Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 77
Filter
1.
Psychiatr Rehabil J ; 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38407064

ABSTRACT

OBJECTIVE: Compared to Western cultures, self-determination needs are expressed and pursued differently in Asian cultures, where interdependence and achieving greater good for the group are prioritized. To accommodate these needs, we propose the use of family-centered decision making (FCDM) to complement the shared decision-making (SDM) practice, fostering collaborative psychiatric care for Asian individuals residing in the United States. METHOD: This article synthesizes various literature to outline the similarities and differences between SDM and FCDM, discuss implementation steps, challenges associated with implementation, potential solutions, and future research considerations. RESULTS: Our review suggests that FCDM is more responsive to and inclusive of Asian cultural experience, better reflecting these cultures' expression of self-determination. We propose a five-step framework for FCDM implementation in psychiatric rehabilitation for Asian and Asian American individuals, while identifying three further practical considerations: logistical difficulties, intrafamilial differences, and making the decision to use FCDM or not. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Given the heterogeneity of Asian individuals in the United States, we urge providers to allow flexibility in practicing FCDM. We outline the important components for providers to help individuals with psychiatric disabilities distinguish between the characteristics of FCDM and SDM, evaluate the potential pros and cons of utilizing FCDM, and then initiate FCDM if appropriate or requested by the individuals. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

2.
Front Mol Biosci ; 10: 1244587, 2023.
Article in English | MEDLINE | ID: mdl-37645217

ABSTRACT

Biliverdin Reductase B (BLVRB) is an NADPH-dependent reductase that catalyzes the reduction of multiple substrates and is therefore considered a critical cellular redox regulator. In this study, we sought to address whether both structural and dynamics changes occur between different intermediates of the catalytic cycle and whether these were relegated to just the active site or the entirety of the enzyme. Through X-ray crystallography, we determined the apo BLVRB structure for the first time, revealing subtle global changes compared to the holo structure and identifying the loss of a critical hydrogen bond that "clamps" the R78-loop over the coenzyme. Amide and Cα chemical shift perturbations were used to identify environmental and secondary structural changes between intermediates, with more distant global changes observed upon coenzyme binding compared to substrate interactions. NMR relaxation rate measurements provided insights into the dynamic behavior of BLVRB during the catalytic cycle. Specifically, the inherently dynamic R78-loop that becomes ordered upon coenzyme binding persists through the catalytic cycle while similar regions experience dynamic exchange. However, the dynamic exchange processes were found to differ through the catalytic cycle with several groups of residues exhibiting similar dynamic responses. Finally, both local and distal structural and dynamic changes occur within BLVRB that are dependent solely on the oxidative state of the coenzyme. Thus, through a comprehensive analysis here, this study revealed structural and dynamic alterations in BLVRB through its catalytic cycle that are not simply relegated to the active site, but instead, are allosterically coupled throughout the enzyme.

