The assessment of heavy metal contents in environmental sectors is important to estimate the carcinogenic and non-carcinogenic doses and risks for the mankind associated with it. The present work ...deals with the assessment of the risk exposure related to heavy metal contents in groundwater and soil samples to two different age groups via three different transits, i.e., ingestion, inhalation and dermal. The concentrations of heavy metals (Zn, Cd, Cu, Pb and Cr) were measured in the villages of lower Himalayas of Reasi district by using microwave plasma atomic emission spectrometer. The calculated mean contamination factors of heavy metals in soil samples were as: Zn, 0.73; Cu, 0.70; Pb, 0.74; and Cr, 0.33; which led to pollution load index less than unity. The overall carcinogenic risks have been varied from 6.4E−08 to 5.1E−07 in soil samples and from 7.3E−06 to 1.1E−04 in ground water samples and were found to be well within the range prescribed by USEPA (Screening level ecological risk assessment protocol for hazardous waste combustion facilities, appendix E: toxicity reference values, US Environmental Protection Agency, Washington, D.C.,
1999
). The mean values of heavy metal contents except lead and chromium in water samples were found to be less than the values prescribed by various agencies. Geo-accumulation Index showed that Pb contribute to the highest contamination (0 <
I
geo
< 1) among the other heavy metals. Cluster analysis and principal component analysis identified that Zn, Cu, Pb and Cr had a relationship and the presence of these heavy metals could be related to vehicle emissions, traffic sources and industrial sources. The overall mean values of the non-carcinogenic doses and associated hazard risks in soil and water samples calculated for children were found to be higher than the adults which may be due to hand to mouth activities.
TFE3 Xp11.2 translocation renal cell carcinoma (TFE3-RCC) generally progresses more aggressively compared with other RCC subtypes, but it is challenging to diagnose TFE3-RCC by traditional visual ...inspection of pathological images. In this study, we collect hematoxylin and eosin- stained histopathology whole-slide images of 74 TFE3-RCC cases (the largest cohort to date) and 74 clear cell RCC cases (ccRCC, the most common RCC subtype) with matched gender and tumor grade. An automatic computational pipeline is implemented to extract image features. Comparative study identifies 52 image features with significant differences between TFE3-RCC and ccRCC. Machine learning models are built to distinguish TFE3-RCC from ccRCC. Tests of the classification models on an external validation set reveal high accuracy with areas under ROC curve ranging from 0.842 to 0.894. Our results suggest that automatically derived image features can capture subtle morphological differences between TFE3-RCC and ccRCC and contribute to a potential guideline for TFE3-RCC diagnosis.
Various research studies have shown that exposure to radon gas is a cause of concern for health effects to the public. The present work has been carried out for the radiological risk assessment to ...the public due to the presence of radon isotopes in drinking water of Barnala district of Punjab, India, for the first time using scintillation-based radiation detector. A total of 100 samples were collected from different sources of water (canal and underground water) from 25 villages on grid pattern of 6 × 6 km
2
in the study area for uniform mapping. In situ measurements were carried out to find out Rn-222 concentration in water samples. The measured values have been found to vary from 0.17 ± 0.01 to 9.84 ± 0.59 BqL
−1
with an average value of 3.37 ± 0.29 BqL
−1
, which is well below the recommended limit of 100 BqL
−1
(WHO 2004). The annual effective dose due to ingestion and inhalation of radon has also been calculated for various age groups like infants, children and adults to understand the age-wise dose distribution. The calculated values suggest that there is no significant health risk to the general public from radon in water.
A comprehensive radio-ecological evaluation of soil samples of Solan and Shimla districts of Himachal Pradesh has been carried out for risk and dose assessment. Twenty-six randomly selected ...environmental soil samples were analysed for natural radionuclide concentrations (
226
Ra,
232
Th and
40
K) using NaI(Tl) scintillator detector. The average concentration of
226
Ra,
232
Th and
40
K was observed as 37, 59 and 430 Bq kg
−1
, respectively, which exceeded the worldwide average of 33, 45 and 412 Bq kg
−1
reported by UNSCEAR (Sources and effects of ionizing radiation. Report to the general assembly with scientific annexes, New York, 2008). Radium equivalent activity (Ra
eq
), hazard indices (H
ex
, H
in
) and radioactivity level indices (I
ϒr
, I
α
, AUI) and Clark value were checked against their threshold limits, and their mean values were safely below the recommended criteria. This confirms the soil applicability for construction purposes. Indoor and outdoor dose rates (Ḋ), age-dependent annual effective doses (AED), organ-specific doses and lifetime attributable cancer risk (both cancer incidence and cancer mortality) were also computed. Strong positive correlation was established between radon/thoron exhalation rate and their parent radionuclides. Multivariate statistical technique was employed to explore spatial distribution of radionuclides and homogeneity between various radiological parameters.
