Effect of Metalaxyl on the incidence and severity of Pearl millet downy mildew disease in Northern Nigeria

Pearl millet downy mildew (DM) incidence, severity and yield losses of two pearl millet varieties (local and improved) due to the disease were determined in the field. Significant differences in the disease incidence and severity were recorded in the plots sown with metalaxyl-treated seeds and those sown with non-treated seeds, indicating the efficacy of the fungicide on the fungus. Yield losses due to non-treatment of seeds with metalaxyl was 40.88 and 45.39% in a local variety and 43.00 and 18.60% in an improved variety in the 2000 and 2001 cropping seasons respectively. Significant differences between plots sown with metalaxyl-treated and those sown with non-treated seeds were obtained for other yield components such as 1000-grains weight, panicle length and weight.     

Gene expression and the evolution of phenotypic diversity in social wasps

Background  

Organisms are capable of developing different phenotypes by altering the genes they express. This phenotypic plasticity provides a means for species to respond effectively to environmental conditions. One of the most dramatic examples of phenotypic plasticity occurs in the highly social hymenopteran insects (ants, social bees, and social wasps), where distinct castes and sexes all arise from the same genes. To elucidate how variation in patterns of gene expression affects phenotypic variation, we conducted a study to simultaneously address the influence of developmental stage, sex, and caste on patterns of gene expression in Vespula wasps. Furthermore, we compared the patterns found in this species to those found in other taxa in order to investigate how variation in gene expression leads to phenotypic evolution.     

Defective P2Y purinergic receptor function: A possible novel mechanism for impaired glucose transport

Extracellular ATP is an ubiquitous mediator that regulates several cellular functions via specific P2 plasma membrane receptors (P2Rs), for which a role in modulating intracellular glucose metabolism has been recently suggested. We have investigated glucose uptake in response to P2Rs stimulation in fibroblasts from type 2 diabetic (T2D) patients and control subjects. P2Rs expression was evaluated by RT-PCR; intracellular calcium release by fluorometry; glucose transporter (GLUT1) translocation by immunoblotting and chemiluminescence; glucose uptake was measured with 2-deoxy-D-[1-(3)H]glucose (2-DOG) and ATP by luminometry. Cells from T2D patients, in contrast to those from healthy controls, showed no increase in glucose uptake after ATP stimulation; extracellular ATP caused, however, a similar GLUT1 recruitment to the plasma membrane in both groups. P2Rs expression did not differ between fibroblasts from diabetic and healthy subjects, but while plasma membrane depolarization, a P2X-mediated response was similar in both groups, no evident intracellular calcium increase was detectable in the cells from the former group. The calcium response in fibroblasts from diabetics was restored by co-incubation with apyrase or hexokinase, suggesting that P2YRs in those cells were normally expressed but chronically desensitised. In support to this finding, fibroblasts from T2D subjects secreted a two-fold larger amount of ATP compared to controls. Pre-treatment with apyrase or hexokinase also restored ATP stimulated glucose uptake in fibroblasts from diabetic subjects. These results suggest that extracellular ATP plays a role in the modulation of glucose transport via GLUT1, and that the P2Y-dependent GLUT1 activation is deficient in fibroblasts from T2D individuals. Our observations may point to additional therapeutic targets for improving glucose utilization in diabetes.     