3.
Biodivers Data J ; 11: e105580, 2023.
Article in English | MEDLINE | ID: mdl-37305449

ABSTRACT

Background: Monitoring of avian populations in Janghang Wetland, Goyang, Republic of Korea (ROK) is based on citizen science (also called community-based monitoring). This monitoring data can be used to track avian density, population status and waterbird census at local, national and regional levels. The Ministry of Environment (MoE) ROK has surveyed since 1999, including Odusan Unification Tower to Ilsan Bride, which connects the cities of Gimpo and Goyang along the Han River estuary. However, it has not covered Janghang Wetland, which is located in the Han River estuary at the transboundary between the two Koreas. The Janghang Wetland is a protected wetland in the Demilitarized Zone (DMZ) between the two Koreas. In 2019, Janghang Wetland was designated as a Flyway Network Site by Goyang City and the East Asian-Australasian Flyway Partnership. This Network site is a voluntary collaboration and includes many internationally significant wetlands for waterbirds that still lack formal national protection. In addition, it was designated as a Ramsar site in 2021. The wetland currently supports wintering population of White-naped Crane (Grusvipio), species listed as vulnerable and Tundra Bean Goose (Ansercygnoides), spring-autumn migration population of Swan Goose (Ansercygnoid), species listed as vulnerable and a breeding population of Black-faced Spoonbill (Plataleaminor), species listed as endangered in summer. New information: We provide data that the Janghang Wetland is a significant area for migration and breeding for waterbirds; and that Han River estuary is also internationally important for waterbirds during the migratory bird season. We observed 14 orders, 42 families and 132 species. The surveys also observed the critically-endangered Black-faced Spoonbill (Plataleaminor), Swan Goose (Ansercygnoides), White-naped Crane (Grusvipio), Whooper Swan (Cygnuscygnus) and Peregrine Falcon (Falcoperegrinus). We also observed the Black-faced Spoonbill, Great Egret, Little Egret, Great Cormorant, Eastern Spot-billed Duck, Pheasant and Brown-eared Bulbul at the sensor camera point and White-naped Crane, Hooded Crane, Bean Goose, White-fronted Goose, Snow Goose, Swan Goose, Great Cormorant and Eastern Spot-billed Duck at the closed-circuit television camera point from the camera-trap surveys. Based on the species recorded, the survey area is of clear importance for biodiversity conservation.

4.
Methods ; 216: 51-57, 2023 08.
Article in English | MEDLINE | ID: mdl-37302521

ABSTRACT

Advances in Nuclear Magnetic Resonance (NMR) spectroscopy have allowed for the identification and characterization of movements in enzymes over the last 20 years that has also revealed the complexities of allosteric coupling. For example, many of the inherent movements of enzymes, and proteins in general, have been shown to be highly localized but nonetheless still coupled over long distances. Such partial couplings provide challenges to both identifying allosteric networks of dynamic communication and determining their roles in catalytic function. We have developed an approach to help identify and engineer enzyme function, called Relaxation And Single Site Multiple Mutations (RASSMM). This approach is a powerful extension of mutagenesis and NMR that is based on the observation that multiple mutations to a single site distal to the active site allosterically induces different effects to networks. Such an approach generates a panel of mutations that can also be subjected to functional studies in order to match catalytic effects with changes to coupled networks. In this review, the RASSMM approach is briefly outlined together with two applications that include cyclophilin-A and Biliverdin Reductase B.


Subject(s)
Proteins , Mutation , Proteins/chemistry , Mutagenesis , Magnetic Resonance Spectroscopy , Catalytic Domain , Allosteric Regulation
5.
Protein Sci ; 32(4): e4603, 2023 04.
Article in English | MEDLINE | ID: mdl-36807437

ABSTRACT

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid protein is the most abundantly expressed viral protein during infection where it targets both RNA and host proteins. However, identifying how a single viral protein interacts with so many different targets remains a challenge, providing the impetus here for identifying the interaction sites through multiple methods. Through a combination of nuclear magnetic resonance (NMR), electron microscopy, and biochemical methods, we have characterized nucleocapsid interactions with RNA and with three host proteins, which include human cyclophilin-A, Pin1, and 14-3-3τ. Regarding RNA interactions, the nucleocapsid protein N-terminal folded domain preferentially interacts with smaller RNA fragments relative to the C-terminal region, suggesting an initial RNA engagement is largely dictated by this N-terminal region followed by weaker interactions to the C-terminal region. The nucleocapsid protein forms 10 nm ribonuclear complexes with larger RNA fragments that include 200 and 354 nucleic acids, revealing its potential diversity in sequestering different viral genomic regions during viral packaging. Regarding host protein interactions, while the nucleocapsid targets all three host proteins through its serine-arginine-rich region, unstructured termini of the nucleocapsid protein also engage host cyclophilin-A and host 14-3-3τ. Considering these host proteins play roles in innate immunity, the SARS-CoV-2 nucleocapsid protein may block the host response by competing interactions. Finally, phosphorylation of the nucleocapsid protein quenches an inherent dynamic exchange process within its serine-arginine-rich region. Our studies identify many of the diverse interactions that may be important for SARS-CoV-2 pathology during infection.


