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1.
J Biomol Struct Dyn ; : 1-12, 2023 Jan 04.
Article in English | MEDLINE | ID: mdl-36598349

ABSTRACT

Aquaporin is a water channel protein that facilitates the movement of water across the cell membrane. Aquaporin from the Antarctic region has been noted for its psychrophilic properties and its ability to perform at a lower temperature but there remains limited understanding of the water mechanism of Antarctic Pseudomonas sp. strain AMS3 However, studies regarding aquaporin isolated from psychrophilic Pseudomonas sp. are still scattered. Recently, the genome sequence of an Antarctic Pseudomonas sp. strain AMS3 revealed a gene sequence encoding for a putative aquaporin designated as AqpZ1 AMS3. In this study, structure analysis and a molecular dynamics (MD) simulation of a predicted model of a fully hydrated aquaporin tetramer embedded in a lipid bilayer was performed at different temperatures for structural flexibility and stability analysis. The MD simulation results revealed that the structures were able to remain stable at low to medium temperatures. The protein was observed to have high flexibility in the loop region as compared to the helices region throughout the simulated temperatures. The selectivity filter and NPA motifs play a major role in solute selectivity and the pore radius of the protein. The structural and functional characterization of this psychrophilic aquaporin provides new insights for the future applications of this protein.Communicated by Ramaswamy H. Sarma.

2.
Mymensingh Med J ; 32(1): 168-176, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36594317

ABSTRACT

Uterine fibroids are benign tumor of the uterus that often appear during child bearing ages. Medical treatments are considered the first-line treatment to preserve fertility, avoid or delaying surgery. This randomized control study was carried out in OPD of Obstetrics and Gynecology Department of BSMMU, Dhaka, Bangladesh from May 2018 to March 2019 to evaluate the efficacy and safety of ulipristal acetate (5mg) once daily in reproductive women with three months treatment courses. Total 52 samples with symptomatic uterine fibroids for treatment course-1, among them 36 were needed for treatment course-2 which was slow or non-responding in treatment course-1. Main outcome measures were amenorrhea, controlled bleeding, fibroid volume, anaemia, quality of life. Sixty one percent (61.0%) of patients were achieved amenorrheic during both treatment courses. Ninety percent (90.0%) patients were control of bleeding during both treatment courses. In treatment course-1, reductions from baseline in fibroid volume were 62.70%, whereas in course-2, reductions in fibroid volume were 75.33%. Five percent (5.0%) of patients were discontinuing Ulipristal acetate due to adverse effects. Renal and liver function tests were performed before and after each course of treatment. The level of creatinine, SGPT in the blood for both treatment courses had no statistically significant effects. Ulipristal acetate may be an alternative to surgical treatment, the safety profiles and prolong effects with improvement of symptoms, quality of life after cessation of drugs. Repeated use of drugs reduces the size and also improves the patient's condition.


Subject(s)
Leiomyoma , Uterine Neoplasms , Humans , Female , Uterine Neoplasms/drug therapy , Quality of Life , Bangladesh , Leiomyoma/drug therapy
3.
BMC Health Serv Res ; 22(1): 1363, 2022 Nov 17.
Article in English | MEDLINE | ID: mdl-36397102

ABSTRACT

BACKGROUND: Drug overuse or drug underuse are the most common causes of adverse drug events and can lead to hospital admissions. Using clinical pharmacists in the emergency department may improve patient safety as they are specialised in recognising of adverse drug events and tackling drug overuse and drug underuse. This study tested the effect of an emergency department pharmacist on the number of medication changes for drug overuse and drug underuse taking place in patients with an adverse drug event-related hospitalisation following an emergency department visit. METHODS: A multicenter prospective non-randomized controlled intervention study was conducted in a university hospital and a general teaching hospital. Trained emergency department pharmacists included patients in the intervention group with a hospital admission related to an adverse drug event. The interdisciplinary intervention consisted of a pharmacist-led medication review, patient counselling regarding medication, and information transmission to general practitioners and community pharmacies after discharge. The control patients were also admitted after an emergency department visit and received the usual care. The primary outcome was the number of medication changes for drug overuse and drug underuse that took place during hospital admission and persisted 6 months thereafter. Poisson regression analysis was used to estimate the difference in these medication changes between the intervention group and the control group. RESULTS: A total of 216 patients were included (intervention group 104, control group 112). In the intervention group, 156 medication changes for drug overuse and drug underuse persisted 6 months after admission compared to 59 in the control group (adjusted rate ratio 1.22 [95%CI 1.01-1.49] p = 0.039). CONCLUSION: Emergency department pharmacists do contribute to reduction of drug overuse and drug underuse of medication in patients with a hospitalisation related to adverse drug events after an emergency department visit.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Pharmacists , Prescription Drug Overuse , Humans , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/prevention & control , Emergency Service, Hospital , Hospitalization , Hospitals, University , Medication Errors/prevention & control , Prospective Studies
4.
Sci Rep ; 12(1): 14974, 2022 Sep 02.
Article in English | MEDLINE | ID: mdl-36056101

