The promoters of human cell cycle genes integrate signals from two tumor suppressive pathways during cellular transformation

Deciphering regulatory events that drive malignant transformation represents a major challenge for systems biology. Here we analyzed genome-wide transcription profiling of an in-vitro transformation process. We focused on a cluster of genes whose expression levels increased as a function of p53 and p16INK4A tumor suppressors inactivation. This cluster predominantly consists of cell cycle genes and constitutes a signature of a diversity of cancers. By linking expression profiles of the genes in the cluster with the dynamic behavior of p53 and p16INK4A, we identified a promoter architecture that integrates signals from the two tumor suppressive channels and that maps their activity onto distinct levels of expression of the cell cycle genes, which in turn, correspond to different cellular proliferation rates. Taking components of the mitotic spindle as an example, we experimentally verified our predictions that p53-mediated transcriptional repression of several of these novel targets is dependent on the activities of p21, NFY and E2F. Our study demonstrates how a well-controlled transformation process allows linking between gene expression, promoter architecture and activity of upstream signaling molecules.Comment: To appear in Molecular Systems Biolog

Phenotypic microarrays suggest Escherichia coli ST131 is not a metabolically distinct lineage of extra-intestinal pathogenic E. coli

Extraintestinal pathogenic E. coli (ExPEC) are the major aetiological agent of urinary tract infections (UTIs) in humans. The emergence of the CTX-M producing clone E. coli ST131 represents a major challenge to public health worldwide. A recent study on the metabolic potential of E. coli isolates demonstrated an association between the E. coli ST131 clone and enhanced utilisation of a panel of metabolic substrates. The studies presented here investigated the metabolic potential of ST131 and other major ExPEC ST isolates using 120 API test reagents and found that ST131 isolates demonstrated a lower metabolic activity for 5 of 120 biochemical tests in comparison to non-ST131 ExPEC isolates. Furthermore, comparative phenotypic microarray analysis showed a lack of specific metabolic profile for ST131 isolates countering the suggestion that these bacteria are metabolically fitter and therefore more successful human pathogens

Sustainable deltas in the Anthropocene

What are the possible trajectories of delta development over the coming decades? Trajectories will be determined by the interactions of biophysical trends such as changing sediment supplies, subsidence due to compaction of sediment and climate change, along with key socio-economic trends of migration and urbanisation, agricultural intensification, demographic transition, economic growth and structural change of the economy. Knowledge and understanding of plausible trajectories can inform management choices for deltas in the Anthropocene, including new policy perspectives and innovative adaptation. The emergence of visionary delta management plans in some large deltas, such as the Bangladesh Delta Plan 2100, is an important and necessary component. This chapter synthesises the state of knowledge and highlights key elements of science that will inform decisions on future management of deltas.<br/

HUBUNGAN TINGGI RAIHAN DENGAN KETEPATAN SMASH OPEN ATLET BOLA VOLI PUTRA KLUB YUSO SLEMAN

AbstrakPenelitian bertujuan untuk mengetahui hubungan tinggi raihan dengan ketepatan smash open atletbola voli putra senior klub YUSO Sleman. Penelitian ini merupakan penelitian korelasional denganmetode survey. Populasi penelitian adalah atlet bola voli putra tim KEJURDA senior YUSO Slemansebanyak 15 atlet. Teknik pengambilan sampel menggunakan teknik purposive sampling. Sampelpenelitian adalah atlet bola voli putra senior di YUSO Sleman Yogyakarta Tahun 2015 sebanyak 13 atlet.Instrumen penelitian berupa tes tinggi raihan atlet dan tes laveage untuk mengukur ketepatan smash.Teknik analisis data menggunakan uji korelasi product moment. Hasil penelitian menunjukkan bahwaterdapat hubungan kuat dan signifikan antara tinggi raihan dengan ketepatan smash open atlet bola voliputra senior klub YUSO Sleman. Hal ini ditunjukkan dari nilai r (0,726) lebih besar dari r tabel (0,553)dan p=0,05.Kata Kunci: Tinggi Raihan, Ketepatan Smash Open, Atlet Bola Voli PutraAbstractThe study aims to determine the relationship of high achievement with the precision of the athletessmash open senior men's volleyball club Yuso Sleman . This study is correlational survey method . Thestudy population was men's volleyball team athletes senior regional championship in Sleman Yuso manyas 15 athletes . The sampling technique used purposive sampling technique . Samples were senior men'svolleyball athletes in Yuso Sleman, Yogyakarta in 2015 as many as 13 athletes . The research instrumentis a high achievement athlete tests and tests to measure accuracy laveage smash . Data were analyzedusing product moment correlation test . The results showed that there is a strong correlation between ahigh and a significant achievement by the precision of the athletes smash open the senior men's volleyballclub Yuso Sleman . It is shown from the value of r ( 0.726 ) is greater than r table ( 0.553 ) and p = 0.05Keywords: High Raihan, Accuracy Smash Open, Men's Volleyball Athlete

Are we failing to protect threatened mangroves in the Sundarbans world heritage ecosystem?