Subject(s)
COVID-19 , RNA , Humans , SARS-CoV-2/metabolism , Cyclophilins/analysis , Nucleocapsid/chemistry , Nucleocapsid/metabolism , Nucleocapsid Proteins/chemistry , Nucleocapsid Proteins/genetics , Nucleocapsid Proteins/metabolism , Arginine , Serine , NIMA-Interacting Peptidylprolyl Isomerase/analysis
6.
Psychiatr Rehabil J ; 46(1): 36-44, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36622729

ABSTRACT

OBJECTIVE: Research is significantly lacking on exploring how Asian Americans with mental illness (AAMI) begin to accept their mental illness and identifying factors that might have a significant impact on mental health service utilization. To bridge the gap, this study aimed to explore mental illness identity development and service utilization experiences among AAMI using a qualitative, narration-based research design. METHOD: Twenty-one AAMI participated in the semistructured interview. Interview questions were designed to assess the participants' perceived experiences of mental illness identity development, microaggression/discrimination experiences, overall positive and negative experiences when using mental health services, and suggestions to make mental health services accessible to AAMI. Thematic analysis was applied to identify key themes throughout multiple steps of coding. RESULTS: Analyses yielded 13 major themes related to the following: (a) contributing factors influencing mental illness identity development, (b) contributing factors utilizing mental health services, and (c) suggestions to make mental health services more available to AAMI. More specifically, it was worth noting that family played a significant role as either a support system or a barrier to adjusting to participants' mental illness and service utilization. Participants also stated that negative attitudes toward mental illness within the Asian community hindered the development of positive self-concept and utilization of mental health services. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Findings from the present study are expected to assist service providers in implementing culturally informed practices when working with AAMI and developing effective strategies to enhance mental health literacy and service utilization. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Subject(s)
Mental Disorders , Mental Health Services , Humans , Asian , Mental Disorders/psychology , Qualitative Research , Mental Health
7.
Commun Biol ; 5(1): 1190, 2022 11 07.
Article in English | MEDLINE | ID: mdl-36336763

ABSTRACT

The mucosal adaptive immune response is dependent on the production of IgA antibodies and particularly IgA1, yet opportunistic bacteria have evolved mechanisms to specifically block this response by producing IgA1 proteases (IgA1Ps). Our lab was the first to describe the structures of a metal-dependent IgA1P (metallo-IgA1P) produced from Gram-positive Streptococcus pneumoniae both in the absence and presence of its IgA1 substrate through cryo-EM single particle reconstructions. This prior study revealed an active-site gating mechanism reliant on substrate-induced conformational changes to the enzyme that begged the question of whether such a mechanism is conserved among the wider Gram-positive metallo-IgA1P subfamily of virulence factors. Here, we used cryo-EM to characterize the metallo-IgA1P of a more distantly related family member from Gemella haemolysans, an emerging opportunistic pathogen implicated in meningitis, endocarditis, and more recently bacteremia in the elderly. While the substrate-free structures of these two metallo-IgA1Ps exhibit differences in the relative starting positions of the domain responsible for gating substrate, the enzymes have similar domain orientations when bound to IgA1. Together with biochemical studies that indicate these metallo-IgA1Ps have similar binding affinities and activities, these data indicate that metallo-IgA1P binding requires the specific IgA1 substrate to open the enzymes for access to their active site and thus, largely conform to an "induced fit" model.


Subject(s)
Immunoglobulin A , Metalloproteases , Humans , Aged , Immunoglobulin A/metabolism , Streptococcus/metabolism , Bacteria/metabolism , Virulence Factors
8.
Biosens Bioelectron ; 218: 114760, 2022 Dec 15.
Article in English | MEDLINE | ID: mdl-36201999

