The effects of grazing depend on productivity,and what else?

In this issue of the Journal of Vegetation Science, Lezama et al. confirm the hypothesis that the effects of grazing increase with productivity, based on data from steppes and prairies in Argentina and Uruguay. Their study can serve as a starting point for further studies addressing questions on the mechanisms behind vegetation dynamics in grassland, emphasizing the need for experimental studies over larger climatic gradients.     

Polo-like kinase-activating kinases: Aurora A,Aurora B and what else?

The events of cell division are regulated by a complex interplay between kinases and phosphatases. Cyclin-dependent kinases (Cdks), polo-like kinases (Plks) and Aurora kinases play central roles in this process. Polo kinase (Plk1 in humans) regulates a wide range of events in mitosis and cytokinesis. To ensure the accuracy of these processes, polo activity itself is subject to complex regulation. Phosphorylation of polo in its T loop (or activation loop) increases its kinase activity several-fold. It has been shown that Aurora A kinase, with its co-factor Bora, activates Plk1 in G₂, and that this is essential for recovery from cell cycle arrest induced by DNA damage. In a recent article published in PLoS Biology, we report that Drosophila polo is activated by Aurora B kinase at centromeres, and that this is crucial for polo function in regulating chromosome dynamics in prometaphase. Our results suggest that this regulatory pathway is conserved in humans. Here, we propose a model for the collaboration between Aurora B and polo in the regulation of kinetochore attachment to microtubules in early mitosis. Moreover, we suggest that Aurora B could also function to activate Polo/Plk1 in cytokinesis. Finally, we discuss recent findings and open questions regarding the activation of polo and polo-like kinases by different kinases in mitosis, cytokinesis and other processes.     

Atrial fibrillation: to map or not to map?

Isolation of the pulmonary veins may be an effective treatment modality for eliminating atrial fibrillation (AF) episodes but unfortunately not for all patients. When ablative therapy fails, it is assumed that AF has progressed from a trigger-driven to a substrate-mediated arrhythmia. The effect of radiofrequency ablation on persistent AF can be attributed to various mechanisms, including elimination of the trigger, modification of the arrhythmogenic substrate, interruption of crucial pathways of conduction, atrial debulking, or atrial denervation. This review discusses the possible effects of pulmonary vein isolation on the fibrillatory process and the necessity of cardiac mapping in order to comprehend the mechanisms of AF in the individual patient and to select the optimal treatment modality.     

Disruptive selection and then what?

Disruptive selection occurs when extreme phenotypes have a fitness advantage over more intermediate phenotypes. The phenomenon is particularly interesting when selection keeps a population in a disruptive regime. This can lead to increased phenotypic variation while disruptive selection itself is diminished or eliminated. Here, we review processes that increase phenotypic variation in response to disruptive selection and discuss some of the possible outcomes, such as sympatric species pairs, sexual dimorphisms, phenotypic plasticity and altered community assemblages. We also identify factors influencing the likelihoods of these different outcomes.     

Actin in the nucleus: what form and what for?

Actin is an abundant protein in most nonmuscle cells. It has often been observed in isolated nuclei, yet cytoplasmic contamination was of course initially regarded as the most plausible origin. Numerous studies on nuclear actin appeared in the 1970s and 1980s, but the picture remained rather muddy. The viewpoint at that time was that actin-shown to move freely between cytoplasm and nucleus-was a mere "thermodynamic wanderer," transiently occupying the nucleus. More recently, evidence has been mounting that actin's presence in the nucleus is not simply governed by the laws of diffusion. The same holds true for the finding of various actin-related proteins in the nucleus, and the case for nuclear myosin, specifically myosin I, is now quite convincing. Moreover, the first intimations of functional roles of nuclear actin are now emerging. Here we examine the overall subject from cell biological and chemical perspectives. The major issue is no longer the presence of actin in the nucleus but rather its supramolecular organization, intranuclear locations, and, of course, functions. These issues interface with recent findings that reveal a surprisingly diverse repertoire of actin conformations and oligomer and polymer forms beyond monomeric G-actin and polymeric F-actin. We present ideas for advancing the nuclear actin field and call for a renewed attack on this major problem in cell biology.     

Statin therapy and stroke prevention: what was known, what is new and what is next?

