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The Hangu Formation (Paleocene) consists of sandstone, siltstone, carbonaceous shale, coal and laterite. It is well exposed in the Trans Indus Surghar range and the southern Hazara basin. The sandstone is yellowish brown, fine to coarse grained and medium to thick bedded. The sandstone of the Hangu Formation is classified as quartz arenite on the Q-F-L diagram. It is mostly grain supported and are cemented by silica cement. The study of different stratigraphic sections reveal that Hangu Formation can be sub-divided into a number of lithofacies on the basis of sedimentary structures and lithological variations.These include lateritic lithofacies, coal and carbonaceous shale, cross-bedded sandstone, bioclastic limestone and bioturbated sandstone. All these lithofacies are well-developed in the Baroch Nala section of the Surghar range except the lateritic lithofacies which contains a thin bed of ferruginous clay. In the studied sections of the Hazara basin, the lateritic lithofacies is the only well-developed lithofacies present in the area. The coal occurs at two stratigraphic levels in the Baroch Nala section. The lower coal seam is thick and its chemical study indicates higher calorific value and carbon content than the upper coal seam and with low moisture/ash content. On the basis of the calorific value, the coal of the Hangu Formation is characterized as highvolatile bituminous. The degree of laterization is strong in the Langrial and Khanpur sections and moderate in Baroch Nala section

The function of the sperm storage tubules is directly correlated with the fertility of laying hens. However, little is known about the molecular mechanisms regulating the fertility traits in chicken. To identify genetic markers associated with reproductive traits, we calculated fertility rate at 61 to 69 wk (51 D) of Jing Hong chickens parent generation as the phenotype and the genotype were detected by the chicken 600K Affymetrix Axiom High Density single nucleotide polymorphisms (SNP)-array. The genome-wide association study using 190 Jing Hong hens showed that the 20 SNP in chromosomes 3 and 13 were significantly associated with fertility rate. To verify these results, a total of 1900 Jing Hong laying hens from 2 populations (P1 and P2) were further genotyped by polymerase chain reaction–restriction fragments length polymorphisms method. The association analysis results revealed that 12 polymorphisms (AX-75769978, AX-76582632, AX-75730546, AX-75730496, AX-75730588, AX-76530282, AX-76530329, AX-76529310, AX-75769906, AX-75755394, AX-80813697 and AX-76582809) out of 20 showed highly significant effects (P

ABSTRACT Pifithrin-α (PFT-α) is a reversible inhibitor of p53-mediated apoptosis, p53-dependent gene transcription, as well as down stream responsive gene function. In response to genotoxic agents, normal cells are instructed [...]

Recent studies in our laboratory indicated that arsenic trioxide has the ability to cause significant cytotoxicity, and induction of a significant number of stress genes in human liver carcinoma cells, HepG2 [1]. However, similar investigations with atrazine did not show any significant effects of this chemical on HepG2 cells, even at its maximum solubility of 100 μg/mL in 1% dimethyl sulfoxide (DMSO). Further cytogenetic studies were therefore carried out to investigate the combined effects of arsenic trioxide and atrazine on cell viability and gene expression in immortalized human hepatocytes. Cytotoxicity was evaluated using the MTT assay for cell viability, while the CAT Tox (L) assay was performed to measure the induction of stress genes in thirteen different recombinant cell lines generated from human liver carcinoma cells (HepG2), by creating stable transfectants of different mammalian promoter – chloramphenicol acetyltransferase (CAT) gene fusions. Cytotoxicity experiments yielded LC50 values of 11.9 ± 2.6 μg/mL for arsenic trioxide in de ionized water, and 3.6 ± 0.4 μg/mL for arsenic trioxide in 100 μg/mL atrazine; indicating a 3 fold increase in arsenic toxicity associated with the atrazine exposure. Co exposure of HepG2 cells to atrazine also resulted in a significant increase in the potency of arsenic trioxide to upregulate a number of stress genes including those of the glutathione S transferase Ya subunit GST Ya, metallothioneinIIa HMTIIA, 70 kDa heat shock protein HSP70, c fos, 153 kDa growth arrest and DNA damage (GADD153), 45 kDa growth arrest and DNA damage (GADD45), and 78 kDa glucose regulated protein GRP78 promoters, as well as the xenobiotic response element XRE, tumor suppressor protein response element p53RE, cyclic adenosine monophosphate response element CRE, and retinoic acid response element RARE. No significant changes were observed with respect to the influence of atrazine on the modulation of cytochrome P450 1A1 CYP 1A1, and nuclear factor kappa (B site) response element NFκBRE by arsenic trioxide. These results indicate that co exposure to atrazine strongly potentiates arsenic trioxide induced cytotoxicity and transcriptional activation of stress genes in transformed human hepatocytes. [ABSTRACT FROM AUTHOR]