Large-scale transcriptome sequencing efforts have vastly expanded the catalog of long non-coding RNAs (lncRNAs) with varying evolutionary conservation, lineage expression, and cancer specificity. ...Here, we functionally characterize a novel ultraconserved lncRNA, THOR (ENSG00000226856), which exhibits expression exclusively in testis and a broad range of human cancers. THOR knockdown and overexpression in multiple cell lines and animal models alters cell or tumor growth supporting an oncogenic role. We discovered a conserved interaction of THOR with IGF2BP1 and show that THOR contributes to the mRNA stabilization activities of IGF2BP1. Notably, transgenic THOR knockout produced fertilization defects in zebrafish and also conferred a resistance to melanoma onset. Likewise, ectopic expression of human THOR in zebrafish accelerated the onset of melanoma. THOR represents a novel class of functionally important cancer/testis lncRNAs whose structure and function have undergone positive evolutionary selection.
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•THOR is a conserved lncRNA expressed in cancers and in normal testis•THOR functions via a conserved interaction with IGF2BP1, stabilizing its targets•Oncogenicity of THOR is corroborated in a zebrafish model
An ultraconserved lncRNA promotes oncogenesis.
The current investigation represents the annual effective dose received due to ingestion and inhalation of radon present in drinking water. As radon itself contributes 3–14% towards the total ...proportion of lung cancer (WHO in Handbook on indoor radon. A public health perspective, World Health Organization, Geneva, 2009). The samples were taken from Sri Ganganagar region of Rajasthan province in India to calculate radon concentration and thereby to study the health risk. Total 100 water samples were taken from different sources of water which have been classified into two different categories as underground water and surface water sources. In-situ measurements of Rn-222 concentration was carried out using scintillation based radon monitor. The values of Rn-222 concentration were found to lie between 0.13 ± 0.04 and 3.74 ± 0.26 BqL
−1
with mean value of 0.92 ± 0.12 BqL
−1
. These values are far below the maximum contamination level of 100 BqL
−1
, recommended by WHO, 2004 (Guidelines for drinking-water quality, WHO, Geneva, 2004). The ingestion and inhalation doses have been calculated for infants, children and adults from the derived radon concentration. The calculated doses are below the recommended level of 100 µSvy
−1
(World Health Organisation in Guidelines for drinking water quality. Health criteria and other information, WHO Press, Geneva, 2003).
The purpose of the present study is to assess dose received by individual tissues or organs of human beings from the exposure of indoor radon (Rn-222), thoron (Rn-220) and their progeny ...concentrations using single entry pinhole dosimeters and deposition based progeny sensors (DRPS/DTPS). The deployment of dosimeters were carried out in 75 dwellings across Hanumangarh district of Rajasthan, India. Annual and seasonal activity concentrations were monitored based on which dose distribution to various tissues and organs were assessed. The estimated average annual effective dose of the study area is 0.8 mSvy
−1
, which is lower than the ICRP recommended limit of 4 mSvy
−1
(at work place) and 14 mSvy
−1
(for residential buildings) (International Commission on Radiological Protection (ICRP) in Radiological protection against radon exposure, ICRP, Stockholm, 2018). Consequently, indoor radon may pose no health risk to the local population of the studied area.
The switch/sucrose non-fermentable (SWI/SNF) complex has a crucial role in chromatin remodelling
and is altered in over 20% of cancers
. Here we developed a proteolysis-targeting chimera (PROTAC) ...degrader of the SWI/SNF ATPase subunits, SMARCA2 and SMARCA4, called AU-15330. Androgen receptor (AR)
forkhead box A1 (FOXA1)
prostate cancer cells are exquisitely sensitive to dual SMARCA2 and SMARCA4 degradation relative to normal and other cancer cell lines. SWI/SNF ATPase degradation rapidly compacts cis-regulatory elements bound by transcription factors that drive prostate cancer cell proliferation, namely AR, FOXA1, ERG and MYC, which dislodges them from chromatin, disables their core enhancer circuitry, and abolishes the downstream oncogenic gene programs. SWI/SNF ATPase degradation also disrupts super-enhancer and promoter looping interactions that wire supra-physiologic expression of the AR, FOXA1 and MYC oncogenes themselves. AU-15330 induces potent inhibition of tumour growth in xenograft models of prostate cancer and synergizes with the AR antagonist enzalutamide, even inducing disease remission in castration-resistant prostate cancer (CRPC) models without toxicity. Thus, impeding SWI/SNF-mediated enhancer accessibility represents a promising therapeutic approach for enhancer-addicted cancers.
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