The Sundarbans, the largest mangrove ecosystem in the world, is under threat from historical and future human exploitation and sea level rise. Limited scientific knowledge on the spatial ecology of the mangroves in this world heritage ecosystem has been a major impediment to conservation efforts. Here, for the first time, we report on habitat suitability analyses and spatial density maps for the four most prominent mangrove species - Heritiera fomes, Excoecaria agallocha, Ceriops decandra and Xylocarpus mekongensis. Globally endangered H. fomes abundances declined as salinity increased. Responses to nutrients, elevation, and stem density varied between species. H. fomes and X. mekongensis preferred upstream habitats. E. agallocha and C. decandra preferred down-stream and mid-stream habitats. Historical harvesting had negative influences on H. fomes, C. decandra and X. mekongensis abundances. The established protected area network does not support the most suitable habitats of these threatened species. We therefore recommend a reconfiguration of the network to include these suitable habitats and ensure their immediate protection. These novel habitat insights and spatial predictions can form the basis for future forest studies and spatial conservation planning, and have implications for more effective conservation of the Sundarbans mangroves and the many other species that rely on them

The "Ram Effect": A "Non-Classical" Mechanism for Inducing LH Surges in Sheep

During spring sheep do not normally ovulate but exposure to a ram can induce ovulation. In some ewes an LH surge is induced immediately after exposure to a ram thus raising questions about the control of this precocious LH surge. Our first aim was to determine the plasma concentrations of oestradiol (E2) E2 in anoestrous ewes before and after the "ram effect" in ewes that had a "precocious" LH surge (starting within 6 hours), a "normal" surge (between 6 and 28h) and "late» surge (not detected by 56h). In another experiment we tested if a small increase in circulating E2 could induce an LH surge in anoestrus ewes. The concentration of E2 significantly was not different at the time of ram introduction among ewes with the three types of LH surge. "Precocious" LH surges were not preceded by a large increase in E2 unlike "normal" surges and small elevations of circulating E2 alone were unable to induce LH surges. These results show that the "precocious" LH surge was not the result of E2 positive feedback. Our second aim was to test if noradrenaline (NA) is involved in the LH response to the "ram effect". Using double labelling for Fos and tyrosine hydroxylase (TH) we showed that exposure of anoestrous ewes to a ram induced a higher density of cells positive for both in the A1 nucleus and the Locus Coeruleus complex compared to unstimulated controls. Finally, the administration by retrodialysis into the preoptic area, of NA increased the proportion of ewes with an LH response to ram odor whereas treatment with the α1 antagonist Prazosin decreased the LH pulse frequency and amplitude induced by a sexually active ram. Collectively these results suggest that in anoestrous ewes NA is involved in ram-induced LH secretion as observed in other induced ovulators

A cost-effectiveness analysis of a hydration response technology dressing in the treatment of venous leg ulcers in the UK

Introduction: Venous leg ulceration causes significant pain and suffering for patients, additionally it places considerable financial and service burden on the National Health Service (NHS). A large proportion of venous leg ulceration do not heal within the standard time frames of 16 – 24 weeks, resulting in static wounds which commonly have issues with increasing exudate production. Static wounds can have significant negative impact on the patients quality of life, the wound bed and periwound skin, increased risk of infection all of which results in delayed wound healing and increased health service costs. As the NHS continues to face times of austerity, services need to find solutions to be able to reduce cost and release nursing time whilst maintaining standards of care. Cutimed® Sorbion® Sachet S is a treatment option for the management of patients with a venous leg ulceration. The objective of this study was to provide an update of the health economic analysis of Cutimed® Sorbion® Sachet S in comparison to relevant comparators in the UK with current cost data. Methods: Cutimed® Sorbion® Sachet S was compared against Zetuvit Plus, DryMax extra, KerraMax Care and Eclypse from a cost effectiveness perspective. Clinical data were derived from literature and expert opinion. Cost input was utilized based on publicly available data and literature. The average patient in the model is assumed to be 65 years with a diagnosed venous leg ulcer. It is assumed that patients in the different treatment arms have the same background mortality, hence the endpoint mortality is not included in the model. The analysis is based on a deterministic Markov model derived from Harding et al. with weekly cycles. The following assumptions are made: First, all patients start in a static health state with a non-healed but non-progressing venous leg ulcer. It is assumed in the model that patients can transition to a deteriorating health state where a wound is improving or the wound could progress. Additionally, venous leg ulcers could be healed from a progressed wound (i.e. improved wound), they could develop into a severe wound with complications (infections) to be treated in hospitals. The time frame for the analysis was fixed for one year and no re-occurence after healing was assumed to happen. Results: The cost-effectiveness analysis demonstrates health economic dominance of Cutimed® Sorbion® Sachet S being more effective and cost-saving against all analysed comparators. When using literature-based input values the incrementally higher healing rates for Cutimed® Sorbion® Sachet S are 11.04 months (versus Zetuvit Plus), 29.04 months (versus DryMax extra), 1.68 months (versus KerraMax Care) and 11.04 months (versus Eclypse). Cost savings per patient were 37.60£ (versus Zetuvit Plus), 171.68£ (versus DryMax extra), 3.13£ (versus KerraMax Care) and 43.63£ (versus Eclypse). Clinical benefits and cost savings are increasing when real life practice assumptions based on expert opinion are included. Conclusions: Based on the underlying health economic model, Cutimed® Sorbion® Sachet S is more effective and less costly than other comparative products in venous leg ulcers in the UK

