Current Knowledge Research Articles

Guardians of Immunity: Toll-Like Receptor Signalling in the Onset and Progression of Multiple Sclerosis, Sketching an Immunopathological Scheme

Background: Multiple Sclerosis (MS) is a chronic autoimmune disorder of the central nervous system, characterized by inflammation, demyelination, and neurodegeneration. The role of toll-like receptors (TLRs) in MS pathogenesis, specifically through MYD88-dependent and -independent pathways, has become a focal point of research. Understanding these pathways offers insights into the mechanisms driving MS and potential therapeutic targets. Objective: This review aims to synthesize current knowledge on the role of TLR signaling in the onset and progression of MS, focusing on the dysregulation of MYD88-dependent and -independent pathways and their implications for disease pathogenesis and therapy. Methods: A systematic search of PubMed, Scopus, Web of Science, and Google Scholar databases was conducted to identify studies related to TLR signaling in MS. Keywords related to "toll-like receptors," "multiple sclerosis," "MYD88-dependent pathway," "MYD88-independent pathway," and "immune response" were used. The evidence synthesis was qualitative, integrating findings from both human and animal studies. Results: The review highlights the central role of NF-kB in mediating the effects of TLR signaling on the inflammatory cascade in MS. Dysregulation in TLR signaling pathways can lead to increased expression of pro-inflammatory cytokines and compromise the blood-brain barrier, exacerbating MS pathogenesis. The evidence points towards the dual role of TLR pathways in promoting inflammatory responses and potentially offering protective mechanisms against the disease. Conclusion: TLR signaling pathways play a crucial role in the immunopathology of MS, with both MYD88-dependent and -independent pathways contributing to disease progression. Targeting these pathways presents a promising therapeutic strategy, emphasizing the need for further research to develop effective treatments.

Fetal Long QT Syndrome - Challenges in Perinatal Management: A Review and Case Report. Induction of Labor and Vaginal Birth Under Continuous Magnesium Therapy.

Congenital LQTS is an often undetected inherited cardiac channel dysfunction and can be a reason for intrauterine fetal demise. It can present in utero as CTG and ultrasound abnormalities, i. e., bradycardia, ventricular tachycardia, or fetal hydrops. Diagnosis is made by CTG, echocardiography, or fMCG. Intrauterine therapy with a ß blocker and i. v. magnesium should be started. Our objective was to examine the current knowledge about diagnosis and treatment of LQTS and in particular to highlight the opportunity of vaginal birth under continuous intravenous magnesium therapy. Therefore, a thorough MEDLINE and Google Scholar search was conducted. Randomized controlled trials, meta-analyses, prospective and retrospective cohort trials, and case reports were considered. We showed the possibility of vaginal delivery under continuous magnesium therapy in a case of suspected fetal LQTS. A stepwise concept for diagnosis, monitoring, and peripartum management in low, intermediate, and high risk cases of fetal LQTS is presented. If risk is low or intermediate, a vaginal delivery under continuous monitoring is reasonable. Induction of labor at term should be evaluated.

The Curvilinear Relationship Between Empowering Leadership and Team Performance: A Self-Regulatory Perspective

Although previous research demonstrated that empowering leadership has both positive and negative impacts on team consequences, our current knowledge of the processes by which and the conditions under which empowering leadership promotes or hinders team performance remains limited. Drawing on the too-much-of-a-good-thing (TMGT) effect and the team self-regulatory perspective, our findings, backed with a time-lagged and multi-source survey, suggested that empowering leadership has a curvilinear impact (i.e., inverted U-shaped) on team performance through team reflexivity, and this impact is contingent on team performance-approach goal orientation. We discuss the implications of our findings from both theoretical and practical perspectives.

