Diverse Roles Research Articles

On the role of dysferlin in striated muscle: membrane repair, t-tubules and Ca2+ handling.

Dysferlin is a 237kDa membrane-associated protein characterised by multiple C2 domains with a diverse role in skeletal and cardiac muscle physiology. Mutations in DYSF are known to cause various types of human muscular dystrophies, known collectively as dysferlinopathies, with some patients developing cardiomyopathy. A myriad of in vitro membrane repair studies suggest that dysferlin plays an integral role in the membrane repair complex in skeletal muscle. In comparison, less is known about dysferlin in the heart, but mounting evidence suggests that dysferlin's role is similar in both muscle types. Recent findings have shown that dysferlin regulates Ca2+ handling in striated muscle via multiple mechanisms and that this becomes more important in conditions of stress. Maintenance of the transverse (t)-tubule network and the tight coordination of excitation-contraction coupling are essential for muscle contractility. Dysferlin regulates the maintenance and repair of t-tubules, and it is suspected that dysferlin regulates t-tubules and sarcolemmal repair through a similar mechanism. This review focuses on the emerging complexity of dysferlin's activity in striated muscle. Such insights will progress our understanding of the proteins and pathways that regulate basic heart and skeletal muscle function and help guide research into striated muscle pathology, especially that which arises due to dysferlin dysfunction.

The Multifaceted Role of Microbial Biosurfactants in Various Fields

This review paper aims to explore the multifaceted roles and applications of microbial surfactants, also known as biosurfactants. These amphiphilic compounds, synthesized by various microorganisms such as Acinetobacter sp., Bacillus sp., Candida antarctica, and Pseudomonas aeruginosa, exhibit both hydrophobic and hydrophilic properties. Through lowering surface tension and interfacial tension, biosurfactants facilitate fluid phase aggregation, imparting organisms with unique physiological and ecological advantages. The synthesis of biosurfactants in bacteria not only contributes to antimicrobial activity but also enhances substrate availability for cellular absorption, particularly in challenging environmental conditions. Categorized based on molecular weight and chemical composition, biosurfactants offer numerous benefits including biodegradability, reduced toxicity, and versatile applications in agriculture, detergent production, biopesticides, and microbial oil enhancement processes. This review synthesizes current knowledge on microbial surfactants, elucidating their diverse roles and promising applications across various industries.

The MCM2-7 Complex: Roles beyond DNA Unwinding

The MCM2-7 complex is a hexameric protein complex that serves as a DNA helicase. It unwinds the DNA double helix during DNA replication, thereby providing the single-stranded replication template. In recent years, it has become clear that the MCM2-7 complex has additional functions that extend well beyond its role in DNA replication. Through physical and functional interactions with different pathways, it impacts other nuclear events and activities, including folding of the genome, histone inheritance, chromosome segregation, DNA damage sensing and repair, and gene transcription. Collectively, the diverse roles of the MCM2-7 complex suggest it plays a critical role in maintaining genome integrity by integrating the regulation of DNA replication with other pathways in the nucleus.

Subthalamic stimulation modulates context-dependent effects of beta bursts during fine motor control

Increasing evidence suggests a considerable role of pre-movement beta bursts for motor control and its impairment in Parkinson’s disease. However, whether beta bursts occur during precise and prolonged movements and if they affect fine motor control remains unclear. To investigate the role of within-movement beta bursts for fine motor control, we here combine invasive electrophysiological recordings and clinical deep brain stimulation in the subthalamic nucleus in 19 patients with Parkinson’s disease performing a context-varying task that comprised template-guided and free spiral drawing. We determined beta bursts in narrow frequency bands around patient-specific peaks and assessed burst amplitude, duration, and their immediate impact on drawing speed. We reveal that beta bursts occur during the execution of drawing movements with reduced duration and amplitude in comparison to rest. Exclusively when drawing freely, they parallel reductions in acceleration. Deep brain stimulation increases the acceleration around beta bursts in addition to a general increase in drawing velocity and improvements of clinical function. These results provide evidence for a diverse and task-specific role of subthalamic beta bursts for fine motor control in Parkinson’s disease; suggesting that pathological beta bursts act in a context dependent manner, which can be targeted by clinical deep brain stimulation.

