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1.
Gastroenterology ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39181168

RESUMEN

BACKGROUND & AIMS: Chronic hepatitis C-related decompensated cirrhosis is associated with lower sustained virologic response (SVR)-12 rates and variable regression of disease severity after direct-acting antiviral agents. We assessed rates of SVR-12, recompensation (Baveno VII criteria), and survival in such patients. METHODS: Between July 2018 and July 2023, patients with decompensated chronic hepatitis C-related cirrhosis after direct-acting antiviral agents treatment were evaluated for SVR-12 and then had 6-monthly follow-up. RESULTS: Of 6516 patients with cirrhosis, 1152 with decompensated cirrhosis (age 53.2 ± 11.5 years; 63% men; Model for End-stage Liver Disease-Sodium [MELD-Na]: 16.5 ± 4.6; 87% genotype 3) were enrolled. SVR-12 was 81.8% after 1 course; ultimately SVR was 90.8% after additional treatment. Decompensation events included ascites (1098; 95.3%), hepatic encephalopathy (191; 16.6%), and variceal bleeding (284; 24.7%). Ascites resolved in 86% (diuretic withdrawal achieved in 24% patients). Recompensation occurred in 284 (24.7%) at a median time of 16.5 (interquartile range, 14.5-20.5) months. On multivariable Cox proportional hazards analysis, low bilirubin (aHR, 0.6; 95% confidence interval [CI], 0.5-0.8; P < 0.001), INR (aHR, 0.2; 95% CI, 0.1-0.3; P < 0.001), absence of large esophageal varices (aHR, 0.4; 95% CI, 0.2-0.9; P = 0.048), or gastric varices (aHR, 0.5; 95% CI, 0.3-0.7; P = 0.022) predicted recompensation. Portal hypertension progressed in 158 (13.7%) patients, with rebleed in 4%. Prior decompensation with variceal bleeding (aHR, 1.6; 95% CI, 1.2-2.8; P = 0.042), and presence of large varices (aHR, 2.9; 95% CI, 1.3-6.5; P < 0.001) were associated with portal hypertension progression. Further decompensation was seen in 221 (19%); 145 patients died and 6 underwent liver transplantation. A decrease in MELDNa of ≥3 was seen in 409 (35.5%) and a final MELDNa score of <10 was seen in 335 (29%), but 2.9% developed hepatocellular carcinoma despite SVR-12. CONCLUSIONS: SVR-12 in hepatitis C virus-related decompensated cirrhosis in a predominant genotype 3 population led to recompensation in 24.7% of patients over a follow-up of 4 years in a public health setting. Despite SVR-12, new hepatic decompensation evolved in 19% and hepatocellular carcinoma developed in 2.9% of patients. (ClinicalTrials.gov, Number: NCT03488485).

2.
Proc Natl Acad Sci U S A ; 119(32): e2204453119, 2022 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-35914159

RESUMEN

Changes in the geometry and topology of self-assembled membranes underlie diverse processes across cellular biology and engineering. Similar to lipid bilayers, monolayer colloidal membranes have in-plane fluid-like dynamics and out-of-plane bending elasticity. Their open edges and micrometer-length scale provide a tractable system to study the equilibrium energetics and dynamic pathways of membrane assembly and reconfiguration. Here, we find that doping colloidal membranes with short miscible rods transforms disk-shaped membranes into saddle-shaped surfaces with complex edge structures. The saddle-shaped membranes are well approximated by Enneper's minimal surfaces. Theoretical modeling demonstrates that their formation is driven by increasing the positive Gaussian modulus, which in turn, is controlled by the fraction of short rods. Further coalescence of saddle-shaped surfaces leads to diverse topologically distinct structures, including shapes similar to catenoids, trinoids, four-noids, and higher-order structures. At long timescales, we observe the formation of a system-spanning, sponge-like phase. The unique features of colloidal membranes reveal the topological transformations that accompany coalescence pathways in real time. We enhance the functionality of these membranes by making their shape responsive to external stimuli. Our results demonstrate a pathway toward control of thin elastic sheets' shape and topology-a pathway driven by the emergent elasticity induced by compositional heterogeneity.