Nitrous oxide and nitric oxide fluxes differ from tea plantation and tropical forest soils after nitrogen addition

South Asia is experiencing a rapid increase in nitrogen (N) pollution which is predicted to continue in the future. One of the possible implications is an increase in gaseous reactive N losses from soil, notably in the form of nitrous oxide (N2O) and nitric oxide (NO). Current knowledge of N2O and NO dynamics in forest ecosystems is not sufficient to understand and mitigate the impacts on climate and air quality. In order to improve the understanding of emissions from two major land uses in Sri Lanka, we investigated the emission potential for N2O and NO fluxes measured by absorption spectroscopy and chemiluminescence, respectively, in response to three different N addition levels (the equivalent of 0, 40 and 100 kg N ha−1 yr.−1 deposition in the form of NH4+) from soils of two typical land uses in Sri Lanka: a secondary montane tropical forest and a tea plantation using soil laboratory incubations of repacked soil cores. We observed an increase in NO fluxes which was directly proportional to the amount of N applied in line with initial expectations (maximum flux ranging from 6–8 ng NO-N g−1 d−1 and from 16–68 ng NO-N g−1 d−1 in forest and tea plantation soils, respectively). However, fluxes of N2O did not show a clear response to N addition, the highest treatment (100 N) did not result in the highest fluxes. Moreover, fluxes of N2O were higher following the addition of a source of carbon (in the form of glucose) across treatment levels and both land uses (maximum flux of 2–34 ng N2O-N g−1 d−1 in forest and 808–3,939 ng N2O-N g−1 d−1 in tea plantation soils). Both N2O and NO fluxes were higher from tea plantation soils compared to forest soils irrespective of treatment level, thus highlighting the importance of land use and land management for gaseous reactive N fluxes and therefore N dynamics.

Single-Cell Mechanics: Structural Determinants and Functional Relevance.

The mechanical phenotype of a cell determines its ability to deform under force and is therefore relevant to cellular functions that require changes in cell shape, such as migration or circulation through the microvasculature. On the practical level, the mechanical phenotype can be used as a global readout of the cell's functional state, a marker for disease diagnostics, or an input for tissue modeling. We focus our review on the current knowledge of structural components that contribute to the determination of the cellular mechanical properties and highlight the physiological processes in which the mechanical phenotype of the cells is of critical relevance. The ongoing efforts to understand how to efficiently measure and control the mechanical properties of cells will define the progress in the field and drive mechanical phenotyping toward clinical applications.

Another renaissance for bile acid gastrointestinal microbiology.

The field of bile acid microbiology in the gastrointestinal tract is going through a current rebirth after a peak of activity in the late 1970s and early 1980s. This renewed activity is a result of many factors, including the discovery near the turn of the century that bile acids are potent signalling molecules and technological advances in next-generation sequencing, computation, culturomics, gnotobiology, and metabolomics. We describe the current state of the field with particular emphasis on questions that have remained unanswered for many decades in both bile acid synthesis by the host and metabolism by the gut microbiota. Current knowledge of established enzymatic pathways, including bile salt hydrolase, hydroxysteroid dehydrogenases involved in the oxidation and epimerization of bile acid hydroxy groups, the Hylemon-Bjӧrkhem pathway of bile acid C7-dehydroxylation, and the formation of secondary allo-bile acids, is described. We cover aspects of bile acid conjugation and esterification as well as evidence for bile acid C3-dehydroxylation and C12-dehydroxylation that are less well understood but potentially critical for our understanding of bile acid metabolism in the human gut. The physiological consequences of bile acid metabolism for human health, important caveats and cautionary notes on experimental design and interpretation of data reflecting bile acid metabolism are also explored.

SRNA molecules participate in hyperosmotic stress response regulation in Sphingomonas melonis TY.

Drought and salinity are ubiquitous environmental factors that pose hyperosmotic threats to microorganisms and impair their efficiency in performing environmental functions. However, bacteria have developed various responses and regulatory systems to cope with these abiotic challenges. Posttranscriptional regulation plays vital roles in regulating gene expression and cellular homeostasis, as hyperosmotic stress conditions can lead to the induction of specific small RNA molecules (sRNAs) that participate in stress response regulation. Here, we report a candidate functional sRNA landscape of Sphingomonas melonis TY under hyperosmotic stress, and 18 sRNAs were found with a clear response to hyperosmotic stress. These findings will help in the comprehensive analysis of sRNA regulation in Sphingomonas species. Weighted correlation network analysis revealed a 263 nucleotide sRNA, SNC251, which was transcribed from its own promoter and showed the most significant correlation with hyperosmotic response factors. Deletion of snc251 affected biofilm formation and multiple cellular processes, including ribosome-related pathways, aromatic compound degradation, and the nicotine degradation capacity of S. melonis TY, while overexpression of SNC251 facilitated biofilm formation by TY under hyperosmotic stress. Two genes involved in the TonB system were further verified to be activated by SNC251, which also indicated that SNC251 is a trans-acting sRNA. Briefly, this research reports a landscape of sRNAs participating in the hyperosmotic stress response in S. melonis and reveals a novel sRNA, SNC251, which contributes to the S. melonis TY biofilm formation and thus enhances its hyperosmotic stress response ability.IMPORTANCESphingomonas species play a vital role in plant defense and pollutant degradation and survive extensively under drought or salinity. Previous studies have focused on the transcriptional and translational responses of Sphingomonas under hyperosmotic stress, but the posttranscriptional regulation of small RNA molecules (sRNAs) is also crucial for quickly modulating cellular processes to adapt dynamically to osmotic environments. In addition, the current knowledge of sRNAs in Sphingomonas is extremely scarce. This research revealed a novel sRNA landscape of Sphingomonas melonis and will greatly enhance our understanding of sRNAs' acting mechanisms in the hyperosmotic stress response.

