and to assess whether MRX-I treatment can prolong survival of infected zebrafish.

Methods

MRX-I inhibitory activity against M. abscessus in vitro was assessed by injecting MRX-I into zebrafish infected with green fluorescent protein-labelled M. abscessus. Thereafter, infected zebrafish were treated with azithromycin (AZM), linezolid (LZD) or MRX-I then maximum tolerated concentrations (MTCs) of drugs were determined based on M. abscessus growth inhibition using one-way ANOVA. Linear trend analysis of CFU counts and fluorescence intensities (mean ± SE values) was performed to detect linear relationships between MRX-I, AZM and LZD concentrations and these parameters.

Results

MRX-I anti-M. abscessus minimum inhibitory concentration (MIC) and MTC were 16 μg/mL and 15.6 μg/mL, respectively. MRX-I MTC-treated zebrafish fluorescence intensities were significantly lower than respective LZD group intensities (whole-body: 439040 ± 3647 vs. 509184 ± 23064, p < 0.01); head: 74147 ± 2175 vs. 95996 ± 8054, p < 0.05). As MRX-I concentration was increased from 0.488 μg/mL to 15.6 μg/mL, zebrafish whole-body, head and heart fluorescence intensities decreased. Statistically insignificant differences between the MRX-I MTC group survival rate (78.33%) vs. corresponding rates of the 62.5 μg/mL-treated AZM MTC group (88.33%, p > 0.05) and the 15.6 μg/mL-treated LZD MTC group (76.67%, p > 0.05) were observed.

Conclusion

MRX-I effectively inhibited M. abscessus growth and prolonged zebrafish survival when administered to M. abscessus-infected zebrafish, thus demonstrating that MRX-I holds promise as a clinical treatment for human M. abscessus infections.
“UDL is a way of thinking”; theorizing UDL teacher knowledge, beliefs, and practices
Authors: Lambert Rachel , McNiff Avery , Schuck Rachel , Imm Kara , Zimmerman Sara
Published: August 2023

Using design research methodology, we explored changes in experienced educators’ beliefs, knowledge, and practices related to Universal Design for Learning (UDL) following a professional development course for in-service teachers and teacher leaders on UDL and design thinking. Data included analysis of focus groups 9 months after the summer professional development course. Findings indicated shifts in educators’ beliefs about UDL, moving from conceptions of UDL as a static, inflexible framework to a “way of thinking” – moment-to-moment responsiveness to students’ access needs. Another finding was the importance of empathy interviews as a practice to learn about students and build relationships. Participants stressed the importance of questioning one’s own deficit thinking about students with disabilities. We call for more investigations into teacher knowledge, beliefs, and practices on UDL.
Age-dependent immune responses in COVID-19-mediated liver injury: focus on cytokines
Authors: Aghamohamadi Nazanin , Shahba Faezeh , Zarezadeh Mehrabadi Ali , Khorramdelazad Hossein , Karimi Milad , Falak Reza , Emameh Reza Zolfaghari
Published: August 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is potentially pathogenic and causes severe symptoms; in addition to respiratory syndromes, patients might experience other severe conditions such as digestive complications and liver complications injury. The abnormality in the liver is manifested by hepatobiliary dysfunction and enzymatic elevation, which is associated with morbidity and mortality. The direct cytopathic effect, immune dysfunction, cytokine storm, and adverse effects of therapeutic regimens have a crucial role in the severity of liver injury. According to aging and immune system alterations, cytokine patterns may also change in the elderly. Moreover, hyperproduction of cytokines in the inflammatory response to SARS-CoV-2 can lead to multi-organ dysfunction. The mortality rate in elderly patients, particularly those with other comorbidities, is also higher than in adults. Although the pathogenic effect of SARS-CoV-2 on the liver has been widely studied, the impact of age and immune-mediated responses at different ages remain unclear. This review discusses the association between immune system responses in coronavirus disease 2019 (COVID-19) patients of different ages and liver injury, focusing on cytokine alterations.
Precocious puberty in patients with Pompe disease
Authors: Tsai Meng-Ju Melody , Chen Mei-Huei , Chien Yin-Hsiu , Tung Yi-Ching
Published: August 2023

Introduction

The life expectancy of Pompe disease patients has increased due to improved neonatal screening and enzyme replacement therapy. Nevertheless, the potential effect of frequent medical device exposure on pubertal development in these patients is not well understood, so further investigation is warranted.

Methods

In this cross-sectional study, we assessed the growth and puberty of nine Pompe disease patients. In addition, to determine the effects of frequent plastic medical device exposure in these patients, we measured urinary phthalate metabolites before and one day after enzyme replacement therapy.

Results

Five out of nine patients (55%) with Pompe disease on enzyme replacement therapy had precocious puberty. Patients with precocious puberty had significantly shorter predicted adult heights compared to those with normal puberty (p = 0.014). The levels of mono-2-ethylhexyl phthalate (MEHP) and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) increased after enzyme replacement therapy, but the average levels of phthalate metabolites did not significantly differ between patients with normal and precocious puberty.

