435 research outputs found

    Recovery Ventilation and Oxygen Debt-A Mathematical Model for the Prediction of Recovery Ventilation

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    A Mathematical model has been evolved for the estimation of recovery ventilation following an exercise. The model has been used to estimate recovery ventilation in moderate to heavy exercise for a period of 32 minutes. The model gives satisfactory predictions for persons of different age groups and under different environment conditions thus establishing its universal applicability

    Biomathematical Study of the Kinetics of Energy Output During Physical Exercise

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    The kinetics of energy production during different grades of activity has been described in terms of rate constant and workload for submaximal, maximal and supermaximal exercises. Equations have been derived for the aerobic and anaerobic components of energy production for the three cases. The theoretical approach has been validated with the available experimental data

    Regression of Body Density on Skinfold Thicknesses in High Altitude Natives: Decline in the Predictive Efficiency on De-Acclimatisation to Low Altitude

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    Body density, stature, body weight and skinfold thickness at 11 sites were experimentally measured on two groups of high altitude natives (HAN) of Ladakh. Group 1, consisting of 38 similar volunteers was studied after 4-week stay at an altitude of 3658 m and Group 2, consisting of 38 similar volunteers was studied after 4-week stay at Delhi (altitude, 200m). Although, there was a strong relationship between skinfolds, other anthropometric measurements and body density (R=0.898) at high altitude (HA), this relationship was significantly reduced at Delhi (R=0.642). Appropriate regression equations predicting body density from skinfold thicknesses, stature and body weight are given for HAN at both the locations. It is concluded that hyperhydration of the lean body and the adipose tissue may be responsible for the weakening of the multiple Rs on de-acclimatisation to low altitude

    Altered sirtuin expression is associated with node-positive breast cancer

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    Sirtuins are genes implicated in cellular and organismal ageing. Consequently, they are speculated to be involved in diseases of ageing including cancer. Various cancers with widely differing prognosis have been shown to have differing and characteristic expression of these genes; however, the relationship between sirtuin expression and cancer progression is unclear. In order to correlate cancer progression and sirtuin expression, we have assessed sirtuin expression as a function of primary cell ageing and compared sirtuin expression in normal, ‘nonmalignant' breast biopsies to breast cancer biopsies using real-time polymerase chain reaction (PCR). Levels of SIRT7 expression were significantly increased in breast cancer (P<0.0001). Increased levels of SIRT3 and SIRT7 transcription were also associated with node-positive breast cancer (P<0.05 and P<0.0001, respectively). This study has demonstrated differential sirtuin expression between nonmalignant and malignant breast tissue, with consequent diagnostic and therapeutic implications

    Mammary epithelial cell transformation: insights from cell culture and mouse models

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    Normal human mammary epithelial cells (HMECs) have a finite life span and do not undergo spontaneous immortalization in culture. Critical to oncogenic transformation is the ability of cells to overcome the senescence checkpoints that define their replicative life span and to multiply indefinitely – a phenomenon referred to as immortalization. HMECs can be immortalized by exposing them to chemicals or radiation, or by causing them to overexpress certain cellular genes or viral oncogenes. However, the most efficient and reproducible model of HMEC immortalization remains expression of high-risk human papillomavirus (HPV) oncogenes E6 and E7. Cell culture models have defined the role of tumor suppressor proteins (pRb and p53), inhibitors of cyclin-dependent kinases (p16(INK4a), p21, p27 and p57), p14(ARF), telomerase, and small G proteins Rap, Rho and Ras in immortalization and transformation of HMECs. These cell culture models have also provided evidence that multiple epithelial cell subtypes with distinct patterns of susceptibility to oncogenesis exist in the normal mammary tissue. Coupled with information from distinct molecular portraits of primary breast cancers, these findings suggest that various subtypes of mammary cells may be precursors of different subtypes of breast cancers. Full oncogenic transformation of HMECs in culture requires the expression of multiple gene products, such as SV40 large T and small t, hTERT (catalytic subunit of human telomerase), Raf, phosphatidylinositol 3-kinase, and Ral-GEFs (Ral guanine nucleotide exchange factors). However, when implanted into nude mice these transformed cells typically produce poorly differentiated carcinomas and not adenocarcinomas. On the other hand, transgenic mouse models using ErbB2/neu, Ras, Myc, SV40 T or polyomavirus T develop adenocarcinomas, raising the possibility that the parental normal cell subtype may determine the pathological type of breast tumors. Availability of three-dimensional and mammosphere models has led to the identification of putative stem cells, but more studies are needed to define their biologic role and potential as precursor cells for distinct breast cancers. The combined use of transformation strategies in cell culture and mouse models together with molecular definition of human breast cancer subtypes should help to elucidate the nature of breast cancer diversity and to develop individualized therapies

    Knockdown of MBP-1 in Human Foreskin Fibroblasts Induces p53-p21 Dependent Senescence

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    MBP-1 acts as a general transcriptional repressor. Overexpression of MBP-1 induces cell death in a number of cancer cells and regresses tumor growth. However, the function of endogenous MBP-1 in normal cell growth regulation remains unknown. To unravel the role of endogenous MBP-1, we knocked down MBP-1 expression in primary human foreskin fibroblasts (HFF) by RNA interference. Knockdown of MBP-1 in HFF (HFF-MBPsi-4) resulted in an induction of premature senescence, displayed flattened cell morphology, and increased senescence-associated beta-galactosidase activity. FACS analysis of HFF-MBPsi-4 revealed accumulation of a high number of cells in the G1-phase. A significant upregulation of cyclin D1 and reduction of cyclin A was detected in HFF-MBPsi-4 as compared to control HFF. Senescent fibroblasts exhibited enhanced expression of phosphorylated and acetylated p53, and cyclin-dependent kinase inhibitor, p21. Further analysis suggested that promyolocytic leukemia protein (PML) bodies are dramatically increased in HFF-MBPsi-4. Together, these results demonstrated that knockdown of endogenous MBP-1 is involved in cellular senescence of HFF through p53-p21 pathway

    miR-17–92 cluster: ups and downs in cancer and aging

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    The miR-17–92 cluster encoding 6 single mature miRNAs was identified a couple of years ago to contain the first oncogenic miRNAs. Now, one of these 6 miRNAs, miR-19 has been identified as the key responsible for this oncogenic activity. This in turn reduces PTEN levels and in consequence activates the AKT/mTOR pathway that is also prominently involved in modulation of organismal life spans. In contrast, miR-19 and other members of the miR-17–92 cluster are found to be commonly downregulated in several human replicative and organismal aging models. Taken together, these findings suggest that miR-19 and the other members of the miR-17–92 cluster might be important regulators on the cross-roads between aging and cancer. Therefore, we here briefly summarize how this cluster is transcriptionally regulated, which target mRNAs have been confirmed so far and how this might be linked to modulation of organismal life-spans

    AsiaPEX:Challenges and Prospects in Asian Precipitation Research

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    The Asian Precipitation Experiment (AsiaPEX) was initiated in 2019 to understand terrestrial precipitation over diverse hydroclimatological conditions for improved predictions, disaster reduction, and sustainable development across Asia under the framework of the Global Hydroclimatology Panel (GHP)/Global Energy and Water Exchanges (GEWEX). AsiaPEX is the successor to GEWEX Asian Monsoon Experiment (GAME; 1995-2005) and Monsoon Asian Hydro-Atmosphere Scientific Research and Prediction Initiative (MAHASRI; 2006-16). While retaining the key objectives of the aforementioned projects, the scientific targets of AsiaPEX focus on land-atmosphere coupling and improvements to the predictability of the Asian hydroclimatological system. AsiaPEX was designed for both fine-scale hydroclimatological processes occurring at the land surface and the integrated Asian hydroclimatological system characterized by multiscale interactions. We adopt six approaches including observation, process studies, scale interactions, high-resolution hydrological modeling, field campaigns, and climate projection, which bridge gaps in research activities conducted in different regions. Collaboration with mesoscale and global modeling researchers is one of the core methods in AsiaPEX. We review these strategies based on the literature and our initial outcomes. These include the estimation and validation of highresolution satellite precipitation, investigations of extreme rainfall mechanisms, field campaigns over the Maritime Continent and Tibetan Plateau, areas of significant impact on the entire AsiaPEX region, process studies on diurnal- to interdecadal-scale interactions, and evaluation of the predictabilities of climate models for long-term variabilities. We will conduct integrated observational and modeling initiative, the Asian Monsoon Year (AMY)-II around 2025-28, whose strategies are the subregional observation platforms and integrated global analysis.</p
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