ABSTRACT

The sensitive detection of the multiple immuno-subtypes of cancer-specific extracellular vesicles (EVs) has emerged as a promising method for multiclass cancer diagnosis; however, its limitations in sensitivity, accessibility, and multiple detection of EV subtypes have hindered its further implementation. Here, we present a platform for sensitive EV detection enabled by sessile droplet array (eSD) that exploits enhanced immuno-capture of EVs via evaporation-driven radial flows in a sessile droplet. Compared to a micro-well without internal flows, this platform demonstrates significantly enhanced EV capture and detection by detecting low levels of EVs with a detection limit of 384.7 EVs per microliter, which is undetectable in the micro-well. In addition, using a small sample consumption of ∼0.2 µL plasma per droplet, the platform detects EV immuno-subtypes against seven different antibodies in patient plasma samples of different cancer types (liver, colon, lung, breast and prostate cancers). Further, using the profiling data, the platform exhibits a sensitivity of 100% (95% confidence interval (CI): 83-100%) and a specificity of 100% (95% CI: 40-100%) for the diagnosis of cancer, and classified cancer types with an overall accuracy of 96% (95% CI: 86-100%) using a two-staged algorithm based on quadratic discriminant analysis technique for machine learning.


Subject(s)
Biosensing Techniques , Extracellular Vesicles , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/diagnosis
10.
Molecules ; 27(14)2022 Jul 14.
Article in English | MEDLINE | ID: mdl-35889366

ABSTRACT

Toll-interleukin receptor (TIR) domains have emerged as critical players involved in innate immune signaling in humans but are also expressed as potential virulence factors within multiple pathogenic bacteria. However, there has been a shortage of structural studies aimed at elucidating atomic resolution details with respect to their interactions, potentially owing to their dynamic nature. Here, we used a combination of biophysical and biochemical studies to reveal the dynamic behavior and functional interactions of a panel of both bacterial TIR-containing proteins and mammalian receptor TIR domains. Regarding dynamics, all three bacterial TIR domains studied here exhibited an inherent exchange that led to severe resonance line-broadening, revealing their intrinsic dynamic nature on the intermediate NMR timescale. In contrast, the three mammalian TIR domains studied here exhibited a range in terms of their dynamic exchange that spans multiple timescales. Functionally, only the bacterial TIR domains were catalytic towards the cleavage of NAD+, despite the conservation of the catalytic nucleophile on human TIR domains. Our development of NMR-based catalytic assays allowed us to further identify differences in product formation for gram-positive versus gram-negative bacterial TIR domains. Differences in oligomeric interactions were also revealed, whereby bacterial TIR domains self-associated solely through their attached coil-coil domains, in contrast to the mammalian TIR domains that formed homodimers and heterodimers through reactive cysteines. Finally, we provide the first atomic-resolution studies of a bacterial coil-coil domain and provide the first atomic model of the TIR domain from a human anti-inflammatory IL-1R8 protein that undergoes a slow inherent exchange.


Subject(s)
Bacteria , Virulence Factors , Animals , Bacteria/metabolism , Bacterial Proteins/metabolism , Gram-Negative Bacteria/metabolism , Humans , Mammals/metabolism , Signal Transduction , Virulence Factors/chemistry
11.
Rehabil Psychol ; 66(3): 265-272, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34472925

ABSTRACT

Objective: The current study assessed self-reported self-compassion, courtesy stigma, life satisfaction, and depression among parents of transition-age youth with intellectual and developmental disabilities (IDDs). This study tests the hypothesis that self-compassion is a mediator between courtesy stigma and parents' psychosocial adjustment. Method: One hundred parents of transition-age youth with IDDs completed a cross-sectional survey assessing courtesy stigma, self-compassion, life satisfaction, and depression. Study information was disseminated via community organizations, and participants self-selected to participate. "PROCESS" macro with 5,000 bootstrapped samples was used to test self-compassion as a mediator between courtesy stigma and parents' life satisfaction (Satisfaction With Life Scale) and depressive symptoms (Center for Epidemiologic Studies Short Depression Scale). Results: Self-compassion partially mediated the relationship between courtesy stigma and caregiver depressive symptoms (effect = .28, CI [.16, .45]). Self-compassion did not mediate the relationship between courtesy stigma and satisfaction with life. Implications: Findings suggest self-compassion could be leveraged to help counter the effects of courtesy stigma on parents. Future research should seek to explore potential differences in these relationships according to cultural factors or by diagnostic group. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Subject(s)
Developmental Disabilities , Empathy , Adolescent , Child , Cross-Sectional Studies , Humans , Parents , Social Stigma
12.
J Mol Biol ; 433(15): 167108, 2021 07 23.
Article in English | MEDLINE | ID: mdl-34161778