Conclusion

Pompe disease patients on enzyme replacement therapy tend to have precocious puberty, which may reduce their adult height. There are no significant differences in urinary phthalate metabolites between normal and precocious puberty patients. Regular follow-up of growth and puberty in Pompe disease patients is important to improve their health outcomes.
Determinants of maternity waiting home utilization among women who gave birth in public health facilities in the Gedeo Zone, southern Ethiopia: an unmatched case–control study
Authors: Tilahun Dawit , Shaka Mohammed Feyisso , Belay Moges Mareg
Published: August 2023

Background

Maternal mortality remains unacceptably high in Ethiopia, although most of its causes are preventable. One way of tackling this problem is by establishing a maternal waiting home (MWH) close to a health facility. Although the benefits of an MWH have been well-documented, the determinants of its use have not been well-studied. This study aims to identify the determinants of utilization of an MWH among women who gave birth in public health facilities in the Gedeo Zone, southern Ethiopia.

Methods

A facility-based unmatched case–control study was conducted between January 2020 and February 2020) among 129 patients belonging to the case group and 257 belonging to the control group. The data were entered into the Epi-Data version 3.1 and exported to the SPSS version 20 statistical package for analysis. Descriptive statistics such as frequency, means, and standard deviations were computed. The association between variables was checked using logistic regression analysis, and odds ratios (ORs) with 95% confidence interval (CI) were used to determine the strength of this association. A p-value of < 0.05 was used as a cutoff point to measure statistical significance.

Result

A total of 378 respondents (126 cases and 252 controls) were included in the study, successfully achieving a response rate of 97.9%. The mean age of the participants was 27.4 (±5.6 SD) years, which was 28.4 (±5.5 SD) years for case group patients and 26.9 (±5.69 SD) years for control group patients. The educational status of women [adjusted odds ratio (AOR): 8.49, 95% CI: 2.91–24.7], travel time (AOR: 2.92, 95% CI:1.41–4.67), antenatal care visits (AOR: 3.54, 95% CI: 1.33–9.38), those having more than two children under the age of 5 years (AOR: 0.12, 95% CI: 0.06–0.26), those with a history of complications in previous childbirths (AOR: 4.52 95% CI: 2.41–8.47), previous place of delivery (AOR: 6.30, 95% CI: 2.71–14.78), and a lack of awareness (AOR: 5.8, 95% CI: 2.23–15.2) were all significantly associated with the utilization of an MWH.

Conclusion

Educational status, antenatal care follow-up, number of children under 5 years old in the household, previous place of delivery, lack of awareness regarding maternal waiting home service, and travel time were all determinants of MWH use. This implies that interventions focusing on promoting antenatal care visits, institutional delivery, and raising awareness of the benefits of MWHs are important for improving their rate of utilization.
Mendelian randomization to evaluate the causal relationship between liver enzymes and the risk of six specific bone and joint-related diseases
Authors: Huang Guiwu , Li Wenchang , Zhong Yonglie , Liao Weiming , Zhang Zhiqi
Published: August 2023

Background

Studies of liver dysfunction in relation to bone and joint-related diseases are scarce, and its causality remains unclear. Our objective was to investigate whether serum liver enzymes are causally associated with bone and joint-related diseases using Mendelian randomization (MR) designs.

Methods

Genetic data on serum liver enzymes (alkaline phosphatase (ALP); alanine transaminase (ALT); gamma-glutamyl transferase (GGT)) and six common bone and joint-related diseases (rheumatoid arthritis (RA), osteoporosis, osteoarthritis (OA), ankylosing spondylitis, psoriatic arthritis, and gout) were derived from independent genome-wide association studies of European ancestry. The inverse variance-weighted (IVW) method was applied for the main causal estimate. Complementary sensitivity analyses and reverse causal analyses were utilized to confirm the robustness of the results.

Results

Using the IVW method, the positive causality between ALP and the risk of osteoporosis diagnosed by bone mineral density (BMD) at different sites was indicated (femoral neck, lumbar spine, and total body BMD, odds ratio (OR) [95% CI], 0.40 [0.23–0.69], 0.35 [0.19–0.67], and 0.33 [0.22–0.51], respectively). ALP was also linked to a higher risk of RA (OR [95% CI], 6.26 [1.69–23.51]). Evidence of potential harmful effects of higher levels of ALT on the risk of hip and knee OA was acquired (OR [95% CI], 2.48 [1.39–4.41] and 3.07 [1.49–6.30], respectively). No causal relationship was observed between GGT and these bone and joint-related diseases. The study also found that BMD were all negatively linked to ALP levels (OR [95% CI] for TBMD, FN-BMD, and LS-BMD: 0.993 [0.991–0.995], 0.993 [0.988–0.998], and 0.993 [0.989, 0.998], respectively) in the reverse causal analysis. The results were replicated via sensitivity analysis in the validation process.

