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1.
Development ; 146(13)2019 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-31292144

RESUMEN

Monensin-sensitive 1 (Mon1) is an endocytic regulator that participates in the conversion of Rab5-positive early endosomes to Rab7-positive late endosomes. In Drosophila, loss of mon1 leads to sterility as the mon1 mutant females have extremely small ovaries with complete absence of late stage egg chambers - a phenotype reminiscent of mutations in the insulin pathway genes. Here, we show that expression of many Drosophila insulin-like peptides (ILPs) is reduced in mon1 mutants and feeding mon1 adults an insulin-rich diet can rescue the ovarian defects. Surprisingly, however, mon1 functions in the tyramine/octopaminergic neurons (OPNs) and not in the ovaries or the insulin-producing cells (IPCs). Consistently, knockdown of mon1 in only the OPNs is sufficient to mimic the ovarian phenotype, while expression of the gene in the OPNs alone can 'rescue' the mutant defect. Last, we have identified ilp3 and ilp5 as critical targets of mon1. This study thus identifies mon1 as a novel molecular player in the brain-gonad axis and underscores the significance of inter-organ systemic communication during development.


Asunto(s)
Encéfalo/metabolismo , Diferenciación Celular/genética , Proteínas de Drosophila/fisiología , Células Germinativas/fisiología , Gónadas/metabolismo , Ovario/crecimiento & desarrollo , Animales , Animales Modificados Genéticamente , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/crecimiento & desarrollo , Femenino , Regulación del Desarrollo de la Expresión Génica , Infertilidad Femenina/genética , Infertilidad Femenina/patología , Insulina/fisiología , Insulinas/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Oocitos/fisiología , Oogénesis/genética , Tamaño de los Órganos/genética , Ovario/anomalías , Ovario/metabolismo , Ovario/patología , Óvulo/fisiología , Comunicación Paracrina/genética , Transducción de Señal/genética
2.
Front Cell Infect Microbiol ; 13: 1104615, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36926513

RESUMEN

The use of nanomaterials in several fields of science has undergone a revolution in the last few decades. It has been reported by the National Institutes of Health (NIH) that 65% and 80% of infections are accountable for at least 65% of human bacterial infections. One of their important applications in healthcare is the use of nanoparticles (NPs) to eradicate free-floating bacteria and those that form biofilms. A nanocomposite (NC) is a multiphase stable fabric with one or three dimensions that are much smaller than 100 nm, or systems with nanoscale repeat distances between the unique phases that make up the material. Using NC materials to get rid of germs is a more sophisticated and effective technique to destroy bacterial biofilms. These biofilms are refractory to standard antibiotics, mainly to chronic infections and non-healing wounds. Materials like graphene and chitosan can be utilized to make several forms of NCs, in addition to different metal oxides. The ability of NCs to address the issue of bacterial resistance is its main advantage over antibiotics. This review highlights the synthesis, characterization, and mechanism through which NCs disrupt Gram-positive and Gram-negative bacterial biofilms, and their relative benefits and drawbacks. There is an urgent need to develop materials like NCs with a larger spectrum of action due to the rising prevalence of human bacterial diseases that are multidrug-resistant and form biofilms.


Asunto(s)
Infecciones Bacterianas , Nanocompuestos , Nanopartículas , Humanos , Biopelículas , Antibacterianos/farmacología , Bacterias
3.
Artículo en Inglés | MEDLINE | ID: mdl-35410623

RESUMEN

Allergies have been known to be an abnormally vigorous immune response in which the immune system fights off an allergen or antigen, initiating mast cells to release histamine into the blood. Substances that prevent mast cells from releasing histamine are considered antiallergic agents. The drugs utilized to treat allergy are mast cell stabilizers, steroids, anti-histamine, leukotriene receptor antagonists, and decongestants. Anti-histamine drugs have side effects such as drowsiness, confusion, constipation, difficulty urinating, blurred vision, etc. The use of medicinal plants for the effective and safe management of diseases has recently received much attention. Various herbs are utilized for their antiallergic and anti-histaminic properties. Some of the herbs useful in the management of allergic diseases of the respiratory tract, like Piper longum, Ocimum tenuiflorum, Solanum xanthocarpum have been discussed. Ample scientific evidence is available for the anti-histaminic and antiallergic activity of Azadirachta indica, Aloe vera, Tinospora cordifolia, and many other such herbs are safer to use as antiallergic agents have been reported. The review summarizes a wide variety of herbs and botanical ingredients with their common scientific names and distribution for easy identification and usage as safe antiallergic agents and discusses their molecular mechanisms involved in combating allergic reactions.


