Foehn winds in the McMurdo Dry Valleys, Antarctic: The origin of extreme warming events

Foehn winds resulting from topographic modification of airflow in the lee of mountain barriers are frequently experienced in the McMurdo Dry Valleys (MDVs) of Antarctica. Strong foehn winds in the MDVs cause dramatic warming at onset and have significant effects on landscape forming processes; however, no detailed scientific investigation of foehn in the MDVs has been conducted. As a result, they are often misinterpreted as adiabatically warmed katabatic winds draining from the polar plateau. Herein observations from surface weather stations and numerical model output from the Antarctic Mesoscale Prediction System (AMPS) during foehn events in the MDVs are presented. Results show that foehn winds in the MDVs are caused by topographic modification of south-southwesterly airflow, which is channeled into the valleys from higher levels. Modeling of a winter foehn event identifies mountain wave activity similar to that associated with midlatitude foehn winds. These events are found to be caused by strong pressure gradients over the mountain ranges of the MDVs related to synoptic-scale cyclones positioned off the coast of Marie Byrd Land. Analysis of meteorological records for 2006 and 2007 finds an increase of 10% in the frequency of foehn events in 2007 compared to 2006, which corresponds to stronger pressure gradients in the Ross Sea region. It is postulated that the intra- and interannual frequency and intensity of foehn events in the MDVs may therefore vary in response to the position and frequency of cyclones in the Ross Sea region

Development and characterisation of a 3D multi-cellular in vitro model of normal human breast: a tool for cancer initiation studies.

Multicellular 3-dimensional (3D) in vitro models of normal human breast tissue to study cancer initiation are required. We present a model incorporating three of the major functional cell types of breast, detail the phenotype and document our breast cancer initiation studies. Myoepithelial cells and fibroblasts were isolated and immortalised from breast reduction mammoplasty samples. Tri-cultures containing non-tumorigenic luminal epithelial cells HB2, or HB2 overexpressing different HER proteins, together with myoepithelial cells and fibroblasts were established in collagen I. Phenotype was assessed morphologically and immunohistochemically and compared to normal breast tissue. When all three cell types were present, polarised epithelial structures with lumens and basement membrane production were observed, akin to normal human breast tissue. Overexpression of HER2 or HER2/3 caused a significant increase in size, while HER2 overexpression resulted in development of a DCIS-like phenotype. In summary, we have developed a 3D tri-cellular model of normal human breast, amenable to comparative analysis after genetic manipulation and with potential to dissect the mechanisms behind the early stages of breast cancer initiation

Two highly divergent alcohol dehydrogenases of melon exhibit fruit ripening-specific expression and distinct biochemical characteristics

Alcohol dehydrogenases (ADH) participate in the biosynthetic pathway of aroma volatiles in fruit by interconverting aldehydes to alcohols and providing substrates for the formation of esters. Two highly divergent ADH genes (15% identity at the amino acid level) of Cantaloupe Charentais melon (Cucumis melo var. Cantalupensis) have been isolated. Cm-ADH1 belongs to the medium-chain zinc-binding type of ADHs and is highly similar to all ADH genes expressed in fruit isolated so far. Cm-ADH2 belongs to the short-chain type of ADHs. The two encoded proteins are enzymatically active upon expression in yeast. Cm-ADH1 has strong preference for NAPDH as a co-factor, whereas Cm-ADH2 preferentially uses NADH. Both Cm-ADH proteins are much more active as reductases with Kms 10–20 times lower for the conversion of aldehydes to alcohols than for the dehydrogenation of alcohols to aldehydes. They both show strong preference for aliphatic aldehydes but Cm-ADH1 is capable of reducing branched aldehydes such as 3-methylbutyraldehyde, whereas Cm-ADH2 cannot. Both Cm-ADH genes are expressed specifically in fruit and up-regulated during ripening. Gene expression as well as total ADH activity are strongly inhibited in antisense ACC oxidase melons and in melon fruit treated with the ethylene antagonist 1-methylcyclopropene (1-MCP), indicating a positive regulation by ethylene. These data suggest that each of the Cm-ADH protein plays a specific role in the regulation of aroma biosynthesis in melon fruit