Nitrous oxide abuse direct measurement for diagnosis and follow-up: update on kinetics and impact on metabolic pathways.

Recreational use of nitrous oxide (N2O) has become a major health issue worldwide, with a high number of clinical events, especially in neurology and cardiology. It is essential to be able to detect and monitor N2O abuse to provide effective care and follow-up to these patients. Current recommendations for detecting N2O in cases of recreational misuse and consumption markers are lacking. We aimed to update current knowledge through a review of the literature on N2O measurement and kinetics. We reviewed the outcomes of experiments, whether in preclinical models (in vitro or in vivo), or in humans, with the aim to identify biomarkers of intoxication as well as biomarkers of clinical severity, for laboratory use. Because N2O is eliminated 5 min after inhalation, measuring it in exhaled air is of no value. Many studies have found that urine and blood matrices concentrations are connected to ambient concentrations, but there is no similar data for direct exposure. There have been no studies on N2O measurement in direct consumers. Currently, patients actively abusing N2O are monitored using effect biomarkers (biomarkers related to the effects of N2O on metabolism), such as vitamin B12, homocysteine and methylmalonic acid.

Not so hidden anymore: Advances and challenges in understanding root growth under water deficits.

Limited water availability is a major environmental factor constraining plant development and crop yields. One of the prominent adaptations of plants to water deficits is the maintenance of root growth that enables sustained access to soil water. Despite early recognition of the adaptive significance of root growth maintenance under water deficits, progress in understanding has been hampered by the inherent complexity of root systems and their interactions with the soil environment. We highlight selected milestones in the understanding of root growth responses to water deficits, with emphasis on founding studies that have shaped current knowledge and set the stage for further investigation. We revisit the concept of integrated biophysical and metabolic regulation of plant growth and use this framework to review central growth-regulatory processes occurring within root growth zones under water stress at subcellular to organ scales. Key topics include the primary processes of modifications of cell wall-yielding properties and osmotic adjustment, as well as regulatory roles of abscisic acid and its interactions with other hormones. We include consideration of long-recognized responses for which detailed mechanistic understanding has been elusive until recently, for example hydrotropism, and identify gaps in knowledge, ongoing challenges, and opportunities for future research.

Numerical investigation of hypervelocity impact simulation with FEM/SPH formulation for space structures

This paper investigates the response of aluminum structures to hypervelocity impact (HVI) and the formation of debris clouds using the Adaptive Finite Element (FEM)/Smoothed Particle Hydrodynamics (SPH) method. The main objective is to accurately replicate the response of curved thin plates to various HVIs and to characterize the resulting debris cloud shapes., for representative of shielding structures against Micrometeoroids and Orbital Debris (MMOD). In particular, the effects of different solid element formulations on the adaptive method are investigated. Experimental data from the literature is used to validate the proposed model, which is then applied to a curved thin plate subjected to varying impact angles. The findings highlight the significant influence of solid element formulation on the effectiveness of the adaptive method. Moreover, a direct correlation is observed between the impact angle and the produced debris cloud shape. These results contribute to the current knowledge on HVI responses and provide valuable insights for predicting and analyzing debris cloud formation in relation to aluminum structures.