Conclusions

Our study revealed a significant association between liver function and bone and joint-related diseases.
Peptide-based vaccine for cancer therapies
Authors: Buonaguro Luigi , Tagliamonte Maria
Published: August 2023

Different strategies based on peptides are available for cancer treatment, in particular to counter-act the progression of tumor growth and disease relapse. In the last decade, in the context of therapeutic strategies against cancer, peptide-based vaccines have been evaluated in different tumor models. The peptides selected for cancer vaccine development can be classified in two main type: tumor-associated antigens (TAAs) and tumor-specific antigens (TSAs), which are captured, internalized, processed and presented by antigen-presenting cells (APCs) to cell-mediated immunity. Peptides loaded onto MHC class I are recognized by a specific TCR of CD8+ T cells, which are activated to exert their cytotoxic activity against tumor cells presenting the same peptide-MHC-I complex. This process is defined as active immunotherapy as the host’s immune system is either de novo activated or restimulated to mount an effective, tumor-specific immune reaction that may ultimately lead to tu-mor regression. However, while the preclinical data have frequently shown encouraging results, therapeutic cancer vaccines clinical trials, including those based on peptides have not provided satisfactory data to date. The limited efficacy of peptide-based cancer vaccines is the consequence of several factors, including the identification of specific target tumor antigens, the limited immunogenicity of peptides and the highly immunosuppressive tumor microenvironment (TME). An effective cancer vaccine can be developed only by addressing all such different aspects. The present review describes the state of the art for each of such factors.
Systematic Mendelian randomization study of the effect of gut microbiome and plasma metabolome on severe COVID-19
Authors: Yan Han , Zhao Si , Huang Han-Xue , Xie Pan , Cai Xin-He , Qu Yun-Dan , Zhang Wei , Luo Jian-Quan , Zhang Longbo , Li Xi
Published: August 2023

Background

COVID-19 could develop severe respiratory symptoms in certain infected patients, especially in the patients with immune disorders. Gut microbiome and plasma metabolome act important immunological modulators in the human body and could contribute to the immune responses impacting the progression of COVID-19. However, the causal relationship between specific intestinal bacteria, metabolites and severe COVID-19 remains not clear.

Methods

Based on two-sample Mendelian randomization (MR) framework, the causal effects of 131 intestinal taxa and 452 plasma metabolites on severe COVID-19 were evaluated. Single nucleotide polymorphisms (SNPs) strongly associated with the abundance of intestinal taxa and the concentration of plasma metabolites had been utilized as the instrument variables to infer whether they were causal factors of severe COVID-19. In addition, mediation analysis was conducted to find the potential association between the taxon and metabolite, and further colocalization analysis had been performed to validate the causal relationships.

Results

MR analysis identified 13 taxa and 53 metabolites, which were significantly associated with severe COVID-19 as causal factors. Mediation analysis revealed 11 mediated relationships. Myo-inositol, 2-stearoylglycerophosphocholine, and alpha-glutamyltyrosine, potentially contributed to the association of Howardella and Ruminiclostridium 6 with severe COVID-19, respectively. Butyrivibrio and Ruminococcus gnavus could mediate the association of myo-inositol and N-acetylalanine, respectively. In addition, Ruminococcus torques abundance was colocalized with severe COVID-19 (PP.H4 = 0.77) and the colon expression of permeability related protein RASIP1 (PP.H4 = 0.95).

Conclusions

Our study highlights the potential causal relationships between gut microbiome, plasma metabolome and severe COVID-19, which potentially serve as clinical biomarkers for risk stratification and prognostication and benefit the mechanism mechanistic investigation of severe COVID-19.
Retinoic acid-inducible gene-I like receptor pathway in cancer: modification and treatment
Authors: Du Guangyuan , Xing Zherui , Zhou Jue , Cui Can , Liu Chenyuan , Liu Yiping , Li Zheng
Published: August 2023

Retinoic acid-inducible gene-I (RIG-I) like receptor (RLR) pathway is one of the most significant pathways supervising aberrant RNA in cells. In predominant conditions, the RLR pathway initiates anti-infection function via activating inflammatory effects, while recently it is discovered to be involved in cancer development as well, acting as a virus-mimicry responder. On one hand, the product IFNs induces tumor elimination. On the other hand, the NF-κB pathway is activated which may lead to tumor progression. Emerging evidence demonstrates that a wide range of modifications are involved in regulating RLR pathways in cancer, which either boost tumor suppression effect or prompt tumor development. This review summarized current epigenetic modulations including DNA methylation, histone modification, and ncRNA interference, as well as post-transcriptional modification like m6A and A-to-I editing of the upstream ligand dsRNA in cancer cells. The post-translational modulations like phosphorylation and ubiquitylation of the pathway’s key components were also discussed. Ultimately, we provided an overview of the current therapeutic strategies targeting the RLR pathway in cancers.
An unsuspected histopathological finding —concomitant IgA nephropathy in a patient with ANCA-associated vasculitis: a case report and literature review
Authors: Tota Maciej , Donizy Piotr , Byrska Martyna , Krajewska Magdalena , Kusztal Mariusz
Published: August 2023

