Biological and cellular responses of humans to high-level natural radiation: A clarion call for a fresh perspective on the linear no-threshold paradigm.

There remains considerable uncertainty in obtaining risk estimates of adverse health outcomes of chronic low-dose radiation. In the absence of reliable direct data, extrapolation through the linear no-threshold (LNT) hypothesis forms the cardinal tenet of all risk assessments for low doses (≤ 100 mGy) and for the radiation protection principle of As Low As Reasonably Achievable (ALARA). However, as recent evidences demonstrate, LNT assumptions do not appropriately reflect the biology of the cell at the low-dose end of the dose-response curve.

Effect of GNE Mutations on Cytoskeletal Network Proteins: Potential Gateway to Understand Pathomechanism of GNEM.

GNE myopathy is an inherited neuromuscular disorder caused by mutations in GNE (UDP-N-acetylglucosamine 2-epimerase/N-acetyl mannosamine kinase) gene catalyzing the sialic acid biosynthesis pathway. The characteristic features include muscle weakness in upper and lower extremities, skeletal muscle wasting, and rimmed vacuole formation. More than 200 GNE mutations in either epimerase or kinase domain have been reported worldwide.

Integrated transcriptomic and proteomic analysis of microplasts derived from macrophage-conditioned medium-treated MCF-7 breast cancer cells.

Microplasts are large extracellular vesicles originating from migratory, invasive, and metastatic cancer cells. Here, to gain insight into the role of microplasts in cancer progression, we performed a proteomic and transcriptomic characterization of microplasts isolated from MCF-7 breast cancer cells treated with macrophage-conditioned medium. These cells were found to be viable, highly migratory, and metabolically active, indicating that microplasts derived from these cells are not apoptotic bodies.

Chronic exposure of humans to high level natural background radiation leads to robust expression of protective stress response proteins.

Understanding exposures to low doses of ionizing radiation are relevant since most environmental, diagnostic radiology and occupational exposures lie in this region. However, the molecular mechanisms that drive cellular responses at these doses, and the subsequent health outcomes, remain unclear. A local monazite-rich high level natural radiation area (HLNRA) in the state of Kerala on the south-west coast of Indian subcontinent show radiation doses extending from ≤ 1 to ≥ 45 mGy/y and thus, serve as a model resource to understand low dose mechanisms directly on healthy humans.

Activation of DNA damage response signaling in mammalian cells by ionizing radiation.

Cellular responses to DNA damage are fundamental to preserve genomic integrity during various endogenous and exogenous stresses. Following radiation therapy and chemotherapy, this DNA damage response (DDR) also determines development of carcinogenesis and therapeutic outcome. In humans, DNA damage activates a robust network of signal transduction cascades, driven primarily through phosphorylation events.

A versatile mouse model of epitope-tagged histone H3.3 to study epigenome dynamics.

The variant histone H3.3 is incorporated into the genome in a transcription-dependent manner. This histone is thus thought to play a role in epigenetic regulation.

Comparative proteomic analysis of human peripheral blood mononuclear cells indicates adaptive response to low-dose radiation in individuals from high background radiation areas of Kerala.

There remain significant uncertainties in estimation of risks with low doses of radiation. The small coastal belt in the southwestern state of Kerala, India, extending from Neendakara in the south to Purakkad in the north is one of the most extensively studied high-level natural background radiation areas (HLNRAs) of the world to address these concerns. The natural radioactivity here is due to occurrence of monazite sand bearing placer deposits along the coastline.

Early antioxidant responses via the concerted activation of NF-κB and Nrf2 characterize the gamma-radiation-induced adaptive response in quiescent human peripheral blood mononuclear cells.

The radiation-induced adaptive response (RI-AR) is a non-targeted effect which is outside the scope of the classical Linear-No-Threshold (LNT) dose-response paradigm. However, the mechanisms of the RI-AR are not well understood. We have studied the RI-AR in quiescent human peripheral blood mononuclear cells (PBMCs).

Gene expression of immediate early genes of AP-1 transcription factor in human peripheral blood mononuclear cells in response to ionizing radiation.

Ionizing radiation (IR) is considered ubiquitous in nature. The immediate early genes are considered the earliest nuclear targets of IR and are induced in the absence of de novo protein synthesis. Many of these genes encode transcription factors that constitute the first step in signal transduction to couple cytoplasmic effects with long-term cellular response.

Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model.

Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging.

Dynamic changes in the proteome of human peripheral blood mononuclear cells with low dose ionizing radiation.