Tamoxifen reduces fat mass by boosting reactive oxygen species

As the pandemic of obesity is growing, a variety of animal models have been generated to study the mechanisms underlying the increased adiposity and development of metabolic disorders. Tamoxifen (Tam) is widely used to activate Cre recombinase that spatiotemporally controls target gene expression and regulates adiposity in laboratory animals. However, a critical question remains as to whether Tam itself affects adiposity and possibly confounds the functional study of target genes in adipose tissue. Here we administered Tam to Cre-absent forkhead box O1 (FoxO1) floxed mice (f-FoxO1) and insulin receptor substrate Irs1/Irs2 double floxed mice (df-Irs) and found that Tam induced approximately 30% reduction (P<0.05) in fat mass with insignificant change in body weight. Mechanistically, Tam promoted reactive oxygen species (ROS) production, apoptosis and autophagy, which was associated with downregulation of adipogenic regulator peroxisome proliferator-activated receptor gamma and dedifferentiation of mature adipocytes. However, normalization of ROS potently suppressed Tam-induced apoptosis, autophagy and adipocyte dedifferentiation, suggesting that ROS may account, at least in part, for the changes. Importantly, Tam-induced ROS production and fat mass reduction lasted for 4–5 weeks in the f-FoxO1 and df-Irs mice. Our data suggest that Tam reduces fat mass via boosting ROS, thus making a recovery period crucial for posttreatment study.Excess fat mass or adiposity is the hallmark of obesity, the rapidly growing epidemic.^{1, 2} In the United States, over two-thirds of adults are overweight or obese according to the statistics of years 2011–2012.³ For children, the overweight or obese population accounts for about 25% in the 2–5-year olds and 33% in school students (including adolescents).³ It is estimated that obesity care accounts for 21% of national healthcare expenditures, that is, 190.2 billion US dollars per year, in the United States.⁴ Because adipose tissue is an important endocrine organ, which secretes adipokines or cytokines that regulate inflammatory responses and metabolic homeostasis, aberrant adiposity dysregulates adipokine levels and leads to a variety of metabolic disorders and complications, such as diabetes and cardiovascular diseases.⁵ As such, the healthcare burden that obesity imposes on the society is far greater.To understand the molecular mechanism of obesity development, various rodent models have been generated to study the gain or loss of functions of different genes.^{6, 7} To this end, the Cre/lox site-specific recombination system has been versatile to generate conditional mouse mutants, controlling gene expression and activity in target tissues.^{8, 9} In particular, Tamoxifen (Tam) is used to activate Cre recombinases spatiotemporally in vivo through intraperitoneal (I.P.) or subcutaneous administration.^{10, 11, 12} Injection of Tam at a dose of 1–8 mg/kg body weight for 5 consecutive days deletes target genes, thus establishing a versatile system to study functional genes in obesity.^{8, 9, 10, 11, 12}The use of Tam in clinical treatments has led to the argument about its potential effect on body fat or weight gain in human patients.^{13, 14} It raises the question as to whether and how Tam influences adipocytes and fat mass in the experimental animal models after administration. Exclusion of direct regulation of adiposity by Tam as a confounding factor in animal models is critical to better understand target genes in adipogenesis and metabolic homeostasis. In the present work, we present the evidence that 5-day administration of Tam significantly reduces mouse fat mass, which persists till weeks 4–5 after the treatment. At the cellular level, Tam promotes the production of reactive oxygen species (ROS), which is accompanied with enhanced apoptosis, autophagy and adipocyte dedifferentiation. However, treatment of adipocytes with antioxidant N-acetyl cysteine (NAC) dramatically counteracted Tam-induced ROS and suppressed apoptotic and autophagic markers, concomitant with reversal of adipocyte dedifferentiation. In vivo, fat mass was restored upon the normalization of ROS, which is associated with suppressed adipocyte dedifferentiation and downregulated apoptotic and autophagic markers. Our data reveal a ROS-mediated mechanism by which Tam induces fat mass reduction. As it may confound the posttreatment study, deliberate determination of the recovery period after Tam administration is essential to understand the functions of target genes using Tam-induced knockout mice.     

Habitat tracking, stasis and survival in Neogene large mammals

Species response to environmental change may vary from adaptation to the new conditions, to dispersal towards territories with better ecological settings (known as habitat tracking), and to extinction. A phylogenetically explicit analysis of habitat tracking in Caenozoic large mammals shows that species moving over longer distances during their existence survived longer. By partitioning the fossil record into equal time intervals, we showed that the longest distance was preferentially covered just before extinction. This supports the idea that habitat tracking is a key reaction to environmental change, and confirms that tracking causally prolongs species survival. Species covering longer distances also have morphologically less variable cheek teeth. Given the tight relationship between cheek teeth form and habitat selection in large mammals, this supports the well-known, yet little tested, idea that habitat tracking bolsters morphological stasis.     

A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial)

Background

There have been increasing concerns regarding the safety and efficacy of neuroleptics in people with dementia, but there are very few long-term trials to inform clinical practice. The aim of this study was to determine the impact of long-term treatment with neuroleptic agents upon global cognitive decline and neuropsychiatric symptoms in patients with Alzheimer disease.

Methods and Findings

Design: Randomised, blinded, placebo-controlled parallel two-group treatment discontinuation trial.Setting: Oxfordshire, Newcastle and Gateshead, London and Edinburgh, United Kingdom.Participants: Patients currently prescribed the neuroleptics thioridazine, chlorpromazine, haloperidol trifluoperazine or risperidone for behavioural or psychiatric disturbance in dementia for at least 3 mo.Interventions: Continue neuroleptic treatment for 12 mo or switch to an identical placebo.Outcome measures: Primary outcome was total Severe Impairment Battery (SIB) score. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory (NPI).Results: 165 patients were randomised (83 to continue treatment and 82 to placebo, i.e., discontinue treatment), of whom 128 (78%) commenced treatment (64 continue/64 placebo). Of those, 26 were lost to follow-up (13 per arm), resulting in 51 patients per arm analysed for the primary outcome. There was no significant difference between the continue treatment and placebo groups in the estimated mean change in SIB scores between baseline and 6 mo; estimated mean difference in deterioration (favouring placebo) −0.4 (95% confidence interval [CI] −6.4 to 5.5), adjusted for baseline value (p = 0.9). For neuropsychiatric symptoms, there was no significant difference between the continue treatment and placebo groups (n = 56 and 53, respectively) in the estimated mean change in NPI scores between baseline and 6 mo; estimated mean difference in deterioration (favouring continue treatment) −2.4 (95% CI −8.2 to 3.5), adjusted for baseline value (p = 0.4). Both results became more pronounced at 12 mo. There was some evidence to suggest that those patients with initial NPI ≥ 15 benefited on neuropsychiatric symptoms from continuing treatment.

Conclusions

For most patients with AD, withdrawal of neuroleptics had no overall detrimental effect on functional and cognitive status. Neuroleptics may have some value in the maintenance treatment of more severe neuropsychiatric symptoms, but this benefit must be weighed against the side effects of therapy.Trial registration: Cochrane Central Registry of Controlled Trials/National Research Register (#ISRCTN33368770).