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Bone morphogenetic protein 2 (BMP2) and BMP6 are key regulators of systemic iron homeostasis. All BMPs are generated as inactive precursor proteins that dimerize and are cleaved to generate the bioactive ligand and inactive prodomain fragments, but nothing is known about how BMP2 or BMP6 homodimeric or heterodimeric precursor proteins are proteolytically activated. Here, we conducted in vitro cleavage assays, which revealed that BMP2 is sequentially cleaved by furin at two sites, initially at a site upstream of the mature ligand, and then at a site adjacent to the ligand domain, while BMP6 is cleaved at a single furin motif. Cleavage of both sites of BMP2 is required to generate fully active BMP2 homodimers when expressed in Xenopus embryos or liver endothelial cells, and fully active BMP2/6 heterodimers in Xenopus . We analyzed BMP activity in Xenopus embryos expressing chimeric proteins consisting of the BMP2 prodomain and BMP6 ligand domain, or vice versa. We show that the prodomain of BMP2 is necessary and sufficient to generate active BMP6 homodimers and BMP2/6 heterodimers, whereas the BMP6 prodomain cannot generate active BMP2 homodimers or BMP2/6 heterodimers. We examined BMP2 and BMP6 homodimeric and heterodimeric ligands generated from native and chimeric precursor proteins expressed in Xenopus embryos. Whereas native BMP6 is not cleaved when expressed alone, it is cleaved to generate BMP2/6 heterodimers when co-expressed with BMP2. Furthermore, BMP2-6 chimeras are cleaved to generate BMP6 homodimers. Our findings reveal an important role for the BMP2 prodomain in dimerization and proteolytic activation of BMP6.
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Background: The world is not on track to meet the World Health Assembly (WHA) global target on Low Birth Weight (LBW). To estimate the prevalence and to identify the associated determinants of LBW among the newborns. Material and Methods: We conducted a cross-sectional study among the 364 mothers registered under the all government health facilities of Dadra & Nagar Haveli (DNH) during November 2021 to January 2022. Results: The prevalence of LBW was found to be 39%. On uni-variable logistic regression, live in relationship, caste, weight of mother, Body Mass Index (BMI), weight gain <5 kg in 2nd and 3rd trimester, high-risk pregnancy, complication present in previous pregnancy and preterm delivery, while on multi-variable logistic regression, weight gain <5 kg in 2nd and 3rd trimester (AOR 2, 95% CI 1.007-4.2) and having high-risk pregnancy (AOR 2, 95% CI 1.1-3.0) were found to be the significant predictors of LBW among the newborns. Conclusions: We conclude from the study that the prevalence of low birth weight among the newborn was high. There is a need to address maternal and child health issues like low birth weight, malnutrition and high-risk pregnancy under the RMNCAH+N program through various effective interventions. Future research should evaluate the feasibility of collaborative activities between RMNCAH+N program and the UNICEF in India.
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Phosphorus to an optimum extent is an essential nutrient for all living organisms and its scarcity may cause food security, and environmental preservation issues vis-à-vis agroeconomic hurdles. Undesirably excess phosphorus intensifies the eutrophication problem in non-marine water bodies and disrupts the natural nutrient balance of the ecosystem. To overcome such dichotomy, biodegradable polymer-based adsorbents have emerged as a cost-effective and implementable approach in striking a "desired optimum-undesired excess" balance pertaining to phosphate in a sustainable manner. So far, the reports on adopting such adsorbent-approach for wastewater remediation remained largely scattered, unstructured, and poorly correlated. In this background, the contextual review comprehensively discusses the current state-of-the-art in utilizing biodegradable polymeric frameworks as an adsorbent system for phosphate removal and its efficient recovery from the aquatic ecosystem, while highlighting their characteristics-specific functional efficiency vis-à-vis easiness of synthetic and commercial viability. The overview further delves into the sources and environmental ramifications of excessive phosphorus in water bodies and associated mechanistic pathways of phosphorus removal via adsorption, precipitation, and membrane filtration enabled by biodegradable (natural and synthetic) polymeric substrates. Finally, functionality optimization, degradability tuning, and adsorption selectivity of biodegradable polymers are highlighted, while aiming to strike a balance in "removal-recovery-reuse" dynamics of phosphate. Thus, the current review not only paves the way for future exploration of biodegradable polymers in sustainable cost-effective adsorbents for phosphorus removal but also can serve as a guide for researchers dealing with this critical issue.
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Fosfatos , Polímeros , Aguas Residuales , Fosfatos/química , Aguas Residuales/química , Adsorción , Polímeros/química , Contaminantes Químicos del Agua/química , Biodegradación Ambiental , Fósforo/química , Eliminación de Residuos Líquidos/métodos , Purificación del Agua/métodosRESUMEN
HIV-infected individuals receiving regular antiretroviral therapy (ART) can present with a high viral load in cerebrospinal fluid (CSF) at times when it is suppressed in blood. This study presents data of HIV-infected patients who had undetectable or low plasma viral load in blood but presented with neurological signs and symptoms and were diagnosed to have CSF HIV viral escape. Records were reviewed for clinical manifestations, details of opportunistic or coinfection, and HIV viral copies in plasma and CSF at time of diagnosis of CSF escape. A total of 10,200 HIV-infected individuals were registered in HIV care till December 31, 2021. Nineteen individuals (14 virologically confirmed and 5 clinically) were diagnosed with high viral copies in CSF from June 2014 to December 2021. Mean age was 41.5 ± 9.2 (median, 39.5; range, 30-62) years. Average duration of antiretroviral treatment received at the time of diagnosis of CSF escape was 10.1 years. Median plasma HIV-viral copies were 2,469.8 (undetectable to 29,418) and in CSF were 12,773.7 (n = 14, range, 1,340-48,530) copies/mL. HIV viral copies in CSF were significantly higher than in plasma at the time of presentation (p = .003). ART regimen switch was done after identification of HIV CSF escape. Seventeen patients were alive with a regular follow-up of average 35 (range 7-66) months. All had documented clinical improvement with reversal of neurological impairment after ART switch. There was one death and one lost to follow-up. Early identification and timely intervention in CSF viral escape could revert severe neurological impairment and improves treatment outcome.
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Soil salinity is one of the major environmental stresses that results in reduction of cultivable land and decreased productivity. In the present study, halotolerant and plant growth-promoting endophytic fungi were isolated from Catharanthus roseus, and their effect in mitigating salt stress in Vigna radiata was evaluated. An isolate CR7, identified to be Aspergillus terreus, showing plant growth promotion activities, viz. IAA production (23.43 ± 0.79 µg/ml), phosphate solubilization (133.63 ± 6.40 µg/ml), ACC deaminase activity (86.36 ± 2.70 µmol α-ketobutyrate/h/mg protein) etc. and ability to grow at 15% NaCl was selected for further in vivo studies. Colonization of CR7 was carried out in V. radiata which was subjected to different concentrations of salt (150, 200, and 250 mM NaCl). Under salt stress, A. terreus CR7 inoculated plants showed substantially improved root and shoot length, biomass, chlorophyll content, relative water content, phenolics, protein content, and DPPH scavenging activity. Endogenous IAA level was enhanced by 5.28-fold in treated plants at maximum salt stress. Inoculation of A. terreus CR7 affected oxidative stress parameters, exhibiting an increase in catalase and superoxide dismutase and reduction in proline, electrolyte leakage, and malondialdehyde content. Fluorescent microscopic analysis of roots revealed improved cell viability and decreased levels of glutathione and hydrogen peroxide under salt stress in treated plants. The isolate A. terreus CR7 also protected against DNA damage induced by salt stress which was evaluated using comet assay. A decrease in DNA tail length, tail moment, and olive tail moment to the extent of 19.87%, 19.76%, and 24.81%, respectively, was observed in A. terreus CR7-colonized plants under salt stress. It can be concluded that A. terreus CR7 can be exploited for alleviating the impact of salt stress in crop plants.