Tumor Stroma as a Therapeutic Target for Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis owing to its desmoplastic stroma. Therefore, therapeutic strategies targeting this tumor stroma should be developed. In this study, we describe the heterogeneity of cancer-associated fibroblasts (CAFs) and their diverse roles in the progression, immune evasion, and resistance to treatment of PDAC. We subclassified the spatial distribution and functional activity of CAFs to highlight their effects on prognosis and drug delivery. Extracellular matrix components such as collagen and hyaluronan are described for their roles in tumor behavior and treatment outcomes, implying their potential as therapeutic targets. We also discussed the roles of extracellular matrix (ECM) including matrix metalloproteinases and tissue inhibitors in PDAC progression. Finally, we explored the role of the adaptive and innate immune systems in shaping the PDAC microenvironment and potential therapeutic strategies, with a focus on immune cell subsets, cytokines, and immunosuppressive mechanisms. These insights provide a comprehensive understanding of PDAC and pave the way for the development of prognostic markers and therapeutic interventions.

Characterization of winged helix domain fusion endonucleases as N6-methyladenine-dependent type IV restriction systems

Winged helix (wH) domains, also termed winged helix-turn-helix (wHTH) domains, are widespread in all kingdoms of life and have diverse roles. In the context of DNA binding and DNA modification sensing, some eukaryotic wH domains are known as sensors of non-methylated CpG. In contrast, the prokaryotic wH domains in DpnI and HhiV4I act as sensors of adenine methylation in the 6mApT (N6-methyladenine, 6mA, or N6mA) context. DNA-binding modes and interactions with the probed dinucleotide are vastly different in the two cases. Here, we show that the role of the wH domain as a sensor of adenine methylation is widespread in prokaryotes. We present previously uncharacterized examples of PD-(D/E)XK—wH (FcyTI, Psp4BI), PUA—wH—HNH (HtuIII), wH—GIY-YIG (Ahi29725I, Apa233I), and PLD—wH (Aba4572I, CbaI) fusion endonucleases that sense adenine methylation in the Dam+ Gm6ATC sequence contexts. Representatives of the wH domain endonuclease fusion families with the exception of the PLD—wH family could be purified, and an in vitro preference for adenine methylation in the Dam context could be demonstrated. Like most other modification-dependent restriction endonucleases (MDREs, also called type IV restriction systems), the new fusion endonucleases except those in the PD-(D/E)XK—wH family cleave close to but outside the recognition sequence. Taken together, our data illustrate the widespread combinatorial use of prokaryotic wH domains as adenine methylation readers. Other potential 6mA sensors in modified DNA are also discussed.

Multiple roles of brassinosteroid signaling in vascular development.

Brassinosteroids (BRs) are plant steroid hormones that control growth and stress responses. In the context of development, BRs play diverse roles in controlling cell differentiation and tissue patterning. The vascular system, which is essential for transporting water and nutrients throughout the plant body, initially establishes a tissue pattern during primary development and then dramatically increases the number of vascular cells during secondary development. This complex developmental process is properly regulated by a network consisting of various hormonal signalling pathways. Genetic studies have revealed that mutants defective in BR biosynthesis or the BR signalling cascade exhibit a multifaceted vascular development phenotype. Furthermore, BR crosstalk with other plant hormones, including peptide hormones, coordinately regulates vascular development. Recently, the involvement of BR in vascular development, especially in xylem differentiation, has also been suggested in plant species other than the model plant Arabidopsis thaliana. In this review, we briefly summarize the recent findings on the roles of BR in primary and secondary vascular development in Arabidopsis and other species.

Miro GTPases at the Crossroads of Cytoskeletal Dynamics and Mitochondrial Trafficking.

