51 research outputs found
Rejection Leads to Revolution of Protagonist inSudhaMurty\u27‘’s‘‘\u27Gently Falls TheBakula‘’
No full textRejections often cause many psychological wounds. The result of rejection leads to anger,erodes confidence and self esteem, and destabilizes our fundamental feeling of belonging. Most human’s desire social contact,being rejected can incite negative feeling. Sudha Murthy is undoubtedly one of the most significant contemporary Indian women novelists in English.Sudha Murty projects the image of modern women who have a career and a development of feminine sensibility beyond being feminist. The present paper elucidates how the rejected woman in the modern world becomes revolutionary woman through SudhaMurty’s ‘Gently falls the Bakula’.In Gently Falls the Bakula, Shrimati falls in love with her neighbourShrikant and get married. But she was badly rejected,ill-treated and demanded money by her mother-in-law. Later on, she was also rejected by her husband. Finally she successfully ends up in doing Ph.D in U.S. in spite of many odds.Sudha Murty projects the marginalization of Indian women at the hands of their husbands through Shrimathi and Shrikant.
 
Beyond Genetics: Clinico-Pathological Recognition of Ullrich Muscular Dystrophy in a Resource-Limited Setting
No full textBackground: Ullrich congenital muscular dystrophy (UCMD) is a rare collagen VI–related myopathy caused by mutations in COL6A1, COL6A2, or COL6A3 genes. Although traditionally considered an autosomal recessive disorder, recent reports have identified autosomal dominant variants that cause the UCMD phenotype. Clinically, it is characterized by early‐onset muscle weakness, proximal joint contractures, and distal joint hyperlaxity. This condition frequently progresses to restrictive respiratory involvement, while typically sparing cognitive, sensory, and autonomic functions. Given this predictable trajectory, early integration of palliative care is increasingly emphasised to optimize quality of life and reduce crisis-driven interventions. UCMD is extremely rare, with an estimated prevalence of fewer than 1 in 1,000,000 births worldwide, though the exact frequency remains unknown. A definitive diagnosis requires genetic confirmation and immunohistochemistry, but such resources are often limited in low- and middle-income countries.
Case summary: A 15-year-old male, born of a third-degree consanguineous marriage, presented to the internal medicine department with recurrent lower respiratory tract infections and respiratory distress.
He was first evaluated at age 4 for progressive motor regression, difficulty ambulating, and multiple joint contractures. Over the next decade, he had progressive motor decline and restrictive pulmonary disease, while cognitive, sensory, autonomic, and cardiac functions remained preserved.
Physical examination revealed proximal muscle weakness, contractures of elbows and ankles, lumbar lordosis, café-au-lait spots, and a waddling gait. Muscle biopsy demonstrated features consistent with a dystrophic process and mild non-specific myopathic changes. A clinical diagnosis of UCMD was established based on characteristic clinical findings and histopathological correlation due to the unavailability of genetic testing and collagen VI immunohistochemistry. The internal medicine team integrated palliative care principles in his management through holistic assessment, symptom management, caregiver support, advanced care planning, and multidisciplinary coordination.
This case illustrates UCMD’s diagnostic challenges, natural history marked by progressive musculoskeletal and respiratory decline, and the imperative for early integration of palliative care principles in management.
Conclusion: UCMD is a rare genetic disorder that is often underdiagnosed due to limited awareness and diagnostic challenges, particularly in resource-limited settings. Early diagnosis is essential to initiate supportive care, which can significantly improve quality of life. This case highlights the diagnostic value of comprehensive clinical evaluation and muscle biopsy in identifying UCMD. Increased awareness and expanded diagnostic testing programs are key to uncovering additional cases. Wider access to genetic testing is critical for diagnostic confirmation. Continued research into the molecular and genetic basis of UCMD will help to improve diagnosis and develop novel therapies. Owing to its rare occurrence, comprehensive epidemiological studies are needed to get more knowledge about its global incidence and natural history. Early palliative care integration is recommended to optimize patient and family well-being
Effects of carbon tetrachloride on mitosis
No full textWe have observed that carbon tetrachloride produces striking effects on Allium cepa, Allium sativum and Zaphranthus sp. root tips. Root tips were treated for five minutes to a half-hour in carbon tetrachloride and later transferred to normal nutrient medium and fixed at various intervals from half an hour to six hours. Among the prominent changes taking place in the resting nucleus is a dissolution of the nuclear membrane and an outflow of its contents. Similar observations have been made in root tips of Allium cepa treated with chloroform and potassium cyanide. It would appear that the lipoid layer of the nuclear membrane is either dissolved or rendered weak by the chemicals, in consequence of which the nuclear contents flow out. After treatment for 15 min. with carbon tetrachloride, resting and premitotic nuclei break up. A number of chemicals are known to produce this effect, for example, urethane and nitrogen mustard. Perhaps the most characteristic changes brought about by carbon tetrachloride are dissolution of chromatin in the resting nucleus and disorganization of the chromosome arms in the premitotic stages, resulting in their progressively negative reaction to the Feulgen reagent
Identification of Immuno-Oncology Crosstalk Pathways in Lung Adenocarcinoma
No full textposter abstractIdentifying dysregulated pathways from the high throughput data for biomarker detection is the rate limiting step in the complex diseases cure. Pathways don’t perform alone; they interact with each other through the overlapping genes. This phenomenon is known as crosstalk of pathways.
The aim of the study is develop a methodology to find the highly interacting (cross-talk) immuneoncological pathways and their drug-gene-pathway modules which can be further validated invivo using Lung Adenocarcinoma (LUAD) as a case study. The reference pathway cross-talk matrix is built using the KEGG Knowledgebase, which consists of the 302 KEGG pathways associated with 6996 genes. The LUAD gene expression data available in The Cancer Genome Atlas (TCGA) is used for the study. The data of 32 patients was used in the study and of these, 9 patients were treated with immunotherapy drugs. A set of 3018 significant genes associated with 296 pathways [C.I. =95%, p-value <=0.05] are identified in this dataset, and a disease crosstalk matrix is constructed. Each cell in the matrix gives the cross-talk score of the pathways computed using the formula:
∩
∪ .
The interaction among the significant genes (3018 genes)
in the crosstalk pathways were identified using the BioGrid physical gene-gene interaction map and a gene interaction network (10102 interaction) is generated. The significant genes in the network are annotated to their drugs as given in the clinical data of TCGA. The drug-genepathway modules of LUAD are identified using Seed-Based-Network Propagation Algorithm. These modules give the profile of the highest cross-talk pathways of LUAD that can be studied further for alternative drug targets. The study identified T-cell receptor signaling pathway and B cell receptor signaling pathway of LUAD have high crosstalk scores with Erbb Signaling pathway (18.67, 15.15) Vegf signaling pathway (17.77, 22.45); Osteoclast differentiation (16.35, 14.89)
Identification of Immuno-Oncology Crosstalk Pathways in Lung Adenocarcinoma
No full textposter abstractIdentifying dysregulated pathways from the high throughput data for biomarker detection is the rate limiting step in the complex diseases cure. Pathways don’t perform alone; they interact with each other through the overlapping genes. This phenomenon is known as crosstalk of pathways.
The aim of the study is develop a methodology to find the highly interacting (cross-talk) immuneoncological pathways and their drug-gene-pathway modules which can be further validated invivo using Lung Adenocarcinoma (LUAD) as a case study. The reference pathway cross-talk matrix is built using the KEGG Knowledgebase, which consists of the 302 KEGG pathways associated with 6996 genes. The LUAD gene expression data available in The Cancer Genome Atlas (TCGA) is used for the study. The data of 32 patients was used in the study and of these, 9 patients were treated with immunotherapy drugs. A set of 3018 significant genes associated with 296 pathways [C.I. =95%, p-value <=0.05] are identified in this dataset, and a disease crosstalk matrix is constructed. Each cell in the matrix gives the cross-talk score of the pathways computed using the formula:
∩
∪ .
