The methanolic extract of Garcinia atroviridis (MeGa) reduces body weight and food intake,and improves lipid profiles by altering the lipid metabolism: a rat model

Garcinia species are widely used for their slimming effects via increased fat burning and suppression of satiety. However, scientific evidence for the biological effects of Garcinia atroviridis (GA) is lacking. We investigated the phytochemical composition, safety profiles, and antioxidant and antiobesity effects of methanolic extracts of Garcinia atroviridis (MeGa) in obese female rats. Repeated dose toxicity studies were conducted according to the OECD guidelines. Upon sacrifice, haematological, biochemical, lipid profile, and serum-based metabolomics analyses were performed to evaluate metabolic expression changes and their related pathways. MeGa contains several phytochemical groups and GA fruit acids. MeGa was found to be nontoxic in both male and female rats with an oral lethal dose (LD50) of 2000 mg/kg. After 9 weeks of treatment, MeGa-treated obese rats had lower weight gain and better lipid profiles (cholesterol and triglyceride), which correlated with the altered metabolic pathways involved in the metabolism of lipid (glycerophospholipid) and biosynthesis of unsaturated fatty acid. In addition, MeGa caused differential metabolism pathways of arachidonic acid and tryptophan that affect the inflammatory response and suppression of appetite. We concluded that MeGa is safe, and its slimming effects are due to the differential metabolism of lipids.     

Hippocampal and Cortical Primary Cilia Are Required for Aversive Memory in Mice

It has been known for decades that neurons throughout the brain possess solitary, immotile, microtubule based appendages called primary cilia. Only recently have studies tried to address the functions of these cilia and our current understanding remains poor. To determine if neuronal cilia have a role in behavior we specifically disrupted ciliogenesis in the cortex and hippocampus of mice through conditional deletion of the Intraflagellar Transport 88 (Ift88) gene. The effects on learning and memory were analyzed using both Morris Water Maze and fear conditioning paradigms. In comparison to wild type controls, cilia mutants displayed deficits in aversive learning and memory and novel object recognition. Furthermore, hippocampal neurons from mutants displayed an altered paired-pulse response, suggesting that loss of IFT88 can alter synaptic properties. A variety of other behavioral tests showed no significant differences between conditional cilia mutants and controls. This type of conditional allele approach could be used to distinguish which behavioral features of ciliopathies arise due to defects in neural development and which result from altered cell physiology. Ultimately, this could lead to an improved understanding of the basis for the cognitive deficits associated with human cilia disorders such as Bardet-Biedl syndrome, and possibly more common ailments including depression and schizophrenia.     

Microbial transformation of diosgenin and its precursor furostanol glycosides

Microorganisms have been screened for biotransformational activity against diosgenin or its precursor furostanol glycosides obtained from fenugreek seed (Trigonella foenum-graecum). Using diosgenin as the substrate, Cunninghamella elegans and Aspergillus nidulans produced some androstenes when α,α′-dipyridyl was supplemented to the transformation medium. Also, using the glycosides as a substrate, Rhizopus sp. produced diosgenin in >90% yield from the glycoside. The parameters were optimized to increase the yield of the androstenes.     

Detection of protein complexes using a protein ranking algorithm

Detecting protein complexes from protein‐protein interaction (PPI) network is becoming a difficult challenge in computational biology. There is ample evidence that many disease mechanisms involve protein complexes, and being able to predict these complexes is important to the characterization of the relevant disease for diagnostic and treatment purposes. This article introduces a novel method for detecting protein complexes from PPI by using a protein ranking algorithm (ProRank). ProRank quantifies the importance of each protein based on the interaction structure and the evolutionarily relationships between proteins in the network. A novel way of identifying essential proteins which are known for their critical role in mediating cellular processes and constructing protein complexes is proposed and analyzed. We evaluate the performance of ProRank using two PPI networks on two reference sets of protein complexes created from Munich Information Center for Protein Sequence, containing 81 and 162 known complexes, respectively. We compare the performance of ProRank to some of the well known protein complex prediction methods (ClusterONE, CMC, CFinder, MCL, MCode and Core) in terms of precision and recall. We show that ProRank predicts more complexes correctly at a competitive level of precision and recall. The level of the accuracy achieved using ProRank in comparison to other recent methods for detecting protein complexes is a strong argument in favor of the proposed method. Proteins 2012;. © 2012 Wiley Periodicals, Inc.     