Asunto(s)
Antialérgicos , Hipersensibilidad , Humanos , Antialérgicos/farmacología , Antialérgicos/uso terapéutico , Estabilizadores de Mastocitos , Antagonistas de Leucotrieno/uso terapéutico , Descongestionantes Nasales/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Hipersensibilidad/tratamiento farmacológico , Histamina/uso terapéutico , Alérgenos
4.
Commun Biol ; 5(1): 687, 2022 07 09.
Artículo en Inglés | MEDLINE | ID: mdl-35810216

RESUMEN

Optogenetic silencing allows to reveal the necessity of selected neuronal populations for various neurophysiological functions. These range from synaptic transmission and coordinated neuronal network activity to control of specific behaviors. An ideal single-component optogenetic silencing tool should be switchable between active and inactive states with precise timing while preserving its activity in the absence of light until switched to an inactive state. Although bistable anion-conducting channelrhodopsins (ACRs) were previously engineered to reach this goal, their conducting state lifetime was limited to only a few minutes and some ACRs were not fully switchable. Here we report Aion, a bistable ACR displaying a long-lasting open state with a spontaneous closing time constant close to 15 min. Moreover, Aion can be switched between the open and closed state with millisecond precision using blue and orange light, respectively. The long conducting state enables overnight silencing of neurons with minimal light exposure. We further generated trafficking-optimized versions of Aion, which show enhanced membrane localization and allow precisely timed, long-lasting all-optical control of nociceptive responses in larvae of Drosophila melanogaster. Thus, Aion is an optogenetic silencing tool for inhibition of neuronal activity over many hours which can be switched between an active and inactive state with millisecond precision.


Asunto(s)
Drosophila melanogaster , Optogenética , Animales , Aniones/metabolismo , Channelrhodopsins/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Neuronas/fisiología
5.
Neurol India ; 70(4): 1643-1648, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36076674

RESUMEN

X-linked myopathy with excessive autophagy (XMEA) is a rare, recently characterized type of autophagic vacuolar myopathy caused by mutations in the VMA21 gene. It is characterized by slowly progressive weakness restricted to proximal limb muscles and generally has a favorable outcome. The characteristic histological and ultrastructural features distinguish this entity from other mimics, notably Danon disease. XMEA is an under recognized disease and should be considered in the differentials of slowly progressive myopathy in children. Awareness of this rare entity is also important for the pathologists in order to distinguish it from other causes of vacuolar myopathy in view of its favourable prognosis. We report the first genetically confirmed case of XMEA from India in an 8-year-old boy which was diagnosed based on the characteristic light microscopic and ultrastructural findings on muscle biopsy and subsequently confirmed by mutation analysis. The differential diagnostic considerations are also discussed.


Asunto(s)
Enfermedades Musculares , ATPasas de Translocación de Protón Vacuolares , Autofagia/genética , Niño , Enfermedades Genéticas Ligadas al Cromosoma X , Humanos , Enfermedades por Almacenamiento Lisosomal , Masculino , Músculo Esquelético/patología , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/genética , Enfermedades Musculares/patología , ATPasas de Translocación de Protón Vacuolares/genética
6.
G3 (Bethesda) ; 8(6): 2027-2041, 2018 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-29669801

RESUMEN

Proper specification of germline stem cells (GSCs) in Drosophila ovaries depends on niche derived non-autonomous signaling and cell autonomous components of transcriptional machinery. Stonewall (Stwl), a MADF-BESS family protein, is one of the cell intrinsic transcriptional regulators involved in the establishment and/or maintenance of GSC fate in Drosophila ovaries. Here we report identification and functional characterization of another member of the same protein family, CG3838/ Brickwall (Brwl) with analogous functions. Loss of function alleles of brwl exhibit age dependent progressive degeneration of the developing ovarioles and loss of GSCs. Supporting the conclusion that the structural deterioration of mutant egg chambers is a result of apoptotic cell death, activated caspase levels are considerably elevated in brwl- ovaries. Moreover, as in the case of stwl mutants, on several instances, loss of brwl activity results in fusion of egg chambers and misspecification of the oocyte. Importantly, brwl phenotypes can be partially rescued by germline specific over-expression of stwl arguing for overlapping yet distinct functional capabilities of the two proteins. Taken together with our phylogenetic analysis, these data suggest that brwl and stwl likely share a common MADF-BESS ancestor and they are expressed in overlapping spatiotemporal domains to ensure robust development of the female germline.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Células Germinativas/metabolismo , Factores de Transcripción/metabolismo , Alelos , Animales , Caspasas/metabolismo , Linaje de la Célula , Elementos Transponibles de ADN/genética , Proteínas de Unión al ADN/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/citología , Activación Enzimática , Evolución Molecular , Femenino , Técnicas de Silenciamiento del Gen , Genes de Insecto , Pruebas Genéticas , Modelos Genéticos , Mutagénesis Insercional/genética , Mutación/genética , Ovario/metabolismo , Fenotipo , Interferencia de ARN , Selección Genética , Células Madre/citología , Células Madre/metabolismo , Factores de Transcripción/genética
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