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Background: Anemia is a common feature in cancer patients. The present research was conducted to explore the mechanisms of induction of anemia in a mouse model of lung cancer. Methods: The lung cancer was induced by treating orally with BaP (50 mg/kg body weight, twice a week for four weeks). The erythrocyte kinetics were studied using a double in vivo biotinylation (DIB) technique. ROS production and apoptosis analysis were done by staining with the CMH2DCFDA stain and anti-mouse Annexin V antibody, followed by flow cytometry. The expression of antioxidant, apoptotic, anti-apoptotic and inflammatory genes was analyzed by quantitative PCR (RT-qPCR). Results: BaP-induced tumour reduced body weight and induced persistent haemolytic anaemia. The kinetics data suggest that, though reticulocyte production was enhanced, the proportion of young erythrocytes did not increase in the same proportion. The young aged erythrocytes were selectively eliminated from blood circulation, but intermediate and old aged erythrocytes persisted for a longer duration. The tumour progression leads to a significant increase in ROS production and apoptosis in the erythrocytes. The molecular data suggests that the expression levels of antioxidants (SOD1, catalase, and GPX1) and erythropoietin (Epo) were significantly increased. The anti-inflammatory genes Interleukin-6 (IL-6), Interleukin-10 (IL-10) were significantly decreased.Apoptotic genes Bax, and caspase 3 were significantly decreased while Bcl 2 was significantly increased in the blood of tumour-bearing mice. Conclusions: The overall data suggest that erythrocyte turnover is severely modulated with the progression of tumor. The apoptosis, ROS levels, antioxidant, anti-apoptotic, and Epo gene expressions were increased, but proapoptotic and anti-inflammatory gene expression were suppressed.
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The emergence of antibiotic resistance in pathogens is one of the major health concerns facing mankind as different bacterial strains have developed resistance to antibiotics over the period of time due to overuse and misuse of antibiotics. Besides this, ability to form biofilms is another major factor contributing to antibiotic resistance, which has necessitated the need for exploration for novel and effective compounds with ability to inhibit biofilm formation. Endophytic fungi are reported to exhibit antibacterial and anti-biofilm potential and could serve as a potent source of novel antibacterial compounds. Majority of the bioactivities have been reported from fungi belonging to phylum Ascomycota. Endophytic basidiomycetes, inspite of their profound ability to serve as a source of bioactive compounds have not been exploited extensively. In present study, an attempt was made to assess the antibacterial, anti-biofilm and biofilm dispersion potential of an endophytic basidiomycetous fungus Schizophyllum commune procured from the culture collection of our lab. Ethyl acetate extract of S. commune showed good antibacterial activity against Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica and Vibrio cholerae. Minimum inhibitory concentration and minimum bactericidal concentration of the extract were in the range of 1.25-10 mg/ml against the tested bacterial pathogens. The mode of action was determined to be bactericidal which was further confirmed by time kill studies. Good anti-biofilm activity of S. commune extract was recorded against K. pneumoniae and S. enterica, which was further validated by fluorescence microscopy. The present study highlights the importance of endophytic basidiomycetes as source of therapeutic compounds.
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Aflatoxin is a naturally occurring mycotoxin that has numerous toxic effects. The main aim of the present study was to evaluate the toxic effects of aflatoxin B1 (AFB1) on the lungs and spleen. Mice were repeatedly exposed to AFB1 (0.3 mg/kg body weight) on alternate days for four weeks via oral route. The histopathological data in AFB1-treated mice show alveolar epithelial hyperplasia with inflammation and the presence of numerous alveolar macrophages with minimal hemorrhage. There was an increase in vascular neutrophils and interstitial inflammation. The branching of vessels was plugged with neutrophils. AFB1 administration also causes splenomegaly. The AFB1-treated spleen shows the tingible body macrophages (TBM) scattered within the splenic white pulp. Apoptosis may lead to atrophy in a selected region of the white pulp area. There is a decrease in cellularity within the periarteriolar lymphatic sheath (PALS). The inflammation causes the congestion of red pulp with the increase in nuclear debris, and vacuoles are also visible. The flow cytometry data further suggests enhanced apoptosis in lung and spleen cells.
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Aflatoxina B1 , Bazo , Ratones , Animales , Aflatoxina B1/toxicidad , Pulmón , Inflamación/inducido químicamente , Inflamación/patología , ApoptosisRESUMEN
Purpose: Although the outer nuclear layer (ONL) and outer plexiform layer (OPL) each exhibit a complex internal organization, near-infrared OCT depicts both as monolithic bands. Here, using visible light OCT in the C57BL/6J mouse retina, sublaminar age-related changes in photoreceptor features were imaged and interpreted. These features were (1) oscillations in reflectivity, or striations, in the ONL and (2) a moderately reflective subband in the OPL. Design: Cross-sectional study. Participants: Pigmented mice (C57BL/6J, n = 14). Methods: A 1.0-µm axial resolution visible light spectral/Fourier domain OCT system was used for in vivo retinal imaging. Light and electron microscopy were performed ex vivo. Linear mixed effects models or regression were employed for statistical analysis. Main Outcome Measures: Comparison of OCT subbands with corresponding histological features, as well as quantification of subband thickness and reflectivity. Results: Corresponding histological comparisons confirm that striations in the ONL arise from the rowlike arrangement of photoreceptor nuclei and reveal that the moderately reflective OPL subband arises from rod spherules. Compression of outer ONL striations with age suggests changes in soma organization. Thinning of the moderately reflective OPL subband with age supports a reduction of synapses in the OPL. Critically, the ONL somas are tightly correlated with the purported spherule layer but not with the rest of the OPL. Conclusions: Visible light OCT imaging of the mouse OPL resolves postsynaptic and synaptic differences. Visible light OCT can study rod photoreceptor changes from the soma to the synapse in the living mouse retina. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.
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Global concern about petroleum hydrocarbon pollution has intensified and gained scientific interest due to its noxious nature, high persistence in environmental matrices, and low degradability. One way to address this is by combining remediation techniques that could overcome the constraints of traditional physio-chemical and biological remediation strategies. The upgraded concept of bioremediation to nano-bioremediation in this direction offers an efficient, economical, and eco-friendly approach to mitigate petroleum contaminants. Here, we review the unique attributes of different types of nanoparticles and their synthesis procedures in remediating various petroleum pollutants. This review also highlights the microbial interaction with different metallic nanoparticles and their consequential alteration in microbial as well as enzymatic activity which expedites the remediating process. Besides, the latter part of the review explores the application of petroleum hydrocarbon degradation and the application of nano supports as immobilizing agents for microbes and enzymes. Further, the challenges and the future prospects of nano-bioremediation have also been discussed.
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Contaminantes Ambientales , Contaminación por Petróleo , Petróleo , Contaminantes del Suelo , Biodegradación Ambiental , Petróleo/metabolismo , Hidrocarburos , Microbiología del SueloRESUMEN
Herein, we have developed a one-pot methodology to synthesise three types of C-dots and their activated counterparts from three different types of waste plastic precursors such as poly-bags, cups and bottles. The optical studies have shown the significant change in the absorption edge in case of C-dots in comparison to their activated counterparts. The respective variation in the sizes is correlated with the change in electronic band gap values of formed particles. The changes in the luminescence behaviour are also correlated with transitions from the edge of the core of formed particles. The obtained variations in the Stokes shift values of C-dots, and their ACs were used to explore the types of surface states and their related transitions in particles. The mode of interaction between C-dots and their ACs was also determined using solvent-dependent fluorescence spectroscopy. This detailed investigation could provide significant insight on the emission behaviour and the potential usage of formed particles as an effective fluorescent probe in sensing applications.
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BACKGROUND: Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease that is embodied by the loss of salivary gland function and immune cell infiltration, but the mechanism(s) are still unknown. The aim of this study was to understand the mechanisms and identify key factors that leads to the development and progression of pSS. METHODS: Immunohistochemistry staining, FACS analysis and cytokine levels were used to detect immune cells infiltration and activation in salivary glands. RNA sequencing was performed to identify the molecular mechanisms involved in the development of pSS. The function assays include in vivo saliva collection along with calcium imaging and electrophysiology on isolated salivary gland cells in mice models of pSS. Western blotting, real-time PCR, alarmin release, and immunohistochemistry was performed to identify the channels involved in salivary function in pSS. RESULTS: We provide evidence that loss of Ca2+ signaling precedes a decrease in saliva secretion and/or immune cell infiltration in IL14α, a mouse model for pSS. We also showed that Ca2+ homeostasis was mediated by transient receptor potential canonical-1 (TRPC1) channels and inhibition of TRPC1, resulting in the loss of salivary acinar cells, which promoted alarmin release essential for immune cell infiltration/release of pro-inflammatory cytokines. In addition, both IL14α and samples from human pSS patients showed a decrease in TRPC1 expression and increased acinar cell death. Finally, paquinimod treatment in IL14α restored Ca2+ homeostasis that inhibited alarmin release thereby reverting the pSS phenotype. CONCLUSIONS: These results indicate that loss of Ca2+ signaling is one of the initial factors, which induces loss of salivary gland function along with immune infiltration that exaggerates pSS. Importantly, restoration of Ca2+ signaling upon paquinimod treatment reversed the pSS phenotype thereby inhibiting the progressive development of pSS.
