Tamarindus indica Extract Alters Release of Alpha Enolase, Apolipoprotein A-I, Transthyretin and Rab GDP Dissociation Inhibitor Beta from HepG2 Cells

Background: The plasma cholesterol and triacylglycerol lowering effects of Tamarindus indica extract have been previously described. We have also shown that the methanol extract of T. indica fruit pulp altered the expression of lipid-associated genes including ABCG5 and APOAI in HepG2 cells. In the present study, effects of the same extract on the release of proteins from the cells were investigated using the proteomics approach. Methodology/Principal Findings: When culture media of HepG2 cells grown in the absence and presence of the methanol extract of T. indica fruit pulp were subjected to 2-dimensional gel electrophoresis, the expression of seven proteins was found to be significantly different (p<0.03125). Five of the spots were subsequently identified as alpha enolase (ENO1), transthyretin (TTR), apolipoprotein A-I (ApoA-I; two isoforms), and rab GDP dissociation inhibitor beta (GDI-2). A functional network of lipid metabolism, molecular transport and small molecule biochemistry that interconnects the three latter proteins with the interactomes was identified using the Ingenuity Pathways Analysis software. Conclusion/Significance: The methanol extract of T. indica fruit pulp altered the release of ENO1, ApoA-I, TTR and GDI-2 from HepG2 cells. Our results provide support on the effect of T. indica extract on cellular lipid metabolism, particularly that of cholesterol

Potential impacts of climate and environmental change on the stored water of Lake Victoria Basin and economic implications

The changing climatic patterns and increasing human population within the Lake Victoria Basin (LVB), together with overexploitation of water for economic activities call for assessment of water management for the entire basin. This study focused on the analysis of a combination of available in situ climate data, Gravity Recovery and Climate Experiment (GRACE), Tropical Rainfall Measuring Mission (TRMM) observations, and high resolution Regional Climate simulations during recent decade(s) to assess the water storage changes within LVB that may be linked to recent climatic variability/changes and anomalies. We employed trend analysis, principal component analysis (PCA), and temporal/spatial correlations to explore the associations and covariability among LVB stored water, rainfall variability, and large-scale forcings associated with El-Niño/Southern Oscillation (ENSO) and Indian Ocean Dipole (IOD). Potential economic impacts of human and climate-induced changes in LVB stored water are also explored.Overall, observed in situ rainfall from lake-shore stations showed a modest increasing trend during the recent decades. The dominant patterns of rainfall data from the TRMM satellite estimates suggest that the spatial and temporal distribution of precipitation have not changed much during the period of 1998–2012 over the basin consistent with in situ observations. However, GRACE-derived water storage changes over LVB indicate an average decline of 38.2 mm/yr for 2003–2006, likely due to the extension of the Owen Fall/Nalubale dam, and an increase of 4.5 mm/yr over 2007–2013, likely due to two massive rainfalls in 2006–2007 and 2010–2011. The temporal correlations between rainfall and ENSO/IOD indices during the study period, based on TRMM and model simulations, suggest significant influence of large-scale forcing on LVB rainfall, and thus stored water. The contributions of ENSO and IOD on the amplitude of TRMM-rainfall and GRACE-derived water storage changes, for the period of 2003–2013, are estimated to be ~2.5 cm and ~1.5 cm, respectively

A Pan-GTPase inhibitor as a molecular probe

Overactive GTPases have often been linked to human diseases. The available inhibitors are limited and have not progressed far in clinical trials. We report here a first-in-class small molecule pan-GTPase inhibitor discovered from a high throughput screening campaign. The compound CID1067700 inhibits multiple GTPases in biochemical, cellular protein and protein interaction, as well as cellular functional assays. In the biochemical and protein interaction assays, representative GTPases from Rho, Ras, and Rab, the three most generic subfamilies of the GTPases, were probed, while in the functional assays, physiological processes regulated by each of the three subfamilies of the GTPases were examined. The chemical functionalities essential for the activity of the compound were identified through structural derivatization. The compound is validated as a useful molecular probe upon which GTPase-targeting inhibitors with drug potentials might be developed

Interactions between Natural Populations of Human and Rodent Schistosomes in the Lake Victoria Region of Kenya: A Molecular Epidemiological Approach

One of the world's most prevalent neglected diseases is schistosomiasis, which infects approximately 200 million people worldwide. Schistosoma mansoni is transmitted to humans by skin penetration by free-living larvae that develop in freshwater snails. The origin of this species is East Africa, where it coexists with its sister species, S. rodhaini. Interactions between these species potentially influence their epidemiology, ecology, and evolutionary biology, because they infect the same species of hosts and can hybridize. Over two years, we examined their distribution in Kenya to determine their degree of overlap geographically, within snail hosts, and in the water column as infective stages. Both species were spatially and temporally patchy, although S. mansoni was eight times more common than S. rodhaini. Both species overlap in the time of day they were present in the water column, which increases the potential for the species to coinfect the same host and interbreed. Peak infective time for S. mansoni was midday and dawn and dusk for S. rodhaini. Three snails were coinfected, which was more common than expected by chance. These findings indicate a lack of obvious isolating mechanisms to prevent hybridization, raising the intriguing question of how the two species retain separate identities

Two-year longitudinal survey reveals high genetic diversity of Schistosoma mansoni with adult worms surviving praziquantel treatment at the start of mass drug administration in Uganda