The interaction among the significant genes (3018 genes)
in the crosstalk pathways were identified using the BioGrid physical gene-gene interaction map and a gene interaction network (10102 interaction) is generated. The significant genes in the network are annotated to their drugs as given in the clinical data of TCGA. The drug-genepathway modules of LUAD are identified using Seed-Based-Network Propagation Algorithm. These modules give the profile of the highest cross-talk pathways of LUAD that can be studied further for alternative drug targets. The study identified T-cell receptor signaling pathway and B cell receptor signaling pathway of LUAD have high crosstalk scores with Erbb Signaling pathway (18.67, 15.15) Vegf signaling pathway (17.77, 22.45); Osteoclast differentiation (16.35, 14.89)
Prevalence of Depression among Infertile Couples Attending a Tertiary-Care Infertility Clinic
No full textBACKGROUND: A large number of people are affected by infertility in their life time indicating that this is a major health challenge globally. Infertility is currently being thought-about as a medical and social condition which can cause social, emotional and psychological distress. It is estimated that psychological factors have an important role in the pathogenesis of infertility. Although depression has been described as a common consequence of infertility, very little has been documented related to its prevalence and severity, especially in India. This might be because those who fall outside the normal range of depression inventories are poorly reported or because of the fact that the psychological impact of infertility differs from that due to other medical conditions. Addressing the psychological issues during infertility treatment is now considered important. This is because of the increasing awareness that depression could be the cause of infertility, its consequence, or both and may interfere success of infertility treatment and the ability to tolerate on-going treatment. Treatments for infertility have effects on estrogen and progesterone levels. These hormones influence mood of the woman through their actions on serotonin. On the other hand emotional distress itself can suppress ovarian function or implantation resulting in decreased fertility and reduced response to its treatment. This interaction creates a vicious circle between depression and infertile status and can result in treatment dropouts or treatment failure. This study aimed to assess the prevalence of depression among infertile couples attending a tertiary care infertility clinic.
METHODS: A Hospital based cross sectional study was conducted and a calculated sample of 126 couples with infertility attending the infertility clinic were consecutively enrolled into the study after obtaining consent. Data was collected using an interviewer-administered semi-structured questionnaire and depression was assessed using PHQ9 depression tool. A couple was considered to have depression if at least one of the partners had depression. Data was analysed using SPSS version 16. Quantitative variables were expressed as mean and standard deviation and qualitative variables as proportions. Chi-square test of independence and Fisher's Exact Test were used to test the association between categorical variables.
RESULTS: The prevalence of depression among infertile couples was 51.6 %( n=65). Depression was more prevalent in females (48.4% n=61) than in males (33.3% n=42) and when the reason for infertility was female-related. There was a significant risk of development of depression when the other partner had depression (p=0.001, Odds ratio=25.196).
CONCLUSION: Females are often blamed for childlessness especially in rural India resulting in an increased prevalence of depression among infertile females. Efforts should be taken to educate people about infertility so that there is less pressure on infertile couples. Counseling methods, especially supportive psychotherapy and interventions to decrease and prevent the development of severe depression among these patients should be considered
Supplemental data of Glucocorticoid Dependent Mesenchymal Cell Differentiation is Required for Perinatal Lung Morphogenesis and Lung Function
No full textSupplemental Figure S1: Single cell
transcriptomic mapping of embryonic pulmonary cells. Single
cell RNA-seq of fetal mouse lung at E16.5 and E18.5 were generated previously
by Fluidigm C1. Cell type mapping and specific signature genes are available in
LGEA web portal. A) Plot depicts a two-dimensional representation (tSNE) of
