Stem cell fate is influenced by specialized microenvironments that remain poorly defined in mammals. To explore the possibility that haematopoietic stem cells derive regulatory information from bone, accounting for the localization of haematopoiesis in bone marrow, we assessed mice that were genetically altered to produce osteoblast-specific, activated PTH/PTHrP receptors (PPRs). Here we show that PPR-stimulated osteoblastic cells that are increased in number produce high levels of the Notch ligand jagged 1 and support an increase in the number of haematopoietic stem cells with evidence of Notch1 activation in vivo. Furthermore, ligand-dependent activation of PPR with parathyroid hormone (PTH) increased the number of osteoblasts in stromal cultures, and augmented ex vivo primitive haematopoietic cell growth that was abrogated by gamma-secretase inhibition of Notch activation. An increase in the number of stem cells was observed in wild-type animals after PTH injection, and survival after bone marrow transplantation was markedly improved. Therefore, osteoblastic cells are a regulatory component of the haematopoietic stem cell niche in vivo that influences stem cell function through Notch activation. Niche constituent cells or signalling pathways provide pharmacological targets with therapeutic potential for stem-cell-based therapies.

/pdf/osteoblastic-cells-regulate-the-haematopoietic-stem-cell-17prhh2a28.pdf

Osteoblastic cells regulate the haematopoietic stem cell niche

Reactive oxygen species (ROS) are generated as by-products of cellular metabolism, primarily in the mitochondria. When cellular production of ROS overwhelms its antioxidant capacity, damage to cellular macromolecules such as lipids, protein, and DNA may ensue. Such a state of “oxidative stress” is thought to contribute to the pathogenesis of a number of human diseases including those of the lung. Recent studies have also implicated ROS that are generated by specialized plasma membrane oxidases in normal physiological signaling by growth factors and cytokines. In this review, we examine the evidence for ligand-induced generation of ROS, its cellular sources, and the signaling pathways that are activated. Emerging concepts on the mechanisms of signal transduction by ROS that involve alterations in cellular redox state and oxidative modifications of proteins are also discussed.

Reactive oxygen species in cell signaling

Cells prepare for S phase during the G1 phase of the cell cycle. Cell biological methods have provided knowledge of cycle kinetics and of substages of G1 that are determined by extracellular signals. Through the use of biochemical and molecular biological techniques to study effects of growth factors, oncogenes, and inhibitors, intracellular events during G1 that lead to DNA synthesis are rapidly being discovered. Many cells in vivo are in a quiescent state (G0), with unduplicated DNA. Cells can be activated to reenter the cycle during G1. Similarly, cells in culture can be shifted between G0 and G1. These switches in and out of G1 are the main determinants of post-embryonic cell proliferation rate and are defectively controlled in cancer cells.

https://science.sciencemag.org/content/sci/246/4930/603.full.pdf

G1 events and regulation of cell proliferation.

https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1006&context=covid19

SARS-CoV-2

Activation of the Hedgehog (Hh) signalling pathway by sporadic mutations or in familial conditions such as Gorlin's syndrome is associated with tumorigenesis in skin, the cerebellum and skeletal muscle. Here we show that a wide range of digestive tract tumours, including most of those originating in the oesophagus, stomach, biliary tract and pancreas, but not in the colon, display increased Hh pathway activity, which is suppressible by cyclopamine, a Hh pathway antagonist. Cyclopamine also suppresses cell growth in vitro and causes durable regression of xenograft tumours in vivo. Unlike in Gorlin's syndrome tumours, pathway activity and cell growth in these digestive tract tumours are driven by endogenous expression of Hh ligands, as indicated by the presence of Sonic hedgehog and Indian hedgehog transcripts, by the pathway- and growth-inhibitory activity of a Hh-neutralizing antibody, and by the dramatic growth-stimulatory activity of exogenously added Hh ligand. Our results identify a group of common lethal malignancies in which Hh pathway activity, essential for tumour growth, is activated not by mutation but by ligand expression.

Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours

Antibacterial activity and chemical composition of essential oil of Pamburus missionis.

Biomimetic acellular detoxified glutaraldehyde cross-linked bovine pericardium for tissue engineering

Gravity is a major physical factor determining the stress and strain around cells. Both in space experiments and ground simulation, change in gravity impacts the viability and function of various types of cells as well as in vivo conditions. Cancer cells have been shown to die under microgravity. This can be exploited for better understanding of the biology and identification of novel avenues for therapeutic intervention. Here, we described the effect of microgravity simulated using Rotational Cell Culture System-High Aspect Ratio Vessel (RCCS-HARV) on the viability and morphological changes of colorectal cancer cells. We observed DLD1, HCT116 and SW620 cells die through apoptosis under simulated microgravity (SM). Gene expression analysis on DLD1 cells showed upregulation of tumor suppressors PTEN and FOXO3; leading to AKT downregulation and further induction of apoptosis, through upregulation of CDK inhibitors CDKN2B, CDKN2D. SM induced cell clumps had elevated hypoxia and mitochondrial membrane potential that led to adaptive responses like morphogenetic changes, migration and deregulated autophagy, when shifted to normal culture conditions. This can be exploited to understand the three-dimensional (3D) biology of cancer in the aspect of stress response. This study highlights the regulation of cell function and viability under microgravity through PTEN/FOXO3/AKT pathway.

PTEN/FOXO3/AKT pathway regulates cell death and mediates morphogenetic differentiation of Colorectal Cancer Cells under Simulated Microgravity

This paper is an attempt to study the issues like use of electronic information resources, its impact on the collection of print and electronic journals its awareness among the users, and the places where the users are accessing these resources. A survey was conducted in the academic year 2006-07 at the Thapar University, Patiala. A total number of 504 users from the undergraduate, postgraduate, research scholar and faculty members were selected and their response was obtained with the help of questionnaire. The findings show that users from all these categories were using e-resources; the awareness about e-resources encourages users to use such resources to the maximum; and the users are using computer centre and hostels more for accessing the information. The impact of e-resources was visible from the decrease in number of printed journals in comparison to the increase in number of electronic journals. The use of e-journals has increased manifold. The printed material is being quickly replaced by the electronic resources. http://dx.doi.org/10.14429/djlit.29.243

http://publications.drdo.gov.in/ojs/index.php/djlit/article/download/243/153

Use of Electronic Information Resources: A Case Study of Thapar University

Purpose – This paper aims to describe the use of electronic resources and services provided at the central library of Indian Institute of Technology, Delhi. The paper is focused to know who these electronic information services users are, how often they use the services and the place where the information is accessed. Also, the users are asked to give their preferences between an electronic and print journal format.Design/methodology/approach – The questionnaire method is used for collecting the data from the users (i.e. undergraduate, postgraduate, research scholar and faculty), categories‐wise.Findings – It has been found that usage of e‐journals is increasing; this is due to awareness among the users about the library e‐resources and services. Owing to an easy access available at various places in the institute, users are accessing these resources at hostels and departments more as compared to the library. The users coming to library have decreased.Originality/value – The present paper will help other ...

Rama Shanker Verma

Papers

Antibacterial activity and chemical composition of essential oil of Pamburus missionis.

Biomimetic acellular detoxified glutaraldehyde cross-linked bovine pericardium for tissue engineering

PTEN/FOXO3/AKT pathway regulates cell death and mediates morphogenetic differentiation of Colorectal Cancer Cells under Simulated Microgravity

Use of Electronic Information Resources: A Case Study of Thapar University

Use and impact of electronic journals in the Indian Institute of Technology, Delhi, India