Climate change over Leh (Ladakh), India

Mountains over the world are considered as the indicators of climate change. The Himalayas are comprised of five ranges, viz., Pir Panjal, Great Himalayas, Zanskar, Ladhak, and Karakorum. The Ladakh region lies in the northernmost state of India, Jammu and Kashmir, in the Ladhak range. It has a unique cold-arid climate and lies immediately south of the Karakorum range. With scarce water resources, such regions show high sensitivity and vulnerability to the change in climate and need urgent attention. The objective of this study is to understand the climate of the Ladakh region and to characterize its changing climate. Using different temperature and precipitation datasets over Leh and surrounding regions, we statistically analyze the current trends of climatic patterns over the region. The study shows that the climate over Leh shows a warming trend with reduced precipitation in the current decade. The reduced average seasonal precipitation might also be associated with some indications of reducing number of days with higher precipitation amounts over the region

Cloudbursts in Indian Himalayas: a review

Cloudbursts in and around the southern rim of the Indian Himalayas are elusive in terms of their position and time of occurrences. Most of the reported cloudbursts are in the interior of the Himalayas and hence their observation itself is limited. Most of these events are reported once their affect in terms of loss to life and property is experienced in the downstream habitats. In addition, they are mostly associated with flash floods as an impact of the torrential precipitation. The principal understanding of the cloudburst is associated with sudden heavy deluge of precipitation in very less time interval over a very small area. Except this understanding and India Meteorology Department (IMD) definition of > 100 mm/h precipitation over a geographical region of approximately 20–30 km2, nothing much else is known about these events. There are a very few studies carried out on understanding of these events. Present paper synthesizes the available information and research on cloudburst events and tries to define it based on associated dynamics, thermodynamics and physical processes leading to a cloudburst event. Thus in the present work, characterizations and impacts of cloudburst leading from precipitation to dynamical to thermodynamical to large scale forcings to orographical forcings to followed geomorphology to impacts are intertwined to present comprehensive portray of it. Most of the cloudburst events are seen occurring in the elevation range of 1000 m to 2500 m within the valley folds of the southern rim of the Indian Himalayas. Apart from some of the large scale flow shown by few of the studies, it is found that cloudburst events are convectively triggered followed by orographically locked systems. These intertwined mechanisms lead cloudburst events to form. Amiss of any one of these mechanisms will not lead the cloudburst mechanism to form. These interactions in the present paper established the vagaries associated with the cloudburst events

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

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

Comparison of climatic trends and variability among glacierized environments in the Western Himalayas

The climate and hydrology of the Western Himalayas is complex and a function of snow and glacier melt, land use, topography, and Indian summer and winter monsoon dynamics. Improving our knowledge about these processes is important from societal and agricultural points of view. In this study, an observational analysis is carried out to assess the changing climatic trends and the associated interannual variability in winter temperature and precipitation at three glacierized regions of Western Himalayas having distinctly different sub-regional characteristics. In situ observations of 23 years (1985–2007) are used. These observations are passed through rigorous statistical quality control checks. Results show higher interannual variability with increasing temperature trends in the glacierized regions of the Siachen (Karakoram Range) and Chotasigri (Great Himalayan Range). Karakoram Range has higher warming trends than the Great Himalayan Range. In case of precipitation, an overall decrease in precipitation is observed with contrasting trends in the last decade. Nino3.4 index is positively correlated with winter precipitation with similar interannual variability. In addition, at Siachen temperature and precipitation show strong negative correlation, and precipitation to spell length correlation is opposite at Siachen and Chotasigri

RNAi-mediated silencing of the Bmi-1 gene causes growth inhibition and enhances doxorubicin-induced apoptosis in MCF-7 cells