PURPOSE OF REVIEW: Randomized trials have shown that statins may reduce the risk of primary stroke. There is no evidence however that statins can reduce recurrent stroke incidence. RECENT FINDINGS: In the SPARCL trial, patients with a recent stroke or transient ischemic attack randomized to atorvastatin 80 mg/day had a significant 16% relative risk reduction of stroke, and a 35% reduction in major coronary events compared with placebo. This was obtained despite 25% of the placebo arm patients receiving a commercially-available statin outside of the trial. Post-hoc analysis used blinded LDL-cholesterol measurements as a marker of adherence to lipid-lowering therapy. Compared with the group with no change or an increase in LDL-cholesterol (the group adherent to placebo or not taking a statin), the group with over 50% reduction in LDL-cholesterol had a significant 31% reduction in stroke. The next step is to define whether achieving LDL-cholesterol below 70 mg/dl is better than a standard dose of statin (LDL around 100-110 mg/dl) in the secondary prevention of stroke. SUMMARY: Statins are effective in reducing both first-ever and recurrent stroke, and this effect seems driven by the extent of LDL-cholesterol lowering.     

Proximate and ultimate causes: how come? and what for?

Proximate and ultimate causes in evolutionary biology have come to conflate two distinctions. The first is a distinction between immediate and historical causes. The second is between explanations of mechanism and adaptive function. Mayr emphasized the first distinction but many evolutionary biologists use proximate and ultimate causes to refer to the second. I recommend that ‘ultimate cause’ be abandoned as ambiguous.     

Sexual selection and environmental change:what do we know and what comes next?

Anthropogenic environmental change is the most significant threat to biodiversity in the 21st century.Animal populations are experi-encing rapid changes in thei...     

Pain and distress: what really matters?

Federal regulations mandate the minimization of both pain and distress in laboratory animals. That no clear definition exists for 'distress' complicates its recognition, quantification, and alleviation. The author argues that IACUCs and investigators should shift their focus from pain to distress, and that in doing so both problems will be better dealt with. She discusses criteria for defining 'significant' distress, and offers suggestions for the conduct of studies to determine levels of distress.     

Statin pharmacogenomics: what have we learned, and what remains unanswered?

PURPOSE OF REVIEW: Statins are widely prescribed and are established as first-line therapy for the primary and secondary prevention of coronary heart disease. Response to treatment varies considerably from person to person; however, inherited traits (genetic variability) may play a central role in this inter-individual variation. The purpose of this review is to summarize recent progress in the research for exploring genetic determinants of clinical efficacy and safety of statin therapy. RECENT FINDINGS: In addition to 41 previous studies of 19 genes, the results of 17 pharmacogenomic studies investigating the relationship between common genetic variants and response to statin therapy in terms of lipid responses, clinical outcomes, and adverse events have been reported since January 2004 - 15 candidate genes related to pharmacodynamics and three to pharmacokinetics of statins. These reported data suggest that genetic variations influencing intestinal cholesterol absorption, cholesterol production, and lipoprotein catabolism may all play a role in modulating responsiveness, as well as genes involved in drug metabolism of statins. They also suggest that combined analysis of multiple variants in several genes, all of which have possible functional relations, is more likely to give significant results, especially when being performed with a larger number of participants. SUMMARY: Pharmacogenomic studies of statin therapy will provide a better picture as to who is most likely and least likely to benefit from treatment, which results in more individualized management of coronary artery disease.     

Atrial fibrillation in β-thalassemia patients with a focus on the role of iron-overload and oxidative stress: A review

Cardiac complications including arrhythmia and especially atrial fibrillation (AF) are common causes of death in β-thalassemia patients. The main factor in the etiopathogenesis of these complications is iron overload, which results in increased oxidative stress. Although there is a known association between cardiac complications and iron overload in β-thalassemia patients, there is no comprehensive review on AF and excessive iron with a focus on oxidative stress in these patients. The aim of this article was to review the different aspects of AF in β-thalassemia patients with a focus on the prevention and treatment of AF by using iron chelators and/or anti-oxidants. AF in β-thalassemia patients is more common than in the general population. One of the most important causes of AF is cardiac iron overload and the harmful effects of increased oxidative stress. Iron-induced AF can be reversed by using an intensive iron chelation regimen. Based on a few experimental studies, the combination of iron chelators with some anti-oxidants, including NAC, vitamin C, and acetaminophen, can lead to improved cardiac protection. However, the effect of such combinations on cardiac arrhythmias should be further evaluated with animal and human studies.