ABSTRACT

The monitoring of leakage current (LC) and voltage characteristics in transmission line insulators is regarded as a good technique for anticipating the physical state of in-service insulators. In the current work, the temporal and frequency characteristics of LC and voltage under various situations were derived for assessing the health condition of porcelain, glass, and silicone rubber insulators. The contamination severity indicated by soluble deposit density, wetting level (Wt), non-soluble deposit density, and uneven pollution distribution (Pu/PL) were chosen as the environmental factors that impact the insulators. Six criteria were utilized to evaluate the physical state of the insulators, with four of those derived from the LC signal in the time domain, namely, the LC signal peak (C1), the phase shift between applied voltage and LC (C2), the LC signal slope between two consecutive peaks (C3), and the crest factor (C4). The remaining two indices, namely, the total harmonics distribution (C5) and the harmonics ratio indicator (C6), were obtained from the frequency domain of the LC signal. In addition, the flashover voltage index (C7) was also employed. The LC indicators were then classified based on the laboratory test results to reflect the physical state of the insulators. The findings revealed that the proposed indicators had an important impact in determining the physical state of the insulators. Furthermore, a confusion matrix was created for the test and prediction data using the suggested indicators to determine the effectiveness of each indicator.

5.
Mymensingh Med J ; 31(3): 779-789, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35780364

ABSTRACT

Patients with HIV or AIDS suffer from wide varieties of complications that are related to infection. The eye as an organ is not spared from HIV-related manifestations. The ocular manifestations can be the presenting sign of a systemic infection in an otherwise asymptomatic HIV-positive person. The disease can have adnexal, anterior segment, posterior segment, orbital and neuro-ophthalmic manifestations. The objective of the study was to evaluate the ophthalmological manifestations among adult HIV infected patients of Bangladesh and co-relate the findings with CD-4+ T cell count. This cross sectional study was conducted in the department of Community Ophthalmology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from January 2013 to September 2015. Purposive sampling technique was applied to enroll the patients. Total 110 patients were enrolled regardless of their immunological status by inclusion and exclusion criteria. Relevant clinical evaluation including history & physical examinations, laboratory investigations and some ocular examinations like- visual acuity, slit lamp biomicroscopy, IOP, indirect ophthalmoscopy with +90D (diopter) and +20D were done. The age of the study population ranged from 20-58 years with mean±SD 37.63±8.16 years. Among the study population 67(60.9%) were male and 43(39.1%) were female. According to ART status, 58(52.7%) were on ART and 52(47.3%) were ART naive. The mean CD4+ T- cells count was 410±281.65 with minimum to maximum was 6-1266 cells/µl. Among them 53(48.2%) had HIV related ocular findings and 57(51.8%) had no HIV related ocular manifestation. In relation with CD+ T- cells count, highly significant relation was found with lower CD4+ T- cells count and ocular manifestation (p=0.001).


Subject(s)
Acquired Immunodeficiency Syndrome , Eye Diseases , HIV Infections , Acquired Immunodeficiency Syndrome/complications , Acquired Immunodeficiency Syndrome/epidemiology , Adult , Bangladesh/epidemiology , CD4-Positive T-Lymphocytes , Cross-Sectional Studies , Eye Diseases/diagnosis , Eye Diseases/epidemiology , Eye Diseases/etiology , Female , HIV Infections/complications , HIV Infections/epidemiology , Humans , Male , Middle Aged , Young Adult
6.
Cureus ; 14(2): e21909, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35265430

ABSTRACT

Acquired hemophilia A (AHA) is an inhibitory coagulopathy that represents a rare variant of hemorrhagic syndromes. We present a case of idiopathic AHA in a 75-year-old male patient with a cutaneous hematoma that could be attributed to a recent COVID-19 vaccination. The aim of this report is to raise awareness of a possible association between AHA and COVID-19 vaccination and to review similar reported cases and management plans to prevent the development of possible morbidity and debilitating complications. This case illustrates an exceptionally rare side effect of the COVID-19 vaccination. The advantages of obtaining the COVID-19 vaccine outweigh the risks.