Miro GTPases are key components in the machinery responsible for transporting mitochondria and peroxisomes along microtubules, and also play important roles in regulating calcium homeostasis and organizing contact sites between mitochondria and the endoplasmic reticulum. Moreover, Miro GTPases have been shown to interact with proteins that actively regulate cytoskeletal organization and dynamics, suggesting that these GTPases participate in organizing cytoskeletal functions and organelle transport. Derailed mitochondrial transport is associated with neuropathological conditions such as Parkinson's and Alzheimer's diseases. This review explores our recent understanding of the diverse roles of Miro GTPases under cytoskeletal control, both under normal conditions and during the course of human diseases such as neuropathological disorders.

Single-Step Low-Temperature Synthesis of Carbon Dots for Advanced Multiparametric Bioimaging Probe Applications.

Carbon dots (CDs) have recently emerged in biomedical and agricultural domains, mainly for their probe applications in developing efficient sensors. However, the existing high-temperature approaches limit the industrial level scaling up to further translate them into different products by mass-scale fabrication of CDs. To address this, we have attempted to lower the synthesis temperature to 140 °C and synthesized different CDs using different organic acids and their combinations in a one-step approach (quantum yield 3.6% to 16.5%; average size 3 to 5 nm). Further, sensing applications of CDs have been explored in three different biological models, mainly Danio rerio (zebrafish) embryos, bacterial strains, and the Lactuca sativa (lettuce) plant. The 72 h exposure of D. rerio embryos to 0.5 and 1 mg/mL concentrations of CDs exhibited significant uptake without mortality, a 100% hatching rate, and nonsignificant alterations in heart rate. Bacterial bioimaging experiments revealed CD compatibility with Gram-positive (Bacillus subtilis) and Gram-negative (Serratia marcescens) strains without bactericidal effects. Furthermore, CDs demonstrated effective conduction and fluorescence within the vascular system of lettuce plants, indicating their potential as in vivo probes for plant tissues. The single-step low-temperature CD synthesis approach with efficient structural and optical properties enables the process as industrially viable to up-scale the technology readiness level. The bioimaging of CDs in different biological models indicates the possibility of developing a CD probe for diverse biosensing roles in diseases, metabolism, microbial contamination sensing, and more.

Cryo-EM structures of pannexin 1 and 3 reveal differences among pannexin isoforms.

Pannexins are single-membrane large-pore channels that release ions and ATP upon activation. Three isoforms of pannexins 1, 2, and 3, perform diverse cellular roles and differ in their pore lining residues. In this study, we report the cryo-EM structure of pannexin 3 at 3.9 Å and analyze its structural differences with pannexin isoforms 1 and 2. The pannexin 3 vestibule has two distinct chambers and a wider pore radius in comparison to pannexins 1 and 2. We further report two cryo-EM structures of pannexin 1, with pore substitutions W74R/R75D that mimic the pore lining residues of pannexin 2 and a germline mutant of pannexin 1, R217H at resolutions of 3.2 Å and 3.9 Å, respectively. Substitution of cationic residues in the vestibule of pannexin 1 results in reduced ATP interaction propensities to the channel. The germline mutant R217H in transmembrane helix 3 (TM3), leads to a partially constricted pore, reduced ATP interaction and weakened voltage sensitivity. The study compares the three pannexin isoform structures, the effects of substitutions of pore and vestibule-lining residues and allosteric effects of a pathological substitution on channel structure and function thereby enhancing our understanding of this vital group of ATP-release channels.

Potential Therapeutic Targets to Modulate the Endocannabinoid System in Alzheimer's Disease.

