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1.
J Neurochem ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38960403

RESUMO

Early-life stress (ES) induced by maternal separation (MS) remains a proven causality of anxiety and memory deficits at later stages of life. Emerging studies have shown that MS-induced gene expression in the hippocampus is operated at the level of transcription. However, the extent of involvement of non-coding RNAs in MS-induced behavioural deficits remains unexplored. Here, we have investigated the role of synapse-enriched long non-coding RNAs (lncRNAs) in anxiety and memory upon MS. We observed that MS led to an enhancement of expression of the lncRNA growth arrest specific 5 (Gas5) in the hippocampus; accompanied by increased levels of anxiety and deficits in spatial memory. Gas5 knockdown in early life was able to reduce anxiety and partially rescue the spatial memory deficits of maternally separated adult mice. However, the reversal of MS-induced anxiety and memory deficits is not attributed to Gas5 activity during neuronal development as Gas5 RNAi did not influence spine development. Gene Ontology analysis revealed that Gas5 exerts its function by regulating RNA metabolism and translation. Our study highlights the importance of MS-regulated lncRNA in anxiety and spatial memory.

2.
Chem Commun (Camb) ; 60(55): 7093-7096, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38899811

RESUMO

In this communication, we explored the synthesis of novel alkoxy-functionalised dihydropyrimido[4,5-b]quinolinones using a microwave-assisted multicomponent reaction. All the synthesized molecules were screened for anti-proliferative and anti-invasive activity against glioblastoma cells. 5c shows the most potent anti-proliferative activity with a half maximal effective concentration of less than 3 µM against primary patient-derived glioblastoma cells. 5c effectively inhibited invasion and tumor growth of 3D primary glioma cultures in a basement membrane matrix. This suggests that the novel compounds could inhibit both the proliferation and invasive spread of glioma and they were selected for further study.


Assuntos
Antineoplásicos , Proliferação de Células , Quinolonas , Humanos , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Quinolonas/química , Quinolonas/farmacologia , Quinolonas/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Linhagem Celular Tumoral , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Estrutura Molecular , Relação Estrutura-Atividade
3.
Indian J Otolaryngol Head Neck Surg ; 76(3): 2619-2625, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38883512

RESUMO

Chronic Otitis Media is characterized by distinct bacteriology compared with Acute Otitis Media, with COM being highly likely to harbor multiple bacteria of anaerobic and aerobic types of organisms (Cameron and Hussam K. El-Kashlan, xxx). In some patients, chronic infection with otorrhea will persist despite aggressive medical therapy. With the large number of cases of COM which presents to Sanjay Gandhi Memorial Hospital, and a majority being resistant to the common medications, we decided to undertake this study to have a better understanding of the bacterial epidemiology, the resistance, and what antibiotic to use in such cases. To determine the prevalence of different bacteriological agents and their antibiotic sensitivity pattern in patients of Chronic Otitis Media-Active Mucosal Disease presenting to ENT OPD at Sanjay Gandhi Memorial Hospital, Mangolpuri, Delhi. An observational cross-sectional study of 200 patients. After an initial examination, two sterile cotton swab sticks were introduced to collect pus samples from the medial part of the external auditory canal. The swabs were sent to the microbiology lab for Gram Staining, Culture, and Biochemical Tests, for identification of the different bacteriological agents and their antibiotic sensitivity patterns. Most common organism seen was Pseudomonas aeruginosa, followed by Staphylococcus aureus, Klebsiella pneumoniae, Proteus mirabilis, mixed bacterial growth, and Candida spp. If regular monitoring of bacteriological profile is done in each hospital, this will help us to choose the antibiotics in a better manner and hence prevent the appearance of newer resistant strains.