8.
Int J Biol Macromol ; 202: 671-680, 2022 Mar 31.
Article in English | MEDLINE | ID: mdl-35007634

ABSTRACT

Hybrid biocomposite scaffolds (HBS) that serve as a carrier for cell proliferation and differentiation are increasingly used for tissue regeneration. 3D hybrid scaffold based on collagen-grafted-chitosan-glucan fiber (CO-g-CGF-HBS) was prepared by freeze-drying technique. The swelling percentage, hydrolytic stability, and modulus of elasticity of HBS were enhanced after the chemical modification of CO with CGF. Pore size and porosity of HBS were decreased with an increased CGF ratio. HBS exhibits a higher reduction rate against different types of bacteria compared with a control sample. Thus, chemical modification of CO with different ratios of CGF significantly improved the physicochemical, antibacterial properties of HBS.


Subject(s)
Chitosan , Biocompatible Materials/chemistry , Cell Proliferation , Chitosan/chemistry , Collagen/chemistry , Glucans , Porosity , Tissue Engineering/methods , Tissue Scaffolds/chemistry
10.
Malays J Pathol ; 43(2): 251-259, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34448789

ABSTRACT

INTRODUCTION: The vast advancement of technology and breakthrough in high-tech disciplines created multiple areas of research activities, including the emergence of the medical drone. Malaysia, a rapidly developing country in Southeast Asia is on track to achieving high-income status. However, the stagnant growth of Malaysian maternal healthcare does not run parallel with the aspiration. This review paper assessed and reported narratively the current condition of maternal healthcare in Malaysia, the possible application of drones in improving the sector, exploring in detail several challenges, and providing recommendations for experts in studying the rising technological phenomena. MATERIALS AND METHODS: A literature search was done from June 2019 to November 2019 with restrictions to the English language. The search was performed in ScienceDirect, PubMed, and EMBASE databases, using a combination of search terms related to drones, Unmanned Aerial Vehicles (UAV), Unmanned Aerial Systems (UAS), maternal, obstetric, healthcare, medical products transportation and Malaysia. A discourse analysis followed and a narrative review was provided on this subject. RESULTS AND DISCUSSION: The validated ability of drones in the delivery of blood products is highlighted as a possible application in improving maternal healthcare in Malaysia, particularly in the state of Sabah. Five key challenges are identified: infrastructure, technicalities, regulations, expertise, and social acceptance. Future predictions of drone technology in healthcare were outlined with the suggestion of three principle arms of application. CONCLUSION: The usage of the medical drone in medical products transportation supports the objectives of WHO MDG 5 for Malaysian maternal health. A study on the impact of drones in reducing the maternal mortality ratio is recommended for further exploration.


Subject(s)
Delivery of Health Care , Unmanned Aerial Devices , Female , Humans , Malaysia , Pregnancy , Social Status , Technology
11.
Med J Malaysia ; 76(3): 441-445, 2021 05.
Article in English | MEDLINE | ID: mdl-34031351

ABSTRACT

Hunter Syndrome is a genetic disease characterized by deficiency of Iduronate-2-Sulfatase enzyme activity, resulting in accumulation of glycoaminoglycans in various organs including the central airways. We report a case of severe tracheomalacia and airway stenosis at Hospital Sultanah Aminah, Johor Bahru, Malaysia requiring mechanical ventilation in a middle aged gentleman who was previously undiagnosed of mucopolysaccharidosis. The patient underwent emergency tracheostomy for failed intubation, when he presented with shortness of breath and acute respiratory failure. A contrast-enhanced computed tomography of the neck and thorax revealed that the trachea distal to the tracheostomy tube had collapsed with narrowed right and left main bronchus. These findings were confirmed via direct visualization of the airway through a flexible bronchoscopy. Eventually, a tracheal stenting were performed to maintain the airway patency and assist in weaning off from mechanical ventilation. Further investigations to identify the aetiology of the central airway stenosis revealed elevated urinary glycoaminoglycans and the absence of iduronate-2-Sulfatase activity tested on dried blood spots, thus confirming the diagnosis of Hunter Syndrome. Managing mucopolysacharidosis with central airway obstruction requires multidisciplinary team effort in handling the difficult airway, anaesthesiology risk, potential comorbidities and providing genetic counselling.