Although associations of IgA nephropathy (IgAN) and ANCA-associated vasculitis (AAV) have been described, this coexistence scarcely occurs and requires multidisciplinary management. Herein, we discuss a course of treatment introduced in a patient with two exacerbations. Furthermore, alterations in histopathological images between two kidney biopsies are presented. The applicability of traditional inflammatory markers, e.g., CRP, in monitoring disease severity in AAV and IgAN is limited. Based on our patient and current literature, we suggest ANCA testing in patients with rapidly progressing IgAN for therapeutic and prognostic purposes. As regards the therapy of IgAN associated with AAV, aggressive immunosuppressive regimens with methylprednisolone and cyclophosphamide are recommended. Alternatively, methylprednisolone with rituximab, plasma exchange, mycophenolate mofetil, and intravenous immunoglobulin (IVIG) could also be considered.
Insertion of an immunodominant T helper cell epitope within the Group A Streptococcus M protein promotes an IFN-γ-dependent shift from a non-protective to a protective immune response
Authors: Emami Shiva , Rojas Converso Thiago , Persson Jenny J. , Johansson-Lindbom Bengt
Published: August 2023

The common pathogen Group A Streptococcus (GAS, Streptococcus pyogenes) is an extracellular bacterium that is associated with a multitude of infectious syndromes spanning a wide range of severity. The surface-exposed M protein is a major GAS virulence factor that is also target for protective antibody responses. In this study, we use a murine immunization model to investigate aspects of the cellular and molecular foundation for protective adaptive immune responses generated against GAS. We show that a wild type M1 GAS strain induces a non-protective antibody response, while an isogenic strain carrying the immunodominant 2W T helper cell epitope within the M protein elicits an immune response that is protective against the parental non-recombinant M1 GAS strain. Although the two strains induce total anti-GAS IgG levels of similar magnitude, only the 2W-carrying strain promotes elevated titers of the complement-fixing IgG2c subclass. Protection is dependent on IFN-γ, and IFN-γ-deficient mice show a specific reduction in IgG2c levels. Our findings suggest that inclusion of the 2W T cell epitope in the M protein confers essential qualitative alterations in the adaptive immune response against GAS, and that sparsity in IFN-γ-promoting Th cell epitopes in the M protein may constitute an immune evasion mechanism, evolved to allow the pathogen to avoid attack by complement-fixing antibodies.
The PID Odyssey 2030: outlooks, unmet needs, hurdles, and opportunities — proceedings from the IPOPI global multi-stakeholders’ summit (June 2022)
Authors: Tadros Susan , Prévot Johan , Meyts Isabelle , Sánchez-Ramón Silvia , Erwa Nahla H. , Fischer Alain , Lefevre Guillaume , Hotchko Matthew , Jaworski Peter M. , Leavis Helen , Boersma Cornelis , Drabwell Jose , van Hagen Martin , Van Coillie Samya , Pergent Martine , Burns Siobhan O. , Mahlaoui Nizar
Published: August 2023

IPOPI held its first Global Multi-Stakeholders’ Summit on 23-24 June 2022 in Cascais, Portugal. This IPOPI initiative was designed to set the stage for a stimulating forward-thinking meeting and brainstorming discussion among stakeholders on the future priorities of the PID community. All participants were actively engaged in the entire Summit, bringing provocative questions to ensure a high level of discussion and engagement, and partnered in identifying the outlooks, unmet needs, hurdles and opportunities of PIDs for 2030. The topics that were covered include diagnosis (e.g., newborn screening [NBS], genomic sequencing— including ethical aspects on the application of genomics on NBS, the role of more accurate and timely diagnostics in impacting personalized management), treatment (e.g., the therapeutic evolution of immunoglobulins in a global environment, new therapies such as targeted therapies, new approaches in curative therapies), the interactions of Primary ID with Secondary ID, Autoinflammatory Diseases and other diseases as the field experiences an incessant evolution, and also the avenues for research in the field of humanities and human sciences such as Patient-Reported Outcome Measures (PROMs), Patient-Reported Experience Measures (PREMs), and Health-Related Quality Of Life (HRQoL). During this meeting, all participants contributed to the drafting of recommendations based on our common understanding of the future opportunities, challenges, and scenarios. As a collection of materials, perspectives and summaries, they are succinct and impactful and may help determine some of the next key steps for the PID community.
Identification of sucrose synthase from Micractinium conductrix to favor biocatalytic glycosylation
Authors: Chen Kai , Lin Lei , Ma Ruiqi , Ding Jiajie , Pan Huayi , Tao Yehui , Li Yan , Jia Honghua
Published: August 2023