4.
Bioorg Chem ; 149: 107485, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38824700

RESUMO

There is a continuous and pressing need to establish new brain-penetrant bioactive compounds with anti-cancer properties. To this end, a new series of 4'-((4-substituted-4,5-dihydro-1H-1,2,3-triazol-1-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile (OTBN-1,2,3-triazole) derivatives were synthesized by click chemistry. The series of bioactive compounds were designed and synthesized from diverse alkynes and N3-OTBN, using copper (II) acetate monohydrate in aqueous dimethylformamide at room temperature. Besides being highly cost-effective and significantly reducing synthesis, the reaction yielded 91-98 % of the target products without the need of any additional steps or chromatographic techniques. Two analogues exhibit promising anti-cancer biological activities. Analogue 4l shows highly specific cytostatic activity against lung cancer cells, while analogue 4k exhibits pan-cancer anti-growth activity. A kinase screen suggests compound 4k has single-digit micromolar activity against kinase STK33. High STK33 RNA expression correlates strongly with poorer patient outcomes in both adult and pediatric glioma. Compound 4k potently inhibits cell proliferation, invasion, and 3D neurosphere formation in primary patient-derived glioma cell lines. The observed anti-cancer activity is enhanced in combination with specific clinically relevant small molecule inhibitors. Herein we establish a novel biochemical kinase inhibitory function for click-chemistry-derived OTBN-1,2,3-triazole analogues and further report their anti-cancer activity in vitro for the first time.


Assuntos
Antineoplásicos , Proliferação de Células , Química Click , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Proteínas Quinases , Proteínas Serina-Treonina Quinases , Triazóis , Humanos , Triazóis/química , Triazóis/farmacologia , Triazóis/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Estrutura Molecular , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Linhagem Celular Tumoral , Nitrilas/química , Nitrilas/farmacologia , Nitrilas/síntese química
5.
Bioessays ; 46(7): e2400053, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38713161

RESUMO

Trypanosoma brucei is the causal agent of African Trypanosomiasis in humans and other animals. It maintains a long-term infection through an antigenic variation based population survival strategy. To proliferate in a mammal, T. brucei acquires iron and haem through the receptor mediated uptake of host transferrin and haptoglobin-hemoglobin respectively. The receptors are exposed to host antibodies but this does not lead to clearance of the infection. Here we discuss how the trypanosome avoids this fate in the context of recent findings on the structure and cell biology of the receptors.


Assuntos
Trypanosoma brucei brucei , Tripanossomíase Africana , Trypanosoma brucei brucei/imunologia , Trypanosoma brucei brucei/metabolismo , Humanos , Animais , Tripanossomíase Africana/imunologia , Tripanossomíase Africana/parasitologia , Haptoglobinas/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/imunologia , Transferrina/metabolismo , Hemoglobinas/metabolismo , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/imunologia , Interações Hospedeiro-Parasita/imunologia , Ferro/metabolismo , Anticorpos Antiprotozoários/imunologia
6.
ACS Infect Dis ; 10(4): 1414-1428, 2024 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-38556987

RESUMO

PDZ protein interacting specifically with Tc10 or PIST is a mammalian trans-Golgi resident protein that regulates subcellular sorting of plasma membrane receptors. PIST has recently emerged as a key player in regulating viral pathogenesis. Nevertheless, the involvement of PIST in parasitic infections remains unexplored. Leishmania parasites infiltrate their host macrophage cells through phagocytosis, where they subsequently multiply within the parasitophorous vacuole (PV). Host cell autophagy has been found to be important in regulating this parasite infection. Since PIST plays a pivotal role in triggering autophagy through the Beclin 1-PI3KC3 pathway, it becomes interesting to identify the status of PIST during Leishmania infection. We found that while macrophage cells are infected with Leishmania major (L. major), the expression of PIST protein remains unaltered; however, it traffics from the Golgi compartment to PV. Further, we identified that in L. major-infected macrophage cells, PIST associates with the autophagy regulatory protein Beclin 1 within the PVs; however, PIST does not interact with LC3. Reduction in PIST protein through siRNA silencing significantly increased parasite burden, whereas overexpression of PIST in macrophages restricted L. major infectivity. Together, our study reports that the macrophage PIST protein is essential in regulating L. major infectivity.


Assuntos
Leishmania major , Leishmaniose , Macrófagos , Animais , Proteína Beclina-1/metabolismo , Proteínas de Transporte/metabolismo , Leishmania major/metabolismo , Macrófagos/parasitologia
7.
RSC Adv ; 14(13): 9300-9313, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38505382