The oncogene Bmi-1 is a member of the Polycomb group gene family. Its expression is found to be greatly increased in a number of malignant tumors including breast cancer. This could suggest Bmi-1 as a potent therapeutic target. In this study, RNAi was introduced to down-regulate the expression of Bmi-1 in a highly malignant breast adenocarcinoma cell line, MCF-7. A thorough study of the biological behavior and chemosensitivity changes of the MCF-7 cells was carried out in context to the therapeutic potential of Bmi-1. The results obtained indicated that siRNA targeting of Bmi-1 could lead to an efficient and specific inhibition of endogenous Bmi-1 activity. The mRNA and protein expression of Bmi-1 were determined by RT-PCR and Western blot, respectively. Furthermore, silencing of Bmi-1 resulted in a drastic inhibition of the growth of MCF-7 cells as well as G1 /S phase transition. The number of target cells was found to increase in phase G 0 /G 1 and decrease in the S phase, but no increase in the basal level of apoptosis was noticed. On the other hand, a reduction in the expression of cyclin D1 and an increase in the expression of p21 were also noticed. Silencing of Bmi-1 made the MCF-7 cells more sensitive to the chemotherapeutic agent doxorubicin and induced a significantly higher percentage of apoptotic cells. Here, we report on a study regarding the RNAi-mediated silencing of the Bmi-1 gene in breast cancer

Transduction of ferret airway epithelia using a pre-treatment and lentiviral gene vector

BACKGROUND: The safety and efficiency of gene therapies for cystic fibrosis (CF) need to be assessed in pre-clinical models. Using the normal ferret, this study sought to determine whether ferret airway epithelia could be transduced with a lysophosphatidylcholine (LPC) pre-treatment followed by a VSV-G pseudotyped HIV-1 based lentiviral (LV) vector, in preparation for future studies in CF ferrets. METHODS: Six normal ferrets (7 -8 weeks old) were treated with a 150 μL LPC pre-treatment, followed one hour later by a 500 μL LV vector dose containing the LacZ transgene. LacZ gene expression in the conducting airways and lung was assessed by X-gal staining after 7 days. The presence of transduction in the lung, as well as off-target transduction in the liver, spleen and gonads, were assessed by qPCR. The levels of LV vector p24 protein bio-distribution in blood sera were assessed by ELISA at 0, 1, 3, 5 and 7 days. RESULTS: The dosing protocol was well tolerated. LacZ gene expression was observed en face in the trachea of all animals. Histology showed that ciliated and basal cells were transduced in the trachea, with rare LacZ transduced single cells noted in lung. p24 levels was not detectable in the sera of 5 of the 6 animals. The LacZ gene was not detected in the lung tissue and no off-target transduction was detected by qPCR. CONCLUSIONS: This study shows that ferret airway epithelia are transducible using our unique two-step pre-treatment and LV vector dosing protocol. We have identified a number of unusual anatomical factors that are likely to influence the level of transduction that can be achieved in ferret airways. The ability to transduce ferret airway epithelium is a promising step towards therapeutic LV-CFTR testing in a CF ferret model.Patricia Cmielewski, Nigel Farrow, Martin Donnelley, Chantelle McIntyre, Jahan Penny-Dimri, Tim Kuchel and David Parson

Expression of BMI-1 and Mel-18 in breast tissue - a diagnostic marker in patients with breast cancer

<p>Abstract</p> <p>Background</p> <p>Polycomb Group (PcG) proteins are epigenetic silencers involved in maintaining cellular identity, and their deregulation can result in cancer. Expression of Mel-18 and Bmi-1 has been studied in tumor tissue, but not in adjacent non-cancerous breast epithelium. Our study compares the expression of the two genes in normal breast epithelium of cancer patients and relates it to the level of expression in the corresponding tumors as well as in breast epithelium of healthy women.</p> <p>Methods</p> <p>A total of 79 tumors, of which 71 malignant tumors of the breast, 6 fibroadenomas, and 2 DCIS were studied and compared to the reduction mammoplastic specimens of 11 healthy women. In addition there was available adjacent cancer free tissue for 23 of the malignant tumors. The tissue samples were stored in RNAlater, RNA was isolated to create expression microarray profile. These two genes were then studied more closely first on mRNA transcription level by microarrays (Agilent 44 K) and quantitative RT-PCR (TaqMan) and then on protein expression level using immunohistochemistry.</p> <p>Results</p> <p>Bmi-1 mRNA is significantly up-regulated in adjacent normal breast tissue in breast cancer patients compared to normal breast tissue from noncancerous patients. Conversely, mRNA transcription level of Mel-18 is lower in normal breast from patients operated for breast cancer compared to breast tissue from mammoplasty. When protein expression of these two genes was evaluated, we observed that most of the epithelial cells were positive for Bmi-1 in both groups of tissue samples, although the expression intensity was stronger in normal tissue from cancer patients compared to mammoplasty tissue samples. Protein expression of Mel-18 showed inversely stronger intensity in tissue samples from mammoplasty compared to normal breast tissue from patients operated for breast cancer.</p> <p>Conclusion</p> <p>Bmi-1 mRNA level is consistently increased and Mel-18 mRNA level is consistently decreased in adjacent normal breast tissue of cancer patients as compared to normal breast tissue in women having had reduction mammoplasties. Bmi-1/Mel-18 ratio can be potentially used as a tool for stratifying women at risk of developing malignancy.</p

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

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

A review of high impact weather for aviation meteorology

This review paper summarizes current knowledge available for aviation operations related to meteorology and provides suggestions for necessary improvements in the measurement and prediction of weather-related parameters, new physical methods for numerical weather predictions (NWP), and next-generation integrated systems. Severe weather can disrupt aviation operations on the ground or in-flight. The most important parameters related to aviation meteorology are wind and turbulence, fog visibility, aerosol/ash loading, ceiling, rain and snow amount and rates, icing, ice microphysical parameters, convection and precipitation intensity, microbursts, hail, and lightning. Measurements of these parameters are functions of sensor response times and measurement thresholds in extreme weather conditions. In addition to these, airport environments can also play an important role leading to intensification of extreme weather conditions or high impact weather events, e.g., anthropogenic ice fog. To observe meteorological parameters, new remote sensing platforms, namely wind LIDAR, sodars, radars, and geostationary satellites, and in situ instruments at the surface and in the atmosphere, as well as aircraft and Unmanned Aerial Vehicles mounted sensors, are becoming more common. At smaller time and space scales (e.g., < 1 km), meteorological forecasts from NWP models need to be continuously improved for accurate physical parameterizations. Aviation weather forecasts also need to be developed to provide detailed information that represents both deterministic and statistical approaches. In this review, we present available resources and issues for aviation meteorology and evaluate them for required improvements related to measurements, nowcasting, forecasting, and climate change, and emphasize future challenges

Dehydroepiandrosterone inhibits the progression phase of mammary carcinogenesis by inducing cellular senescence via a p16-dependent but p53-independent mechanism

INTRODUCTION: Dehydroepiandrosterone (DHEA), an adrenal 17-ketosteroid, is a precursor of testosterone and 17β-estradiol. Studies have shown that DHEA inhibits carcinogenesis in mammary gland and prostate as well as other organs, a process that is not hormone dependent. Little is known about the molecular mechanisms of DHEA-mediated inhibition of the neoplastic process. Here we examine whether DHEA and its analog DHEA 8354 can suppress the progression of hyperplastic and premalignant (carcinoma in situ) lesions in mammary gland toward malignant tumors and the cellular mechanisms involved. METHODS: Rats were treated with N-nitroso-N-methylurea and allowed to develop mammary hyperplastic and premalignant lesions with a maximum frequency 6 weeks after carcinogen administration. The animals were then given DHEA or DHEA 8354 in the diet at 125 or 1,000 mg/kg diet for 6 weeks. The effect of these agents on induction of apoptosis, senescence, cell proliferation, tumor burden and various effectors of cellular signaling were determined. RESULTS: Both agents induced a dose-dependent decrease in tumor multiplicity and in tumor burden. In addition they induced a senescent phenotype in tumor cells, inhibited cell proliferation and increased the number of apoptotic cells. The DHEA-induced cellular effects were associated with increased expression of p16 and p21, but not p53 expression, implicating a p53-independent mechanism in their action. CONCLUSION: We provide evidence that DHEA and DHEA 8354 can suppress mammary carcinogenesis by altering various cellular functions, inducing cellular senescence, in tumor cells with the potential involvement of p16 and p21 in mediating these effects