Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Big steps toward understanding dynein.

ABSTRACT: Dynein is a microtubule-based molecular motor that is involved in various biological functions, such as axonal transport, mitosis, and cilia/flagella movement. Although dynein was discovered 50 years ago, the progress of dynein research has been slow due to its large size and flexible structure. Recent progress in understanding the force-generating mechanism of dynein using x-ray crystallography, cryo-electron microscopy, and single molecule studies has provided key insight into the structure and mechanism of action of this complex motor protein.

SUBMITTER: Kikkawa M

PROVIDER: S-EPMC3704981 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Big steps toward understanding dynein.

Kikkawa Masahide M

The Journal of cell biology 20130701 1

Dynein is a microtubule-based molecular motor that is involved in various biological functions, such as axonal transport, mitosis, and cilia/flagella movement. Although dynein was discovered 50 years ago, the progress of dynein research has been slow due to its large size and flexible structure. Recent progress in understanding the force-generating mechanism of dynein using x-ray crystallography, cryo-electron microscopy, and single molecule studies has provided key insight into the structure an ...[more]

PMID: 23836927

Similar Datasets

Crossing Boundaries: Steps Toward Measuring Undergraduates' Interdisciplinary Science Understanding.

Project description:A desired outcome of education reform efforts is for undergraduates to effectively integrate knowledge across disciplines in order to evaluate and address real-world issues. Yet there are few assessments designed to measure if and how students think interdisciplinarily. Here, a sample of science faculty were surveyed to understand how they currently assess students' interdisciplinary science understanding. Results indicate that individual writing-intensive activities are the most frequently used assessment type (69%). To understand how writing assignments can accurately assess students' ability to think interdisciplinarily, we used a preexisting rubric, designed to measure social science students' interdisciplinary understanding, to assess writing assignments from 71 undergraduate science students. Semistructured interviews were conducted with 25 of those students to explore similarities and differences between assignment scores and verbal understanding of interdisciplinary science. Results suggest that certain constructs of the instrument did not fully capture this competency for our population, but instead, an interdisciplinary framework may be a better model to guide assessment development of interdisciplinary science. These data suggest that a new instrument designed through the lens of this model could more accurately characterize interdisciplinary science understanding for undergraduate students.

| S-EPMC8697648 | biostudies-literature

Specificity of cytoplasmic dynein subunits in discrete membrane-trafficking steps.

Project description:The cytoplasmic dynein motor complex is known to exist in multiple forms, but few specific functions have been assigned to individual subunits. A key limitation in the analysis of dynein in intact mammalian cells has been the reliance on gross perturbation of dynein function, e.g., inhibitory antibodies, depolymerization of the entire microtubule network, or the use of expression of dominant negative proteins that inhibit dynein indirectly. Here, we have used RNAi and automated image analysis to define roles for dynein subunits in distinct membrane-trafficking processes. Depletion of a specific subset of dynein subunits, notably LIC1 (DYNC1LI1) but not LIC2 (DYNC1LI2), recapitulates a direct block of ER export, revealing that dynein is required to maintain the steady-state composition of the Golgi, through ongoing ER-to-Golgi transport. Suppression of LIC2 but not of LIC1 results in a defect in recycling endosome distribution and cytokinesis. Biochemical analyses also define the role of each subunit in stabilization of the dynein complex; notably, suppression of DHC1 or IC2 results in concomitant loss of Tctex1. Our data demonstrate that LIC1 and LIC2 define distinct dynein complexes that function at the Golgi versus recycling endosomes, respectively, suggesting that functional populations of dynein mediate discrete intracellular trafficking pathways.

| S-EPMC2695796 | biostudies-literature

Three more steps toward better science.

Project description:Science has striven to do better since its inception and has given us good philosophies, methodologies and statistical tools that, in their own way, do reasonably well for purpose. Unfortunately, progress has also been marred by historical clashes among perspectives, typically between frequentists and Bayesians, leading to troubles such as the current reproducibility crises. Here I wish to propose that science could do better with more resilient structures, more useful methodological tutorials, and clearer signaling regarding how much we can trust what it produces.

| S-EPMC6468710 | biostudies-literature

Steps toward Cell Therapy for Cystic Fibrosis.

Project description: Not available

| S-EPMC7462341 | biostudies-literature

Pharmacogenomics in osteoporosis: Steps toward personalized medicine.

Project description:Osteoporosis is a complicated and preventable disease with major morbidity complications that affects millions of people. In the last 15 years, there have been numerous studies and research in the new fields of pharmacogenetics and pharmacogenomics related to osteoporosis. Numerous "candidate genes" have been identified and have been found to be associated with osteoporosis as well as the treatment of osteoporosis. Many studies have found conflicting results on different polymorphisms and whether or not they are related to bone mineral density and osteoporosis. There is a need for larger and better designed pharmacogenomic studies related to osteoporosis incorporating a greater variety of candidate genes. The evaluation of osteoporosis and fracture risk is moving from a risk stratification approach to a more individualized approach, in which an individual's absolute risk of fracture is evaluable as a constellation of the individual's environmental exposure and genetic makeup. Therefore, the identification of gene variants associated with osteoporosis phenotypes or response to therapy might help individualize the prognosis, treatment, and prevention of fracture. This review focuses on major candidate genes and what needs to be done to take the genetics of osteoporosis and incorporate them into the pharmacogenomics of the management of osteoporosis.

| S-EPMC3513203 | biostudies-literature

Steps Toward an Integrative Clinical Systems Psychology.