Asunto(s)
Membrana Dobles de Lípidos , Elasticidad , Membrana Dobles de Lípidos/química , Membranas/metabolismo , Distribución Normal
3.
Biophys J ; 123(10): 1173-1183, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38515300

RESUMEN

We present a method to differentiate organisms solely by their motion based on the generalized Langevin equation (GLE) and use it to distinguish two different swimming modes of strongly confined unicellular microalgae Chlamydomonas reinhardtii. The GLE is a general model for active or passive motion of organisms and particles that can be derived from a time-dependent general many-body Hamiltonian and in particular includes non-Markovian effects (i.e., the trajectory memory of its past). We extract all GLE parameters from individual cell trajectories and perform an unbiased cluster analysis to group them into different classes. For the specific cell population employed in the experiments, the GLE-based assignment into the two different swimming modes works perfectly, as checked by control experiments. The classification and sorting of single cells and organisms is important in different areas; our method, which is based on motion trajectories, offers wide-ranging applications in biology and medicine.


Asunto(s)
Chlamydomonas reinhardtii , Chlamydomonas reinhardtii/citología , Chlamydomonas reinhardtii/fisiología , Movimiento , Modelos Biológicos , Análisis de la Célula Individual , Análisis por Conglomerados , Movimiento (Física)
4.
Proteomics ; 24(11): e2300391, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38556629

RESUMEN

Arterial thrombosis manifesting as heart attack and stroke is the leading cause of death worldwide. Platelets are central mediators of thrombosis that can be activated through multiple activation pathways. Platelet-derived extracellular vesicles (pEVs), also known as platelet-derived microparticles, are granular mixtures of membrane structures produced by platelets in response to various activating stimuli. Initial studies have attracted interest on how platelet agonists influence the composition of the pEV proteome. In the current study, we used physiological platelet agonists of varying potencies which reflect the microenvironments that platelets experience during thrombus formation: adenosine diphosphate, collagen, thrombin as well as a combination of thrombin/collagen to induce platelet activation and pEV generation. Proteomic profiling revealed that pEVs have an agonist-dependent altered proteome in comparison to their cells of origin, activated platelets. Furthermore, we found that various protein classes including those related to coagulation and complement (prothrombin, antithrombin, and plasminogen) and platelet activation (fibrinogen) are attributed to platelet EVs following agonist stimulation. This agonist-dependent altered proteome suggests that protein packaging is an active process that appears to occur without de novo protein synthesis. This study provides new information on the influence of physiological agonist stimuli on the biogenesis and proteome landscape of pEVs.


Asunto(s)
Plaquetas , Vesículas Extracelulares , Activación Plaquetaria , Proteoma , Proteómica , Trombina , Plaquetas/metabolismo , Plaquetas/efectos de los fármacos , Humanos , Proteoma/metabolismo , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/efectos de los fármacos , Activación Plaquetaria/efectos de los fármacos , Trombina/farmacología , Trombina/metabolismo , Proteómica/métodos , Adenosina Difosfato/farmacología , Adenosina Difosfato/metabolismo , Colágeno/metabolismo
5.
Biochem Biophys Res Commun ; 734: 150627, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39236588