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Síndrome de Sjögren , Humanos , Animales , Ratones , Síndrome de Sjögren/tratamiento farmacológico , Síndrome de Sjögren/diagnóstico , Alarminas/análisis , Alarminas/metabolismo , Glándulas Salivales/metabolismo , Saliva/química , Saliva/metabolismo , FenotipoRESUMEN
In modern era, wireless communications at ultrafast speed are need of the hour and search for its solution through cutting edge sciences is a new perspective. To address this issue, the data rates in order of terabits per second (TBPS) could be a key step for the realization of emerging sixth generation (6G) networks utilizing terahertz (THz) frequency regime. In this context, new class of transition metal dichalcogenides (TMDs) have been introduced as potential candidates for future generation wireless THz technology. Herein, a strategy has been adopted to synthesize high-quality monolayer of molybdenum di-sulfide (MoS2) using indigenously developed atmospheric pressure chemical vapor deposition (APCVD) set-up. Further, the time-domain transmission and sheet conductivity were studied as well as a plausible mechanism of terahertz response for monolayer MoS2 has been proposed and compared with bulk MoS2. Hence, the obtained results set a stepping stone to employ the monolayer MoS2 as potential quantum materials benefitting the next generation terahertz communication devices.
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Aflatoxin is a naturally occurring mycotoxin that has various toxic effects to humans and various other animals. In the current study, we have investigated the toxic effects of Aflatoxin B1 (AFB1) on erythrocytes in the blood circulation of mice. Mice were administered orally with repeated doses of AFB1 (0.3 mg/kg of body weight three times a week for four weeks). AFB1 administration resulted in sustained anemia and a significant reduction in blood erythrocyte number as well as hemoglobin level was seen at different time schedules. Body weight, erythrocyte count, and Hb were significantly decreased on days 30 and 45 post-AFB1 administration. The reticulocytes proportion in circulation was analyzed by staining the cells with anti-mouse CD71 monoclonal antibody and flow cytometric analysis. The ROS level and apoptotic cell proportion were determined by staining with CM-H2DCFDA and Annexin V antibody. AFB1 treatment leads to an increment in reticulocytes production. A significant increase in reactive oxygen species (ROS) and apoptotic cells were also observed in erythrocytes.
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Aflatoxina B1 , Apoptosis , Humanos , Animales , Ratones , Especies Reactivas de Oxígeno , Aflatoxina B1/toxicidad , Eritrocitos , Peso Corporal , Estrés OxidativoRESUMEN
BACKGROUND: Oxidative stress is responsible for the onset of several chronic and degenerative diseases. Exogenous supply of antioxidants is reported to neutralize the effects of oxidative stress. Several synthetic antioxidants suffer from various side effects which necessitates the exploration of antioxidant compounds from natural sources. Endophytic fungi residing in the plants are gaining the attention of researchers as a source of novel antioxidants. Majority of the research conducted so far on endophytic fungi has been restricted to the members of phylum ascomycota. Basidiomycota, inspite of their immense bioactive potential remain relatively unexploited. This study aimed to assess the ameliorative effects of an endophytic Schizophyllum commune (basidiomycetous fungus) against oxidative stress associated altered antioxidant levels, genotoxicity and cellular damage to different organs in bisphenol A exposed fresh water fish Channa punctatus. RESULTS: Good antioxidant and genoprotective potential was exhibited by S. commune extract in in vitro studies conducted using different antioxidant, DNA damage protection, and cytokinesis blocked micronuclei assays. In vivo studies were performed in fresh water fish Channa punctatus exposed to bisphenol A. A significant decrease in the considered parameters for DNA damage (% micronuclei and comet assay) were recorded in fish treated with S. commune extract on comparison with untreated bisphenol A exposed group. The S. commune extract treated fish also exhibited an increase in the level of antioxidant enzymes viz. catalase, superoxide dismutase and glutathione reductase as well as histoprotective effect on various organs. GC-MS analysis revealed the presence of 3-n-propyl-2,4-pentanedione, n-heptadecanol-1, trans-geranylgeraniol, 3-ethyl-2-pentadecanone, 1-heneicosanol and squalene as some of the compounds in S. commune extract. CONCLUSION: The study highlights the significance of an endophytic basidiomycetous fungus S. commune as a source of antioxidant compounds with possible therapeutic potential.