Microbial Diseases of Laboratory Animals and its monitoring Tools

Microbial diseases pose significant challenges in experimental research, impacting both animal welfare and research outcomes. The review covers a wide range of microbial pathogens, including bacteria, viruses, fungi, and parasites, that commonly affect laboratory animals. It explores the etiology, pathogenesis, and clinical manifestations associated with these pathogens, highlighting their influence on experimental results. Extensively discussed about the monitoring assays employed for microbial disease detection in experimental animals. Traditional and modern techniques are considered, including microbiological culturing, serological assays, molecular diagnostics, histopathology, and advanced imaging methods. Regular health monitoring programs for laboratory animals, emphasizing the significance of early detection and intervention to prevent disease outbreaks and maintain animal welfare. Emerging trends and technologies in microbial disease monitoring, such as next-generation sequencing, metagenomics, and high-throughput screening, are also explored. This review aims to provide researchers, laboratory animal professionals, and regulatory authorities with a comprehensive resource for understanding microbial diseases in experimental animals and selecting appropriate monitoring assay. For the Scientists and Veterinarians this overall review gives a glimpse for implementing effective monitoring strategies, identifying and managing microbial diseases, ensuring the well-being of laboratory animals. The synthesis of current knowledge and best practices will enhance the scientific rigor and reproducibility of experimental studies involving animals. In conclusion, this review emphasizes the critical importance of microbial disease monitoring in experimental animals. Robust and accurate monitoring assays enable researchers to effectively detect and manage microbial diseases, safeguarding animal health and ensuring reliable research outcomes.

Pathogenic Variants Associated with Epigenetic Control and the NOTCH Pathway Are Frequent in Classic Hodgkin Lymphoma.

Classic Hodgkin lymphoma (cHL) constitutes a B-cell neoplasm derived from germinal center lymphocytes. Despite high cure rates (80-90%) obtained with the current multiagent protocols, a significant proportion of cHL patients experience recurrences, characterized by a lower sensitivity to second-line treatments. The genomic background of chemorefractory cHL is still poorly understood, limiting personalized treatment strategies based on molecular features. In this study, using a targeted next-generation sequencing (NGS) panel specifically designed for cHL research, we compared chemosensitive and chemorefractory diagnostic tissue samples of cHL patients. Furthermore, we longitudinally examined paired diagnosis-relapsesamples of chemorefractory cHL in order to define patterns of dynamic evolution and clonal selection. Pathogenic variants in NOTCH1 and NOTCH2 genes frequently arise in cHL. Mutations in genes associated with epigenetic regulation (CREBBP and EP300) are particularly frequent in relapsed/refractory cHL. The appearance of novel clones characterized by mutations previously not identified at diagnosis is a common feature in cHL cases showing chemoresistance to frontline treatments. Our results expand current molecular and pathogenic knowledge of cHL and support the performance of molecular studies in cHL prior to the initiation of first-line therapies.

P53 and Rb Aberrations in Small Cell Lung Cancer (SCLC): From Molecular Mechanisms to Therapeutic Modulation.

The genes coding for the tumor suppressors p53 and retinoblastoma (Rb) are inactivated in the vast majority of small cell lung cancer (SCLC) tumors. Data support the notion that these two deleterious genetic events represent the initial steps in the development of SCLC, making them essential for a lung epithelial cell to progress toward the acquisition of a malignant phenotype. With the loss of TP53 and RB1, their broad tumor suppressive functions are eliminated and a normal cell is able to proliferate indefinitely, escape entering into cellular senescence, and evade death, no matter the damage it has experienced. Within this setting, lung epithelial cells accumulate further oncogenic mutations and are well on their way to becoming SCLC cells. Understanding the molecular mechanisms of these genetic lesions and their effects within lung epithelial cells is of paramount importance, in order to tackle this aggressive and deadly lung cancer. The present review summarizes the current knowledge on p53 and Rb aberrations, their biological significance, and their prospective therapeutic potential, highlighting completed and ongoing clinical trials with agents that target downstream pathways.