Optimality of mutation and selection in germinal centers

The population dynamics theory of B cells in a typical germinal center could play an important role in revealing how affinity maturation is achieved. However, the existing models encountered some conflicts with experiments. To resolve these conflicts, we present a coarse-grained model to calculate the B cell population development in affinity maturation, which allows a comprehensive analysis of its parameter space to look for optimal values of mutation rate, selection strength, and initial antibody-antigen binding level that maximize the affinity improvement. With these optimized parameters, the model is compatible with the experimental observations such as the ~100-fold affinity improvements, the number of mutations, the hypermutation rate, and the "all or none" phenomenon. Moreover, we study the reasons behind the optimal parameters. The optimal mutation rate, in agreement with the hypermutation rate in vivo, results from a tradeoff between accumulating enough beneficial mutations and avoiding too many deleterious or lethal mutations. The optimal selection strength evolves as a balance between the need for affinity improvement and the requirement to pass the population bottleneck. These findings point to the conclusion that germinal centers have been optimized by evolution to generate strong affinity antibodies effectively and rapidly. In addition, we study the enhancement of affinity improvement due to B cell migration between germinal centers. These results could enhance our understandings to the functions of germinal centers.Comment: 5 figures in main text, and 4 figures in Supplementary Informatio

Climate change adaptation in European river basins

This paper contains an assessment and standardized comparative analysis of the current water management regimes in four case-studies in three European river basins: the Hungarian part of the Upper Tisza, the Ukrainian part of the Upper Tisza (also called Zacarpathian Tisza), Alentejo Region (including the Alqueva Reservoir) in the Lower Guadiana in Portugal, and Rivierenland in the Netherlands. The analysis comprises several regime elements considered to be important in adaptive and integrated water management: agency, awareness raising and education, type of governance and cooperation structures, information management and—exchange, policy development and—implementation, risk management, and finances and cost recovery. This comparative analysis has an explorative character intended to identify general patterns in adaptive and integrated water management and to determine its role in coping with the impacts of climate change on floods and droughts. The results show that there is a strong interdependence of the elements within a water management regime, and as such this interdependence is a stabilizing factor in current management regimes. For example, this research provides evidence that a lack of joint/participative knowledge is an important obstacle for cooperation, or vice versa. We argue that there is a two-way relationship between information management and collaboration. Moreover, this research suggests that bottom-up governance is not a straightforward solution to water management problems in large-scale, complex, multiple-use systems, such as river basins. Instead, all the regimes being analyzed are in a process of finding a balance between bottom-up and top–down governance. Finally, this research shows that in a basin where one type of extreme is dominant—like droughts in the Alentejo (Portugal) and floods in Rivierenland (Netherlands)—the potential impacts of other extremes are somehow ignored or not perceived with the urgency they might deserv

Influence of polar solvents on the enhancement of light-ends in heavy crude oil distillation

Crude oil ‘micelle’ can be dispersed into fuels, oil and resin/asphalthene components using some hydrocarbon solvents. This can be adapted towards influencing/enhancing its product slates during the processing of crude oils. This research was carried out to investigate the effect of polar solvents (ethanol and acetone) in the enhancement of the light-ends in the True Boiling Point (TBP) distillation of Venezuela heavy crude oil. The oil was procured from Kaduna Refining and Petrochemical Company, Nigeria Ltd, Kaduna, Nigeria. Different concentrations of ethanol with crude oil blends were prepared using 2.5 wt.%, 5 wt.%, 7.5 wt.%, and 10 wt.%. Their spectro photometric analysis was carried out to determine their micelle diameter. The graphs of the micelle diameter of the blends against the various concentrations of the ethanol were plotted from which the minimum and maximum obtained, were 26.322×10-9m and 28.312×10-9m corresponding to 2.5 wt.% and 5 wt.% ethanol concentrations respectively. The same procedure was also repeated for acetone and the values for the minimum and maximum were 24.31×10-9m and 31.798×10-9m respectively. These concentrations were blended with 400g of the oil and their TBP distillations were carried out. From the data generated, 2.5% and 5% ethanol were respectively found to enhance the light ends recovery by 6.133% and 9.008% for fractions between IBP-360oC for ethanol and 9.500% and 11.693 % for 5% and 2.5% acetone concentration. The authors are of the opinion that this work can be adapted to enhance light ends recovery in the atmospheric/vacuum distillation units (ADU/VDU) of the Crude Oil Refineries.  http://dx.doi.org/10.4314/njt.v35i4.2