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This study investigated the age related variations in luteinizing hormone (LH), androstenedione, testosterone, and total estrogens response to exogenous gonadotropin-releasing hormone (GnRH) in Holstein-Friesian (HF) × Tharparkar bull calves. Fifteen bull calves were selected and, based on their age, were divided into Group I (14-16 months, n = 5), Group II (9-12 months, n = 5), and Group III (6-8 months, n = 5). All bull calves were administered with 10 µg of GnRH intramuscularly. Blood samples were collected at an interval of 30 min commencing 1 h prior to GnRH treatment until 4 h post-GnRH treatment and thereafter, at an interval of 1 h for the next 3 h. Endocrine response in terms of pretreatment values, peak values, area under curve, and time taken to attain peak values for LH, androstenedione, testosterone, and total estrogens was evaluated in all the bull calves. Significant differences were observed in pretreatment values, peak concentrations, and area under curve for androstenedione and testosterone between the groups; with response being higher in Group I bull calves. The results indicated that the HF × Tharparkar bull calves of 14 months age and above respond to exogenous GnRH by secreting significant amounts of testosterone.

Ethnopharmacological Relevance: The Gaddi community has been known for its shepherd profession from time immemorial. At least one family member or 4-5 people from a village adopt a nomadic lifestyle with their sheep flocks in between the hills of north western Himalaya. In Jammu and Kashmir, India, law enforcement has banned the collection of the medicinal plants from the wild except for the Gaddi, Gujjar and Bakerwal tribes who are permitted to collect the species for their personal use only. As a consequence, knowledge of medicinal plants lies with these tribes only. This study has been undertaken to assess the status of Oral Traditional Knowledge (OTK) on medicinal plant usage in one of these tribes, known as the Gaddi. The study has focused specifically on the Gaddi Shepherds as their nomadic lifestyle means that they are closely associated with nature and dependent on natural resources for their livelihood including treatment of various ailments., Material and Methods: Data on indigenous knowledge has been collected through direct interviews of 53 shepherds of the Gaddi tribe and analyzed for quantitative parameters such as use-value and factor informant consensus., Results: A total of 190 plant species belonging to 70 families, growing along the migratory route of the Gaddi Shepherds are used to treat more than 80 different ailments and disorders. Leaves are the most common plant parts used by the Gaddi Shepherds. The older shepherds are much more aware about the traditional knowledge on medicinal plant usage than the younger ones. 56 plant species are used to treat a range of gastrointestinal and liver disorders, however, diabetic conditions and stings/bites by snakes/scorpions are treated using only two plant species each. Mentha longifolia with UV = 0.26 is the species most commonly used by the informants for medicinal purposes. The low UV (below 1) and low Fic (near 0) is a common observation in the present study., Conclusions: The UV and Fic, analysis reveals that OTK on the medicinal plants is dwindling among the Gaddi Shepherds in Jammu and Kashmir, India., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

As an alternative to radioimmunoassay a simple and highly sensitive enzyme immunoassay (EIA) was developed and validated for androstenedione quantification in plasma of Karan Fries bulls using second antibody coating technique. The wells of the microtitreplate were coated with affinity-purified goat immunoglobulin (antirabbit IgG) that binds the hormone specific antibody. The EIA was performed to analyze androstenedione directly in 40 μl of bull plasma. The androstenedione standards ranged from 0.20 to 200 pg/40 μl /well and the sensitivity of the assay was 5 pg/ml plasma. Serially diluted bull plasma containing high endogenous androstenedione showed good parallelism with bovine androstenedione standard curve. Intra- and inter-assay coefficients of variation (CV) were found to be 8 and 9%, respectively. Peripheral plasma androstenedione concentrations determined in young and adult bull samples ranged between 104-990 pg/ml and 184-2040 pg/ml, respectively.

