Thunderstorm environments in Europe

Meteorological environments favorable for thunderstorms are studied across Europe, including rare thunderstorm conditions from seasons with climatologically few thunderstorms. Using cluster analysis on ERA5 reanalysis data and EUCLID (European Cooperation for Lightning Detection) lightning data, two major thunderstorm environments are found: wind-field thunderstorms, characterized by increased wind speeds, high shear, strong large-scale vertical velocities, and low CAPE values compared to other thunderstorms in the same region, and mass-field thunderstorms, characterized by large CAPE values, high dew point temperatures, and elevated isotherm heights. Wind-field thunderstorms occur mainly in winter and more over the seas, while mass-field thunderstorms occur more frequently in summer and over the European mainland. Several sub-environments of these two major thunderstorm environments exist. Principal component analysis is used to identify four topographically distinct regions in Europe that share similar thunderstorm characteristics: the Mediterranean, Alpine–central, continental, and coastal regions, respectively. Based on these results it is possible to differentiate lightning conditions in different seasons from coarse reanalysis data without a static threshold or a seasonal criterion.</p

Targeting the Mitotic Checkpoint to Kill Tumor Cells

One of the most common hallmarks of cancer cells is aneuploidy or an abnormal number of chromosomes. This abnormal chromosome content is a consequence of chromosome missegregation during mitosis, a defect that is seen more frequently in tumor cell divisions as in normal cell divisions. In fact, a large fraction of human tumors display a chromosome instable phenotype, meaning that they very frequently missegregate chromosomes. This can cause variegated aneuploidy within the tumor tissue. It has been argued that this hallmark of cancer could be exploited in anti-cancer therapies. Here we test this hypothesis by inactivation of the mitotic checkpoint through RNAi-mediated depletion of an essential checkpoint component, Mps1. The mitotic checkpoint delays segregation of chromosomes during mitosis until all chromosomes are properly attached to the mitotic spindle. Its inactivation will therefore lead to increased segregation errors. Indeed, we show that this can lead to increased cell death in tumor cells. We demonstrate that increased cell death is associated with a dramatic increase in segregation errors. This suggests that inhibition of the mitotic checkpoint might represent a useful anti-cancer strategy

Cdc28/Cdk1 Regulates Spindle Pole Body Duplication through Phosphorylation of Spc42 and Mps1

AbstractDuplication of the Saccharomyces cerevisiae spindle pole body (SPB) once per cell cycle is essential for bipolar spindle formation and accurate chromosome segregation during mitosis. We have investigated the role that the major yeast cyclin-dependent kinase Cdc28/Cdk1 plays in assembly of a core SPB component, Spc42, to better understand how SPB duplication is coordinated with cell cycle progression. Cdc28 is required for SPB duplication and Spc42 assembly, and we found that Cdc28 directly phosphorylates Spc42 to promote its assembly into the SPB. The Mps1 kinase, previously shown to regulate Spc42 phosphorylation and assembly, is also a Cdc28 substrate, and Cdc28 phosphorylation of Mps1 is needed to maintain wild-type levels of Mps1 in cells. Analysis of nonphosphorylatable mutants in SPC42 and MPS1 indicates that direct Spc42 phosphorylation and indirect regulation of Spc42 through Mps1 are two overlapping pathways by which Cdc28 regulates Spc42 assembly and SPB duplication during the cell cycle

Mps1 directs the assembly of Cdc20 inhibitory complexes during interphase and mitosis to control M phase timing and spindle checkpoint signaling

Cdc20 and Mad2 or Bub1 don’t come together in Mps1-null cells, resulting in a dramatic acceleration of anaphase onset (see also related papers by Hewitt et al. and Santaguida et al. in this issue)

A RAC-GEF network critical for early intestinal tumourigenesis.

RAC1 activity is critical for intestinal homeostasis, and is required for hyperproliferation driven by loss of the tumour suppressor gene Apc in the murine intestine. To avoid the impact of direct targeting upon homeostasis, we reasoned that indirect targeting of RAC1 via RAC-GEFs might be effective. Transcriptional profiling of Apc deficient intestinal tissue identified Vav3 and Tiam1 as key targets. Deletion of these indicated that while TIAM1 deficiency could suppress Apc-driven hyperproliferation, it had no impact upon tumourigenesis, while VAV3 deficiency had no effect. Intriguingly, deletion of either gene resulted in upregulation of Vav2, with subsequent targeting of all three (Vav2-/- Vav3-/- Tiam1-/-), profoundly suppressing hyperproliferation, tumourigenesis and RAC1 activity, without impacting normal homeostasis. Critically, the observed RAC-GEF dependency was negated by oncogenic KRAS mutation. Together, these data demonstrate that while targeting RAC-GEF molecules may have therapeutic impact at early stages, this benefit may be lost in late stage disease

A prospective study of complications from comprehensive abortion care services in Nepal

<p>Abstract</p> <p>Background</p> <p>In March 2002, Nepal's Parliament approved legislation to permit abortion on request up to 12 weeks of pregnancy. Between 2004 and 2007, 176 comprehensive abortion care (CAC) service sites were established in Nepal, leading to a rise in safe, legal abortions. Though monitoring systems have been developed, reporting of complications has not always been complete or accurate. The purpose of this study was to report the frequency and type of abortion complications arising from CAC procedures in different types of facilities in Nepal.</p> <p>Methods</p> <p>A total of 7,386 CAC clients from a sample of facilities across Nepal were enrolled over a three-month period in 2008. Data collection included an initial health questionnaire at the time of abortion care and a follow-up questionnaire assessing complications, administered two weeks after the abortion procedure. A total of 7,007 women (95%) were successfully followed up. Complication rates were assessed overall and by facility type. Multivariable logistic regression was used to assess the association between experiencing a complication and client demographic and facility characteristics.</p> <p>Results</p> <p>Among the 7,007 clients who were successfully followed, only 1.87% (n = 131) experienced signs and symptoms of complications at the two-week follow up, the most common being retained products of conception (1.37%), suspected sepsis (0.39%), offensive discharge (0.51%) and moderate bleeding (0.26%). Women receiving care at non-governmental organization (NGO) facilities were less likely to experience complications than women at government facilities, adjusting for individual and facility characteristics (AOR = 0.18; 95% CI: 0.08-0.40). Compared to women receiving CAC at 4-5 weeks gestation, women at 10-12 weeks gestation were more likely to experience complications, adjusting for individual and facility characteristics (AOR = 4.21; 95% CI: 1.38-12.82).</p> <p>Conclusions</p> <p>The abortion complication rate in Nepali CAC facilities is low and similar to other settings; however, significant differences in complication rates were observed by facility type and gestational age. Interventions such as supportive supervision to improve providers' uterine evacuation skills and investment in equipment for infection control may lower complication rates in government facilities. In addition, there should be increased focus on early pregnancy detection and access to CAC services early in pregnancy in order to prevent complications.</p