Paleoseismic History of the Dead Sea Fault Zone

International audienceThe aim of this entry is to describe the DSF as a transform plate boundary pointing out the rate of activedeformation, fault segmentation, and geometrical complexities as a control of earthquake ruptures. Thedistribution of large historical earthquakes from a revisited seismicity catalogue using detailedmacroseismic maps allows the correlation between the location of past earthquakes and fault segments.The recent results of paleoearthquake investigations (paleoseismic and archeoseismic) with a recurrenceinterval of large events and long-term slip rate are presented and discussed along with the identification ofseismic gaps along the fault. Finally, the implications for the seismic hazard assessment are also discussed

Design, synthesis and mechanistic anticancer activity of new acetylated 5-aminosalicylate-thiazolinone hybrid derivatives

The development of hybrid compounds has been widely considered as a promising strategy to circumvent the difficulties that emerge in cancer treatment. The well-established strategy of adding acetyl groups to certain drugs has been demonstrated to enhance their therapeutic efficacy. Based on our previous work, an approach of accommodating two chemical entities into a single structure was implemented to synthesize new acetylated hybrids (HH32 and HH33) from 5-aminosalicylic acid and 4-thiazolinone derivatives. These acetylated hybrids showed potential anticancer activities and distinct metabolomic profile with antiproliferative properties. The in-silico molecular docking predicts a strong binding of HH32 and HH33 to cell cycle regulators, and transcriptomic analysis revealed DNA repair and cell cycle as the main targets of HH33 compounds. These findings were validated using in vitro models. In conclusion, the pleiotropic biological effects of HH32 and HH33 compounds on cancer cells demonstrated a new avenue to develop more potent cancer therapies

Developmental changes in human dopamine neurotransmission: cortical receptors and terminators

<p>Abstract</p> <p>Background</p> <p>Dopamine is integral to cognition, learning and memory, and dysfunctions of the frontal cortical dopamine system have been implicated in several developmental neuropsychiatric disorders. The dorsolateral prefrontal cortex (DLPFC) is critical for working memory which does not fully mature until the third decade of life. Few studies have reported on the normal development of the dopamine system in human DLPFC during postnatal life. We assessed pre- and postsynaptic components of the dopamine system including tyrosine hydroxylase, the dopamine receptors (D1, D2 short and D2 long isoforms, D4, D5), catechol-<it>O</it>-methyltransferase, and monoamine oxidase (A and B) in the developing human DLPFC (6 weeks -50 years).</p> <p>Results</p> <p>Gene expression was first analysed by microarray and then by quantitative real-time PCR. Protein expression was analysed by western blot. Protein levels for tyrosine hydroxylase peaked during the first year of life (p < 0.001) then gradually declined to adulthood. Similarly, mRNA levels of dopamine receptors D2S (p < 0.001) and D2L (p = 0.003) isoforms, monoamine oxidase A (p < 0.001) and catechol-<it>O</it>-methyltransferase (p = 0.024) were significantly higher in neonates and infants as was catechol-<it>O</it>-methyltransferase protein (32 kDa, p = 0.027). In contrast, dopamine D1 receptor mRNA correlated positively with age (p = 0.002) and dopamine D1 receptor protein expression increased throughout development (p < 0.001) with adults having the highest D1 protein levels (p ≤ 0.01). Monoamine oxidase B mRNA and protein (p < 0.001) levels also increased significantly throughout development. Interestingly, dopamine D5 receptor mRNA levels negatively correlated with age (r = -0.31, p = 0.018) in an expression profile opposite to that of the dopamine D1 receptor.</p> <p>Conclusions</p> <p>We find distinct developmental changes in key components of the dopamine system in DLPFC over postnatal life. Those genes that are highly expressed during the first year of postnatal life may influence and orchestrate the early development of cortical neural circuitry while genes portraying a pattern of increasing expression with age may indicate a role in DLPFC maturation and attainment of adult levels of cognitive function.</p

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified