Stress can promote the development of psychiatric disorders, though some individuals are more vulnerable to stress compared to others who are more resilient. Here we show that the ...sphingosine-1-phosphate receptor 3 (S1PR3) in the medial prefrontal cortex (mPFC) of rats regulates resilience to chronic social defeat stress. S1PR3 expression is elevated in the mPFC of resilient compared to vulnerable and control rats. Virally-mediated over-expression of S1PR3 in the mPFC produces a resilient phenotype whereas its knock-down produces a vulnerable phenotype, characterized by increased anxiety- and depressive-like behaviors, and these effects are mediated by TNFα. Furthermore, we show that S1PR3 mRNA in blood is reduced in veterans with PTSD compared to combat-exposed control subjects and its expression negatively correlates with symptom severity. Together, these data identify S1PR3 as a regulator of stress resilience and reveal sphingolipid receptors as important substrates of relevance to stress-related psychiatric disorders.
In many cases of inherited retinal degenerations, ganglion cells are spared despite photoreceptor cell death, making it possible to stimulate them to restore visual function. Several studies have ...shown that it is possible to express an optogenetic protein in ganglion cells and make them light sensitive, a promising strategy to restore vision. However the spatial resolution of optogenetically-reactivated retinas has rarely been measured, especially in the primate. Since the optogenetic protein is also expressed in axons, it is unclear if these neurons will only be sensitive to the stimulation of a small region covering their somas and dendrites, or if they will also respond to any stimulation overlapping with their axon, dramatically impairing spatial resolution. Here we recorded responses of mouse and macaque retinas to random checkerboard patterns following an in vivo optogenetic therapy. We show that optogenetically activated ganglion cells are each sensitive to a small region of visual space. A simple model based on this small receptive field predicted accurately their responses to complex stimuli. From this model, we simulated how the entire population of light sensitive ganglion cells would respond to letters of different sizes. We then estimated the maximal acuity expected by a patient, assuming it could make an optimal use of the information delivered by this reactivated retina. The obtained acuity is above the limit of legal blindness. Our model also makes interesting predictions on how acuity might vary upon changing the therapeutic strategy, assuming an optimal use of the information present in the retinal activity. Optogenetic therapy could thus potentially lead to high resolution vision, under conditions that our model helps to determinine.
Assessment of genetic diversity and extent of trait variation among germplasm accessions facilitate the effective use of genetic resources for varietal development. In linseed (
Linum usitatissimum
...L.), early maturity is desirable as it helps avoid several biotic and abiotic stress. In present study, genetic variability of 220 accessions of linseed was studied using 25 agro-morphological traits for 2 years, 2017–2018 and 2018–2019. Remarkable variability was observed for flowering, maturity and other economically important traits such as thousand seed weight, capsule number, seed, and capsule area. Based on 2-year evaluation data for flowering and maturity traits, a panel of 34 accessions was constructed to study genetic diversity using SSR markers. Total 89 alleles were amplified with a mean of 3.069 alleles per locus. Polymorphism information content value ranged from 0.20 to 0.66 with mean of 0.42. Clustering based on SSR data followed the flowering-maturity trait pattern to a large extent. Genetic population structure analysis showed two populations in similarity with the trait groups. Analysis of molecular variance revealed 16% variance among the populations. Shannon's diversity information index within population I and II were 0.67 and 0.78, respectively. Additionally, allelic variation in a putative floral homeotic gene encoding APETALA2 transcription factor was studied in two early and two late accessions by PCR amplification and sequencing. Total 12 SNPs were identified, of which six could distinguish early and late accessions. The genetic and genomic resources identified here are expected to aid in linseed genetic improvement programme targeted to specific traits, especially, early flowering and maturity.