The suspended particulate organic matter (SPOM) in transitional waters such as the Maryland Coastal Bays (MCBs) is derived from allochthonous and autochthonous sources. Little is known, however, about the contribution of terrestrially derived organic matter to SPOM in the MCBs. The sources of SPOM in the MCBs were evaluated using stable isotope ratios of nitrogen (δ15N) and carbon (δ13C), and C/N molar ratios. The values of SPOM δ15N, δ13C and C/N ratios from samples collected seasonally (July 2014 to October 2017) at 13 sites ranged from −0.58 to 10.51‰, −26.85 to −20.33‰, and 1.67 to 11.36, respectively, indicating a mixture of terrestrial SPOM transported by tributaries, marine organic matter from phytoplankton, and sewage. SPOM δ13C levels less than −24‰, suggesting the dominance of terrestrially derived carbon, occurred mainly at sites close to the mouths of tributaries, and were less depleted at sites near the ocean. The mean value of SPOM δ13C was higher in October 2014 (−22.76‰) than in October 2015 (−24.65‰) and 2016 (−24.57‰) likely due to differences in river discharge. Much lower values (<4‰) of δ15N observed in February 2016 coincided with a high freshwater inflow that accompanied a major storm, indicating a strong influence of untreated sewage. Results from a two end-member mixing model suggest that on average, the SPOM in the MCBs is composed of 44% terrestrial materials with the highest percent contributions in October 2015 and 2016 (61%), and lowest (28%) in July 2015. The contribution of terrestrial materials to the SPOM was highest (58%) near the mouth of St. Martin River and lowest (25%) near the Ocean City inlet. SPOM composition and distribution in MCBs are, therefore, a function of land use, freshwater inflow, and water circulation that influence in situ phytoplankton production, and the transport and distribution of terrestrially derived materials. [ABSTRACT FROM AUTHOR]

The CAT-Tox (L) assay has recently been developed and validated for detecting and quantifying the specific molecular mechanisms that underlie toxicity of various xenobotic chemicals. We performed this assayto measure the transcriptional responses associated with 2,4,6-trinitrotoluene (TNT) and 2 of its byproducts [2,4 and 2,6-dinitotoluenes (DNTs)] to 13 different recombinant cell lines generated from human liver carcinoma cells (HepG2) by creating stabletransfectants of mammalian promoter chloramphenicol acetyltransferase (CAT) gene fusions. Cytoxicity test with the parental HepG2 cells, using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazol ium bromide]-based assay for cell viability, yielded LC50 values of 10516 mug/mL for TNT in 1% dimethyl sulfoxide (DMSO), and >300 m;g/mL for DNTs, upon 48 h of exposure. TNT appeared to bemore toxic than 2,4-DNT, which also showed a higher toxicity compared to 2,6-DNT. Of the 13 recombinant constructs evaluated, 8 (CYP 1A1,GST Ya, XRE, HMTIIA, c-fos, HSP70, GADD153, and GADD45), 5 (c-fos, HSP70, GADD153, GADD45, and GRP78), and none showed inductions to significant levels (p<0.05), for TNT, 2,4-DNT, and 2,6-DNT, respectively.For most constructs, the induction of stress genes was concentration-dependent. These results show the potential for TNT and 2,4-DNT to cause protein damage and/or perturbations of protein biosynthesis (HSP70 and GRP78), alterations in DNA sequence or its helical structure (c-fos, GADD153, GADD45), and the potential involvement of TNT in the biotransformation process (CYP 1A1, GST Ya, XRE), and in the toxicokinetics of metal ions (HMTIIA). Within the range of concentrations tested (0-300 mg TNT or DNT/mL in 1% DMSO), no significant inductions (p>0.05) of NFKBRE, p53RE, CRE, and RARE were found. [ABSTRACT FROM AUTHOR]