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Antioxidantes , Schizophyllum , Antioxidantes/farmacología , Agua Dulce , Extractos VegetalesRESUMEN
Purpose: We employ visible light optical coherence tomography (OCT) to investigate the relationship between the myoid, ellipsoid, and band 2 in the living human retina. Rather than refute existing theories, we aim to reveal new bands and better delineate the structures at hand. Methods: An upgraded spectral/Fourier domain visible light OCT prototype, with 1.0-µm axial resolution, imaged 13 eyes of 13 young adult human subjects (23-40 years old) without a history of ocular pathology. The external limiting membrane (band 1) and band 2 edges were segmented. Reflectivity was examined along the inner segment (IS), defined as extending from band 1 to the band 2 center, and within band 2 itself. Results: Images highlight a nearly continuously resolved extrafoveal internal limiting membrane, the peripheral single-cell thick ganglion cell layer, and the peripheral photoreceptor axonal fiber layer, a peripheral division of band 2 into bands 2a and 2b, and a reflectivity-based division of the IS into "m" and "e" zones. Discussion: Topography and transverse intensity variations of the outermost band 2b suggest an association with rods. The "m" and "e" zone border is consistent with the myoid-ellipsoid boundary, even recapitulating the well-documented distribution of mitochondria throughout the IS at the foveal center. Theories of outer retinal reflectivity in OCT must adequately explain these observations. Translational Relevance: Findings support that band 2 does partially overlap with the ellipsoid in transversally averaged OCT images due to photoreceptor IS length dispersion but argue that the inner ellipsoid must be inner to band 2, as suggested by prior quantitative measurements.
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Retina , Tomografía de Coherencia Óptica , Adulto , Humanos , Luz , Retina/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Adulto JovenRESUMEN
Purpose: We employed in vivo, 1.0-µm axial resolution visible-light optical coherence tomography (OCT) and ex vivo electron microscopy (EM) to investigate three subcellular features in the mouse outer retina: reflectivity oscillations inner to band 1 (study 1); hyperreflective band 2, attributed to the ellipsoid zone or inner segment/outer segment (IS/OS) junction (study 2); and the hyperreflective retinal pigment epithelium (RPE) within band 4 (study 3). Methods: Pigmented (C57BL/6J, n = 10) and albino (BALB/cJ, n = 3) mice were imaged in vivo. Enucleated eyes were processed for light and electron microscopy. Using well-accepted reference surfaces, we compared micrometer-scale axial reflectivity of visible-light OCT with subcellular organization, as revealed by 9449 annotated EM organelles and features across four pigmented eyes. Results: In study 1, outer nuclear layer reflectivity peaks coincided with valleys in heterochromatin clump density (-0.34 ± 2.27 µm limits of agreement [LoA]). In study 2, band 2 depth on OCT and IS/OS junction depth on EM agreed (-0.57 ± 0.76 µm LoA), with both having similar distributions. In study 3, RPE electron dense organelle distribution did not agree with reflectivity in C57BL/6J mice, with OCT measures of RPE thickness exceeding those of EM (2.09 ± 0.89 µm LoA). Finally, RPE thickness increased with age in pigmented mice (slope = 0.056 µm/mo; P = 6.8 × 10-7). Conclusions: Visible-light OCT bands arise from subcellular organization, enabling new measurements in mice. Quantitative OCT-EM comparisons may be confounded by hydration level, particularly in the OS and RPE. Caution is warranted in generalizing results to other species.