RESUMO

Owing to the massive importance of dihydropyrimidine (DHPMs) scaffolds in the pharmaceutical industry and other areas, we developed an effective and sustainable one-pot reaction protocol for the synthesis of (R/S)-2-thioxo-DHPM-5-carboxanilides via the Biginelli-type cyclo-condensation reaction of aryl aldehydes, thiourea and various acetoacetanilide derivatives in ethanol at 100 °C. In this protocol, taurine was used as a green and reusable bio-organic catalyst. Twenty-three novel derivatives of (R/S)-TDHPM-5-carboxanilides and their structures were confirmed by various spectroscopy techniques. The aforementioned compounds were synthesized via the formation of one asymmetric centre, one new C-C bond, and two new C-N bonds in the final product. All the newly synthesized compounds were obtained in their racemic form with up to 99% yield. In addition, the separation of the racemic mixture of all the newly synthesized compounds was carried out by chiral HPLC (Prep LC), which provided up to 99.99% purity. The absolute configuration of all the enantiomerically pure isomers was determined using a circular dichroism study and validated by a computational approach. With up to 99% yield of 4d, this one-pot synthetic approach can also be useful for large-scale industrial production. One of the separated isomers (4R)-(+)-4S developed as a single crystal, and it was found that this crystal structure was orthorhombic.

8.
Sci Rep ; 14(1): 3213, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332231

RESUMO

Extremely rare topologically protected acoustic energy sink is presented in this article. Acoustic topological phenomena are generally described using quantum anomalous hall effects (QAHE), quantum valley hall effects (QVHE), and quantum spin hall effects (QSHE) where spin orbit coupling is predominant. Topological edge states are demonstrated by bulk-boundary distinction when the bulk is insulated. In this article topological acoustic conductor and its phenomena are theoretically demonstrated where the boundaries are insulated. This is exactly opposite to the behavior of a topological acoustic insulator. Phenomena presented in this article could not be explained by any of the trio Quantum Hall effects. To explain the phenomenon phononic crystals or PnCs were designed to obtain accidental triple degeneracies, resulting a Dirac-like cone at the Γ point ([Formula: see text]). The phenomenon is microarchitecture and microrotation field independent. Here time reversal symmetry or the space inversion symmetry is not broken, and the degenerated 'Deaf band' dominates the local dispersion with a syncline top band. This scenario results in continuously changing 'up spin' and 'down spin' of the wave energy in the media and remain trapped without specific preferential direction of wave transport. The spin was found to generate the spin angular momentum, causing the switching in geometric phase from [Formula: see text] in cyclic pattern, keeping the energy trapped inside the bulk media.

9.
Sensors (Basel) ; 24(2)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38276335

RESUMO

The article presents the design concept of a surface acoustic wave (SAW)-based lab-on-a-chip sensor with multifrequency and multidirectional sensitivity. The conventional SAW sensors use delay lines that suffer from multiple signal losses such as insertion, reflection, transmission losses, etc. Most delay lines are designed to transmit and receive continuous signal at a fixed frequency. Thus, the delay lines are limited to only a few features, like frequency shift and change in wave velocity, during the signal analysis. These facts lead to limited sensitivity and a lack of opportunity to utilize the multi-directional variability of the sensing platform at different frequencies. Motivated by these facts, a guided wave sensing platform that utilizes simultaneous tone burst-based excitation in multiple directions is proposed in this article. The design incorporates a five-count tone burst signal for the omnidirectional actuation. This helps the acquisition of sensitive long part of the coda wave (CW) signals from multiple directions, which is hypothesized to enhance sensitivity through improved signal analysis. In this article, the design methodology and implementation of unique tone burst interdigitated electrodes (TB-IDT) are presented. Sensing using TB-IDT enables accessing multiple frequencies simultaneously. This results in a wider frequency spectrum and allows better scope for the detection of different target analytes. The novel design process utilized guided wave analysis of the substrate, and selective directional focused interdigitated electrodes (F-IDT) were implemented. The article demonstrates computational simulation along with experimental results with validation of multifrequency and multidirectional sensing capability.