In response to genotoxic agents, normal tissue cells are instructed by p53 either to perform DNA repair or to undergo apoptosis. Studies showed that chemo and/or radiotherapy damage both normal and cancerous cells indiscriminately. To this end, severe side effects inflicted by p53 activation in normal tissues, would possibly be abrogated by p53 inhibition. Pifithrin-alpha (PFT-alpha) is a reversible inhibitor of p53-mediated apoptosis, p53-dependent gene transcription, as well as down stream responsive gene function. The objective of this study was (1) to evaluate PFT-alpha for differential cellular protection in response to arsenic trioxide and cadmium chloride exposure of normal and neoplastic cells, and (2) to evaluate the transcriptional activation of p53 and p53-responsive genes in rat liver cells and HepG2 carcinoma cell line. Cell survival was detected by fluorescein diacetate (FDA) and fluorospectroscopy. Mean LC50 and (SD) for HepG2 cells following exposure to arsenic were 13.7 (+/-1.0) microg/ml with PFT- alpha and 13.4 (+/- 0.5) microg/ml without PFT-alpha (p>0.05). For rat liver cells it was 670 (+/- 8.15) microg/ml with and 573.15 (+/-1.0) microg/ml without PFT-alphha (p<0.05). On exposure to cadmium Chloride, LC50's were 6.95 (+/-2.5) microg/ml for HepG2 cell line in presence of PFT-alpha and 7.35 (+/-1.9) microg/ml in its absence (p>0.5). The results revealed significant differences from controls only upon exposure of rat liver cells to arsenic trioxide in presence of PFT-alpha. PFT-alpha inhibited the transactivation of p53 in rat liver cells and resulted in repression of Bcl2, PCNA, MDM2, Cyclin G and P21 genes by arsenic trioxide. HepG2 cells exposed to arsenic trioxide and PFT-alpha showed expression of only the P53 and PCNA genes. We conclude that PFT-alpha exhibits cytoprotective effect, modifies the detrimental influences of known genotoxic agents in normal cells and has the potential for use as an adjuvant to cancer therapy.

Vitellogenin (vtg) concentrations were measured in plasma and liver samples from 12 hybrid Tilapia oreochromis niloticus x O. aureus to compare concentrations in these tissues. The results were calculated under two different normalizations: volume per gram of sample used (similar to normalization usually published in the literature and typically used for ELISA) and volume per total protein (similar to normalization used in polyacrylamide gel electrophoresis; PAGE). It was observed that the normalization procedure used in PAGE (per gram total protein) minimized the method detection limit by about 1000 and 2500 times in plasma and liver respectively, compared to the normalization usually reported in the literature. It was also observed that normalizing per gram total protein makes it possible to eliminate a potential problem of accidental dilution of plasma samples during sample collection. Moreover, the normalization on a per gram of total protein makes it possible even to compare results from the two different methods namely PAGE and ELISA. It also allows comparison between different tissues. Using the normalization procedures as used in PAGE (per gram total protein) for liver and the normalization method as reported in literature for ELISA (per volume of sample used), it was observed that liver samples had higher vtg levels (mean: 62 microg vtg/g) compared to the corresponding plasma samples (mean: 0.24 microg vtg/ml). However, when both results were normalized per gram total protein all but one liver sample were lower (62 microg vtg/g) than the corresponding plasma concentrations (mean = 246 microg vtg/g).