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Epitelio Pigmentado de la Retina , Tomografía de Coherencia Óptica , Animales , Ratones , Ratones Endogámicos C57BL , Microscopía Electrónica , Retina/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodosRESUMEN
Neutrophil extracellular traps (NETs) are implicated in host defense and inflammatory pathologies alike. A wide range of pathogen- and host-derived factors are known to induce NETs, yet the knowledge about specific receptor-ligand interactions in this response is limited. We previously reported that macrophage-inducible C-type lectin (Mincle) regulates NET formation. In this article, we identify glycosphingolipid ß-glucosylceramide (ß-GlcCer) as a specific NET-inducing ligand of Mincle. We found that purified ß-GlcCer induced NETs in mouse primary neutrophils in vitro and in vivo, and this effect was abrogated in Mincle deficiency. Cell-free ß-GlcCer accumulated in the lungs of pneumonic mice, which correlated with pulmonary NET formation in wild-type, but not in Mincle-/-, mice infected intranasally with Klebsiella pneumoniae Although leukocyte infiltration by ß-GlcCer administration in vivo did not require Mincle, NETs induced by this sphingolipid were important for bacterial clearance during Klebsiella infection. Mechanistically, ß-GlcCer did not activate reactive oxygen species formation in neutrophils but required autophagy and glycolysis for NET formation, because ATG4 inhibitor NSC185058, as well as glycolysis inhibitor 2-deoxy-d-glucose, abrogated ß-GlcCer-induced NETs. Forced autophagy activation by tamoxifen could overcome the inhibitory effect of glycolysis blockage on ß-GlcCer-mediated NET formation, suggesting that autophagy activation is sufficient to induce NETs in response to this metabolite in the absence of glycolysis. Finally, ß-GlcCer accumulated in the plasma of patients with systemic inflammatory response syndrome, and its levels correlated with the extent of systemic NET formation in these patients. Overall, our results posit ß-GlcCer as a potent NET-inducing ligand of Mincle with diagnostic and therapeutic potential in inflammatory disease settings.
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Trampas Extracelulares , Infecciones por Klebsiella , Animales , Trampas Extracelulares/metabolismo , Glucosilceramidas , Glucolípidos , Inflamación/metabolismo , Infecciones por Klebsiella/metabolismo , Ligandos , Ratones , Neutrófilos/metabolismoRESUMEN
Agronomical providence of nanoparticles in enhancing food productivity has brought new revolution in agricultural sector. However, the comprehensive ingenuity of their synergetic impact on environment and living flora and fauna is still poorly explored. The current study endeavours to tackle this apprehension by systematically exploring the agronomical paradigm of six different types of C-dots derived from natural biomass and plastic waste on the four different types of seeds viz. black chick peas (Cicer arietinum), barley (Hordeum vulgare), mung beans (Vigna radiata) and wheat (Triticum aestivum) at room temperature. C-dots have displayed a dose responsive effect (250 to 5000 mg/L) on the growth of chosen seeds, including the elongation of root length and coleoptile length. The development of seedlings under atmospheric conditions exhibited excellent physiological stability in presence of synthesized C-dots for all types of seeds with concentrations as high as 3000 mg/L for dry seed. The direct exposure of C-dots resulted in enhanced growth as compared to the water exposure and considered as the most important novel aspect of present work. The developed C-dots provide more nutrient content and easy penetration to the seeds due to their enhanced surface area and very small size. The germination and Vigor index have also been augmented in presence of C-dots after 7 days of exposure. C-dots have affected the chlorophyll content in mung beans as a function of time and concentration. The developed C-dots possess excellent biocompatible behaviour and help in the complete growth of the different types of seeds which suggest their enhanced utilization in the agronomical field. This is one of the detailed studies, which explore the impact of C-dots on widely used food crops with the non-toxic and biocompatible C-dots. The information achieved herein will allow the usage of C-dots as a capable nanopriming agent for the natural germination of seeds.
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Cicer , Fabaceae , Hordeum , Vigna , Biomasa , Germinación , Plásticos/toxicidad , Semillas , TriticumRESUMEN
In the recent era, carbon dots (C-dots) have been extensively considered as a potential tool in drug delivery analysis. However, there have been fewer reports in the literature on their application in the sensing of amino acids. As part of our ongoing research on coconut-husk-derived C-dots, we synthesized C-dots under different temperature conditions and utilized them in the field of amino acid sensing and found them to be highly selective and sensitive towards tyrosine. The detailed characterization of the prepared C-dots was carried out. The developed C-dots exhibit good values of quantum yield. BSA, HSA and glutamic acid were utilized to explore the binding efficiency of C-dots with biologically active components. Hemolysis, blood clotting index activity and cell viability assays using the prepared C-dots were evaluated and they were found to be biocompatible. Therefore, the C-dots described in this work have high potential to be utilized in the field of amino acid sensing, especially L-tyrosine. The limit of detection and the binding constant for the developed C-dots in the presence of tyrosine were found to be 0.96 nM and 296.38 nM-1, respectively. The efficiency of the developed C-dots was also investigated in the presence of various other amino acids and different water mediums in order to enhance the working scope of the developed sensors.