Subject(s)
Airway Obstruction , Mucopolysaccharidosis II , Tracheomalacia , Airway Obstruction/etiology , Airway Obstruction/surgery , Bronchoscopy , Constriction, Pathologic , Humans , Male , Middle Aged , Mucopolysaccharidosis II/complications , Mucopolysaccharidosis II/diagnosis , Tracheomalacia/diagnostic imaging , Tracheomalacia/etiology , Tracheostomy
12.
Compr Rev Food Sci Food Saf ; 8(3): 195-201, 2009 Jul.
Article in English | MEDLINE | ID: mdl-33467796

ABSTRACT

This review article highlights the thermal behaviors of selected starches that were studied using differential scanning calorimetery (DSC) with data shown in various research publications. The starches of sago, potato, sweet potato, cassava, yam, and corn are included in this overview. Our examinations indicate that thermal properties are highly affected by the type of starch, its amylose/amylopectin content, and the presence of other food ingredients such as sugar, sodium chloride, water, milk, hydrocolloids, and meat. When the heating temperatures of the starches were increased, the DSC measurements also showed an increase in the temperatures of the gelatinization (onset [To ], peak [Tp ], and conclusion [Tc ]). This may be attributed to the differences in the degree of crystallinity of the starch, which provides structural stability and makes the granule more resistant to gelatinization.

13.
Clin Case Rep ; 8(12): 3515-3519, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33363963

ABSTRACT

The authors urge clinicians to consider the possibility of Kikuchi-Fujimoto Disease associated with autoimmune hemolytic anemia with possible correlation with systemic lupus erythematosus in patients presented with lymphadenopathy and fever.

14.
J Environ Manage ; 280: 111703, 2021 Feb 15.
Article in English | MEDLINE | ID: mdl-33288318

ABSTRACT

Disused Sealed Radioactive Sources (DSRS) borehole disposal is an innovative concept recommended by international atomic energy agency (IAEA) to improve the safety and security of the management end point for these sources. A green application of Palm Oil Fuel Ash (POFA) as a supplementary material for cementitious backfill barrier in DSRS borehole disposal facility is proposed. Samples with up to 50% POFA replacement complied with the mechanical and hydraulic performance requirements for backfill barriers in retrievable radioactive waste disposal facilities. The structures of one year old OPC and optimum OPC-POFA cement backfills were evaluated using FESEM, XRD, EDXRF, BET, and TGA and their 226 Ra confinement performances were assessed. 30% POFA replacement improved the geochemical conditions by reducing competitive Ca2+ release into the disposal environment. It enhanced 226Ra confinement performance independently on the amount of water intrusion or releases below 2% of 1 Ci source. The improved performance is attributed to the higher fraction of active sites of OPC-POFA backfill compared to that of OPC backfill. 226Ra sorption onto C-S-H is irreversible, spontaneous, endothermic, and independent on the degree of the surface filling. The provided experimental data and theoretical analysis proved the feasibility of this green use of POFA in reducing the radiological hazard of 226Ra.


Subject(s)
Radioactive Waste , Refuse Disposal , Construction Materials , Palm Oil , Radioactive Waste/analysis , Water
15.
Transl Psychiatry ; 10(1): 415, 2020 11 30.
Article in English | MEDLINE | ID: mdl-33257661

ABSTRACT

NMDA autoantibody encephalitis presenting as schizophrenia suggests the possible role of adaptive cell-mediated immunity in idiopathic schizophrenia. However, to our knowledge there have been no trials of the immune-suppressant methotrexate in schizophrenia. We tested if low-dose methotrexate as used in the treatment of systemic autoimmune disorders would be tolerable and effective in people with schizophrenia in a feasibility study. Ninety-two participants within 5 years of schizophrenia diagnosis were recruited from inpatient and outpatient facilities in Karachi, Pakistan. They were randomised to receive once weekly 10-mg oral methotrexate (n = 45) or matching placebo (n = 47) both with daily 5-mg folic acid, in addition to treatment as usual for 12 weeks. There were eight dropouts per group. Side effects were non-significantly more common in those on methotrexate and were not severe. One person developed leukopenia. Positive symptom scores improved more in those receiving methotrexate than placebo (ß = -2.5; [95% CI -4.7 to -0.4]), whereas negative symptoms were unaffected by treatment (ß = -0.39; [95% CI -2.01 to 1.23]). There were no immune biomarkers but methotrexate did not affect group mean leucocyte counts or C-reactive protein. We conclude that further studies are feasible but should be focussed on subgroups identified by advances in neuroimmune profiling. Methotrexate is thought to work in autoimmune disorders by resetting systemic regulatory T-cell control of immune signalling; we show that a similar action in the CNS would account for otherwise puzzling features of the immuno-pathogenesis of schizophrenia.