Humans are continually exposed to ionizing radiation from natural as well as anthropogenic sources. Though biological effects of high dose radiation exposures have been well accepted, studies on low-to-moderate dose exposures (in the range of 50-500 mGy) have been strongly debated even as researchers continue to search for elusive 'radiation signatures' in humans. Proteins are considered as dynamic functional players that drive cellular responses.

Role of ATM in bystander signaling between human monocytes and lung adenocarcinoma cells.

The response of a cell or tissue to ionizing radiation is mediated by direct damage to cellular components and indirect damage mediated by radiolysis of water. Radiation affects both irradiated cells and the surrounding cells and tissues. The radiation-induced bystander effect is defined by the presence of biological effects in cells that were not themselves in the field of irradiation.

Effect of proton and gamma irradiation on human lung carcinoma cells: Gene expression, cell cycle, cell death, epithelial-mesenchymal transition and cancer-stem cell trait as biological end points.

Proton beam therapy is a cutting edge modality over conventional gamma radiotherapy because of its physical dose deposition advantage. However, not much is known about its biological effects vis-a-vis gamma irradiation. Here we investigated the effect of proton- and gamma- irradiation on cell cycle, death, epithelial-mesenchymal transition (EMT) and "stemness" in human non-small cell lung carcinoma cells (A549).

The bromodomain protein Brd4 stimulates G1 gene transcription and promotes progression to S phase.

Brd4 is a bromodomain protein that binds to acetylated chromatin. It regulates cell growth, although the underlying mechanism has remained elusive. Brd4 has also been shown to control transcription of viral genes, whereas its role in transcription of cellular genes has not been fully elucidated.

Simultaneous extraction of nuclear and mitochondrial DNA from human blood.

A method of simultaneous isolation of nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) from human blood has been proposed by improvising Lahiri's method of isolation of nuclear DNA. The approach presented here provides selectively enriched fractions and eliminates the need for two different methods or separate reagent sets for the extraction of nDNA and mtDNA. It employs an initial nuclear/ cytoplasm partitioning, followed by the similar procedural steps for the two fractions separately.

Indian ethnic populations characterized by dopamine (D4) receptor VNTR polymorphism.

Background: The human dopamine receptor D4 gene (DRD4) contains a 48-bp tandem repeat in exon 3 and shows alleles varying between repeats 2 and 11. The gene shows a high level of expression in the prefrontal cortex of the brain and association of particular alleles of this locus with various neuropsychiatric and personality disorders have been reported.

Objective: The present study reports allele frequency distribution at the DRD4 variable number tandem repeat (VNTR) locus among five ethnic populations of India.

STR polymorphism among two tribal populations of India.

Two tribal populations of India, Bison Horn Maria and Muria from Bastar district of Madhya Pradesh in Central India were studied for DNA polymorphisms at tetranucleotide short tandem repeat (STR) loci (F13A01 and HUMvWA). A total of 63 random adult individuals for F13A01 locus and 53 samples for HUMvWA were analyzed in the present study.

Characterization of TP53 microsatellite locus among selected ethnic populations of India.

A total of 253 individuals belonging to five ethnic populations of India were analyzed for pentanucleotide microsatellite TP53. These included Konkanasthas and Marathas (from Maharashtra, western India) representing Indo-Aryan lineage and Ezhavas, Nairs and Muslims (from Kerala, southwest India) representing Indo-Dravidian lineage. To the best of our knowledge, allele frequency data at TP53 microsatellite locus exists only for German Caucasians (1,2), Northern Portuguese (3) and West African from S.

Population genetic analysis among five Indian population groups using six microsatellite markers.

Genetic variation at six tetranucleotide microsatellites (HUMTHO1, HUMVWA, F13A01, D3S1359, D12S66, and D12S67) has heen determined in five endogamous ethnic population groups of India belonging to two major linguistic families. The populations analyzed were Konkanastha Brahmins and Marathas (Maharashtra state) from the Indo-Aryan linguistic family and Nairs, Ezhavas, and Muslims (Kerala state) from the Dravidian family. All six loci show high gene diversity, ranging from 0.

Genetic polymorphism study at four minisatellite loci (D1S80, D17S5, D19S20, and APOB) among five Indian population groups.

The present study reports the genetic variation observed among five anthropologically distinct population groups of India, using four highly polymorphic minisatellite loci (D1S80, D17S5, D19S20, and APOB 3' VNTR) in order to examine the effect of geographical and linguistic affiliations on the genetic affinities among these groups. Random individuals from five ethnic groups were studied; the sample size ranged from 235 to 364. The population groups belong to two geographically separated regions of India, the state of Maharashtra (western India) and the state of Kerala (southern India).