Geofold: topology-based protein unfolding pathways capture the effects of engineered disulfides on kinetic stability

Protein unfolding is modeled as an ensemble of pathways, where each step in each pathway is the addition of one topologically possible conformational degree of freedom. Starting with a known protein structure, GeoFold hierarchically partitions (cuts) the native structure into substructures using revolute joints and translations. The energy of each cut and its activation barrier are calculated using buried solvent accessible surface area, side chain entropy, hydrogen bonding, buried cavities, and backbone degrees of freedom. A directed acyclic graph is constructed from the cuts, representing a network of simultaneous equilibria. Finite difference simulations on this graph simulate native unfolding pathways. Experimentally observed changes in the unfolding rates for disulfide mutants of barnase, T4 lysozyme, dihydrofolate reductase, and factor for inversion stimulation were qualitatively reproduced in these simulations. Detailed unfolding pathways for each case explain the effects of changes in the chain topology on the folding energy landscape. GeoFold is a useful tool for the inference of the effects of disulfide engineering on the energy landscape of protein unfolding.     

Effects of altered temperature and precipitation on desert protozoa associated with biological soil crusts

Biological soil crusts are diverse assemblages of bacteria, cyanobacteria, algae, fungi, lichens, and mosses that cover much of arid land soils. The objective of this study was to quantify protozoa associated with biological soil crusts and test the response of protozoa to increased temperature and precipitation as is predicted by some global climate models. Protozoa were more abundant when associated with cyanobacteria/lichen crusts than with cyanobacteria crusts alone. Amoebae, flagellates, and ciliates originating from the Colorado Plateau desert (cool desert, primarily winter precipitation) declined 50-, 10-, and 100-fold, respectively, when moved in field mesocosms to the Chihuahuan Desert (hot desert, primarily summer rain). However, this was not observed in protozoa collected from the Chihuahuan Desert and moved to the Sonoran desert (hot desert, also summer rain, but warmer than Chihuahuan Desert). Protozoa in culture began to encyst at 37 degrees C. Cysts survived the upper end of daily temperatures (37-55 degrees C), and could be stimulated to excyst if temperatures were reduced to 15 degrees C or lower. Results from this study suggest that cool desert protozoa are influenced negatively by increased summer precipitation during excessive summer temperatures, and that desert protozoa may be adapted to a specific desert's temperature and precipitation regime.     

Synergistic Effects of Arsenic Trioxide and Silibinin on Apoptosis and Invasion in Human Glioblastoma U87MG Cell Line

Patients with glioblastoma multiforme (GBM) have poor therapeutic outcomes despite their current therapy. In an attempt to increase the efficacy of therapy for GBM, we studied the efficacy of arsenic trioxide (ATO), a newly introduced treatment for glioma, combined with silibinin, a natural polyphenolic flavonoid, in the GBM cell line, U87MG. The combination therapy synergically inhibited metabolic activity, cell proliferation, and gelatinase A and B activities; it also increased apoptosis. Additionally, it decreased the mRNA level of cathepsin B, uPA, matrix metalloproteinase-2 and 9, membrane type 1-MMP, survivin, BCL2, CA9; it increased mRNA level of caspase-3. Altogether, these results showed that ATO and silibinin in some cases improved and/or complemented the anticancer effects. This study may supply insight into the design of new combination cancer therapies to cells intrinsically less sensitive to routine therapies and suggested a new combination therapy for the highly invasive human glioma treatment.     

Effect of plant growth promoting rhizobacteria,nematode parasitic fungi and root-nodule bacterium on root-knot nematodes Meloidogyne javanica and growth of chickpea

Effects of plant growth promoting rhizobacteria (Pseudomonas putida MTCC No. 3604 and Pseudomonas alcaligenes MTCC No. 493) and parasitic fungi (Pochonia chlamydosporia KIA and Paecilomyces lilacinus KIA) were studied, alone and together with Rhizobium sp. (charcoal commercial culture) on the growth of chickpea and multiplication of Meloidogyne javanica. Individually, P. putida 3604, P. alcaligenes 493 and Rhizobium caused a significant increase in the growth of chickpea in both nematode inoculated and uninoculated plants. Inoculation of Rhizobium with a parasitic fungus or with plant growth promoting rhizobaterium caused a greater increase in the growth of plants inoculated with nematodes than caused by either of them singly. Individually, P. lilacinus KIA caused a greater increase in the growth of nematode inoculated plants than caused by P. putida 3604 or P. alcaligenes 493. P. lilacinus KIA caused a greater reduction in galling and nematode multiplication followed by P. chlamydosporia KIA, P. putida 3604 and P. alcaligenes 493. Combined use of P. lilacinus KIA with Rhizobium was better in reducing galling and nematode multiplication than any other treatment. P. putida 3604 caused a greater colonization of root than P. alcaligenes 493 while P. lilacinus KIA was isolated from more nematodes than P. chlamydosporia KIA.