10.
Arch Pharm (Weinheim) ; 357(4): e2300673, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38247229

RESUMO

In the face of escalating challenges of microbial resistance strains, this study describes the design and synthesis of 5-({1-[(1H-1,2,3-triazol-4-yl)methyl]-1H-indol-3-yl}methylene)thiazolidine-2,4-dione derivatives, which have demonstrated significant antimicrobial properties. Compared with the minimum inhibitory concentrations (MIC) values of ciprofloxacin on the respective strains, compounds 5a, 5d, 5g, 5l, and 5m exhibited potent antibacterial activity with MIC values ranging from 16 to 25 µM. Almost all the synthesized compounds showed lower MIC compared to standards against vancomycin-resistant enterococcus and methicillin-resistant Staphylococcus aureus strains. Additionally, the majority of the synthesized compounds demonstrated remarkable antifungal activity, against Candida albicans and Aspergillus niger, as compared to nystatin, griseofulvin, and fluconazole. Furthermore, the majority of compounds exhibited notable inhibitory effects against the Plasmodium falciparum strain, having IC50 values ranging from 1.31 to 2.79 µM as compared to standard quinine (2.71 µM). Cytotoxicity evaluation of compounds 5a-q on SHSY-5Y cells at up to 100 µg/mL showed no adverse effects. Comparison with control groups highlights their noncytotoxic characteristics. Molecular docking confirmed compound binding to target active sites, with stable protein-ligand complexes displaying drug-like molecules. Molecular dynamics simulations revealed dynamic stability and interactions. Rigorous tests and molecular modeling unveil the effectiveness of the compounds against drug-resistant microbes, providing hope for new antimicrobial compounds with potential safety.


Assuntos
Antimaláricos , Staphylococcus aureus Resistente à Meticilina , Tiazolidinedionas , Antibacterianos/química , Antimaláricos/farmacologia , Triazóis/farmacologia , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Indóis/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular
11.
Nat Commun ; 14(1): 7616, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37993455

RESUMO

Long noncoding RNAs (lncRNAs) represent a multidimensional class of regulatory molecules that are involved in many aspects of brain function. Emerging evidence indicates that lncRNAs are localized to the synapse; however, a direct role for their activity in this subcellular compartment in memory formation has yet to be demonstrated. Using lncRNA capture-seq, we identified a specific set of lncRNAs that accumulate in the synaptic compartment within the infralimbic prefrontal cortex of adult male C57/Bl6 mice. Among these was a splice variant related to the stress-associated lncRNA, Gas5. RNA immunoprecipitation followed by mass spectrometry and single-molecule imaging revealed that this Gas5 isoform, in association with the RNA binding proteins G3BP2 and CAPRIN1, regulates the activity-dependent trafficking and clustering of RNA granules. In addition, we found that cell-type-specific, activity-dependent, and synapse-specific knockdown of the Gas5 variant led to impaired fear extinction memory. These findings identify a new mechanism of fear extinction that involves the dynamic interaction between local lncRNA activity and RNA condensates in the synaptic compartment.


Assuntos
Medo , RNA Longo não Codificante , Camundongos , Masculino , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Extinção Psicológica , Córtex Pré-Frontal/metabolismo , Sinapses/metabolismo
12.
Sci Rep ; 13(1): 20215, 2023 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-37980454

RESUMO

Sonodynamic therapy (SDT) is currently on critical path for glioblastoma therapeutics. SDT is a non-invasive approach utilising focused ultrasound to activate photosensitisers like 5-ALA to impede tumour growth. Unfortunately, the molecular mechanisms underlying the therapeutic functions of SDT remain enigmatic. This is primarily due to the lack of intricately optimised instrumentation capable of modulating SDT delivery to glioma cells in vitro. Consequently, very little information is available on the effects of SDT on glioma stem cells which are key drivers of gliomagenesis and recurrence. To address this, the current study has developed and validated an automated in vitro SDT system to allow the application and mapping of focused ultrasound fields under varied exposure conditions and setup configurations. The study optimizes ultrasound frequency, intensity, plate base material, thermal effect, and the integration of live cells. Indeed, in the presence of 5-ALA, focused ultrasound induces apoptotic cell death in primary patient-derived glioma cells with concurrent upregulation of intracellular reactive oxygen species. Intriguingly, primary glioma stem neurospheres also exhibit remarkably reduced 3D growth upon SDT exposure. Taken together, the study reports an in vitro system for SDT applications on tissue culture-based disease models to potentially benchmark the novel approach to the current standard-of-care.