ABSTRACT

The nucleocapsid protein is one of four structural proteins encoded by SARS-CoV-2 and plays a central role in packaging viral RNA and manipulating the host cell machinery, yet its dynamic behavior and promiscuity in nucleotide binding has made standard structural methods to address its atomic-resolution details difficult. To begin addressing the SARS-CoV-2 nucleocapsid protein interactions with both RNA and the host cell along with its dynamic behavior, we have specifically focused on the folded N-terminal domain (NTD) and its flanking regions using nuclear magnetic resonance solution studies. Studies performed here reveal a large repertoire of interactions, which includes a temperature-dependent self-association mediated by the disordered flanking regions that also serve as binding sites for host cell cyclophilin-A while nucleotide binding is largely mediated by the central NTD core. NMR studies that include relaxation experiments have revealed the complicated dynamic nature of this viral protein. Specifically, while much of the N-terminal core domain exhibits micro-millisecond motions, a central ß-hairpin shows elevated inherent flexibility on the pico-nanosecond timescale and the serine/arginine-rich region of residues 176-209 undergoes multiple exchange phenomena. Collectively, these studies have begun to reveal the complexities of the nucleocapsid protein dynamics and its preferred interaction sites with its biological targets.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Mutation , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Angiotensin-Converting Enzyme 2/chemistry , Binding Sites , Evolution, Molecular , HEK293 Cells , Humans , Immune Evasion , Models, Molecular , Protein Conformation , Protein Domains , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/genetics
13.
Cells ; 10(3)2021 02 24.
Article in English | MEDLINE | ID: mdl-33668388

ABSTRACT

Ginseng is a traditional herbal medicine in eastern Asian countries. Most active constituents in ginseng are prepared via fermentation or organic acid pretreatment. Extracellular vesicles (EVs) are released by most organisms from prokaryotes to eukaryotes and play central roles in intra- and inter-species communications. Plants produce EVs upon exposure to microbes; however, their direct functions and utility for human health are barely known, except for being proposed as delivery vehicles. In this study, we isolated EVs from ginseng roots (GrEVs) or the culture supernatants of ginseng cells (GcEVs) derived from Panax ginseng C.A. Meyer and investigated their biological effects on human skin cells. GrEV or GcEV treatments improved the replicative senescent or senescence-associated pigmented phenotypes of human dermal fibroblasts or ultraviolet B radiation-treated human melanocytes, respectively, by downregulating senescence-associated molecules and/or melanogenesis-related proteins. Based on comprehensive lipidomic analysis using liquid chromatography mass spectrometry, the lipidomic profile of GrEVs differed from that of the parental root extracts, showing significant increases in 70 of 188 identified lipid species and prominent increases in diacylglycerols, some phospholipids (phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine), and sphingomyelin, revealing their unique vesicular properties. Therefore, our results imply that GEVs represent a novel type of bioactive and sustainable nanomaterials that can be applied to human tissues for improving tissue conditions and targeted delivery of active constituents.


Subject(s)
Chromatography, High Pressure Liquid/methods , Extracellular Vesicles/drug effects , Mass Spectrometry/methods , Panax/chemistry , Plants, Medicinal/chemistry , Skin/drug effects , Cell Proliferation , Humans
14.
Psychiatr Serv ; 72(1): 114-116, 2021 01 01.
Article in English | MEDLINE | ID: mdl-33138713

ABSTRACT

Self-determination is a critical element of shared decision making among people recovering from mental illness. However, shared decision making between the patient and caregiver may not align with the accepted values of East Asian communities. Family-centered decision making may be considered a more adaptive approach for use among East Asian service users and their mental health care providers.