A Review on Organic Manure and Plant Growth Promoting Rhizobacteria’s Use in Horticultural Crops

The sustainable and eco-friendly management of horticulture crops has become increasingly imperative in contemporary agricultural practices. This review summarizes the current knowledge on the synergistic utilization of organic manure and plant growth-promoting rhizobacteria (PGPR) to enhance the growth, yield, and overall health of horticulture crops. Organic manures, derived from natural sources such as compost, animal manure, and green manure, offer a sustainable alternative to synthetic fertilizers, providing essential nutrients while promoting soil fertility and structure. PGPR can affect on plant growth by production and releases secondary metabolites, helps in preventing deleterious effects of phyto-pathogenic organisms in the rhizosphere. This will ultimately support for better yield and quality of horticultural crops.

About this title - Carbonate Reservoirs: Applying Current Knowledge to Future Energy Needs

This Special Publication is a compendium of studies on carbonate petroleum reservoirs from several key areas, together with subsurface examples of renewable energy generation, storage and sequestration. It shows how the tools developed entirely for petroleum reservoir exploitation are now being utilized to enable aspects of our new low-carbon environment.

The mitochondrial quality control system: a new target for exercise therapeutic intervention in the treatment of brain insulin resistance-induced neurodegeneration in obesity.

Obesity is a major global health concern because of its strong association with metabolic and neurodegenerative diseases such as diabetes, dementia, and Alzheimer's disease. Unfortunately, brain insulin resistance in obesity is likely to lead to neuroplasticity deficits. Since the evidence shows that insulin resistance in brain regions abundant in insulin receptors significantly alters mitochondrial efficiency and function, strategies targeting the mitochondrial quality control system may be of therapeutic and practical value in obesity-induced cognitive decline. Exercise is considered as a powerful stimulant of mitochondria that improves insulin sensitivity and enhances neuroplasticity. It has great potential as a non-pharmacological intervention against the onset and progression of obesity associated neurodegeneration. Here, we integrate the current knowledge of the mechanisms of neurodegenration in obesity and focus on brain insulin resistance to explain the relationship between the impairment of neuronal plasticity and mitochondrial dysfunction. This knowledge was synthesised to explore the exercise paradigm as a feasible intervention for obese neurodegenration in terms of improving brain insulin signals and regulating the mitochondrial quality control system.

Violence against women associated factors with the menstrual period: a narrative review

Violence constitutes a pervasive infringement of human rights on a global scale, impacting approximately one-third of women throughout their lives. Menstruation-related violence remains an underreported issue globally, with causative factors spanning social class, education, ethnic discrimination, financial access, and other concealed influences. The objective was to identify and analyze de most factors associated with violence against women during the menstrual period. A narrative review of existing literature was conducted, utilizing databases and academic repositories. The search strategy focused on identifying studies that specifically addressed violence against women in the context of the menstrual period. The inclusion criteria encompassed research from diverse disciplines, including sociology, psychology, public health, and gender studies. This literature review investigates the intricate nexus between violence against women and the menstrual period, aiming to elucidate the associated factors that contribute to this complex relationship. Recognizing the need for a comprehensive understanding of the subject, the study delves into existing research to explore the multifaceted dynamics surrounding violence during the menstrual cycle. The synthesis of literature revealed a spectrum of factors associated with violence against women during the menstrual period. These factors span cultural, social, psychological, and physiological dimensions, highlighting the complexity of the issue. The results provide insights into patterns, risk factors, and consequences, offering a holistic perspective on the dynamics at play. The findings illuminate the multifaceted nature of this phenomenon, emphasizing the importance of tailored interventions that address cultural, social, and psychological aspects. By consolidating current knowledge, this review serves as a foundation for future research and the development of targeted strategies to mitigate and prevent violence against women in the context of the menstrual period.

Interaction of Zinc Mineral Nutrition and Plant Growth-Promoting Bacteria in Tropical Agricultural Systems: A Review.