Assuntos
Glioblastoma , Glioma , Terapia por Ultrassom , Humanos , Glioblastoma/patologia , Ácido Aminolevulínico/farmacologia , Glioma/patologia , Apoptose , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral
13.
BMJ Case Rep ; 16(10)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37857539

RESUMO

Posterior fossa ependymomas (PFEs) are designated histologically as low-grade neoplasms. Despite being characterised as benign, cases of metastasis have been reported only a few times with the patients concurrently diagnosed with the primary tumour. Interval drop metastasis or spontaneous second distal tumours are extremely rare and, in most cases, are diagnosed within a few months of primary tumour resection. Here, we report a patient with a grade 2 paediatric PFE exhibiting a 20-year interval to a second sacral ependymoma. The patient was initially diagnosed with a PFE at the age of 10 years and underwent tumour resection and postoperative radiotherapy. In their late 20s, the patient presented with basilar artery occlusion complicated by life-threatening epistaxis. Post-thrombolysis, the patient presented with a large sacral grade 1 myxopapillary ependymoma with cauda equina syndrome-like symptoms. Here, we present a rare case of two ependymomas with a 20-year interval in the same patient with compounding comorbidities.


Assuntos
Ependimoma , Neoplasias da Medula Espinal , Humanos , Criança , Ependimoma/diagnóstico , Ependimoma/cirurgia , Ependimoma/patologia , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/cirurgia , Neoplasias da Medula Espinal/complicações
14.
Curr Protoc ; 3(9): e886, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37755318

RESUMO

Investigating the RNA regulation landscape primarily relies on understanding how RNA-protein interactions are governed in various cell types, including neurons. Analysis of RNA-protein interactions in physiological environments warrants the development of new tools that rely on RNA manipulation. Recently, a CRISPR-based RNA-editing tool (dCas13b-ADAR2DD ) was developed to mitigate disease-associated point mutations in cell lines. Here, we explored the targeted sequence editing potential of the tool (dCas13b-ADAR2DD system) by adapting it to manipulate RNA function to visualize RNA editing in primary hippocampal neurons. This two-component system includes a programmable guide RNA (gRNA) complementary to the target RNA and a catalytically dead version of the Cas13b enzyme fused to ADAR. The RNA editing protocol outlined in this article relies on gRNA-dependent targeting of the dCas13b-ADAR fusion protein to the mutant form of the Dendra2 transcript. Dendra2 is not required for intrinsic cellular functioning. It was ectopically expressed for fluorescent detection as a proof-of-principle demonstration of targeted RNA editing. We first abrogated the fluorescence of Dendra2 by introducing a nonsense mutation that precludes the formation of the functional protein. To visualize the efficacy of the RNA editing in neurons, we used the dCas13b-ADAR2DD system to edit specific nucleotides within the Dendra2 mRNA to restore the amino acid codes critical for Dendra2 fluorescence. This method lays the foundation for future studies on the dynamics of activity-induced RNA-protein interactions in neurons and can be extended to manipulate the endogenous RNome in diverse neuronal subtypes. Furthermore, this methodology will enable investigators to visualize the spatial and temporal resolution of RNA-protein interactions without altering the genomes via conventional methods. © 2023 Wiley Periodicals LLC. Support Protocol: Preparation of mouse primary hippocampal culture Basic Protocol: Targeted editing of RNA.

15.
Cell Commun Signal ; 21(1): 258, 2023 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-37749555

RESUMO

Homocysteine (Hcy), produced physiologically in all cells, is an intermediate metabolite of methionine and cysteine metabolism. Hyperhomocysteinemia (HHcy) resulting from an in-born error of metabolism that leads to accumulation of high levels of Hcy, is associated with vascular damage, neurodegeneration and cognitive decline. Using a HHcy model in neuronal cells, primary cortical neurons and transgenic zebrafish, we demonstrate diminished autophagy and Hcy-induced neurotoxicity associated with mitochondrial dysfunction, fragmentation and apoptosis. We find this mitochondrial dysfunction is due to Hcy-induced proteotoxicity leading to ER stress. We show this sustained proteotoxicity originates from the perturbation of upstream autophagic pathways through an aberrant activation of mTOR and that protetoxic stress act as a feedforward cues to aggravate a sustained ER stress that culminate to mitochondrial apoptosis in HHcy model systems. Using chemical chaperones to mitigate sustained ER stress, Hcy-induced proteotoxicity and consequent neurotoxicity were rescued. We also rescue neuronal lethality by activation of autophagy and thereby reducing proteotoxicity and ER stress. Our findings pave the way to devise new strategies for the treatment of neural and cognitive pathologies reported in HHcy, by either activation of upstream autophagy or by suppression of downstream ER stress. Video Abstract.