Alzheimer's disease (AD), the most common neurodegenerative disease (NDD), is characterized by chronic neuronal cell death through progressive loss of cognitive function. Amyloid beta (Aβ) deposition, neuroinflammation, oxidative stress, and hyperphosphorylated tau proteins are considered the hallmarks of AD pathology. Different therapeutic approaches approved by the Food and Drug Administration can only target a single altered pathway instead of various mechanisms that are involved in AD pathology, resulting in limited symptomatic relief and almost no effect in slowing down the disease progression. Growing evidence on modulating the components of the endocannabinoid system (ECS) proclaimed their neuroprotective effects by reducing neurochemical alterations and preventing cellular dysfunction. Recent studies on AD mouse models have reported that the inhibitors of the fatty acid amide hydrolase (FAAH) and monoacylglycerol (MAGL), hydrolytic enzymes for N-arachidonoyl ethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), respectively, might be promising candidates as therapeutical intervention. The FAAH and MAGL inhibitors alone or in combination seem to produce neuroprotection by reversing cognitive deficits along with Aβ-induced neuroinflammation, oxidative responses, and neuronal death, delaying AD progression. Their exact signaling mechanisms need to be elucidated for understanding the brain intrinsic repair mechanism. The aim of this review was to shed light on physiology and pathophysiology of AD and to summarize the experimental data on neuroprotective roles of FAAH and MAGL inhibitors. In this review, we have also included CB1R and CB2R modulators with their diverse roles to modulate ECS mediated responses such as anti-nociceptive, anxiolytic, and anti-inflammatory actions in AD. Future research would provide the directions in understanding the molecular mechanisms and development of new therapeutic interventions for the treatment of AD.

The molecular principles underlying diverse functions of the SLC26 family of proteins

Mammalian SLC26 proteins are membrane-based anion transporters that belong to the large SLC26/SulP family, and many of their variants are associated with hereditary diseases. Recent structural studies revealed a strikingly similar homodimeric molecular architecture for several SLC26 members, implying a shared molecular principle. Now a new question emerges as to how these structurally similar proteins execute diverse physiological functions. In this study we sought to identify the common vs. distinct molecular mechanism among the SLC26 proteins using both naturally occurring and artificial missense changes introduced to SLC26A4, SLC26A5, and SLC26A9. We found: (i) the basic residue at the anion binding site is essential for both anion antiport of SLC26A4 and motor functions of SLC26A5, and its conversion to a nonpolar residue is crucial but not sufficient for the fast uncoupled anion transport in SLC26A9; (ii) the conserved polar residues in the N- and C-terminal cytosolic domains are likely involved in dynamic hydrogen-bonding networks and are essential for anion antiport of SLC26A4 but not for motor (SLC26A5) and uncoupled anion transport (SLC26A9) functions; (iii) the hydrophobic interaction between each protomer’s last transmembrane helices, TM14, is not of functional significance in SLC26A9 but crucial for the functions of SLC26A4 and SLC26A5, likely contributing to optimally orient the axis of the relative movements of the core domain with respect to the gate domains within the cell membrane. These findings advance our understanding of the molecular mechanisms underlying the diverse physiological roles of the SLC26 family of proteins.

Transmembrane proteins with unknown function (TMEMs) as ion channels: electrophysiological properties, structure, and pathophysiological roles.

A transmembrane (TMEM) protein with an unknown function is a type of membrane-spanning protein expressed in the plasma membrane or the membranes of intracellular organelles. Recently, several TMEM proteins have been identified as functional ion channels. The structures and functions of these proteins have been extensively studied over the last two decades, starting with TMEM16A (ANO1). In this review, we provide a summary of the electrophysiological properties of known TMEM proteins that function as ion channels, such as TMEM175 (KEL), TMEM206 (PAC), TMEM38 (TRIC), TMEM87A (GolpHCat), TMEM120A (TACAN), TMEM63 (OSCA), TMEM150C (Tentonin3), and TMEM43 (Gapjinc). Additionally, we examine the unique structural features of these channels compared to those of other well-known ion channels. Furthermore, we discuss the diverse physiological roles of these proteins in lysosomal/endosomal/Golgi pH regulation, intracellular Ca2+ regulation, spatial memory, cell migration, adipocyte differentiation, and mechanical pain, as well as their pathophysiological roles in Parkinson's disease, cancer, osteogenesis imperfecta, infantile hypomyelination, cardiomyopathy, and auditory neuropathy spectrum disorder. This review highlights the potential for the discovery of novel ion channels within the TMEM protein family and the development of new therapeutic targets for related channelopathies.

In Vitro Assessment of Cardiac Fibroblast Activation at Physiologic Stiffness.