Subject(s)
Psychotic Disorders , Schizophrenia , Humans , Immunosuppressive Agents , Methotrexate/therapeutic use , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy
16.
Nat Commun ; 11(1): 6124, 2020 Nov 30.
Article in English | MEDLINE | ID: mdl-33257680

ABSTRACT

Tunneling is a fundamental quantum process with no classical equivalent, which can compete with Coulomb interactions to give rise to complex phenomena. Phosphorus dopants in silicon can be placed with atomic precision to address the different regimes arising from this competition. However, they exploit wavefunctions relying on crystal band symmetries, which tunneling interactions are inherently sensitive to. Here we directly image lattice-aperiodic valley interference between coupled atoms in silicon using scanning tunneling microscopy. Our atomistic analysis unveils the role of envelope anisotropy, valley interference and dopant placement on the Heisenberg spin exchange interaction. We find that the exchange can become immune to valley interference by engineering in-plane dopant placement along specific crystallographic directions. A vacuum-like behaviour is recovered, where the exchange is maximised to the overlap between the donor orbitals, and pair-to-pair variations limited to a factor of less than 10 considering the accuracy in dopant positioning. This robustness remains over a large range of distances, from the strongly Coulomb interacting regime relevant for high-fidelity quantum computation to strongly coupled donor arrays of interest for quantum simulation in silicon.

17.
Med J Malaysia ; 75(6): 717-721, 2020 11.
Article in English | MEDLINE | ID: mdl-33219183

ABSTRACT

BACKGROUND: Regarding the long-term safety issues with the use of inhaled corticosteroids (ICS) and the clinical predominance of dual bronchodilators in enhancing treatment outcomes in chronic obstructive pulmonary disease (COPD), ICS is no longer a "preferred therapy" according to the Global Initiative for Chronic Obstructive Lung Disease except on top of a dual bronchodilator. This has necessitated a change in the current therapy for many COPD patients. OBJECTIVE: To determine a standardised algorithm to reassess and personalise the treatment COPD patients based on the available evidence. METHODS: A consensus statement was agreed upon by a panel of pulmonologists in from 11 institutes in Malaysia whose members formed this consensus group. RESULTS: According to the consensus, which was unanimously adopted, all COPD patients who are currently receiving an ICS-based treatment should be reassessed based on the presence of co-existence of asthma or high eosinophil counts and frequency of moderate or severe exacerbations in the previous 12 months. When that the patients meet any of the aforementioned criteria, then the patient can continue taking ICS-based therapy. However, if the patients do not meet the criteria, then the treatment of patients need to be personalised based on whether the patient is currently receiving long-acting beta-agonists (LABA)/ICS or triple therapy. CONCLUSION: A flowchart of the consensus providing a guidance to Malaysian clinicians was elucidated based on evidences and international guidelines that identifies the right patients who should receive inhaled corticosteroids and enable to switch non ICS based therapies in patients less likely to benefit from such treatments.


Subject(s)
Adrenal Cortex Hormones , Pulmonary Disease, Chronic Obstructive , Adrenal Cortex Hormones/therapeutic use , Algorithms , Bronchodilator Agents/therapeutic use , Consensus , Drug Therapy, Combination , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy
18.
Mymensingh Med J ; 29(2): 488-494, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32506111

