RAD51 haploinsufficiency causes congenital mirror movements in humans

Congenital mirror movements (CMM) are characterized by involuntary movements of one side of the body that mirror intentional movements on the opposite side. CMM reflect dysfunctions and structural abnormalities of the motor network and are mainly inherited in an autosomal-dominant fashion. Recently, heterozygous mutations in DCC, the gene encoding the receptor for netrin 1 and involved in the guidance of developing axons toward the midline, have been identified but CMM are genetically heterogeneous. By combining genome-wide linkage analysis and exome sequencing, we identified heterozygous mutations introducing premature termination codons in RAD51 in two families with CMM. RAD51 mRNA was significantly downregulated in individuals with CMM resulting from the degradation of the mutated mRNA by nonsense-mediated decay. RAD51 was specifically present in the developing mouse cortex and, more particularly, in a subpopulation of corticospinal axons at the pyramidal decussation. The identification of mutations in RAD51, known for its key role in the repair of DNA double-strand breaks through homologous recombination, in individuals with CMM reveals a totally unexpected role of RAD51 in neurodevelopment. These findings open a new field of investigation for researchers attempting to unravel the molecular pathways underlying bimanual motor control in humans.     

Interaction of plant cell signaling molecules, salicylic acid and jasmonic acid, with the mitochondria of Helicoverpa armigera

The cotton bollworm, Helicoverpa armigera is a polyphagous pest in Asia, Africa, and the Mediterranean Europe. Salicylic acid (SA) and jasmonic acid (JA) are the cell signaling molecules produced in response to insect attack in plants. The effect of these signaling molecules was investigated on the oxidative phosphorylation and oxidative stress of H. armigera. SA significantly inhibited the state III and state IV respiration, respiratory control index (RCI), respiratory complexes I and II, induced mitochondrial swelling, and cytochrome c release in vitro. Under in vivo conditions, SA induced state IV respiration as well as oxidative stress in time- and dose-dependent manner, and also inhibited the larval growth. In contrast, JA did not affect the mitochondrial respiration and oxidative stress. SA affected the growth and development of H. armigera, in addition to its function as signaling molecules involved in both local defense reactions at feeding sites and the induction of systemic acquired resistance in plants.     

Reactive Oxygen Species Formation and Cell Death in Catalase-Deficient Tobacco Leaf Discs Exposed to Paraquat

In the present work, the response of tobacco (Nicotiana tabaccum L.) wild-type SR1 and transgenic CAT1AS plants (with a basal reduced CAT activity) was evaluated after exposure to the herbicide paraquat (PQ). Superoxide anion (O₂^.−) formation was inhibited at 3 or 21 h of exposure, but H₂O₂ production and ion leakage increased significantly, both in SR1 or CAT1AS leaf discs. NADPH oxidase activity was constitutively 57% lower in non-treated transgenic leaves than in SR1 leaves and was greatly reduced both at 3 or 21 h of PQ treatment. Superoxide dismutase (SOD) activity was significantly reduced by PQ after 21 h, showing a decrease from 70% to 55%, whereas catalase (CAT) activity decreased an average of 50% after 3 h of treatment, and of 90% after 21 h, in SR1 and CAT1AS, respectively. Concomitantly, total CAT protein content was shown to be reduced in non-treated CAT1AS plants compared to control SR1 leaf discs at both exposure times. PQ decreased CAT expression in SR1 or CAT1AS plants at 3 and 21 h of treatment. The mechanisms underlying PQ-induced cell death were possibly not related exclusively to ROS formation and oxidative stress in tobacco wild-type or transgenic plants.     

International NeuroAIDS: prospects of HIV-1 associated neurological com-plications

INTRODUCTION AND NEUROEPIDEMIO- LOGY OF HIV/AIDS AIDS was first recognized as a new and distinct clini- cal entity in 1981 [1] and the HIV-1 as their casual agent in 1983 [2]. Since then, the HIV/AIDS epidemic has reached epidemic proportions with a total accumulative number of more than 60 million people, according to the Joint United Nations Programme on HIV/AIDS (UNAIDS) and WHO. The extensive spread of HIV-1 epidemics in Asia was not appreciated in the 1980s,…     

siRNA, miRNA and HIV: promises and challenges

INTRODUCTION The recent discovery of small interfering RNA (siRNA) revealed an important role for small RNAs in regulating gene expression. First described in plants, as “post- trancriptional gene silencing” (PTGS) [1], RNA interfer- ence (RNAi) is a nucleic-acid based immune defense against viruses, transgenes and transposons [2]. Triggered by double-stranded RNA (dsRNA), RNAi leads to the se- quence specific degradation of a target mRNA [3]. In eukaryotic cells, long dsRN…     

Fish-oil supplementation in patients with implantable cardioverter defibrillators: a meta-analysis

Background

A recent Cochrane meta-analysis did not confirm the benefits of fish and fish oil in the secondary prevention of cardiac death and myocardial infarction. We performed a meta-analysis of randomized controlled trials that examined the effect of fish-oil supplementation on ventricular fibrillation and ventricular tachycardia to determine the overall effect and to assess whether heterogeneity exists between trials.

Methods

We searched electronic databases (MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, CINAHL) from inception to May 2007. We included randomized controlled trials of fish-oil supplementation on ventricular fibrillation or ventricular tachycardia in patients with implantable cardioverter defibrillators. The primary outcome was implantable cardioverter defibrillator discharge. We calculated relative risk [RR] for outcomes at 1-year follow-up for each study. We used the DerSimonian and Laird random-effects methods when there was significant heterogeneity between trials and the Mantel-Hanzel fixed-effects method when heterogeneity was negligible.