In vivo and in vitro expression of steroid-converting enzymes in human breast tumours: associations with interleukin-6

Enzymes modulating local steroid availability play an important role in the progression of human breast cancer. These include isoforms of 17β-hydroxysteroid dehydrogenase (17-HSD), aromatase and steroid sulphatase (STS). The aim of this study was to investigate the expression, by reverse transcription polymerase chain reaction, of 17-HSD types I–IV, aromatase and steroid STS in a series of 51 human breast tumour biopsies and 22 primary cultures of epithelial and stromal cells derived from these tumours, giving a profile of the steroid-regulating network for individual tumours. Correlations between enzyme expression profiles and expression of the interleukin (IL)-6 gene were also sought. All except one tumour expressed at least one isoform of 17-HSD, either alone or in combination with aromatase and STS. Expression of 17-HSD isoforms I–IV were observed in nine tumours. Of the 15 tumours which expressed three isoforms, a combination of 17-HSD II, III and IV was most common (6/15 samples). The majority of tumours (n = 17) expressed two isoforms of 17-HSD with combinations of 17-HSD II and IV predominant (7/17 samples). Eight tumours expressed a single isoform and of these, 17-HSD I was in the majority (5/8 samples). In primary epithelial cultures, enzyme expression was ranked: HSD I (86%) > STS (77%) > HSD II (59%) > HSD IV (50%) = aromatase (50%) > HSD III (32%). Incidence of enzyme expression was generally reduced in stromal cultures which were ranked: HSD I (68%) > STS (67%) > aromatase (48%) > HSD II (43%) > HSD IV (28%) > HSD III (19%). Expression of IL-6 was associated with tumours that expressed ≥ 3 steroid-converting enzymes. These tumours were of higher grade and tended to come from patients with family history of breast cancer. In conclusion, we propose that these enzymes work in tandem with cytokines thereby providing sufficient quantities of bioactive oestrogen from less active precursors which stimulates tumour growth. © 1999 Cancer Research Campaig

Methane emissions : choosing the right climate metric and time horizon

Methane is a more potent greenhouse gas (GHG) than CO2, but it has a shorter atmospheric lifespan, thus its relative climate impact reduces significantly over time. Different GHGs are often conflated into a single metric to compare technologies and supply chains, such as the global warming potential (GWP). However, the use of GWP is criticised, regarding: (1) the need to select a timeframe; (2) its physical basis on radiative forcing; and (3) the fact that it measures the average forcing of a pulse over time rather than a sustained emission at a specific end-point in time. Many alternative metrics have been proposed which tackle different aspects of these limitations and this paper assesses them by their key attributes and limitations, with respect to methane emissions. A case study application of various metrics is produced and recommendations are made for the use of climate metrics for different categories of applications. Across metrics, CO2 equivalences for methane range from 4-199 gCO2eq./gCH4, although most estimates fall between 20 and 80 gCO2eq./gCH4. Therefore the selection of metric and time horizon for technology evaluations is likely to change the rank order of preference, as demonstrated herein with the use of natural gas as a shipping fuel versus alternatives. It is not advisable or conservative to use only a short time horizon, e.g. 20 years, which disregards the long-term impacts of CO2 emissions and is thus detrimental to achieving eventual climate stabilisation. Recommendations are made for the use of metrics in 3 categories of applications. Short-term emissions estimates of facilities or regions should be transparent and use a single metric and include the separated contribution from each GHG. Multi-year technology assessments should use both short and long term static metrics (e.g. GWP) to test robustness of results. Longer term energy assessments or decarbonisation pathways must use both short and long-term metrics and where this has a large impact on results, climate models should be incorporated. Dynamic metrics offer insight into the timing of emissions, but may be of only marginal benefit given uncertainties in methodological assumptions