ABSTRACT

Since the first recorded case of SARS-CoV-2 in Bangladesh on 8th March 2020, COVID-19 has spread widely through different regions of the country, resulting in a necessity to re-evaluate the delivery of cardiovascular services, particularly procedures pertaining to interventional cardiology in resource-limited settings. Given its robust capacity for human-to-human transmission and potential of being a nosocomial source of infection, the disease has specific implications on healthcare systems and health care professionals faced with performing essential cardiac procedures in patients with a suspected or confirmed diagnosis of COVID-19. The limited resources in terms of cardiac catheterization laboratories that can be designated to treat only COVID positive patients are further compounded by the additional challenges of unavailability of widespread rapid testing on-site at tertiary cardiac hospitals in Bangladesh. This document prepared for our nation by the Bangladesh Society of Cardiovascular Interventions (BSCI) is intended to serve as a clinical practice guideline for cardiovascular health care professionals, with a focus on modifying standard practice of care during the COVID-19 pandemic, in order to ensure continuation of adequate and timely treatment of cardiovascular emergencies avoiding hospital-based transmission of SARS-COV-2 among healthcare professionals and the patients. This is an evolving document based on currently available global data and is tailored to healthcare systems in Bangladesh with particular focus on, but not limited to, invasive cardiology facilities (cardiac catheterization, electrophysiology & pacing labs). This guideline is limited to the provision of cardiovascular care, and it is expected that specific targeted pharmaco-therapeutics against SARS-CoV-2 be prescribed as stipulated by the National Guidelines on Clinical Management of Corona virus Disease 2019 (COVID-19) published by the Director General of Health Services, Ministry of Health and Family Welfare of Bangladesh.


Subject(s)
Cardiovascular Diseases , Cardiovascular Surgical Procedures , Coronavirus Infections , Pandemics , Pneumonia, Viral , Bangladesh , Betacoronavirus , COVID-19 , Cardiovascular Diseases/therapy , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Humans , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , SARS-CoV-2
19.
Environ Res ; 185: 109402, 2020 06.
Article in English | MEDLINE | ID: mdl-32213353

ABSTRACT

The feasibility of using Cyanex 301 impregnated onto biopolymer resin for removing cobalt from radioactive waste streams is investigated. The emulsion compositions for resin preparation were optimized to ensure compliance with nuclear grade resin specifications on particle size distribution and chemical stabilities using multi-variant analysis. The enhanced chemical stabilities of the resins in different solutions are attributed to the interaction between Cyanex 301 and the emulsifier with alginate via a reaction with the glycosidic bond. The structure and morphology of the three optimized samples were studied using FTIR, SEM, and TGA and their end-of-life cycle treatment was preliminarily investigated. Equilibrium sorption investigations revealed that the sorption is taking place via bi-layers onto two sites on the surface layer independently from the cobalt contamination level and the nature of these sites were characterized by determining the energy barriers and fraction of the weak and strong sites. Cobalt adsorption is chemical spontaneous endothermic reaction and the loaded material spectroscopic analysis and thermodynamics calculations referred to chemical coordination and hydrogen bonding. The enhanced radiological stabilities of the optimum resins at irradiation fields <100 KGy were explained and the relations between the loss of exchange capacity and the doses were quantified. The resins could be regenerated using 0.5 M HCl and the effect of the elution cycles on cobalt uptake was presented.


Subject(s)
Cobalt , Water Pollutants, Chemical , Adsorption , Hydrogen-Ion Concentration , Kinetics , Solutions , Thermodynamics
20.
Sci Adv ; 5(12): eaay2670, 2019 12.
Article in English | MEDLINE | ID: mdl-31897430

ABSTRACT

The cellular and the molecular mechanisms by which long noncoding RNAs (lncRNAs) may regulate presynaptic function and neuronal activity are largely unexplored. Here, we established an integrated screening strategy to discover lncRNAs implicated in neurotransmitter and synaptic vesicle release. With this approach, we identified neuroLNC, a neuron-specific nuclear lncRNA conserved from rodents to humans. NeuroLNC is tuned by synaptic activity and influences several other essential aspects of neuronal development including calcium influx, neuritogenesis, and neuronal migration in vivo. We defined the molecular interactors of neuroLNC in detail using chromatin isolation by RNA purification, RNA interactome analysis, and protein mass spectrometry. We found that the effects of neuroLNC on synaptic vesicle release require interaction with the RNA-binding protein TDP-43 (TAR DNA binding protein-43) and the selective stabilization of mRNAs encoding for presynaptic proteins. These results provide the first proof of an lncRNA that orchestrates neuronal excitability by influencing presynaptic function.


Subject(s)
DNA-Binding Proteins/metabolism , RNA, Long Noncoding/metabolism , Synaptic Vesicles/metabolism , Animals , Cell Movement/genetics , DNA-Binding Proteins/genetics , HEK293 Cells , Hippocampus/cytology , Humans , Mice , Mice, Transgenic , Neurogenesis/genetics , Neurons/metabolism , Neurotransmitter Agents/metabolism , RNA, Messenger/metabolism , Rats , Rats, Wistar , Transfection
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