RESUMEN

Cell attachment to the extracellular matrix significantly impacts the integrity of tissues and human health. The integrin α5ß1 is a heterodimer of α5 and ß1 subunits and has been identified as a crucial modulator in several human carcinomas. Integrin α5ß1 significantly regulates cell proliferation, angiogenesis, inflammation, tumor metastasis, and invasion. This regulatory role of integrin α5ß1 in tumor metastasis makes it an appealing target for cancer therapy. The majority of the drugs targeting integrin α5ß1 are limited only to clinical trials. In our study, we have performed 94287 compounds screening to determine potential drugs against α5ß1 integrin. We have used ATN-161 as a reference and employed combined bioinformatic methodologies, including molecular modelling, virtual screening, MM-GBSA, cell-line cytotoxicity prediction, ADMET, Density Functional Theory (DFT), Non-covalent Interactions (NCI) and molecular simulation, to identify putative integrin α5ß1 inhibitors. We found Taxifolin, PD133053, and Acebutolol that possess inhibitory activity against α5ß1 integrin and could act as effective drug for the cancer treatment. Taxifolin, PD133053, and Acebutolol exhibited excellent binding to the druggable pocket of integrin α5ß1, and also maintained a unique binding mechanism with extra hydrophobic contacts at molecular level. Overall, our study gives new pharmacological candidates that may act as a potential drug against integrin α5ß1.

6.
Soft Matter ; 19(44): 8493-8506, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37723876

RESUMEN

We study the mechanics of standing columns formed during the repose of flexible granular chains. It is one of the many intriguing behaviours exhibited by granular materials when links capable of transmitting tension exist between particles. We develop and calibrate a discrete element method contact model to simulate the mechanics of the macroscopic flexible granular chains and conduct simulations of the angle of repose experiments of these chains by extracting a chain-filled cylinder and allowing the material to flow out under gravity and repose. We evaluate various micro-mechanical, topological and macroscopic parameters to elucidate the mechanics of the repose behaviour of chain ensembles. It is the ability of the links connecting the individual particles to transmit tensile forces along the chain backbone that provides lateral stability to the column, enabling them to stand. In particular, the contact force rearrangement inside the columns generates a self-confining radial stress near the base of the columns, which provides an important stabilizing stress.

7.
J Vector Borne Dis ; 60(1): 94-100, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37026225

RESUMEN

BACKGROUND & OBJECTIVES: The main aim of this research is to provide literature on the Ocimum plant, and to know the significance of the Ocimum species carried out by pharmacognostic study and experimental design for GC-MS. Ocimum genus are very important for their therapeutic potential among the most important aromatic herbs. METHODS: Extreme attention has been put on literature reports in which the utilization of tulsi and their pharmacognostic study has been done by performing morphological and microscopic leaf experimental design and by using essential oil through the GC-MS instrumentation method. RESULTS: The utilization of these characteristics would be important for the drug discovery scientist to develop a specific formulation of the crude drug, which will be a magical therapeutic agent in the future, with many advantages. GC-MS chromatogram of Ocimum sanctum, Ocimum canum, and Ocimum gratissimum oil showed major peaks and has been identified after comparison of the mass spectra with the NIST library, indicating the presence of three phytocomponents. From the results, the GC-MS study suggested that anethole which is well reported antimicrobial compound is more in O. canum (2.66%) in comparison to O. sanctum (1,28%) but absent in O. gratissimum. The results indicated that the antimicrobial activity is more in O. canum due to the presence ofa high amount of anethole in comparison to O. gratissimum and O. sanctum. INTERPRETATION & CONCLUSION: The result revealed that O. canum has a microscopic character that can be identified by the characteristic GC MS analysis of extracts to distinguish between different species of the ocimum plant.


Asunto(s)
Ocimum , Aceites Volátiles , Aceites Volátiles/análisis , Ocimum sanctum , Cromatografía de Gases y Espectrometría de Masas
8.
Molecules ; 28(18)2023 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-37764213

RESUMEN

Antibody engineering has developed into a wide-reaching field, impacting a multitude of industries, most notably healthcare and diagnostics. The seminal work on developing the first monoclonal antibody four decades ago has witnessed exponential growth in the last 10-15 years, where regulators have approved monoclonal antibodies as therapeutics and for several diagnostic applications, including the remarkable attention it garnered during the pandemic. In recent years, antibodies have become the fastest-growing class of biological drugs approved for the treatment of a wide range of diseases, from cancer to autoimmune conditions. This review discusses the field of therapeutic antibodies as it stands today. It summarizes and outlines the clinical relevance and application of therapeutic antibodies in treating a landscape of diseases in different disciplines of medicine. It discusses the nomenclature, various approaches to antibody therapies, and the evolution of antibody therapeutics. It also discusses the risk profile and adverse immune reactions associated with the antibodies and sheds light on future applications and perspectives in antibody drug discovery.