Sucrose synthase (SuSy, EC 2.4.1.13) is a unique glycosyltransferase (GT) for developing cost-effective glycosylation processes. Up to now, some SuSys derived from plants and bacteria have been used to recycle uridine 5′-diphosphate glucose in the reactions catalyzed by Leloir GTs. In this study, after sequence mining and experimental verification, a SuSy from Micractinium conductrix (McSuSy), a single-cell green alga, was overexpressed in Escherichia coli, and its enzymatic properties were characterized. In the direction of sucrose cleavage, the specific activity of the recombinant McSuSy is 9.39 U/mg at 37°C and pH 7.0, and the optimum temperature and pH were 60°C and pH 7.0, respectively. Its nucleotide preference for uridine 5′-diphosphate (UDP) was similar to plant SuSys, and the enzyme activity remained relatively high when the DMSO concentration below 25%. The mutation of the predicted N-terminal phosphorylation site (S31D) significantly stimulated the activity of McSuSy. When the mutant S31D of McSuSy was applied by coupling the engineered Stevia glycosyltransferase UGT76G1 in a one-pot two-enzyme reaction at 10% DMSO, 50 g/L rebaudioside E was transformed into 51.06 g/L rebaudioside M in 57 h by means of batch feeding, with a yield of 76.48%. This work may reveal the lower eukaryotes as a promising resource for SuSys of industrial interest.
Endophytic Beauveria bassiana promotes plant biomass growth and suppresses pathogen damage by directional recruitment
Authors: Sui Li , Lu Yang , Zhou Linyan , Li Nannan , Li Qiyun , Zhang Zhengkun
Published: August 2023

Introduction

Entomopathogenic fungi (EPF) can colonize and establish symbiotic relationships with plants as endophytes. Recently, EPF have been reported to suppress plant pathogens and induce plant resistance to diseases. However, the potential mechanisms via which EPF as endophytes control major plant diseases in situ remain largely unknown.

Methods

Pot and field experiments were conducted to investigate the mechanisms via which an EPF, Beauveria bassiana, colonizes tomato, under Botrytis cinerea infection stress. B. bassiana blastospores were inoculated into tomato plants by root irrigation. Tomato resistance to tomato gray mold caused by B. cinerea was evaluated by artificial inoculation, and B. bassiana colonization in plants and rhizosphere soil under B. cinerea infection stress was evaluated by colony counting and quantitative PCR. Furthermore, the expression levels of three disease resistance-related genes (OXO, CHI, and atpA) in tomato leaves were determined to explore the effect of B. bassiana colonization on plant disease resistance performance in pot experiments.

Results

B. bassiana colonization could improve resistance of tomato plants to gray mold caused by B. cinerea. The incidence rate, lesion diameter, and disease index of gray mold decreased in both the pot and field experiments following B. bassiana colonization. B. bassiana was more likely to accumulate in the pathogen infected leaves, while decreasing in the rhizosphere soil, and induced the expression of plant resistance genes, which were up-regulated in leaves.

Discussion

The results indicated that plants could “recruit” B. bassiana from rhizosphere soil to diseased plants as directional effects, which then enhanced plant growth and resistance against pathogens, consequently inhibiting pathogen infection and multiplication in plants. Our findings provide novel insights that enhance our understanding of the roles of EPF during pathogen challenge.
Radiomic markers of intracerebral hemorrhage expansion on non-contrast CT: independent validation and comparison with visual markers
Authors: Haider Stefan P. , Qureshi Adnan I. , Jain Abhi , Tharmaseelan Hishan , Berson Elisa R. , Zeevi Tal , Werring David J. , Gross Moritz , Mak Adrian , Malhotra Ajay , Sansing Lauren H. , Falcone Guido J. , Sheth Kevin N. , Payabvash Seyedmehdi
Published: August 2023

Objective

To devise and validate radiomic signatures of impending hematoma expansion (HE) based on admission non-contrast head computed tomography (CT) of patients with intracerebral hemorrhage (ICH).

Methods

Utilizing a large multicentric clinical trial dataset of hypertensive patients with spontaneous supratentorial ICH, we developed signatures predictive of HE in a discovery cohort (n = 449) and confirmed their performance in an independent validation cohort (n = 448). In addition to n = 1,130 radiomic features, n = 6 clinical variables associated with HE, n = 8 previously defined visual markers of HE, the BAT score, and combinations thereof served as candidate variable sets for signatures. The area under the receiver operating characteristic curve (AUC) quantified signatures’ performance.

Results

A signature combining select radiomic features and clinical variables attained the highest AUC (95% confidence interval) of 0.67 (0.61–0.72) and 0.64 (0.59–0.70) in the discovery and independent validation cohort, respectively, significantly outperforming the clinical (pdiscovery = 0.02, pvalidation = 0.01) and visual signature (pdiscovery = 0.03, pvalidation = 0.01) as well as the BAT score (pdiscovery < 0.001, pvalidation < 0.001). Adding visual markers to radiomic features failed to improve prediction performance. All signatures were significantly (p < 0.001) correlated with functional outcome at 3-months, underlining their prognostic relevance.