Cardiac fibroblasts (CF) are an essential cell type in cardiac physiology, playing diverse roles in maintaining structural integrity, extracellular matrix (ECM) synthesis, and tissue repair. Under normal conditions, these cells reside in the interstitium in a quiescent state poised to sense and respond to injury by synthesizing and secreting collagen, vimentin, hyaluronan, and other ECM components. In response to mechanical and chemical stimuli, these "resident" fibroblasts can undergo a transformation through a continuum of activation states into what is commonly known as a "myofibroblast," in a process critical for injury response. Despite progress in understanding the contribution of fibroblasts to cardiac health and disease, much remains unknown about the signaling mediating this activation, in part owing to technical challenges in evaluating CF function and activation status in vitro. Given their role in monitoring the ECM, CFs are acutely sensitive to stiffness and pressure. High basal activation of isolated CFs is common due to the super-physiologic stiffness of traditional cell culture substrates, making assays dependent on quiescent cells challenging. To overcome this problem, cell culture parameters must be tightly controlled, and the use of dishes coated with biocompatible reduced-stiffness substrates, such as 8-kPa polydimethylsiloxane (PDMS), has shown promise in reducing basal activation of fibroblasts. Here, we describe cell culture protocol for maintaining CF quiescence in vitro to enable a dynamic range for the assessment of activation status in response to fibrogenic stimuli using PDMS-coated coverslips. Our protocol provides a cost-effective tool to study fibroblast signaling and activity, allowing researchers to better understand the underlying mechanisms involved in cardiac fibrosis. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Generation of 8-kPa polydimethylsiloxane (PDMS)/gelatin-coated coverslips for cardiac fibroblast cell culture Basic Protocol 2: Isolation of adult cardiac fibroblasts and plating onto PDMS coverslips Basic Protocol 3: Assessment of cardiac fibroblast activation by α smooth muscle actin (αSMA) immunocytochemistry.

Economy as a Social Institution in the Tribal Society: A Scale to 
Measure the Perceived 
Role Performance of Economic Institutions

Economic institutions play a pivotal role in achieving sustainable development goals (SDGs) among tribal communities. Despite improved access to economic institutions and their services through government and private interventions, a majority of tribals in India continue to face extreme poverty. This study focuses on developing and validating a scale to measure the perceived role performance of economic institutions in tribal societies. Employing Likert’s summated rating scale construction technique, a scale comprising 10 statements related to economic institutions’ roles has been developed. Standardisation through reliability and validity measures, as well as confirmatory factor analysis (CFA), confirms the robustness of the scale. Administered to 270 tribal respondents in Salem, Tiruvannamalai and Viluppuram Districts of Tamil Nadu, our findings unveil diverse roles and challenges faced by economic institutions in tribal societies. The study reveals a nuanced perception among tribal respondents, with a majority indicating a medium to high level of perception. However, a notable proportion demonstrates a low perception level, highlighting areas of concern. The study underscores the importance of targeted strategies to boost financial inclusion and empower tribal communities. It also provides policy recommendations for addressing challenges and fostering sustainable development within tribal societies.

Diversified Roles of Insects in Essential Ecosystem through Pollination for Achieving Sustainable Goals

Pollination is an ecological process that involves the transfer of pollen from the male to the female part of the flower with the help of various abiotic and biotic pollen dispersal agents and is an essential pre-requisite for fertilization and fruit/seed dispersal. Insects constitute one of the primary groups of pollinating agents, as the association between insects and flowers is well established. As flowers radiated so did the mouthparts of the insects exploiting them. Various insect groups, which are of prime significance in the pollination of agricultural and horticultural crops mainly belong to the orders Hymenoptera (bees, ants and wasps), Diptera (flies, mosquitoes, fungus gnats, midges), Coleoptera (beetles and weevils), Lepidoptera (moths and butterflies), Thysanoptera (thrips), Hemiptera (bugs) and Neuropteran (lace wing flies). This work is mainly based on detailed and through observations/study made from various cash crops viz., Brassica nigra, Coriandrum sativum, Tagetes erecta and Helianthus annuus from North 24 Parganas of South Bengal region.