Asunto(s)
Enfermedades Autoinmunes , Productos Biológicos , Medicina , Humanos , Anticuerpos Monoclonales/uso terapéutico , Enfermedades Autoinmunes/tratamiento farmacológico , Relevancia Clínica
9.
Soft Matter ; 18(10): 2054-2059, 2022 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-35195646

RESUMEN

The repose angle is a key geometric property that characterises the inter-particle friction and thereby granular flows. One of the common methods to measure this property is to deposit a pile by extracting a pre-filled cylinder and letting the material flow out. While the repose angle of spherical beads is insensitive to the aspect ratio of this pre-filled column, we find that long flexible granular chains show a remarkable transition from stable vertical columns to conical piles depending on the aspect ratio. Below a critical aspect ratio, the cessation of flow of granular chains due to inter-chain entanglement stabilises the columns, while above the critical aspect ratio the conical piles of long granular chains arise not out of shear flow but instead through a series of column collapse instabilities during the deposition process. We also identify the critical chain length below which the granular chains flow and behave similar to spherical particles.

10.
Proc Natl Acad Sci U S A ; 116(32): 15792-15801, 2019 08 06.
Artículo en Inglés | MEDLINE | ID: mdl-31320590

RESUMEN

Membrane-mediated particle interactions depend both on the properties of the particles themselves and the membrane environment in which they are suspended. Experiments have shown that chiral rod-like inclusions dissolved in a colloidal membrane of opposite handedness assemble into colloidal rafts, which are finite-sized reconfigurable droplets consisting of a large but precisely defined number of rods. We systematically tune the chirality of the background membrane and find that, in the achiral limit, colloidal rafts acquire complex structural properties and interactions. In particular, rafts can switch between 2 chiral states of opposite handedness, which alters the nature of the membrane-mediated raft-raft interactions. Rafts with the same chirality have long-ranged repulsions, while those with opposite chirality acquire attractions with a well-defined minimum. Both attractive and repulsive interactions are qualitatively explained by a continuum model that accounts for the coupling between the membrane thickness and the local tilt of the constituent rods. These switchable interactions enable assembly of colloidal rafts into intricate higher-order architectures, including stable tetrameric clusters and "ionic crystallites" of counter-twisting domains organized on a binary square lattice. Furthermore, the properties of individual rafts, such as their sizes, are controlled by their complexation with other rafts. The emergence of these complex behaviors can be rationalized purely in terms of generic couplings between compositional and orientational order of fluids of rod-like elements. Thus, the uncovered principles might have relevance for conventional lipid bilayers, in which the assembly of higher-order structures is also mediated by complex membrane-mediated interactions.