The human LMNA gene encodes the essential nuclear envelope proteins lamin A and C (lamin A/C). Mutations in LMNA result in altered nuclear morphology, but how this impacts the mechanisms that maintain genomic stability is unclear. Here, we report that lamin A/C-deficient cells have a normal response to ionizing radiation but are sensitive to agents that cause interstrand cross-links (ICLs) or replication stress. In response to treatment with ICL agents (cisplatin, camptothecin, and mitomycin), lamin A/C-deficient cells displayed normal γ-H2AX focus formation but a higher frequency of cells with delayed γ-H2AX removal, decreased recruitment of the FANCD2 repair factor, and a higher frequency of chromosome aberrations. Similarly, following hydroxyurea-induced replication stress, lamin A/C-deficient cells had an increased frequency of cells with delayed disappearance of γ-H2AX foci and defective repair factor recruitment (Mre11, CtIP, Rad51, RPA, and FANCD2). Replicative stress also resulted in a higher frequency of chromosomal aberrations as well as defective replication restart. Taken together, the data can be interpreted to suggest that lamin A/C has a role in the restart of stalled replication forks, a prerequisite for initiation of DNA damage repair by the homologous recombination pathway, which is intact in lamin A/C-deficient cells. We propose that lamin A/C is required for maintaining genomic stability following replication fork stalling, induced by either ICL damage or replicative stress, in order to facilitate fork regression prior to DNA damage repair.

Present study was carried out on forty four apparently healthy Murrah buffaloes of different age groups of both sexes to investigate the effects of sex steroids on cell mediated immunity in vitro. Estrogen inhibited proliferation in mitogen-stimulated lymphocytes from prepubertal but not post pubertal buffaloes of either sex. Estrogen at 100 pg/mL concentration stimulating the proliferation significantly (P < 0.05). in all groups and had higher stimulatory effect in lymphocytes from day 10 than day 0 of estrous cycle. Progesterone inhibited lymphocyte proliferation, and inhibition was directly related to the dose, in all groups of either sex. Testosterone did not inhibit proliferation at any dose level and did not show any consistent and lucid effects on lymphocyte proliferation. Present study revealed that buffalo lymphocytes produce appreciable amounts of NO in culture system after treatment with estradiol. Significantly high levels of NO in culture supernatant were found in prepubertal buffalo calves and least in post pubertal buffaloes, which had an inverse relation with lymphocyte proliferation in presence of estradiol. NO in culture supernatant was high at the lowest dose of progesterone which was proportional to the lymphocyte proliferation when treated with progesterone. No significant difference in NO culture supernatant was observed between different concentrations of testosterone treatment.

Twelve healthy lactating Murrah buffaloes of similar parity (3rd) between 90 and 120 days of lactation, selected from the herd of National Dairy Research Institute (Karnal, India) and maintained at managemental practices as followed at the Institute they were included in this experiment. The animals were divided into two groups based on their production level in previous lactation. The average milk production level of group 1 and II was 9.3 and 6 lit/day, respectively. Blood was collected from these buffaloes on three occasions 10 days apart. The lymphocytes were separated and cultured in RPMI 1640 medium with PHA-P for 24 h at 37°C in a humidified CO(2) incubator (95% air and 5%  CO(2)). The lymphocyte responsiveness was also evaluated in response to the in vivo heat stress and in vitro cortisol. Mitogen-induced stimulation index was not affected by production level (P < .01). Stimulation index was significantly reduced (P < .01) in both the groups when cortisol was added at 2.0 ng level in the culture. However, in heat-stressed buffaloes stimulation index did not vary despite increasing levels of cortisol, thus indicating that lymphocyte may become cortisol resistant during periods of acute heat stress. The results showed that lymphocyte proliferation response can be effectively used to study buffalo cell-mediated immunity in vitro.

The ataxia telangiectasia-mutated gene product (ATM), whose loss of function is responsible for ataxia telangiectasia (A-T), is a protein kinase that interacts with several substrates and is implicated in mitogenic signal transduction, chromosome condensation, meiotic recombination, cell-cycle control and telomere maintenance (Pandita, Expert Reviews in Molecular Medicine 5:1-21, 2003; Pandita, Oncogene 21:611-618, 2002; Matsuoka et al., Science 316:1160-1166, 2007). The ATM protein kinase is primarily activated in response to DNA double-strand breaks (DSBs) caused by ionizing radiation (IR) or radiomimetic drugs (Pandita et al., Oncogene 19:1386-1391, 2000). ATM is also activated by heat shock, which occurs independent of DNA damage (Hunt et al., Can Res 69:3010-3017, 2007). ATM is observed at the sites of DNA damage, where it is autophosphorylated and is dissociated from its non-active dimeric form to the active monomeric form (Bakkenist and Kastan, Nature 421:499-506, 2003). The ATM protein appears to be a part of the sensory machinery that detects DSBs during meiosis or mitosis, or breaks consequent to the damage by free radicals. Recent studies support the argument that ATM activation is regulated by chromatin modifications (Gupta, Mol Cell Biol 25:5292-5305, 2005). This review summarizes the multiple approaches used to discern the role of ATM in chromatin modification in response to DNA damage as well as heat shock.