Subject(s)
Mental Disorders , Patient Participation , Adult , Decision Making , Decision Making, Shared , Health Personnel , Humans , Mental Disorders/therapy
15.
Community Ment Health J ; 56(5): 854-866, 2020 07.
Article in English | MEDLINE | ID: mdl-31925654

ABSTRACT

One major concern of Asian Americans with psychiatric disabilities is underutilization of services, furthermore their service needs and accessibility have been significantly understudied. This study examined the effects of the public vocational rehabilitation (VR) services on employment outcomes for Asian Americans with psychiatric disabilities in the United States. This study investigated which individual characteristics, work disincentives, and VR service types were related to competitive employment outcomes among Asian Americans with psychiatric disabilities and compared the findings to other racial/ethnic groups. Logistic regression analyses were used to analyze a sample of RSA-911 data from fiscal year 2013. The results provided empirical support regarding VR services and employment outcomes for Asian Americans with psychiatric disabilities. Specifically, level of education, work experiences, and receipt of health insurance benefits were significantly related to employment outcomes among the Asian American group. Regarding VR services, job placement assistance, on-the-job supports, maintenance, miscellaneous training, and other services also predicted employment outcomes. Future research needs to address the impact of specific cultural factors on access to VR services, service utilization, and employment outcomes.


Subject(s)
Asian , Disabled Persons , Educational Status , Employment , Humans , Rehabilitation, Vocational , United States
16.
Ann Geriatr Med Res ; 24(4): 267-273, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33389973

ABSTRACT

BACKGROUND: While aging causes muscle weakness, type 2 diabetes mellitus (T2DM) is also considered a high-risk factor for the induction of skeletal muscle weakness. Previous studies have reported increased collagen content in insulin-resistant skeletal muscles. Here, we studied the mechanical properties of aged skeletal muscle in subjects with T2DM to investigate whether aged skeletal muscles with T2DM induce higher passive tension due to the abundance of extracellular matrix (ECM) inside or outside of the muscle fibers. METHODS: Samples from the gluteus maximus muscles of older adults with diabetes (T2DM) and non-diabetic (non-DM) older adults who underwent elective orthopedic surgery were collected. Permeabilized single muscle fibers from these samples were used to identify their mechanical properties. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to quantify titin and fiber type distributions in these samples. RESULTS: We confirmed a significant predominance of type I fiber ratio in both T2DM and non-DM aged muscles. While the average cross-sectional area and maximal active tension of the single fibers were smaller in the T2DM group than those in the non-DM group, the difference was not statistically significant. T2DM subjects showed significantly greater passive tension and lower titin-/ECM-based passive tension ratios than those in non-DM subjects, which indicated that more ECM but less titin contributed to the total passive tension. CONCLUSION: Based on our findings, we concluded that T2DM may cause increased passive stiffness of single skeletal muscle fibers in older adults because of an excessive accumulation of ECM in and around single muscle fibers due to increased insulin resistance.

17.
PLoS One ; 14(11): e0224467, 2019.
Article in English | MEDLINE | ID: mdl-31721788

ABSTRACT

Nemaline myopathy (NEM) is a congenital neuromuscular disorder primarily caused by nebulin gene (NEB) mutations. NEM is characterized by muscle weakness for which currently no treatments exist. In NEM patients a predominance of type I fibers has been found. Thus, therapeutic options targeting type I fibers could be highly beneficial for NEM patients. Because type I muscle fibers express the same myosin isoform as cardiac muscle (Myh7), the effect of omecamtiv mecarbil (OM), a small molecule activator of Myh7, was studied in a nebulin-based NEM mouse model (Neb cKO). Skinned single fibers were activated by exogenous calcium and force was measured at a wide range of calcium concentrations. Maximal specific force of type I fibers was much less in fibers from Neb cKO animals and calcium sensitivity of permeabilized single fibers was reduced (pCa50 6.12 ±0.08 (cKO) vs 6.36 ±0.08 (CON)). OM increased the calcium sensitivity of type I single muscle fibers. The greatest effect occurred in type I fibers from Neb cKO muscle where OM restored the calcium sensitivity to that of the control type I fibers. Forces at submaximal activation levels (pCa 6.0-6.5) were significantly increased in Neb cKO fibers (~50%) but remained below that of control fibers. OM also increased isometric force and power during isotonic shortening of intact whole soleus muscle of Neb cKO mice, with the largest effects at physiological stimulation frequencies. We conclude that OM has the potential to improve the quality of life of NEM patients by increasing the force of type I fibers at submaximal activation levels.