Assuntos
Hiper-Homocisteinemia , Animais , Peixe-Zebra , Apoptose , Autofagia , Homocisteína , Controle de Qualidade
16.
PLoS Genet ; 19(8): e1010885, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37603562

RESUMO

Regulation of the microtubule cytoskeleton is crucial for the development and maintenance of neuronal architecture, and recent studies have highlighted the significance of regulated RNA processing in the establishment and maintenance of neural circuits. In a genetic screen conducted using mechanosensory neurons of C. elegans, we identified a mutation in muscleblind-1/mbl-1 as a suppressor of loss of kinesin-13 family microtubule destabilizing factor klp-7. Muscleblind-1(MBL-1) is an RNA-binding protein that regulates the splicing, localization, and stability of RNA. Our findings demonstrate that mbl-1 is required cell-autonomously for axon growth and proper synapse positioning in the posterior lateral microtubule (PLM) neuron. Loss of mbl-1 leads to increased microtubule dynamics and mixed orientation of microtubules in the anterior neurite of PLM. These defects are also accompanied by abnormal axonal transport of the synaptic protein RAB-3 and reduction of gentle touch sensation in mbl-1 mutant. Our data also revealed that mbl-1 is genetically epistatic to mec-7 (ß tubulin) and mec-12 (α tubulin) in regulating axon growth. Furthermore, mbl-1 is epistatic to sad-1, an ortholog of BRSK/Brain specific-serine/threonine kinase and a known regulator of synaptic machinery, for synapse formation at the correct location of the PLM neurite. Notably, the immunoprecipitation of MBL-1 resulted in the co-purification of mec-7, mec-12, and sad-1 mRNAs, suggesting a direct interaction between MBL-1 and these transcripts. Additionally, mbl-1 mutants exhibited reduced levels and stability of mec-7 and mec-12 transcripts. Our study establishes a previously unknown link between RNA-binding proteins and cytoskeletal machinery, highlighting their crucial roles in the development and maintenance of the nervous system.


Assuntos
Caenorhabditis elegans , Tubulina (Proteína) , Animais , Tubulina (Proteína)/genética , Caenorhabditis elegans/genética , RNA Mensageiro , Citoesqueleto/genética , Microtúbulos/genética , Neurônios
17.
J Biol Chem ; 299(8): 105064, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37468101

RESUMO

Leishmania parasites are heavily dependent on efficient iron acquisition from a tightly regulated host iron pool for survival and virulence. Prior studies uncovered multiple strategies adopted by the parasite to hijack the iron-regulatory network of macrophages. Despite these extensive studies with infected macrophages, there is limited knowledge of the effect of Leishmania infection on systemic iron homeostasis. This issue is particularly relevant for Leishmania major, which causes localized skin infection with minimal lymphatic spread. We show for the first time that L. major infection in the mouse footpad induced influx of iron at the site of infection through blood with simultaneous upregulation of transferrin receptor 1 and downregulation of phagolysosomal iron exporter Nramp1 expression in the footpad tissue. Interestingly, localized L. major infection had far-reaching effects beyond the infection site triggering anemia-like symptoms. This was evident from depleted physiological iron stores from the liver and bone marrow as well as reduced hemoglobin levels and deformed erythrocytes. The infected mice also developed splenomegaly with signs of splenic stress erythropoiesis as indicated by upregulation of several erythroid-related genes. These observations prompted us to provide oral iron supplementations to the L. major-infected mice, which resulted in a drastic reduction of the parasite load and restoration of iron homeostasis.


Assuntos
Homeostase , Ferro , Leishmaniose Cutânea , Animais , Camundongos , Suplementos Nutricionais , Eritrócitos/metabolismo , Ferro/administração & dosagem , Ferro/metabolismo , Leishmania major , Leishmaniose Cutânea/metabolismo
18.
Brain Sci ; 13(5)2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37239234