HEPNet is an electronic representation of metabolic reactions occurring within human cellular organization focusing on inflow and outflow of the energy currency ATP, GTP and other energy associated ...moieties. The backbone of HEPNet consists of primary bio-molecules such as carbohydrates, proteins and fats which ultimately constitute the chief source for the synthesis and obliteration of energy currencies in a cell. A series of biochemical pathways and reactions constituting the catabolism and anabolism of various metabolites are portrayed through cellular compartmentalization. The depicted pathways function synchronously toward an overarching goal of producing ATP and other energy associated moieties to bring into play a variety of cellular functions. HEPNet is manually curated with raw data from experiments and is also connected to KEGG and Reactome databases. This model has been validated by simulating it with physiological states like fasting, starvation, exercise and disease conditions like glycaemia, uremia and dihydrolipoamide dehydrogenase deficiency (DLDD). The results clearly indicate that ATP is the master regulator under different metabolic conditions and physiological states. The results also highlight that energy currencies play a minor role. However, the moiety creatine phosphate has a unique character, since it is a ready-made source of phosphoryl groups for the rapid synthesis of ATP from ADP. HEPNet provides a framework for further expanding the network diverse age groups of both the sexes, followed by the understanding of energetics in more complex metabolic pathways that are related to human disorders.
Early flowering, maturity, and plant height are important traits for linseed to fit in rice fallows, for rainfed agriculture, and for economically viable cultivation. Here, Multi-Locus Genome-Wide ...Association Study (ML-GWAS) was undertaken in an association mapping panel of 131 accessions, genotyped using 68,925 SNPs identified by genotyping by sequencing approach. Phenotypic evaluation data of five environments comprising 3 years and two locations were used. GWAS was performed for three flowering time traits including days to 5%, 50%, and 95% flowering, days to maturity, and plant height by employing five ML-GWAS methods: FASTmrEMMA, FASTmrMLM, ISIS EM-BLASSO, mrMLM, and pLARmEB. A total of 335 unique QTNs have been identified for five traits across five environments. 109 QTNs were stable as observed in ≥2 methods and/or environments, explaining up to 36.6% phenotypic variance. For three flowering time traits, days to maturity, and plant height, 53, 30, and 27 stable QTNs, respectively, were identified. Candidate genes having roles in flower, pollen, embryo, seed and fruit development, and xylem/phloem histogenesis have been identified. Gene expression of candidate genes for flowering and plant height were studied using transcriptome of an early maturing variety
Sharda
(IC0523807). The present study unravels QTNs/candidate genes underlying complex flowering, days to maturity, and plant height traits in linseed.
is a melanized fungus pathogenic to both plants and animals including humans, causing from mild, febrile to life-threatening illness if not well treated. In humans, it is an etiological agent of ...keratomycosis, sinusitis, and onychomycosis in immunocompromised and immunocompetent patients. The development of multiple-drug-resistant strains poses a critical treatment issue as well as public health problem. Natural products are attractive prototypes for drug discovery due to their broad-spectrum efficacy and lower side effects. The present study explores possible targets of natural antifungal compounds (α-pinene, eugenol, berberine, and curcumin) against
gene expression analysis, molecular docking interaction, and molecular dynamics (MD) studies. Curcumin, berberine, eugenol, and α-pinene exhibited
antifungal activity at 78 μg/ml, 156 μg/ml, 156 μg/ml, and 1250 μg/ml, respectively. In addition, treatment by these compounds led to the complete inhibition of conidial germination and hindered the adherence when observed on onion epidermis. Several pathogenic factors of fungi are crucial for their survival inside the host including those involved in melanin biosynthesis, hyphal growth, sporulation, and mitogen-activated protein kinase (MAPK) signalling. Relative gene expression of
,
,
, and
responsible for conidiation, melanin, and cell wall integrity was down-regulated significantly. Results of molecular docking possessed good binding affinity of compounds and have confirmed their potential targets as THR and VelB proteins. The docked structures, having good binding affinity among all, were further refined, and rescored from their docked poses through 100-ns long MD simulations. The MDS study revealed that curcumin formed a stable and energetically stabilized complex with the target protein. Therefore, the study concludes that the antifungal compounds possess significant efficacy to inhibit
growth targeting virulence proteins/genes involved in spore formation and melanin biosynthesis.
Objective:
We aimed to describe the scope of cleft-related infanticide and identify issues that might inform prevention strategies.
Design:
Systematic reviews of both academic (eg, PubMed, EBSCOhost) ...and lay literature (eg, LexisNexis Academic, Google) databases were performed to identify all primary reports of cleft-related infanticide. All languages were included. Records before 1985 were excluded. Reference lists of all included reports were screened for potentially relevant records.
Main Outcome Measures:
Country of origin and excerpts that pertained to the concepts surrounding cleft-related infanticide were extracted. Extracted excerpts were examined using a content analysis framework.