11.
Reprod Health ; 19(1): 148, 2022 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-35739585

RESUMEN

BACKGROUND: Menstrual hygiene management (MHM) and practices by adolescent females of low and middle-income countries (LMICs) are a severe public health issue. The current systematic review and meta-analysis aimed to estimate the pooled proportion of the hygiene practices, menstrual problems with their associated factors, and the effectiveness of educational interventions on menstrual hygiene among adolescent school girls in India. METHODS: PRISMA checklist and PICO guidelines were used to screen the scientific literature from 2011 to 2021. The Newcastle-Ottawa Scale was used to assess the quality of studies. Four themes were developed for data analysis, including hygiene practices, type of absorbent used, menstruation associated morbidities and interventions performed regarding menstruation. Eighty-four relevant studies were included and a meta-analysis, including subgroup analysis, was performed. RESULTS: Pooled data revealed a statistically significant increase in sanitary pad usage "(SMD = 48.83, 95% CI = 41.38-57.62, p < 0.00001)" and increased perineum practices during menstruation "(SMD = 55.77, 95% CI = 44.27-70.26, p < 0.00001)". Results also reported that most prevalent disorders are dysmenorrhea "(SMD = 60.24, 95% CI = 50.41-70.06, p < 0.0001)", Pre-menstrual symptoms "(SMD = 62.67, 95% CI = 46.83-78.50, p < 0.00001)", Oligomenorrhea "(SMD = 23.57, CI = 18.05-29.10, p < 0.00001), Menorrhagia "(SMD = 25.67, CI = 3.86-47.47, p < 0.00001)", PCOS "(SMD = 5.50, CI = 0.60-10.40, p < 0.00001)", and Polymenorrhea "(SMD = 4.90, CI = 1.87-12.81, p < 0.0001)". A statistically significant improvement in knowledge "(SMD = 2.06, 95% CI = 0.75-3.36, p < 0.00001)" and practice "(SMD = 1.26, 95% CI = 0.13-2.65, p < 0.00001)" on menstruation was observed. Infections of the reproductive system and their repercussions can be avoided with better awareness and safe menstruation practices. CONCLUSIONS: Learning about menstrual hygiene and health is essential for adolescent girls' health education to continue working and maintaining hygienic habits. Infections of the reproductive system and their repercussions can be avoided with better awareness and safe menstruation practices.


Menstrual hygiene management (MHM) and practices by adolescent females of low and middle-income countries (LMICs) are severe problems for girls, parents, society, and policymakers. Menstrual-related problems are widespread among adolescent girls in India. Different menstrual abnormalities are found in different populations, suggesting socio-cultural and regional variation. Menstrual abnormalities and disorders are frequently linked to physical, mental, social, psychological, and reproductive issues, affecting adolescents' daily lives and their families lives by various psychosocial problems such as anxiety. We have the intention to compile, summarise, and critically analyse peer-reviewed and published scientific evidence from 2011 to 2021 on menstrual hygiene management methods used, most typical menstrual morbidities and their associated factors among Indian adolescent girls, and to evaluate the evidence for existing interventions like educational programs and absorbent distribution. Program planners and policymakers could use the findings of this study to build relevant initiatives to incorporate safe MHM in the country so that interventions can be designed taking into account the current needs of adolescent girls to reduce menstrual morbidities and improve their quality of life. A statistically significant improvement in knowledge and practice on menstruation was observed. Learning about menstrual hygiene and health is an essential aspect of adolescent girls' health education to continue working and maintaining hygienic habits. Infections of the reproductive system and their repercussions can be avoided with better awareness and safe menstruation practices.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Higiene , Menstruación , Adolescente , Femenino , Humanos , India , Productos para la Higiene Menstrual , Instituciones Académicas
12.
Mol Cell Biochem ; 476(3): 1517-1527, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33392922