Embryos of the Japanese medaka (Oryzias latipes) were exposed to serial concentrations of atrazine (0, 25, 50, and 100 ppm) and arsenic trioxide (0, 0.025, 0.05, 0.1 ppm) until hatching. Stasis of circulation, blood islands, titanic convulsions, tube heart and mortality were observed in atrazine-treated embryos. Each endpoint exhibited a concentration-response relationship. Only 4% of the embryos hatched in the 25 ppm, and none in the 50 and 100 ppm, probably due to cell death attributed to the embryos' inability to break from the chorion. With arsenic exposure, hatching was inversely correlated to chemical concentration: 86%, 75% and 54% for 0.025, 0.05 and 0.1 ppm, respectively. Hatching periods were also reduced from 7-13 days in controls to 7-11 days in arsenic-treated embryos. This observation was more pronounced with the 0.05 ppm concentration, showing a reduction of about 4 days. Despite this shortage in hatching time, there were no observable morphological abnormalities, as seen with atrazine. The ecological significance of these findings and implications for the development of sublethal toxicity tests using Japanese medaka embryos are important.

Dinitrotoluenes (DNTs) are nitroaromatic compounds appearing as pale yellow crystalline solids at room temperature. Dinitrotoluenes exist as a mixture of 2 to 6 isomers, with 2,4-DNT, and 2,6-DNT being the most significant. About 500 persons are estimated to be potentially exposed yearly to 2,4-DNT and 2,6-DNT during the production of munitions and explosives. The main route of human exposure at ammunition facilities is inhalation, but dermal contact and inadvertent ingestion can also be substantial. In factory workers, exposure to DNTs has been linked to many adverse health effects, including cyanosis, vertigo, headache, metallic taste, dyspnea, weakness and lassitude, loss of appetite, nausea, and vomiting. Other symptoms including pain or parasthesia in extremities, abdominal discomfort, tremors, paralysis, chest pain, and unconsciousness have also been reported. The primary targets of DNT toxicity are the hematopoietic system (pallor, cyanosis, anemia, and leukocytosis), the cardiovascular system (ischemic heart disease), the nervous system (muscular weakness, headache, dizziness, nausea, insomnia, and tingling pains in the extremities) and the reproductive system (reduction of sperm counts, alteration of sperm morphology, and aspermatogenesis). An association between DNT exposure and increased risk of hepatocellular carcinomas and subcutaneous tumors in rats, as well as renal tumors in mice, has been established. Epidemiologic studies of DNT toxicity have been limited to small groups of workers who had been occupationally exposed at various ammunitions production facilities. Clearly defining the health effects of DNTs with a high degree of confidence has therefore been difficult because of the multigenic nature of occupational exposure. In an attempt to update the toxicologic profile of the DNTs, we hereby provide a critical review of the environmental and toxicologic pathology of DNTs, with a special emphasis on their potential implications for public health.

In response to genotoxic agents, normal cells are instructed by p53 to either perform DNA repair or to commit suicide. Since chemo and/or radiotherapy damage both normal and cancerous cells, the use of PFT-alpha, a reversible inhibitor of down stream function of p53, was suggested as a temporary inhibitor of p53-induced cell damage. Our objective therefore, was (1) to assess the inherent response of HepG2 and rat liver cells to the effects of arsenic and cadmium and (2) to evaluate the role of PFT-alpha in the differential protection of rat liver and HepG2 cells. Following cellular growth to 90% confluency, exposure to cytotoxic agents in presence of PFT-alpha (10 ppm) or its absence was performed. Cell survival was detected fluorometrically using fluorescein diacetate (FDA) and an Ascent Fluoroskan. Toxicity index (LC50) was calculated from percent survival using regression analysis. Results showed an average of 46 fold inherent resistance of rat liver cells to arsenic in comparison to HepG2 cells (LC50 range of 573.15-670 vs. 13.4-13.7 ppm respectively). An average of 8 fold inherent resistance was also attributed to rat liver cells in response to cadmium (LC50 range of 57.72-58.1 vs. 6.99-7.35 ppm respectively). PFT-alpha did not show significant difference in protecting HepG2 cells against cadmium or arsenic. In contrast, there was significant difference in the protection of rat liver cells upon exposure to arsenic. We conclude that Pifithrin-alpha exhibits protection to normal cells, which can play an important role in cancer chemotherapy.