Competitive behaviour amongst members of the same sex is termed intrasexual competition. The tendency to engage in such competition appears to be strongly related to stable individual characteristics such as personality traits. Additionally, recent studies have revealed transient fluctuations in competitiveness according to the female menstrual cycle. To date, no German questionnaire exists to measure intrasexual competition. Our first study aimed to translate and validate the Intrasexual Competition Scale (ICS) by Buunk and Fisher (J Evol Psychol 7:37–48, 2009) in a population of healthy Swiss females (n = 241). Our second study applied the validated German ICS in a group of healthy, regularly cycling females (n = 49) in order to examine possible associations between the menstrual cycle phase and ICS scores. The psychometric properties suggest that the German ICS is a reliable and valid tool to assess individual differences in female intrasexual competition. Furthermore, our second study demonstrated that on average, women showed higher intrasexual competition scores when tested in the late follicular phase (M = 35.77 ± SD = 12.03) compared to the mid-luteal phase (M = 30.93 ± SD = 10.20). Our studies support previous findings of an association between ICS scores and relatively stable individual characteristics such as personality traits. Furthermore, our research endorses the assumption of cycle-dependent fluctuations in intrasexual competition. Future research should clarify the precise mechanisms underlying these findings and include biomarkers such as oestrogen and testosterone.
Introduction: 3-Phosphoinositide-dependent kinase 1 (PDK1), the ‘master kinase of the AGC protein kinase family’, plays a key role in cancer development and progression. Although it has been rather overlooked, in the last decades a growing number of molecules have been developed to effectively modulate the PDK1 enzyme.
Areas covered: This review collects different PDK1 inhibitors patented from October 2014 to December 2018. The molecules have been classified on the basis of the chemical structure/type of inhibition, and for each general structure, examples have been discussed in extenso.
Expert opinion: The role of PDK1 in cancer development and progression as well as in metastasis formation and in chemoresistance has been confirmed by many studies. Therefore, the pharmaceutical discovery in both public and private institutions is still ongoing despite the plentiful molecules already published. The majority of the new molecules synthetized interact with binding sites different from the ATP binding site (i.e. PIF pocket or DFG-out conformation). However, many researchers are still looking for innovative PDK1 modulation strategy such as combination of well-known inhibitory agents or multitarget ligands, aiming to block, together with PDK1, other different critical players in the wide panorama of proteins involved in tumor pathways. 相似文献
Numerous data have pointed to an association between migraine and cardiovascular diseases. The majority of the available data have indicated that migraine with aura can be considered a risk factor for ischemic stroke, whereas migraine without aura cannot be reliably considered as such. High frequency of attacks and a recent onset of migraine have been related to an increased ischemic stroke risk. In addition, in young subjects with ischemic stroke migraine with aura represents an independent risk factor of overall recurrent vascular events and of recurrent ischemic stroke. Also the risk of transient ischemic attack seems to be increased in migraineurs, although this issue has not been extensively investigated. Several studies have also addressed the possible association between migraine and hemorrhagic stroke. Although the results of these individual studies were conflicting, their meta-analysis showed that migraine is associated with a 1.5-fold increase in the risk of hemorrhagic stroke (including intracerebral and subarachnoid hemorrhage). Some studies have identified migraine also as a possible risk factor for cardiac vascular events while others have yielded negative results. A meta-analysis did not show an increased risk of myocardial infarction in subjects with any migraine vs no migraine but subsequently, data has pointed to an association between any migraine with cardiac ischemic disease. Migraine has also been associated by some studies with vascular mortality and with vascular diseases in regions other than the brain and the heart. Several studies have also indicated that compared with nonmigraineurs, migraineurs have a higher burden of asymptomatic white matter brain lesions and, according to some studies, also infarct-like lesions at brain magnetic resonance. The mechanisms underlying the relationship between migraine and cardiovascular disease are still unclear. The possible explanation may rely on a peculiar vascular vulnerability of migraineurs that may contribute to the pathogenesis of migraine and, in the presence of some other unknown factors may also contribute, over time, to the development of cardiovascular disease. At the moment, there are no reliable features that may indicate which subjects, across the overall migraine population, will develop vascular events and so far, no drugs are recommended for the vascular prevention in migraineurs unless other clear indications are present. In general, the acute treatment and the secondary prevention measures of a patient with stroke who has a history of migraine do not differ from that of other stroke patients. There is currently no direct evidence to support that a migraine prophylactic treatment will reduce future stroke risk in secondary prevention. 相似文献
Compelling evidence demonstrated that melatonin increases p53 activity in cancer cells. p53 undergoes acetylation to be stabilized and activated for driving cells destined for apoptosis/growth inhibition. Over‐expression of p300 induces p53 acetylation, leading to cell growth arrest by increasing p21 expression. In turn, p53 activation is mainly regulated in the nucleus by MDM2. MDM2 also acts as E3 ubiquitin ligase, promoting the proteasome‐dependent p53 degradation. MDM2 entry into the nucleus is finely tuned by two different modulations: the ribosomal protein L11, acts by sequestering MDM2 in the cytosol, whereas the PI3K‐AkT‐dependent MDM2 phosphorylation is mandatory for MDM2 translocation across the nuclear membrane. In addition, MDM2‐dependent targeting of p53 is regulated in a nonlinear fashion by MDM2/MDMX interplay. Melatonin induces both cell growth inhibition and apoptosis in MCF7 breast cancer cells. We previously reported that this effect is associated with reduced MDM2 levels and increased p53 activity. Herein, we demonstrated that melatonin drastically down‐regulates MDM2 gene expression and inhibits MDM2 shuttling into the nucleus, given that melatonin increases L11 and inhibits Akt‐PI3K‐dependent MDM2 phosphorylation. Melatonin induces a 3‐fold increase in both MDMX and p300 levels, decreasing simultaneously Sirt1, a specific inhibitor of p300 activity. Consequently, melatonin‐treated cells display significantly higher values of both p53 and acetylated p53. Thus, a 15‐fold increase in p21 levels was observed in melatonin‐treated cancer cells. Our results provide evidence that melatonin enhances p53 acetylation by modulating the MDM2/MDMX/p300 pathway, disclosing new insights for understanding its anticancer effect. 相似文献