RESUMO

BACKGROUND: Endothelial dysfunction is implicated in various inflammatory diseases such as ischemic stroke, heart attack, organ failure, and COVID-19. Recent studies have shown that endothelial dysfunction in the brain is attributed to excessive inflammatory responses caused by the SARS-CoV-2 infection, leading to increased permeability of the blood-brain barrier and consequently neurological damage. Here, we aim to examine the single-cell transcriptomic landscape of endothelial dysfunction in COVID-19 and its implications for glioblastoma (GBM) progression. METHODS: Single-cell transcriptome data GSE131928 and GSE159812 were obtained from the gene expression omnibus (GEO) to analyze the expression profiles of key players in innate immunity and inflammation between brain endothelial dysfunction caused by COVID-19 and GBM progression. RESULTS: Single-cell transcriptomic analysis of the brain of COVID-19 patients revealed that endothelial cells had undergone significant transcriptomic changes, with several genes involved in immune responses and inflammation upregulated. Moreover, transcription factors were observed to modulate this inflammation, including interferon-regulated genes. CONCLUSIONS: The results indicate a significant overlap between COVID-19 and GBM in the context of endothelial dysfunction, suggesting that there may be an endothelial dysfunction link connecting severe SARS-CoV-2 infection in the brain to GBM progression.

19.
Sensors (Basel) ; 23(9)2023 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-37177431

RESUMO

Artificial methods for noise filtering are required for the twenty-first century's Factory vision 4.0. From various perspectives of physics, noise filtering capabilities could be addressed in multiple ways. In this article, the physics of noise control is first dissected into active and passive control mechanisms and then further different physics are categorized to visualize their respective physics, mechanism, and target of their respective applications. Beyond traditional passive approaches, the comparatively modern concept for sound isolation and acoustic noise filtering is based on artificial metamaterials. These new materials demonstrate unique interaction with acoustic wave propagation exploiting different physics, which is emphasized in this article. A few multi-functional metamaterials were reported to harvest energy while filtering the ambient noise simultaneously. It was found to be extremely useful for next-generation noise applications where simultaneously, green energy could be generated from the energy which is otherwise lost. In this article, both these concepts are brought under one umbrella to evaluate the applicability of the respective methods. An attempt has been made to create groundbreaking transformative and collaborative possibilities. Controlling of acoustic sources and active damping mechanisms are reported under an active mechanism. Whereas Helmholtz resonator, sound absorbing, spring-mass damping, and vibration absorbing approaches together with metamaterial approaches are reported under a passive mechanism. The possible application of metamaterials with ventilation while performing noise filtering is reported to be implemented for future Smart Cities.

20.
Membranes (Basel) ; 13(2)2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36837734

RESUMO

In this work, we report the effect of steady-state atmospheric plasma (Corona discharge) in nanofibers and nanocomposite membranes for piezoelectric applications. The investigation was performed in PVDF (Poly vinylidene fluoride) nanofibers, CNT (Carbon Nanotubes)-reinforced PVDF nanocomposites, and PAN (Poly acrylonitrile) nanofiber membranes. Steady-state plasma was generated with a high voltage power source with 1 mA discharge current output and 6 kV discharge voltage, and the gap between tip and the material was maintained to be 1 cm. For the fabrication of nanofibers and nanocomposite membranes, an electrospinning method was used. The electrospinning parameters, such as flow rate and voltage, were optimally tuned for obtaining uniform nanofibers and nanomembranes. Along with the plasma treatment, heat treatment above the glass transition temperature was also conducted on the nanofiber membranes. Using a Scanning Electron Microscope (SEM), the morphology of the nanofibers was observed. X-ray Diffraction (XRD) demonstrated the polycrystallinity of the nanofibers. Fourier Transform Infrared Spectroscopy (FTIR) analysis of the PVDF nanofibers shows a peak at 796 cm-1 representing α-phase (C-H rocking) in the control sample which is absent in the treated samples. Raman spectroscopy of PVDF nanofibers identifies a Raman shift from 873 cm-1 to 877 cm-1 (denoting ß-phase) for plasma-treated samples only. Electron Paramagnetic Resonance (EPR) concludes that the intensity of the free radicals increases from 1.37 to 1.46 (a.u.) after plasma treatment. Then, sensors were fabricated from the PVDF nanofibers, MWCNT-reinforced PVDF nanofibers, and PAN nanofibers to characterize their piezoelectric properties. The impact test results showed that the atmospheric plasma and heat-treated samples had 86%, 277%, and 92% increases of the d33 value (piezoelectric coefficient) in the case of PVDF nanofibers, MWCNT-reinforced nanofibers, and PAN nanofibers, respectively. It was also observed that the capacitance of the nanofiber membranes has increased due to the plasma treatment.

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