'Nomadic' Hematopoietic Stem Cells Navigate the Embryonic Landscape.

Hematopoietic stem cells are a unique population of tissue-resident multipotent cells with an extensive ability to self-renew and regenerate the entire lineage of differentiated blood cells. Stem cells reside in a highly specialized microenvironment with surrounding supporting cells, forming a complex and dynamic network to preserve and maintain their function. The survival, activation, and quiescence of stem cells are largely influenced by niche-derived signals, with aging niche contributing to a decline in stem cell function.

Molecular dynamics simulations involving different β-propeller mutations reported in Swiss and French patients correlate with their disease phenotypes.

Integrin αIIbβ3 is the predominant receptor for fibrinogen which mediates platelet aggregation, an important step in hemostasis and thrombosis. Several mutations have been reported in the genes encoding αIIb and β3 subunits among patients with Glanzmann thrombasthenia, of which 177 are in the β-propeller domain. The two subunits form a heterodimer at the interface between β-propeller and β-I domains of αIIb and β3, respectively with their stability critical for intracellular trafficking, surface expression, and ligand binding.

Cardiovascular adaptations in microgravity conditions.

Gravity has had a significant impact on the evolution of life on Earth with organisms developing necessary biological adaptations over billions of years to counter this ever-existing force. There has been an exponential increase in experiments using real and simulated gravity environments in the recent years. Although an understanding followed by discovery of counter measures to negate diminished gravity in space had been the driving force of research initially, there has since been a phenomenal leap wherein a force unearthly as microgravity is beginning to show promising potential.

Diagnosis and treatment of cystic fibrosis in India: What is at stake for developing countries?

Cystic fibrosis (CF) is a life-threatening monogenic disease affecting thousands of people worldwide. Cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel that facilitates transportation of water and salts across epithelial cell membranes through the conductance of Cl and other anions. A dysfunctional CFTR due to abnormalities in the gene causes CF, which is believed to be a rare disease in India mainly due to mis/underdiagnosis.

Targeting host-virus interactions: in silico analysis of the binding of human milk oligosaccharides to viral proteins involved in respiratory infections.

Respiratory viral infections, a major public health concern, necessitate continuous development of novel antiviral strategies, particularly in the face of emerging and re-emerging pathogens. In this study, we explored the potential of human milk oligosaccharides (HMOs) as broad-spectrum antiviral agents against key respiratory viruses. By examining the structural mimicry of host cell receptors and their known biological functions, including antiviral activities, we assessed the ability of HMOs to bind and potentially inhibit viral proteins crucial for host cell entry.

Role of innate immunity and systemic inflammation in cystic fibrosis disease progression.

Pathophysiological manifestations of cystic fibrosis (CF) result from a functional defect in the cystic fibrosis transmembrane conductance regulator (CFTR) paving way for mucus obstruction and pathogen colonization. The role of CFTR in modulating immune cell function and vascular integrity, irrespective of mucus thickening, in determining the host cell response to pathogens/allergens and causing systemic inflammation is least appreciated. Since CFTR plays a key role in the conductance of anions like Cl, loss of CFTR function could affect various basic cellular processes, such as cellular homeostasis, lysosome acidification, and redox balance.

Molecular dynamics simulations corroborate recombinant expression studies carried out on three αIIb β-propeller mutations reported in Indian Glanzmann thrombasthenia patients.

Mutations in the αIIb β-propeller domain have long been known to disrupt heterodimerization and intracellular trafficking of αIIbβ3 complexes leading to diminished surface expression and/or function, resulting in Glanzmann thrombasthenia. Our previous study on three β-propeller mutations, namely G128S, S287L, and G357S, showed variable defects in protein transport correlated with the patient's clinical phenotypes. Pulse-chase experiments revealed differences in αIIbβ3 complex maturation among the three mutations.

Effects of short-term hypergravity on hematopoiesis and vasculogenesis in embryonic zebrafish.

Microgravity and hypergravity-induced changes affect both molecular and organismal responses as demonstrated in various animal models. In addition to its inherent advantages, zebrafish have been shown to be incredibly resilient to altered gravity conditions. To understand the effects of altered gravity on animal physiology, especially the cardiovascular system, we used 2 h centrifugations to simulate short-term hypergravity and investigated its effects on zebrafish development.