Conclusion

Radiomic features of ICH on admission non-contrast head CT can predict impending HE with stable generalizability; and combining radiomic with clinical predictors yielded the highest predictive value. By enabling selective anti-expansion treatment of patients at elevated risk of HE in future clinical trials, the proposed markers may increase therapeutic efficacy, and ultimately improve outcomes.
Task-based functional neuroimaging in infants: a systematic review
Authors: Agyeman Kofi , McCarty Tristan , Multani Harpreet , Mattingly Kamryn , Koziar Katherine , Chu Jason , Liu Charles , Kokkoni Elena , Christopoulos Vassilios
Published: August 2023

Background

Infancy is characterized by rapid neurological transformations leading to consolidation of lifelong function capabilities. Studying the infant brain is crucial for understanding how these mechanisms develop during this sensitive period. We review the neuroimaging modalities used with infants in stimulus-induced activity paradigms specifically, for the unique opportunity the latter provide for assessment of brain function.

Methods

Conducted a systematic review of literature published between 1977–2021, via a comprehensive search of four major databases. Standardized appraisal tools and inclusion/exclusion criteria were set according to the PRISMA guidelines.

Results

Two-hundred and thirteen papers met the criteria of the review process. The results show clear evidence of overall cumulative growth in the number of infant functional neuroimaging studies, with electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) to be the most utilized and fastest growing modalities with behaving infants. However, there is a high level of exclusion rates associated with technical limitations, leading to limited motor control studies (about 6%) in this population.

Conclusion

Although the use of functional neuroimaging modalities with infants increases, there are impediments to effective adoption of existing technologies with this population. Developing new imaging modalities and experimental designs to monitor brain activity in awake and behaving infants is vital.
Engineered neurogenesis in naïve adult rat cortex by Ngn2-mediated neuronal reprogramming of resident oligodendrocyte progenitor cells
Authors: Bazarek Stanley F. , Thaqi Mentor , King Patrick , Mehta Amol R. , Patel Ronil , Briggs Clark A. , Reisenbigler Emily , Yousey Jonathon E. , Miller Elis A. , Stutzmann Grace E. , Marr Robert A. , Peterson Daniel A.
Published: August 2023

Adult tissue stem cells contribute to tissue homeostasis and repair but the long-lived neurons in the human adult cerebral cortex are not replaced, despite evidence for a limited regenerative response. However, the adult cortex contains a population of proliferating oligodendrocyte progenitor cells (OPCs). We examined the capacity of rat cortical OPCs to be re-specified to a neuronal lineage both in vitro and in vivo. Expressing the developmental transcription factor Neurogenin2 (Ngn2) in OPCs isolated from adult rat cortex resulted in their expression of early neuronal lineage markers and genes while downregulating expression of OPC markers and genes. Ngn2 induced progression through a neuronal lineage to express mature neuronal markers and functional activity as glutamatergic neurons. In vivo retroviral gene delivery of Ngn2 to naive adult rat cortex ensured restricted targeting to proliferating OPCs. Ngn2 expression in OPCs resulted in their lineage re-specification and transition through an immature neuronal morphology into mature pyramidal cortical neurons with spiny dendrites, axons, synaptic contacts, and subtype specification matching local cytoarchitecture. Lineage re-specification of rat cortical OPCs occurred without prior injury, demonstrating these glial progenitor cells need not be put into a reactive state to achieve lineage reprogramming. These results show it may be feasible to precisely engineer additional neurons directly in adult cerebral cortex for experimental study or potentially for therapeutic use to modify dysfunctional or damaged circuitry.
Systems biology approach discovers comorbidity interaction of Parkinson's disease with psychiatric disorders utilizing brain transcriptome
Authors: Nashiry Md Asif , Sumi Shauli Sarmin , Alyami Salem A. , Moni Mohammad Ali
Published: August 2023

Several studies found that most patients with Parkinson's disorder (PD) appear to have psychiatric symptoms such as depression, anxiety, hallucination, delusion, and cognitive dysfunction. Therefore, recognizing these psychiatrically symptoms of PD patients is crucial for both symptomatic therapy and better knowledge of the pathophysiology of PD. In order to address this issue, we created a bioinformatics framework to determine the effects of PD mRNA expression on understanding its relationship with psychiatric symptoms in PD patients. We have discovered a significant overlap between the sets of differentially expressed genes from PD exposed tissue and psychiatric disordered tissues using RNA-seq datasets. We have chosen Bipolar disorder and Schizophrenia as psychiatric disorders in our study. A number of significant correlations between PD and the occurrence of psychiatric diseases were also found by gene set enrichment analysis, investigations of the protein-protein interaction network, gene regulatory network, and protein-chemical agent interaction network. We anticipate that the results of this pathogenetic study will provide crucial information for understanding the intricate relationship between PD and psychiatric diseases.
Effect of high-fructose consumption in pregnancy on the bone growth of offspring rats
Authors: Li Yijing , Liu Xiaoqian , Chu Yuning , Li Cai , Gao Tianlin , Jiang Xiuli , Zhu Zihan , Sheng Qi , Han Lei
Published: August 2023