Project description:Clinical fields of the "sciences of the mind" (psychotherapy, psychiatry, etc.) lack integrative conceptual frameworks that have explanatory power. Mainly descriptive-classificatory taxonomies like DSM dominate the field. New taxonomies such as Research Domain Criteria (RDoC) aim to collect scientific knowledge regarding "systems" for "processes" of the brain. These terms have a supradisciplinary" meaning if they are considered in context of Systems Science. This field emerges as a platform of theories like general systems theory, catastrophe theory, synergetics, chaos theory, etc. It provides a lot of abstract concepts, constructs, methods and models. We assume that these tools also enable theoretical integration in the diversified field of clinical practice in the sciences of the mind. Additionally, systems thinking in clinical psychology improves conceptual links to currently network-oriented neurobiology. However, clear definitions of systemic terms are necessary to emerge from their mainly metaphorical use. Here we revise mainly terms like "structure", "process" and "dynamics" as they are used already in psychology, psychoanalysis, psychopathology and psychiatry in an ill-defined way. For instance, affective-cognitive structures like "life space" or "object representations" can be seen as products of mental processing. These structures, in turn, modulate dynamics of mental processes. Additionally, we suggest a coupled network concept of emotions and motivations as the main subsystem that modulates mental dynamics that results in a qualitative systemic model of the mind. Finally, we assume that a revisited systemic approach could improve interdisciplinary understanding of the mental.

| S-EPMC6157403 | biostudies-other

Novel biomarkers to assess in utero effects of maternal opioid use: First steps toward understanding short- and long-term neurodevelopmental sequelae.

Project description:Maternal opioid use disorder is common, resulting in significant neonatal morbidity and cost. Currently, it is not possible to predict which opioid-exposed newborns will require pharmacotherapy for neonatal abstinence syndrome. Further, little is known regarding the effects of maternal opioid use disorder on the developing human brain. We hypothesized that novel methodologies utilizing fetal central nervous system-derived extracellular vesicles isolated from maternal blood can address these gaps in knowledge. Plasma from opioid users and controls between 9 and 21 weeks was precipitated and extracellular vesicles were isolated. Mu opioid and cannabinoid receptor levels were quantified. Label-free proteomics studies and unbiased small RNA next generation sequencing was performed in paired fetal brain tissue. Maternal opioid use disorder increased mu opioid receptor protein levels in extracellular vesicles independent of opioid equivalent dose. Moreover, cannabinoid receptor levels in extracellular vesicles were upregulated with opioid exposure indicating cross talk with endocannabinoids. Maternal opioid use disorder was associated with significant changes in extracellular vesicle protein cargo and fetal brain micro RNA expression, especially in male fetuses. Many of the altered cargo molecules and micro RNAs identified are associated with adverse clinical neurodevelopmental outcomes. Our data suggest that assays relying on extracellular vesicles isolated from maternal blood extracellular vesicles may provide information regarding fetal response to opioids in the setting of maternal opioid use disorder. Prospective clinical studies are needed to evaluate the association between extracellular vesicle biomarkers, risk of neonatal abstinence syndrome and neurodevelopmental outcomes.

| S-EPMC7074845 | biostudies-literature

First Steps toward Personalized Therapies for ABCA3 Deficiency.

Project description: Not available

| S-EPMC8990116 | biostudies-literature

Toward understanding Machado-Joseph disease.

Project description:Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is the most common inherited spinocerebellar ataxia and one of many polyglutamine neurodegenerative diseases. In MJD, a CAG repeat expansion encodes an abnormally long polyglutamine (polyQ) tract in the disease protein, ATXN3. Here we review MJD, focusing primarily on the function and dysfunction of ATXN3 and on advances toward potential therapies. ATXN3 is a deubiquitinating enzyme (DUB) whose highly specialized properties suggest that it participates in ubiquitin-dependent proteostasis. By virtue of its interactions with VCP, various ubiquitin ligases and other ubiquitin-linked proteins, ATXN3 may help regulate the stability or activity of many proteins in diverse cellular pathways implicated in proteotoxic stress response, aging, and cell differentiation. Expansion of the polyQ tract in ATXN3 is thought to promote an altered conformation in the protein, leading to changes in interactions with native partners and to the formation of insoluble aggregates. The development of a wide range of cellular and animal models of MJD has been crucial to the emerging understanding of ATXN3 dysfunction upon polyQ expansion. Despite many advances, however, the principal molecular mechanisms by which mutant ATXN3 elicits neurotoxicity remain elusive. In a chronic degenerative disease like MJD, it is conceivable that mutant ATXN3 triggers multiple, interconnected pathogenic cascades that precipitate cellular dysfunction and eventual cell death. A better understanding of these complex molecular mechanisms will be important as scientists and clinicians begin to focus on developing effective therapies for this incurable, fatal disorder.

| S-EPMC3306771 | biostudies-literature

A path toward understanding neurodegeneration.

Project description: Not available

| S-EPMC6028188 | biostudies-literature