Results:
Of the 1,151 records retrieved, 70 reports documented cleft-related infanticide from 27 countries. The largest number of reports was from China (14 reports; 48% of reports), followed by India (4; 14%) and Nigeria (4; 14%). However, 2 countries had 3 reports, 5 countries had 2 reports, and 17 countries had 1 report. Themes that emerged from excerpt analysis included stigma, lack of affordable cleft care, abandonment, orphanage overcrowding, and abuse and slavery.
Conclusions:
Cleft-related infanticide is a global problem. Initiatives to sensitize communities to cleft lip and/or cleft palate, provide timely and affordable cleft care, and build support systems for affected families may prove beneficial. Cleft care organizations have the opportunity to advocate for these initiatives, reduce the incidence of infanticide by providing or supporting timely and affordable cleft care, and demonstrate that children with successful cleft repairs reassimilate well into their communities.
Vitiligo is a chronic asymptomatic disorder affecting melanocytes from the basal layer of the epidermis which leads to a patchy loss of skin color. Even though it is one of the neglected disease ...conditions, people suffering from vitiligo are more prone to psychological disorders. As of now, various studies have been done in order to project auto-immune implications as the root cause. To understand the complexity of vitiligo, we propose the Vitiligo Information Resource (VIRdb) that integrates both the drug-target and systems approach to produce a comprehensive repository entirely devoted to vitiligo, along with curated information at both protein level and gene level along with potential therapeutics leads. These 25,041 natural compounds are curated from Natural Product Activity and Species Source Database. VIRdb is an attempt to accelerate the drug discovery process and laboratory trials for vitiligo through the computationally derived potential drugs. It is an exhaustive resource consisting of 129 differentially expressed genes, which are validated through gene ontology and pathway enrichment analysis. We also report 22 genes through enrichment analysis which are involved in the regulation of epithelial cell differentiation. At the protein level, 40 curated protein target molecules along with their natural hits that are derived through virtual screening. We also demonstrate the utility of the VIRdb by exploring the Protein–Protein Interaction Network and Gene–Gene Interaction Network of the target proteins and differentially expressed genes. For maintaining the quality and standard of the data in the VIRdb, the gold standard in bioinformatics toolkits like Cytoscape, Schrödinger’s GLIDE, along with the server installation of MATLAB, are used for generating results. VIRdb can be accessed through “
http://www.vitiligoinfores.com/
”.
Vitiligo is a disease of mysterious origins in the context of its occurrence and pathogenesis. The autoinflammatory theory is perhaps the most widely accepted theory that discusses the occurrence of ...Vitiligo. The theory elaborates the clinical association of vitiligo with autoimmune disorders such as Psoriasis, Multiple Sclerosis and Rheumatoid Arthritis and Diabetes. In the present work, we discuss the comprehensive set of differentially co-expressed genes involved in the crosstalk events between Vitiligo and associated autoimmune disorders (Psoriasis, Multiple Sclerosis and Rheumatoid Arthritis). We progress our previous tool, Vitiligo Information Resource (VIRdb), and incorporate into it a compendium of Vitiligo-related multi-omics datasets and present it as VIRdb 2.0. It is available as a web-resource consisting of statistically sound and manually curated information. VIRdb 2.0 is an integrative database as its datasets are connected to KEGG, STRING, GeneCards, SwissProt, NPASS. Through the present study, we communicate the major updates and expansions in the VIRdb and deliver the new version as VIRdb 2.0. VIRdb 2.0 offers the maximum user interactivity along with ease of navigation. We envision that VIRdb 2.0 will be pertinent for the researchers and clinicians engaged in drug development for vitiligo.
Retroperitoneal nonfunctional extraadrenal paragangliomas are uncommon neoplasms arising from the aorticosympathetic chain of paraganglia. Biopsy of these tumors shows diverse cytomorphological ...features which can pose a significant diagnostic challenge to the histopathologist. We report a case of a 36-year-old male presenting with abdominal pain and a retroperitoneal mass anterior to the left kidney observed on ultrasound and computed tomography (CT) scan. CT-guided needle core biopsy was carried out which revealed varied cytological features suggesting a wide spectrum of differential diagnosis. Knowledge of the histological features along with immunohistochemistry helped us to diagnose this case. Since surgical excision is the preferred treatment of choice, early and accurate diagnosis is of utmost importance.
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