Growing evidence suggests that bone health is programmed in early life. Maternal diet may influence the skeletal development of offspring. We aimed to determine the possible effects of high-fructose intake during pregnancy on different aspects of long bone morphology in the offspring of rats and to initially explore the possible mechanisms. Pregnant Sprague-Dawley rats were randomly divided into four groups and intragastrically administered the same dose of distilled water (CON, n = 12), 20 g/kg/day glucose (GLU, n = 12), 10 g/kg/day fructose (LFRU, n = 12), or 20 g/kg/day fructose (HFRU, n = 12) for 21 days during gestation. Computed tomography was used to analyze the cortical and cancellous bones of the distal femur of the offspring rats, and circulating bone metabolic biomarkers were measured using enzyme immunoassay. The results showed that high-fructose intake during pregnancy could decrease body weight, impair glucose metabolism, and increase serum leptin and uric acid in offspring. The offspring in the HFRU group had higher levels of the N-terminal propeptide of type I procollagen (PINP) and the C-telopeptide of type I collagen (CTX). The bone mean density (BMD), the total cross-sectional area inside the periosteal envelope (Tt.Ar), cortical bone area (Ct.Ar), medullary (or marrow) area (Ma.Ar), and trabecular mean density of the offspring in the HFRU group were lower than those in the CON group. Tartrate-resistant acid phosphatase (Trap) staining showed that high-fructose intake during pregnancy could increase the number of osteoclasts and increase the absorption area. Our results suggested that excessive fructose intake during pregnancy could inhibit skeletal development in offspring. Thus, attention to fructose intake during pregnancy is important for bone development in offspring.
Associations between dietary diversity score and migraine headaches: the results from a cross-sectional study
Authors: Amani Tirani Shahnaz , Askari Gholamreza , Khorvash Fariborz , As’habi Atefeh , Arab Arman
Published: August 2023

Aims

There is limited evidence on the link between diet quality and migraine headaches. The present study aimed to evaluate the association between dietary diversity score (DDS), as a good representative of overall diet quality, and clinical features of migraine headaches.

Methods

In total, 262 subjects (224 females and 34 males), aged 20 to 50  years old were included in the present cross-sectional study. The migraine headache was diagnosed according to the third edition of the International Classification of Headache Disorders (ICHD-3). Clinical features of migraine headaches including frequency, severity, and duration of migraine headaches, headache impact test-6 (HIT-6), and serum levels of nitric oxide (NO) were assessed by standard procedures. The dietary intake of participants has been assessed by a validated 168-item food frequency questionnaire (FFQ) and used to calculate DDS. The association between DDS and clinical variables of migraine headaches was investigated using multiple linear regression analysis, and the beta (β) estimates with 95% confidence intervals (CIs) were reported.

Results

A significant inverse association was found between DDS and headache frequency (β = −2.19, 95% CI: −4.25, −0.14) and serum levels of NO (β = −6.60, 95% CI: −12.58, −0.34), when comparing patients in the third tertile of DDS to those in the first tertile. The association remained significant and became stronger after adjustment for confounders for both outcomes of headache frequency (β = −3.36, 95% CI: −5.88, −0.84) and serum levels of NO (β = −9.86, 95% CI: −18.17, −1.55). However, no significant association was found between DDS with HIT-6 score, migraine headache duration, and severity.

Conclusion

The present study demonstrates that higher dietary diversity is correlated with lower migraine frequency and serum levels of NO.
Assessing brain function in stressed healthy individuals following the use of a combination of green tea, Rhodiola, magnesium, and B vitamins: an fMRI study
Authors: Pickering Gisèle , Noah Lionel , Pereira Bruno , Goubayon Jonathan , Leray Vincent , Touron Ambre , Macian Nicolas , Bernard Lise , Dualé Christian , Roux Veronique , Chassain Carine
Published: August 2023

Introduction

This randomized, controlled, single-blinded trial assessed the effect of magnesium (Mg)-Teadiola (Mg, vitamins B6, B9, B12, Rhodiola, and green tea/L-theanine) versus placebo on the brain response to stressful thermal stimulus in chronically stressed, but otherwise healthy subjects. Impacts on stress-related quality-of-life parameters (depression, anxiety, sleep, and perception of pain) were also explored.

Methods

The study recruited a total of 40 adults (20 per group), suffering from stress for more than 1 month and scaling ≥14 points on the Depression Anxiety Stress Scale (DASS)-42 questionnaire at the time of inclusion. Individuals received oral Mg-Teadiola or placebo for 28 days (D). fMRI analysis was used to visualize the interplay between stress and pain cerebral matrices, using thermal stress model, at baseline (D0) and after D28.