The evolving role of oestrogen receptor beta in clinical breast cancer

Controversy surrounds the potential clinical importance of oestrogen receptor (ER)β in breast cancer, and three recent papers have sought to resolve this. In the present issue of Breast Cancer Research Novelli and colleagues explored the significance of ERβ1 expression in 936 breast cancer patients, and they showed diverse relationships according to lymph node status. A second paper examined 442 breast cancers in which ERβ1 was an independent predictor of recurrence, disease-free survival and overall survival. Finally a third paper showed that ERβ2 was a powerful prognostic indicator in 757 breast cancers but this was dependent on cellular location, with nuclear ERβ2 expression predicting good survival whilst cytoplasmic expression predicted worse outcome. These papers point to a clinical role for ERβ in breast cancer and shall be discussed

Nonequilibrium phase transition in the sedimentation of reproducing particles

We study numerically and analytically the dynamics of a sedimenting suspension of active, reproducing particles, such as growing bacteria in a gravitational field. In steady state we find a non-equilibrium phase transition between a `sedimentation' regime, analogous to the sedimentation equilibrium of passive colloids, and a `uniform' regime, in which the particle density is constant in all but the top and bottom of the sample. We discuss the importance of fluctuations in particle density in locating the phase transition point, and report the kinetics of sedimentation at early times.Comment: 4 pages, 4 figure

Analysis of the ATR-Chk1 and ATM-Chk2 pathways in male breast cancer revealed the prognostic significance of ATR expression

The ATR-Chk1 and ATM-Chk2 pathways are central in DNA damage repair (DDR) and their over-activation may confer aggressive molecular features, being an adaptive response to endogenous DNA damage and oncogene-induced replication stress. Herein we investigated the ATR-Chk1 and ATM-Chk2 signalings in male breast cancer (MBC). The expression of DDR kinases (pATR, pATM, pChk1, pChk2, and pWee1) and DNA damage markers (pRPA32 and γ-H2AX) was evaluated by immunohistochemistry in 289 MBC samples to assess their association. Survival analyses were carried out in 112 patients. Survival curves were estimated with the Kaplan-Meier method and compared by log-rank test. Cox proportional regression models were generated to identify variables impacting survival outcomes. The expression of pATR conferred poorer survival outcomes (log rank p = 0.013, p = 0.007 and p = 0.010 for overall, 15- and 10-year survival, respectively). Multivariate Cox models of 10-year survival and overall indicated that pATR expression, alone or combined with pChk2, was an independent predictor of adverse outcomes (10-year survival: pATR: HR 2.74, 95% CI: 1.23–6.10; pATR/pChk2: HR 2.92, 95% CI: 1.35–6.33; overall survival: pATR: HR 2.58, 95% CI: 1.20–5.53; pATR/pChk2: HR 2.89, 95% CI: 1.37–6.12). Overall, the ATR/ATM-initiated molecular cascade seems to be active in a fraction of MBC patients and may represent a negative prognostic factor

Joint angle, range of motion, force, and moment assessment: responses of the lower limb to ankle plantarflexion and dorsiflexion

There is limited research on the biomechanical assessment of the lower limb joints in relation to dynamic movements that occur at the hip, knee, and ankle joints when performing dorsiflexion (DF) and plantarflexion (PF) among males and females. This study investigated the differences in joint angles (including range of motion (ROM)) and forces (including moments) between the left and right limbs at the ankle, knee, and hip joints during dynamic DF and PF movements in both males and females. Using a general linear model employing multivariate analysis in relation to the joint angle, ROM, force, and moment datasets, the results revealed significant main effects for gender, sidedness, phases, and foot position with respect to joint angles. Weak correlations were observed between measured biomechanical variables. These results provide insightful information for clinicians and biomechanists that relate to lower limb exercise interventions and modelling efficacy standpoints