The relationship between zinc mineral nutrition and plant growth-promoting bacteria (PGPB) is pivotal in enhancing agricultural productivity, especially in tropical regions characterized by diverse climatic conditions and soil variability. This review synthesizes and critically evaluates current knowledge regarding the synergistic interaction between zinc mineral nutrition and PGPB in tropical agricultural systems. Zinc is an essential and fundamental micronutrient for various physiological and biochemical processes in plants. Its deficiency affects plant growth and development, decreasing yields and nutritional quality. In tropical regions, where soil zinc availability is often limited or imbalanced, the PGPB, through different mechanisms such as Zn solubilization; siderophore production; and phytohormone synthesis, supports Zn uptake and assimilation, thereby facilitating the adverse effects of zinc deficiency in plants. This review outlines the impacts of Zn-PGPB interactions on plant growth, root architecture, and productivity in tropical agricultural systems. The positive relationship between PGPB and plants facilitates Zn uptake and improves nutrient use efficiency, overall crop performance, and agronomic biofortification. In addition, this review highlights the importance of considering indigenous PGPB strains for specific tropical agroecosystems, acknowledging their adaptability to local conditions and their potential in sustainable agricultural practices. It is concluded that Zn fertilizer and PGPBs have synergistic interactions and can offer promising avenues for sustainable agriculture, addressing nutritional deficiencies, improving crop resilience, and ensuring food security.

Inspiring self-regulated learning in everyday classrooms: teachers’ professional competences and promotion of self-regulated learning

AbstractToday’s success metrics extend beyond traditional literacy and numeracy to encompass strategic learning with a growth mindset, equipping individuals with the attitude and skills to navigate and surmount new challenges. In a digital era, where information is readily available and knowledge constantly evolves, the value placed on learners is not merely based on their current knowledge but on their courage and capability to continually engage cognitive, metacognitive, motivational, social, and emotional resources for lifelong learning. In this dynamic landscape, self-regulated learning (SRL) skills are crucial, empowering students of all ages to take control of their learning journey. SRL, the goal-directed process of monitoring and regulating one’s learning activities, has been shown to significantly influence academic outcomes. Although teachers acknowledge SRL’s relevance, it remains underrepresented in everyday teaching practices, impacting not just student learning but also the training and experiences of preservice teachers in the classroom. This gap perpetuates misconceptions about SRL and hinders its integration into educational settings. Therefore, this special issue first introduces the INSPIRE model of teachers’ multiple roles as instructors, navigators, strategists, promoters, innovators, role models, and encouragers in supporting students to become self-regulated learners and describes teachers’ professional competences to fulfil these roles. Second, it dedicates four articles to exploring teachers’ professional competences in SRL and its promotion in everyday school. The articles address particular aspects of the INSPIRE model and highlight the importance of teachers equipped with the necessary training and competences to guide students in becoming self-regulated learners. Linking the research areas of teachers’ professional competences in SRL and teachers’ promotion of SRL in the classroom this special issue offers a comprehensive approach to SRL in everyday school and opens up perspectives for the transfer into practice.

Under explored roles of microbial ligninolytic enzymes in aerobic polychlorinated biphenyl transformation.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants in the environment that are responsible for many adverse health effects. Bioremediation appears to be a healthy and cost-effective alternative for remediating PCB-contaminated environments. While some microbial species have been observed to be capable of transforming PCBs, only two different microbial pathways (rdh and bph pathways) have been described to be involved in PCB transformations. Ligninolytic enzymes have been observed or are under suspicion in some microbial PCB transformations. However, the role of these promising PCB-transforming enzymes, which are produced by fungi and some aerobic bacteria, is still unclear. The present review describes their role by identifying microbial PCB-transforming species and their reported ligninolytic enzymes whether proven or suspected to be involved in PCB transformations. There are several lines of evidence that ligninolytic enzymes are responsible for PCB transformations such as (1) the ability of purified laccases from Myceliophthora thermophila, Pycnoporus cinnabarinus, Trametes versicolor, Cladosporium sp, and Coprinus cumatus to transform hydroxy-PCBs; (2) the increased production of laccases and peroxidases by many fungi in the presence of PCBs; and (3) the enhanced PCB transformation by Pseudomonas stutzeri and Sinorhizobium meliloti NM after the addition of ligninolytic enzyme enhancers. However, if the involvement of ligninolytic enzymes in PCB transformation is clearly demonstrated in some fungal species, it does not seem to be implicated in all microbial species suggesting other still unknown metabolic pathways involved in PCB transformation and different from the bph and rdh pathways. Therefore, PCB transformation may involve several metabolic pathways, some involving ligninolytic enzymes, bph or rdh genes, and some still unknown, depending on the microbial species. In addition, current knowledge does not fully clarify the role of ligninolytic enzymes in PCB oxidation and dechlorination. Therefore, further studies focusing on purified ligninolytic enzymes are needed to clearly elucidate their role in PCB transformation.