Trehalose augments autophagy to mitigate stress induced inflammation in human corneal cells.

Purpose: Cornea acts as a structural barrier and protects the eye from environmental stresses. Inflammation in ocular surface causes discomfort and visual distortion. Defective autophagy has been associated with inflammation and ocular surface diseases.

Efficiency of different fragment lengths of the ubiquitous chromatin opening element HNRPA2B1-CBX3 in driving human CD18 gene expression within self-inactivating lentiviral vectors for gene therapy applications.

Patients with leukocyte adhesion deficiency type 1 (LAD1) suffer from life-threatening bacterial infections due to mutations in the common β integrin subunit (CD18/ITGB2 gene). We tested different fragments of the ubiquitous chromatin opening element (UCOE) from the human HNRPA2B1-CBX3 locus for their efficiency in driving the human CD18 gene expression and compared it with that of an elongation factor 1 alpha promoter (EF1αL, 1169 bp; EF1αS 248 bp) and a murine stem cell virus (MSCV) promoter within the context of the same lentiviral vector backbone. These vectors were tested in vitro for the human CD18 gene expression on the surface of CD34 hematopoietic stem cells (HSCs) isolated from both moderate and severe LAD1 patients.

Corneal tomographic features of postrefractive surgery ectasia.

The purpose of this study was to evaluate the tomographic features of postrefractive surgery eyes. This was a retrospective evaluation of clinical data. Three patients with post-LASIK (laser-assisted in situ keratomileusis) and two patients with post-SMILE (small incision lenticule extraction) ectasia were imaged with Scheimpflug imaging (SI, Pentacam) and optical coherence tomography (OCT, RTVue).

Noncontact Quantification of Topography of Anterior Corneal Surface and Bowman's Layer With High-Speed OCT.

Purpose: To quantify keratometry and wavefront aberration of the anterior corneal surface and epithelium-Bowman's layer interface using anterior segment optical coherence tomography (OCT).

Methods: Twenty-five normal eyes and 25 eyes with keratoconus were retrospectively analyzed. The anterior corneal edge and epithelium-Bowman's layer interface were segmented from 12 distortion-corrected OCT B-scans.

Contemporary Animal Models For Human Gene Therapy Applications.

Over the past three decades, gene therapy has been making considerable progress as an alternative strategy in the treatment of many diseases. Since 2009, several studies have been reported in humans on the successful treatment of various diseases. Animal models mimicking human disease conditions are very essential at the preclinical stage before embarking on a clinical trial.

Gene therapy in India: a focus.

Gene therapy refers to the treatment of genetic diseases using normal copies of the defective genes. It has the potential to cure any genetic disease with long-lasting therapeutic benefits. It remained an enigma for a long period of time, which was followed by a series of setbacks in the late 1990s.

Effect of various immunosuppressive monotherapies on survival and histopathology of monkey islet xenografts in rats.

Background: The isolation and testing of monkey islets after transplantation in small animal models provides basic information about their functional capacity. We describe the effect of cyclosporine A (CsA), tacrolimus (FK506) or prednisolone monotherapy on preventing monkey islet graft rejection after xenoTx in a rat model. Histopathological aspects are reported.

Molecular diversity of Glanzmann thrombasthenia in southern India: new insights into mRNA splicing and structure-function correlations of alphaIIbbeta3 integrin (ITGA2B, ITGB3).

The molecular basis of Glanzmann thrombasthenia (GT) was studied in 40 families from southern India. Of 23 identified mutations (13 in the alphaIIb (ITGA2B) gene and 10 in the beta3 (ITGB3) gene), 20 were novel and three were described previously. Three mutations in the beta3 gene-p.

Prenatal diagnosis of Glanzmann thrombasthenia.

Background: Glanzmann thrombasthenia (GT) is an autosomal recessive disorder of platelet function, which results in major morbidity due to persistent, spontaneous, mucocutaneous bleeding and menorrhagia in women. Platelet transfusions are often needed to control the bleeding. Glanzmann thrombasthenia results from mutations in the genes located on chromosome 17q21-23, encoding the platelet glycoprotein (GP) IIb/IIIa receptor.