Hyperthermia is a potent sensitizer of cell killing by ionizing radiation (IR), however, the precise mechanism of heat-induced cell death is not yet clear. Radiosensitization can be attributed to the fact that heat is a pleiotropic damaging agent, affecting multiple cell components to varying degrees by altering protein structures, thus influencing the DNA damage response. Hyperthermia alone induces several steps associated with IR signaling in cells. For example, hyperthermia enhances ATM kinase activity and increases cellular ATM autophosphorylation. This prior activation of ATM or other components of the IR-induced signaling pathway by heat interferes with the normal IR-induced signaling required for chromosomal DNA double-strand break repair, thus resulting in increased cell killing post irradiation. Hyperthermia also induces heat shock protein 70 (HSP70) synthesis and enhances telomerase activity. HSP70 expression is associated with radioresistance. Inactivation of HSP70 and telomerase increases residual DNA DSBs post IR exposure, which correlates with increased cell killing, supporting the role of HSP70 and telomerase in IR-induced DNA damage repair. Thus, hyperthermia influences several molecular parameters involved in sensitizing tumor cells to radiation and can enhance the potential of targeted radiotherapy.

Hyperthermia is a potent sensitizer of cell killing by ionizing radiation (IR); however, hyperthermia also induces heat shock protein 70 (HSP70) synthesis and HSP70 expression is associated with radioresistance. Because HSP70 interacts with the telomerase complex and expression of the telomerase catalytic unit (hTERT) extends the life span of the human cells, we determined if heat shock influences telomerase activity and whether telomerase inhibition enhances heat-mediated IR-induced cell killing. In the present study, we show that moderate hyperthermia (43 degrees C) enhances telomerase activity. Inhibition of telomerase activity with human telomerase RNA-targeted antisense agents, and in particular GRN163L, results in enhanced hyperthermia-mediated IR-induced cell killing, and ectopic expression of catalytic unit of telomerase (TERT) decreased hyperthermia-mediated IR-induced cell killing. The increased cell killing by heat and IR exposure in telomerase-inhibited cells correlates with delayed appearance and disappearance of gamma-H2AX foci as well as decreased chromosome repair. These results suggest that inactivation of telomerase before combined hyperthermia and radiotherapy could improve tumor killing.

The mammalian ortholog of the Drosophila MOF (males absent on the first) gene product is a histone H4 lysine 16-specific acetyltransferase. Recent studies have shown that depletion of human MOF (hMOF) in human cell lines leads to genomic instability, spontaneous chromosomal aberrations, cell cycle defects, altered nuclear morphology, reduced transcription of certain genes, and defective DNA damage response to ionizing radiation (IR). Here we show that MOF plays an essential role in mammals during embryogenesis and oncogenesis. Ablation of the mouse Mof gene (mMof) by gene targeting resulted in early embryonic lethality and cell death. Lethality correlated with the loss of H4 lysine 16 acetylation (H4K16ac) and could not be rescued by concomitant inactivation of ATM or p53. In comparison to primary cells or normal tissue, all immortalized human normal and tumor cell lines and primary tumors demonstrated similar or elevated hMOF and H4K16ac levels. Accordingly, MOF overexpression correlated with increased cellular proliferation, oncogenic transformation, and tumor growth. Thus, these data reveal that the acetylation of histone H4 at K16 by MOF is an epigenetic signature of cellular proliferation common to both embryogenesis and oncogenesis and that MOF is an essential factor for embryogenesis and oncogenesis.

China, India, Indonesia, and Thailand are among the largest consumers of asbestos. Because markets in the West are dwindling, asbestos is heavily promoted in Asia. In spite of widespread usage, asbestos-related diseases are surprisingly few and reported cases of mesothelioma are rare in Asia except in Japan, Korea, and Singapore. The problem lies in diagnosis. Most of the asbestos-related diseases are not diagnosed in Asia and thus do not appear in government statistics. This deadly substance is killing workers. Unless drastic action is taken to stop its use, Asian workers as well as the general population will pay a heavy price.