RESUMEN

Latest strategies for cancer treatment primarily focus on the use of chemosensitizers to enhance therapeutic outcome. N-3 PUFAs have emerged as the strongest candidate for the prevention of colorectal cancer (CRC). Our previous studies have demonstrated that fish oil (FO) rich in n-3 PUFAs not only increased therapeutic potential of 5-Fluorouracil(5-FU) in colon cancer but also ameliorated its toxicity. Henceforth, the present study is designed to elucidate mechanistic insights of FO as a chemosensitizer to circumvent drug resistance in experimental colon carcinoma. The colon cancer was induced by 1,2-dimethylhydrazine(DMH)/dextran sulfate sodium(DSS) in male Balb/c mice and these animals were treated with 5-FU(12.5 mg/kg b.w.), FO(0.2 ml), or 5-FU + FO(12.5 mg/kg b.w + 0.2 ml) orally for 14 days. The molecular mechanism of overcoming 5-FU resistance using FO in colon cancer was delineated by estimating expression of cancer stem cell markers using flowcytometric method and drug transporters by immunohistochemistry and immunoblotting. Additionally, distribution profile of 5-FU and its cytotoxic metabolite, 5-FdUMP at target(colon), and non-target sites (serum, kidney, liver, spleen) was assessed using high-performance liquid chromatography(HPLC) method. The observations revealed that expression of CSCs markers was remarkably reduced after using fish oil along with 5-FU in carcinogen-treated animals. Interestingly, the use of FO alongwith 5-FU also significantly declined the expression of drug transporters (ABCB1,ABCC5) and consequently resulted in an increased cellular uptake of 5-FU and its metabolite, 5-FdUMP at target site (colon). It could be possibly associated with change in permeability of cell membrane owing to the alteration in membrane fluidity. The present study revealed the mechanistic insights of FO as a MDR revertant which successfully restored 5-FU-mediated chemoresistance in experimental colon carcinoma.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias del Colon/tratamiento farmacológico , Resistencia a Antineoplásicos , Ácidos Grasos Omega-3/metabolismo , Aceites de Pescado/química , Aceites de Pescado/uso terapéutico , Fluorouracilo/farmacología , 1,2-Dimetilhidrazina , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Animales , Antimetabolitos Antineoplásicos/farmacología , Membrana Celular/metabolismo , Colon/citología , Colon/efectos de los fármacos , Neoplasias del Colon/inducido químicamente , Sulfato de Dextran , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Células Madre Neoplásicas/citología , Permeabilidad
13.
Pharmacol Res ; 158: 104894, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32407960

RESUMEN

BACKGROUND: Many flavonoids have various beneficial actions like anti-inflammatory, anti-carcinogenic properties and many other clinical conditions. Astilbin is one such flavanoid compound having many physiological as well as pharmacological actions. PURPOSE: To summarize the important findings from the research conducted using astilbin having significance to its physiological and pharmacological activities as well as the patents filed using astilbin. STUDY DESIGN: Systematic review and compilation of the collected literature. METHOD: An extensive investigation of literature was done using several worldwide electronic scientific databases like PUBMED, SCOPUS, Science Direct and Google Scholar etc. All the article available in the English language that used our compound of interest i.e. astilbin, on the basis of inclusion criteria decided were retrieved from these databases, thoroughly reviewed and were summarized. RESULT: It has been established that astilbin can play a vital in the management of diseases associated with immune system. It also possesses antibacterial, anti-oxidative and hepatoprotective activity. CONCLUSION: These researches provide evidence that astilbin possesses great potential and thus can be utilized in the management of various disorders, thus establishing itself as a potential candidate for novel drug development. Also, there is still room for research on astilbin like it can be evaluated for anticancer potential, protective effect in various diabetic complications and many more. Overall observations from data suggested that astilbin is a promising compound and proved its efficacy in every preclinical study which is conducted till date. Some of the pharmacological activity is still unexplored. After successful preclinical trials, astilbin can go for further clinical trials.


Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Flavonoles/uso terapéutico , Inmunosupresores/uso terapéutico , Fitoterapia/tendencias , Alopecia/tratamiento farmacológico , Alopecia/metabolismo , Animales , Antidepresivos/uso terapéutico , Antioxidantes/uso terapéutico , Artritis/tratamiento farmacológico , Artritis/metabolismo , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/metabolismo , Humanos , Fitoterapia/métodos
14.
EMBO Rep ; 19(12)2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30404817