single cell RNA profiles of cells isolated from E16.5 lung. Distinct cell types
were identified including epithelial, endothelial, pericytes, myeloid/immune,
proliferative mesenchymal progenitor (PMP), myofibroblast/smooth muscle
(MyoFB), matrix fibroblast (MFB), and two intermediate fibroblast cell types
(IF1 and IF2 cells). B) tSNE of single cell RNA profiles of cells isolated from
E18.5 lung shows distinct cell types including alveolar type I (AT1) and type
II (AT2), ciliated, club, endothelial, myeloid/immune, lipo/matrix fibroblasts
and myofibroblast/smooth muscle cells. C, D) E16.5 epithelial cells were further
dissected into four subtypes via principle components analysis: Sox9+
progenitors (red), Foxa2+ progenitors (green), pre-AT1 cells (blue) and pre-AT2
cells (orange). Top 300 most variable genes were used to PCA plots. Genes are
displayed in four different color markers to represent four subtypes. PCA
biplots (principle components 1-3) projects the sub-cluster of genes and cells
into different sub-spaces based on matrix correlation. Supplemental Figure S2. Lung
sacculation defect in mice with mesenchymal deletion of glucocorticoid receptor. A) H&E stained lung sections
from E18.5 control (panels A-C) or littermate Twist2Cre:Nr3c1fl/fl mice (panels
D-F). Note decreased airspaces in Twist2Cre:Nr3c1fl/fl
lungs as compared to littermate controls. B) Quantification of airspace area in
E18.5 controls and Twist2Cre:Nr3c1fl/fl mice. Scale bars = 100um. Supplemental Figure S3. Immunofluorescence
staining of CD106, FN1 and ACTA2 protein in control E18.5 lung tissue. CD106
expression is restricted to the mesenchyme, similar to vimentin. Note lack of
CD106 co-expression with SMA and lack of CD106 staining in proximal (solid
arrow) and distal (open arrow) epithelial cells. Scale bar = 40um.Supplemental
Figure S4: Expression
of cell type selective markers in CD106+ vs. CD106- cells. Expression
of cell type selective markers in CD106+ (blue bars) vs CD106- (orange bars)
cells. Marker genes for matrix fibroblasts (MFB, red), proliferative
mesenchymal progenitors (PMP, dark blue), myofibroblasts/smooth muscle
(MyoFB/SM, violet), endothelial (Endo, green), and epithelial cells (Epi, light
blue) are shown on the X-axis. Y-axis represents normalized RNA expression
(FPKM), Mean±SEM.Supplemental
Figure S5: Functional enrichment analysis of genes with ATAC-seq open chromatin
peaks at E16.5 and E18.5. CD106+ cells were isolated from normal
mouse fetal lungs at E16.5 and E18.5 using negative selection (CD45/CD31/CD309)
followed by positive selection of CD106. Cells were treated with 100nM Dex or
saline for 4 hours in vitro and subjected to ATACseq. ATAC-seq peaks with more
than 2 fold enrichment in Dex treated vs. saline controls at E16.5 (blue) and
E18.5 (orange) were selected and nearby genes were annotated based on mm10
genome using Homer. Those genes were subject to functional enrichment analysis
using ToppGene suite. Shared functional enrichment by Dex treatment were
observed at both time points.Supplemental Figure S6: NR3C1
centered transcription regulatory network. Upstream analysis was
performed on differentially expressed genes in lung mesenchymal cells from GR
gain- (MFB cells identified from scRNA-seq analysis of fetal lungs whose dams
were treated with Dex in vivo, details see method section) and loss-of-function
(lung RNA from mesenchyme-specific GR knockout (Col1a2Cre;Nr3c1fl/fl))
conditions at E18.5 using Ingenuity Pathway Analysis. Common key regulators in
both GR gain- and loss-of-function conditions were depicted in the NR3C1
centered network (blue nodes). Genes induced in Dex treated MFB cells are shown
in green and genes decreased in Nr3c1 mesenchymal deletion lungs are shown in
red. The biological relationship between regulators and differential expressed
genes are represented by an edge (line). The network was generated in Cytoscape
v3.7.1. As shown, differentially expressed genes in response to GR gain and
loss-of-function are likely regulated by a same group of upstream regulators
(i.e., shared same regulatory mechanism mediated by GR). Supplemental
Figure S7: Predicted GC/GR dependent mesenchymal-epithelial
ligand-Receptor interactions. Supplemental Table S1: E16.5
differentially expressed genes from MicroarraySupplemental Table S2: E18.5
differentially expressed genes from MicroarraySupplemental Table S3: Motif
enrichment analysis results of ATAC-seq samples
Supplemental Table S4: Fisher's
exact test on occurrence of the known GR targets in ATAC-seq samples</p
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