Subject(s)
Muscle Contraction/drug effects , Muscle Fibers, Skeletal/drug effects , Muscle Proteins/genetics , Myopathies, Nemaline/drug therapy , Urea/analogs & derivatives , Animals , Calcium/metabolism , Disease Models, Animal , Mice , Mice, Knockout , Muscle Contraction/physiology , Muscle Fibers, Skeletal/physiology , Myopathies, Nemaline/genetics , Myopathies, Nemaline/physiopathology , Urea/pharmacology , Urea/therapeutic use
18.
Int J Mol Sci ; 20(20)2019 Oct 10.
Article in English | MEDLINE | ID: mdl-31658633

ABSTRACT

Respiratory failure due to diaphragm dysfunction is considered a main cause of death in nemaline myopathy (NM) and we studied both isometric force and isotonic shortening of diaphragm muscle in a mouse model of nebulin-based NM (Neb cKO). A large contractile deficit was found in nebulin-deficient intact muscle that is frequency dependent, with the largest deficits at low-intermediate stimulation frequencies (e.g., a deficit of 72% at a stimulation frequency of 20 Hz). The effect of the fast skeletal muscle troponin activator (FSTA) tirasemtiv on force was examined. Tirasemtiv had a negligible effect at maximal stimulation frequencies, but greatly reduced the force deficit of the diaphragm at sub-maximal stimulation levels with an effect that was largest in Neb cKO diaphragm. As a result, the force deficit of Neb cKO diaphragm fell (from 72% to 29% at 20 Hz). Similar effects were found in in vivo experiments on the nerve-stimulated gastrocnemius muscle complex. Load-clamp experiments on diaphragm muscle showed that tirasemtiv increased the shortening velocity, and reduced the deficit in mechanical power by 33%. Thus, tirasemtiv significantly improves muscle function in a mouse model of nebulin-based nemaline myopathy.


Subject(s)
Diaphragm/physiology , Imidazoles/metabolism , Muscle Proteins/metabolism , Muscle, Skeletal/metabolism , Myopathies, Nemaline/metabolism , Pyrazines/metabolism , Troponin/metabolism , Animals , Copper Transporter 1/genetics , Disease Models, Animal , Mice , Mice, Inbred C57BL , Mice, Knockout , Muscle Contraction , Muscle Proteins/genetics
19.
Soft Matter ; 15(23): 4647-4655, 2019 Jun 12.
Article in English | MEDLINE | ID: mdl-31073554

ABSTRACT

Passive droplet generation for an aqueous two-phase system (ATPS) was performed with a fracture-based variable microchannel. A jet of dextran-rich phase (DEX) in a polyethylene-glycol (PEG)-rich phase was created by focused flow. The width of the inlet channel could be varied over the range 1-10 µm via mechanical strain, which extended the range of operational back pressure. This enabled the spontaneous formation of DEX droplets with an ultralow surface tension of 12 µN m-1. The production of DEX droplets were examined with regard to driving pressure, flow rate, DEX/PEG concentration. The droplet properties are analyzed in terms of production rate (2-20 droplets per s), droplet diameter (10-100 µm), and diameter variance (5-20%). Controlling the inlet-channel width with other operating conditions widened the range of droplet properties. This simple and robust method significantly strengthened droplet-generation in microfluidics, especially for ATPS of low solute concentrations relevant to live cells.

SELECTION OF CITATIONS
SEARCH DETAIL
...