Navigating The Media Maze: Perceived Work-Life Balance Among Women Journalists

Maintaining a balance between work and personal life is a dream for anyone with multiple roles to play in their daily routines. Women journalists are no exception, and their work requires them to possess a broad range of knowledge and skills to deliver accurate and timely information to the public. Despite having multiple responsibilities in their personal lives, women journalists have embraced this challenge. However, issues such as long working hours, inflexible work schedules, excessive workloads, the dual responsibility of childcare, workplace discrimination, lack of support from supervisors and family, and the spillover of work into family life can make it challenging to maintain a healthy work-life balance. This study aims to explore the perception of women journalists towards work-life balance. The Spillover and Role Theories offer insights into the challenges faced by women journalists in balancing their personal and professional lives. The study conducted in-depth interviews with 16 journalists, including single and married women, working in various environments at the media headquarters and state bureau. The perception towards work-life balance was categorised into three themes: work and family environment, mental well-being, and personality traits. This article highlights the difficulties that women journalists face in managing their diverse roles during the convergence period of the media industry and emphasises the need to address work-life balance concerns in the Malaysian media sector. Keywords: Women, journalists, work-life balance, Spillover Theory, Role Theory.

A Torreya grandis ARF transcription factor TgARF15 enhances drought stress tolerance

Auxin response factors (ARFs) are central components of the growth hormone signaling pathway, responsible for regulating the expression of corresponding growth hormone genes. To date, ARFs have demonstrated diverse functions and roles, with identification in various species, including Arabidopsis thaliana and Oryza sativa. However, their specific functions in Torreya grandis, an evergreen and economically significant tree species primarily found in China, remain elusive. In this study, we identified 15 ARF genes (TgARF1-TgARF15) in T. grandis and observed their distribution across 11 chromosomes. We analyzed the expression patterns of TgARFs in various tissues and their responses to drought stress. Our findings revealed a significant reduction of TgARF15 expression in leaf tissues under drought conditions, implying a potential key role for TgARF15 in drought stress resistance. Additionally, we determined that TgARF15 was localized in the nucleus. Furthermore, overexpression of TgARF15 in Arabidopsis resulted in enhanced drought resistance, attributed to increased enzymatic activity of antioxidant enzymes. Moreover, we identified a direct interaction between TgARF15 and TgIAA1, both in vivo and in yeast. These findings will facilitate future efforts in establishing a foundation for in-depth exploration of their specific mechanisms related to drought resistance, and addressing challenges in the T. grandis industry.

Different but Synergistic Effects of Union and Manager Leadership on Member Job Satisfaction

Existing research has tended to overlook the diverse roles of union leadership in contributing to member attitudes. Drawing on the social information processing theory, this study examines how union leaders’ (shop stewards) service-oriented leadership relates to member job satisfaction. To clarify the mechanism underlying this relationship, this study focuses on union instrumentality as a mediator. The research also examines managers’ ethical leadership as a conditional factor in the relationship between union leaders’ service-oriented leadership and member job satisfaction through union instrumentality. To test our hypothesis, this study analyzed the results of a survey of 603 respondents from two branches of the Korean Metal Workers’ Union. The findings of this study indicate that union instrumentality is the link between service-oriented union leadership and member job satisfaction. Additionally, the strength of the mediated relationship between the aforementioned factors through union instrumentality is contingent on managerial ethical leadership. This study contributes to an integrated understanding of the way in which service-oriented union stewards and ethical managers influence member job satisfaction through their leadership.

From Harems to Thrones: The Ascendancy of Women in Mughal Royalty

This Article delves into the diverse roles of women in Mughal Civilization, highlighting their significant contributions in the cultural, political, and administrative arenas. Using historical documents, Mughal-era literature, and academic articles, this study examines not just how women in Central Asian culture were educated, but also the Mughal dynasty's socio-cultural effect. They also have a significant impact on the landscape. These results show Mughal women's important roles in government and cultural dissemination, contradicting traditional narratives and demonstrating their frequently underappreciated importance in history. The major goal of this article is to illustrate the status of women in the royal family during the Mughal era in India and to demonstrate how crucial Mughal women played in both day-to-day state administration and long-term political and economic activities of the state. Planning This article will also include a list of cultural domains that Mughal women helped to develop, cultivate, and promote.