Results

We identified 3 trials of 1–2 years'' duration. These trials included a total of 573 patients who received fish oil and 575 patients who received a control. Meta-analysis of data collected at 1 year showed no overall effect of fish oil on the relative risk of implantable cardioverter defibrillator discharge. There was significant heterogeneity between trials. The second largest study showed a significant benefit of fish oil (relative risk [RR] 0.74, 95% confidence interval [CI] 0.56–0.98). The smallest showed an adverse tendency at 1 year (RR 1.23, 95% CI 0.92–1.65) and significantly worse outcome at 2 years among patients with ventricular tachycardia at study entry (log rank p = 0.007).

Conclusion

These data indicate that there is heterogeneity in the response of patients to fish-oil supplementation. Caution should be used when prescribing fish-oil supplementation for patients with ventricular tachycardia.There is a public perception that fish and fish oil can be recommended uniformly for the prevention of coronary artery disease.^1–3 However, the scientific evidence is divided^4,5 and official agencies have called for more research.⁶It is estimated that 0.5% of patients with coronary heart disease, 1% of patients with diabetes or hypertension and 2% of the general population at low risk of coronary heart disease take fish-oil supplements.⁷ In 2004, the price of fish oils overtook that of vegetable oils, and in 2006, the price rose to US$750 per ton.⁸ The value of fish oil as a nutraceutical in the European market was US$194 million in 2004, and it is anticipated that the price will continue to rise as availability declines.⁸ Canada is both a consumer and an exporter of fish oil, and it exported 15 000 tons in 2006.⁹The scientific debate over the clinical value of fish oil is highlighted by a recent Cochrane review, which concluded that long-chain omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) had no clear effect on total mortality, combined cardiovascular events or cancer.⁴ Furthermore, another recent meta-analysis¹⁰ only showed a significant positive association between fish-oil consumption and prevention of restenosis after coronary angioplasty in a select subgroup after excluding key negative papers.¹¹ Finally, the antiarrhythmic effect, which is proposed to be the principal mechanism of their benefit in cardiovascular disease, has not been demonstrated clearly in clinical trials.^12–14We therefore performed a meta-analysis of randomized controlled trials that examined the effect of fish-oil supplementation in patients with implantable cardioverter defibrillators who are at risk of ventricular arrhythmia to determine the overall effect of fish oils. We also sought to investigate whether there was significant heterogeneity between trials.     

Polyamines and abiotic stress: recent advances

Summary. In this review we will concentrate in the results published the last years regarding the involvement of polyamines in the plant responses to abiotic stresses, most remarkably on salt and drought stress. We will also turn to other types of abiotic stresses, less studied in relation to polyamine metabolism, such as mineral deficiencies, chilling, wounding, heavy metals, UV, ozone and paraquat, where polyamine metabolism is also modified. There is a great amount of data demonstrating that under many types of abiotic stresses, an accumulation of the three main polyamines putrescine, spermidine and spermine does occur. However, there are still many doubts concerning the role that polyamines play in stress tolerance. Several environmental challenges (osmotic stress, salinity, ozone, UV) are shown to induce ADC activity more than ODC. The rise in Put is mainly attributed to the increase in ADC activity as a consequence of the activation of ADC genes and their mRNA levels. On the other hand, free radicals are now accepted as important mediators of tissue injury and cell death. The polycationic nature of polyamines, positively charged at physiological pH, has attracted the attention of researchers and has led to the hypothesis that polyamines could affect physiological systems by binding to anionic sites, such as those associated with nucleic acids and membrane phospholipids. These amines, involved with the control of numerous cellular functions, including free radical scavenger and antioxidant activity, have been found to confer protection from abiotic stresses but their mode of action is not fully understood yet. In this review, we will also summarize information about the involvement of polyamines as antioxidants against the potential abiotic stress-derived oxidative damage. Authors’ address: Dr. María Patricia Benavides, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, Buenos Aires 1113, Argentina     

Inhibition of Root Growth and Polyamine Metabolism in Sunflower (Helianthus annuus) Seedlings Under Cadmium and Copper Stress

Although sunflower is usually regarded as a highly tolerant crop, impairment of root growth at initial stages of plant development may result in poor crop establishment and higher susceptibility to pathogen attack. In order to evaluate if Cd2+ and Cu2+ may impact on sunflower germination and initial root development, a pot experiment under controlled conditions was carried out. Possible involvement of polyamine metabolism in sunflower response to these stressors was also investigated. Although Cd2+ and Cu2+ treatments affect neither seed germination nor radical emergence, sunflower seedlings grown in the presence of these heavy metals showed significant inhibition of root growth, being this inhibition greater for Cd2+. Both metals caused significant increases in proline contents at the highest concentrations tested (0.5 and 1 mM), and these increments were more pronounced for Cd2+ treatments, especially between days 3 and 10. Metals also increased putrescine (Put) contents at all concentrations assayed from the seventh day onward, causing no variations on this polyamine time-course pattern. Spermine and spermidine contents, however, were increased only by 1 mM Cd2+. Arginine decarboxylase seems to have been the enzyme responsible for Put increases under both metal treatments. This work demonstrates that initial root growth of sunflower seedlings may be significantly impaired in Cd2+ or Cu2+ contaminated soils. It also shows that polyamines are key biological compounds, which are probably involved in signaling pathways triggered under stress environmental conditions.