RESUMEN

Recycling endosomes (REs) are transient endosomal tubular intermediates of early/sorting endosomes (E/SEs) that function in cargo recycling to the cell surface and deliver the cell type-specific cargo to lysosome-related organelles such as melanosomes in melanocytes. However, the mechanism of RE biogenesis is largely unknown. In this study, by using an endosomal Rab-specific RNAi screen, we identified Rab22A as a critical player during RE biogenesis. Rab22A-knockdown results in reduced RE dynamics and concurrent cargo accumulation in the E/SEs or lysosomes. Rab22A forms a complex with BLOC-1, BLOC-2 and the kinesin-3 family motor KIF13A on endosomes. Consistently, the RE-dependent transport defects observed in Rab22A-depleted cells phenocopy those in BLOC-1-/BLOC-2-deficient cells. Further, Rab22A depletion reduced the membrane association of BLOC-1/BLOC-2. Taken together, these findings suggest that Rab22A promotes the assembly of a BLOC-1-BLOC-2-KIF13A complex on E/SEs to generate REs that maintain cellular and organelle homeostasis.


Asunto(s)
Proteínas Portadoras/metabolismo , Endosomas/metabolismo , Complejos Multiproteicos/metabolismo , Proteínas Nucleares/metabolismo , Biogénesis de Organelos , Proteínas de Unión al GTP rab/metabolismo , Animales , Membrana Celular/metabolismo , Proteínas de Unión al ADN , Células HEK293 , Células HeLa , Humanos , Cinesinas/metabolismo , Melanocitos/metabolismo , Melanosomas/metabolismo , Ratones , Pigmentación , Pigmentos Biológicos/metabolismo , Interferencia de ARN , Proteínas de Unión al ARN , Transducción de Señal
15.
Soft Matter ; 16(45): 10310-10319, 2020 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-33237118

RESUMEN

Colloidal membranes, self assembled monolayers of aligned rod like molecules, offer a template for designing membranes with definite shapes and curvature, and possibly new functionalities in the future. Often the constituent rods, due to their molecular chirality, are tilted with respect to the membrane normal. Spatial patterns of this tilt on curved membranes result from a competition among depletion forces, nematic interactions, molecular chirality and boundary effects. We present a covariant theory for the tilt pattern on minimal surfaces, like helicoids and catenoids, which have been generated in the laboratory only recently. We predict several non-uniform tilt patterns, some of which are consistent with experimental observations and some, which are yet to be discovered.

16.
Nature ; 513(7516): 77-80, 2014 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-25186901

RESUMEN

Liquid-liquid phase separation is ubiquitous in suspensions of nanoparticles, proteins and colloids. It has an important role in gel formation, protein crystallization and perhaps even as an organizing principle in cellular biology. With a few notable exceptions, liquid-liquid phase separation in bulk proceeds through the continuous coalescence of droplets until the system undergoes complete phase separation. But when colloids, nanoparticles or proteins are confined to interfaces, surfaces or membranes, their interactions differ fundamentally from those mediated by isotropic solvents, and this results in significantly more complex phase behaviour. Here we show that liquid-liquid phase separation in monolayer membranes composed of two dissimilar chiral colloidal rods gives rise to thermodynamically stable rafts that constantly exchange monomeric rods with the background reservoir to maintain a self-limited size. We visualize and manipulate rafts to quantify their assembly kinetics and to show that membrane distortions arising from the rods' chirality lead to long-range repulsive raft-raft interactions. Rafts assemble into cluster crystals at high densities, but they can also form bonds to yield higher-order structures. Taken together, our observations demonstrate a robust membrane-based pathway for the assembly of monodisperse membrane clusters that is complementary to existing methods for colloid assembly in bulk suspensions. They also reveal that chiral inclusions in membranes can acquire long-range repulsive interactions, which might more generally have a role in stabilizing assemblages of finite size.

17.
Proc Natl Acad Sci U S A ; 114(17): E3376-E3384, 2017 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-28411214

RESUMEN

In the presence of a nonadsorbing polymer, monodisperse rod-like particles assemble into colloidal membranes, which are one-rod-length-thick liquid-like monolayers of aligned rods. Unlike 3D edgeless bilayer vesicles, colloidal monolayer membranes form open structures with an exposed edge, thus presenting an opportunity to study elasticity of fluid sheets. Membranes assembled from single-component chiral rods form flat disks with uniform edge twist. In comparison, membranes composed of a mixture of rods with opposite chiralities can have the edge twist of either handedness. In this limit, disk-shaped membranes become unstable, instead forming structures with scalloped edges, where two adjacent lobes with opposite handedness are separated by a cusp-shaped point defect. Such membranes adopt a 3D configuration, with cusp defects alternatively located above and below the membrane plane. In the achiral regime, the cusp defects have repulsive interactions, but away from this limit we measure effective long-ranged attractive binding. A phenomenological model shows that the increase in the edge energy of scalloped membranes is compensated by concomitant decrease in the deformation energy due to Gaussian curvature associated with scalloped edges, demonstrating that colloidal membranes have positive Gaussian modulus. A simple excluded volume argument predicts the sign and magnitude of the Gaussian curvature modulus that is in agreement with experimental measurements. Our results provide insight into how the interplay between membrane elasticity, geometrical frustration, and achiral symmetry breaking can be used to fold colloidal membranes into 3D shapes.

18.
Biophys J ; 117(8): 1508-1513, 2019 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-31586523

RESUMEN

Phototaxis is one of the most fundamental stimulus-response behaviors in biology wherein motile microorganisms sense light gradients to swim toward the light source. Apart from single-cell survival and growth, it plays a major role at the global scale of aquatic ecosystems and bioreactors. We study phototaxis of single-celled algae Chlamydomonas reinhardtii as a function of cell number density and light stimulus using high spatiotemporal video microscopy. Surprisingly, the phototactic efficiency has a minimum at a well-defined number density, for a given light gradient, above which the phototaxis behavior of a collection of cells can even exceed the performance obtainable from single isolated cells. We show that the origin of enhancement of performance above the critical concentration lies in the slowing down of the cells, which enables them to sense light more effectively. We also show that this steady-state phenomenology is well captured by modeling the phototactic response as a density-dependent torque acting on an active Brownian particle.


Asunto(s)
Chlamydomonas reinhardtii/fisiología , Fototaxis , Fenómenos Biomecánicos , Análisis de la Célula Individual
19.
Soft Matter ; 15(35): 7033-7042, 2019 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-31435626

RESUMEN

Inclusions dissolved in an anisotropic quasi-2D membrane acquire new types of interactions that can drive assembly of complex structures and patterns. We study colloidal membranes composed of a binary mixture of long and short rods, such that the length ratio of the long to short rods is approximately two. At very low volume fractions, short rods dissolve in the membrane of long rods by strongly anchoring to the membrane polymer interface. At higher fractions, the dissolved short rods phase separate from the background membrane, creating a composite structure comprised of bilayer droplets enriched in short rods that coexist with the background monolayer membrane. These results demonstrate that colloidal membranes serve as a versatile platform for assembly of soft materials, while simultaneously providing new insight into universal membrane-mediated interactions.

20.
Soft Matter ; 15(34): 6791-6802, 2019 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-31408077

RESUMEN

In the presence of a non-adsorbing polymer, monodisperse rod-like colloids assemble into one-rod-length thick liquid-like monolayers, called colloidal membranes. The density of the rods within a colloidal membrane is determined by a balance between the osmotic pressure exerted by the enveloping polymer suspension and the repulsion between the colloidal rods. We developed a microfluidic device for continuously observing an isolated membrane while dynamically controlling the osmotic pressure of the polymer suspension. Using this technology we measured the membrane rod density over a range of osmotic pressures than is wider that what is accessible in equilibrium samples. With increasing density we observed a first-order phase transition, in which the in-plane membrane order transforms from a 2D fluid into a 2D solid. In the limit of low osmotic pressures, we measured the rate at which individual rods evaporate from the membrane. The developed microfluidic technique could have wide applicability for in situ investigation of various soft materials and how their properties depend on the solvent composition.

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