Impacts of climate change on rice production in Africa and causes of simulated yield changes

This study is the first of its kind to quantify possible effects of climate change on rice production in Africa. We simulated impacts on rice in irrigated systems (dry season and wet season) and rainfed systems (upland and lowland). We simulated the use of rice varieties with a higher temperature sum as adaptation option. We simulated rice yields for 4 RCP climate change scenarios and identified causes of yield declines. Without adaptation, shortening of the growing period due to higher temperatures had a negative impact on yields (?24% in RCP 8.5 in 2070 compared with the baseline year 2000). With varieties that have a high temperature sum, the length of the growing period would remain the same as under the baseline conditions. With this adaptation option rainfed rice yields would increase slightly (+8%) but they remain subject to water availability constraints. Irrigated rice yields in East Africa would increase (+25%) due to more favourable temperatures and due to CO2 fertilization. Wet season irrigated rice yields in West Africa were projected to change by ?21% or +7% (without/with adaptation). Without adaptation irrigated rice yields in West Africa in the dry season would decrease by ?45% with adaptation they would decrease significantly less (?15%). The main cause of this decline was reduced photosynthesis at extremely high temperatures. Simulated heat sterility hardly increased and was not found a major cause for yield decline. The implications for these findings are as follows. For East Africa to benefit from climate change, improved water and nutrient management will be needed to benefit fully from the more favourable temperatures and increased CO2 concentrations. For West Africa, more research is needed on photosynthesis processes at extreme temperatures and on adaptation options such as shifting sowing dates.     

Adding psychotherapy to antidepressant medication in depression and anxiety disorders: a meta‐analysis

We conducted a meta‐analysis of randomized trials in which the effects of treatment with antidepressant medication were compared to the effects of combined pharmacotherapy and psychotherapy in adults with a diagnosed depressive or anxiety disorder. A total of 52 studies (with 3,623 patients) met inclusion criteria, 32 on depressive disorders and 21 on anxiety disorders (one on both depressive and anxiety disorders). The overall difference between pharmacotherapy and combined treatment was Hedges' g = 0.43 (95% CI: 0.31‐0.56), indicating a moderately large effect and clinically meaningful difference in favor of combined treatment, which corresponds to a number needed to treat (NNT) of 4.20. There was sufficient evidence that combined treatment is superior for major depression, panic disorder, and obsessive‐compulsive disorder (OCD). The effects of combined treatment compared with placebo only were about twice as large as those of pharmacotherapy compared with placebo only, underscoring the clinical advantage of combined treatment. The results also suggest that the effects of pharmacotherapy and those of psychotherapy are largely independent from each other, with both contributing about equally to the effects of combined treatment. We conclude that combined treatment appears to be more effective than treatment with antidepressant medication alone in major depression, panic disorder, and OCD. These effects remain strong and significant up to two years after treatment. Monotherapy with psychotropic medication may not constitute optimal care for common mental disorders.     

Cell-Autonomous Progeroid Changes in Conditional Mouse Models for Repair Endonuclease XPG Deficiency

As part of the Nucleotide Excision Repair (NER) process, the endonuclease XPG is involved in repair of helix-distorting DNA lesions, but the protein has also been implicated in several other DNA repair systems, complicating genotype-phenotype relationship in XPG patients. Defects in XPG can cause either the cancer-prone condition xeroderma pigmentosum (XP) alone, or XP combined with the severe neurodevelopmental disorder Cockayne Syndrome (CS), or the infantile lethal cerebro-oculo-facio-skeletal (COFS) syndrome, characterized by dramatic growth failure, progressive neurodevelopmental abnormalities and greatly reduced life expectancy. Here, we present a novel (conditional) Xpg^−/− mouse model which -in a C57BL6/FVB F1 hybrid genetic background- displays many progeroid features, including cessation of growth, loss of subcutaneous fat, kyphosis, osteoporosis, retinal photoreceptor loss, liver aging, extensive neurodegeneration, and a short lifespan of 4–5 months. We show that deletion of XPG specifically in the liver reproduces the progeroid features in the liver, yet abolishes the effect on growth or lifespan. In addition, specific XPG deletion in neurons and glia of the forebrain creates a progressive neurodegenerative phenotype that shows many characteristics of human XPG deficiency. Our findings therefore exclude that both the liver as well as the neurological phenotype are a secondary consequence of derailment in other cell types, organs or tissues (e.g. vascular abnormalities) and support a cell-autonomous origin caused by the DNA repair defect itself. In addition they allow the dissection of the complex aging process in tissue- and cell-type-specific components. Moreover, our data highlight the critical importance of genetic background in mouse aging studies, establish the Xpg^−/− mouse as a valid model for the severe form of human XPG patients and segmental accelerated aging, and strengthen the link between DNA damage and aging.     

Acidic elements in histamine H3 receptor antagonists

Antagonists of the human histamine H₃ receptor (hH₃R) often contain a second basic moiety, which is well known to boost affinity on this histamine receptor subtype. Here, we prepared compounds with acidic moieties of different pK_a values to figure out that the hH₃R tolerates these functionalities when added to a common pharmacophore blueprint. Depending on the acidic, electronic and steric features the designed ligands showed hH₃R affinities in the nanomolar concentration range. Additionally, selected ligands were tested but failed as dual acting hH₃R/hPPAR (human peroxisome proliferator-activated receptor) ligands.     

Design and synthesis of a new class of malonyl-CoA decarboxylase inhibitors with anti-obesity and anti-diabetic activities

A new series of thiazole-substituted 1,1,1,3,3,3-hexafluoro-2-propanols were prepared and evaluated as malonyl-CoA decarboxylase (MCD) inhibitors. Key analogs caused dose-dependent decreases in food intake and body weight in obese mice. Acute treatment with these compounds also led to a drop in elevated blood glucose in a murine model of type II diabetes.     

Regulatory factors and cell populations involved in skeletal muscle regeneration

Skeletal muscle regeneration is a complex process, which is not yet completely understood. Satellite cells, the skeletal muscle stem cells, become activated after trauma, proliferate, and migrate to the site of injury. Depending on the severity of the myotrauma, activated satellite cells form new multinucleated myofibers or fuse to damaged myofibers. The specific microenvironment of the satellite cells, the niche, controls their behavior. The niche contains several components that maintain satellite cells quiescence until they are activated. In addition, a great diversity of stimulatory and inhibitory growth factors such as IGF‐1 and TGF‐β1 regulate their activity. Donor‐derived satellite cells are able to improve muscle regeneration, but their migration through the muscle tissue and across endothelial layers is limited. Less than 1% of their progeny, the myoblasts, survive the first days upon intra‐muscular injection. However, a range of other multipotent muscle‐ and non‐muscle‐derived stem cells are involved in skeletal muscle regeneration. These stem cells can occupy the satellite cell niche and show great potential for the treatment of skeletal muscle injuries and diseases. The aim of this review is to discuss the niche factors, growth factors, and other stem cells, which are involved in skeletal muscle regeneration. Knowledge about the factors regulating satellite cell activity and skeletal muscle regeneration can be used to improve the treatment of muscle injuries and diseases. J. Cell. Physiol. 224:7–16, 2010 © 2010 Wiley‐Liss, Inc.