Results

Based on blood-oxygen-level-dependent (BOLD) signal variations during the stress stimulation (before pain perception), a significantly increased activation between D0 and D28 was observed for left and right frontal area (p = 0.001 and p = 0.002, respectively), left and right anterior cingulate cortex (ACC) (p = 0.035 and p = 0.04, respectively), and left and right insula (p = 0.034 and p = 0.0402, respectively) in Mg-Teadiola versus placebo group. During thermal pain stimulation, a significantly diminished activation of the pain matrix was observed between D0 and D28, for left and right prefrontal area (both p = 0.001), left and right insula (p = 0.008 and p = 0.019, respectively), and left and right ventral striatum (both p = 0.001) was observed in Mg-Teadiola versus placebo group. These results reinforce the clinical observations, showing a perceived benefit of Mg-Teadiola on several parameters. After 1 month of treatment, DASS-42 stress score significantly decreased in Mg-Teadiola group [effect size (ES) −0.46 (−0.91; −0.01), p = 0.048]. Similar reductions were observed on D14 (p = 0.011) and D56 (p = 0.008). Sensitivity to cold also improved from D0 to D28 for Mg-Teadiola versus placebo [ES 0.47 (0.02; 0.92) p = 0.042].

Conclusion

Supplementation with Mg-Teadiola reduced stress on D28 in chronically stressed but otherwise healthy individuals and modulated the stress and pain cerebral matrices during stressful thermal stimulus.
Oxidative balance score inversely associated with the prevalence and incidence of metabolic syndrome: analysis of two studies of the Korean population
Authors: Park Hye-Min , Han Tea-Hwa , Kwon Yu-Jin , Lee Jun-Hyuk
Published: August 2023

Background

Pro-oxidant/antioxidant imbalances leading to chronic inflammation and insulin resistance can contribute to the development of metabolic syndrome (MetS). Oxidative Balance Score (OBS), a comprehensive measure of exposure to pro- and anti-oxidants, represents an individual’s total oxidative balance. This study aimed to evaluate the association between OBS and MetS using two large datasets.

Methods

We analyzed data from 2,735 adults older than 19 years from the 2021 Korean National Health and Nutritional Examination Survey (KNHANES) and 5,807 adults aged 40–69 years from the Korean Genome and Epidemiology Study (KoGES). In each dataset, OBS was categorized into sex-specific tertiles (T).

Results

In KNHANES, the odds ratios and 95% confidence intervals for prevalent MetS in T3, compared to T1, were 0.44 (0.29–0.65) in men and 0.34 (0.23–0.50) in women after adjusting for confounders. In KoGES, the hazard ratios and 95% confidence intervals for incident MetS in T3, compared to T1, were 0.56 (0.48–0.65) in men and 0.63 (0.55–0.73) in women after adjusting for confounders.

Conclusion

OBS appears to be inversely related to MetS, which suggests that adopting lifestyle behaviors that decrease oxidative stress could be an important preventive strategy for MetS.
A 20:1 synergetic mixture of cafedrine/theodrenaline accelerates particle transport velocity in murine tracheal epithelium via IP3 receptor-associated calcium release
Authors: Schmidt Götz , Rienas Gerrit , Müller Sabrina , Edinger Fabian , Sander Michael , Koch Christian , Henrich Michael
Published: August 2023

Background: Mucociliary clearance is a pivotal physiological mechanism that protects the lung by ridding the lower airways of pollution and colonization by pathogens, thereby preventing infections. The fixed 20:1 combination of cafedrine and theodrenaline has been used to treat perioperative hypotension or hypotensive states due to emergency situations since the 1960s. Because mucociliary clearance is impaired during mechanical ventilation and critical illness, the present study aimed to evaluate the influence of cafedrine/theodrenaline on mucociliary clearance.

Material and Methods: The particle transport velocity (PTV) of murine trachea preparations was measured as a surrogate for mucociliary clearance under the influence of cafedrine/theodrenaline, cafedrine alone, and theodrenaline alone. Inhibitory substances were applied to elucidate relevant signal transduction cascades.

Results: All three applications of the combination of cafedrine/theodrenaline, cafedrine alone, or theodrenaline alone induced a sharp increase in PTV in a concentration-dependent manner with median effective concentrations of 0.46 µM (consisting of 9.6 µM cafedrine and 0.46 µM theodrenaline), 408 and 4 μM, respectively. The signal transduction cascades were similar for the effects of both cafedrine and theodrenaline at the murine respiratory epithelium. While PTV remained at its baseline value after non-selective inhibition of β-adrenergic receptors and selective inhibition of β1 receptors, cafedrine/theodrenaline, cafedrine alone, or theodrenaline alone increased PTV despite the inhibition of the protein kinase A. However, IP3 receptor activation was found to be the pivotal mechanism leading to the increase in murine PTV, which was abolished when IP3 receptors were inhibited. Depleting intracellular calcium stores with caffeine confirmed calcium as another crucial messenger altering the PTV after the application of cafedrine/theodrenaline.

Discussion: Cafedrine/theodrenaline, cafedrine alone, and theodrenaline alone exert their effects via IP3 receptor-associated calcium release that is ultimately triggered by β1-adrenergic receptor stimulation. Synergistic effects at the β1-adrenergic receptor are highly relevant to alter the PTV of the respiratory epithelium at clinically relevant concentrations. Further investigations are needed to assess the value of cafedrine/theodrenaline-mediated alterations in mucociliary function in clinical practice.