Background: A key component of schistosomiasis control is mass drug administration with praziquantel. While control interventions have been successful in several endemic regions, mass drug administration has been less effective in others. Here we focus on the impact of repeated praziquantel treatment on the population structure and genetic diversity of Schistosoma mansoni. Methods: We examined S. mansoni epidemiology, population genetics, and variation in praziquantel susceptibility in parasites isolated from children across three primary schools in a high endemicity region at the onset of the Ugandan National Control Programme. Children were sampled at 11 timepoints over two years, including one week and four weeks post-praziquantel treatment to evaluate short-term impacts on clearance and evidence of natural variation in susceptibility to praziquantel. Results: Prevalence of S. mansoni was 85% at baseline. A total of 3576 miracidia larval parasites, isolated from 203 individual children, were genotyped at seven loci. Overall, genetic diversity was high and there was low genetic differentiation, indicating high rates of parasite gene flow. Schistosome siblings were found both pre-treatment and four weeks post-treatment, demonstrating adult worms surviving treatment and natural praziquantel susceptibility variation in these populations at the beginning of mass drug administration. However, we did not find evidence for selection on these parasites. While genetic diversity decreased in the short-term (four weeks post-treatment), diversity did not decrease over the entire period despite four rounds of mass treatment. Furthermore, within-host genetic diversity was affected by host age, host sex, infection intensity and recent praziquantel treatment. Conclusions: Our findings suggest that praziquantel treatments have short-term impacts on these parasite populations but impacts were transient and no long-term reduction in genetic diversity was observed. High gene flow reduces the likelihood of local adaptation, so even though parasites surviving treatment were observed, these were likely to be diluted at the beginning of the Ugandan National Control Programme. Together, these results suggest that MDA in isolation may be insufficient to reduce schistosome populations in regions with high genetic diversity and gene flow

Metal-Organic Framework Nanoparticle-Assisted Cryopreservation of Red Blood Cells

The development of hybrid nanomaterials mimicking antifreeze proteins that can modulate/inhibit the growth of ice crystals for cell/tissue cryopreservation has attracted increasing interests. Herein, we describe the first utilization of zirconium (Zr)-based metal–organic framework (MOF) nanoparticles (NPs) with well-defined surface chemistries for the cryopreservation of red blood cells (RBCs) without the need of any (toxic) organic solvents. Distinguishing features of this cryoprotective approach include the exceptional water stability, low hemolytic activity, and the long periodic arrangement of organic linkers on the surface of MOF NPs, which provide a precise spacing of hydrogen donors to recognize and match the ice crystal planes. Five kinds of Zr-based MOF NPs, with different pore size, surface chemistry, and framework topologies, were used for the cryoprotection of RBCs. A “splat” assay confirmed that MOF NPs not only exhibited ice recrystallization inhibition activities but also acted as a “catalyst” to accelerate the melting of ice crystals. The human RBC cryopreservation tests displayed RBC recoveries of up to ∼40%, which is higher than that obtained via commonly used hydroxyethyl starch polymers. This cryopreservation approach will inspire the design and utilization of MOF-derived nanoarchitectures for the effective cryopreservation of various cell types as well as tissue samples

SupraCells: Living Mammalian Cells Protected within Functional Modular Nanoparticle-Based Exoskeletons

Creating a synthetic exoskeleton from abiotic materials to protect delicate mammalian cells and impart them with new functionalities could revolutionize fields like cell-based sensing and create diverse new cellular phenotypes. Herein, the concept of "SupraCells," which are living mammalian cells encapsulated and protected within functional modular nanoparticle-based exoskeletons, is introduced. Exoskeletons are generated within seconds through immediate interparticle and cell/particle complexation that abolishes the macropinocytotic and endocytotic nanoparticle internalization pathways that occur without complexation. SupraCell formation is shown to be generalizable to wide classes of nanoparticles and various types of cells. It induces a spore-like state, wherein cells do not replicate or spread on surfaces but are endowed with extremophile properties, for example, resistance to osmotic stress, reactive oxygen species, pH, and UV exposure, along with abiotic properties like magnetism, conductivity, and multifluorescence. Upon decomplexation cells return to their normal replicative states. SupraCells represent a new class of living hybrid materials with a broad range of functionalities

Modular Metal-Organic Polyhedra Superassembly: From Molecular-Level Design to Targeted Drug Delivery

Targeted drug delivery remains at the forefront of biomedical research but remains a challenge to date. Herein, the first superassembly of nanosized metal-organic polyhedra (MOP) and their biomimetic coatings of lipid bilayers are described to synergistically combine the advantages of micelles and supramolecular coordination cages for targeted drug delivery. The superassembly technique affords unique hydrophobic features that endow individual MOP to act as nanobuilding blocks and enable their superassembly into larger and well-defined nanocarriers with homogeneous sizes over a broad range of diameters. Various cargos are controllably loaded into the MOP with high payloads, and the nanocages are then superassembled to form multidrug delivery systems. Additionally, functional nanoparticles are introduced into the superassemblies via a one-pot process for versatile bioapplications. The MOP superassemblies are surface-engineered with epidermal growth factor receptors and can be targeted to cancer cells. In vivo studies indicated the assemblies to have a substantial circulation half-life of 5.6 h and to undergo renal clearance-characteristics needed for nanomedicines

Robust and long-term cellular protein and enzymatic activity preservation in biomineralized mammalian cells

Preservation of evolved biological structure and function in robust engineering materials is of interest for storage of biological samples before diagnosis and development of vaccines, sensors, and enzymatic reactors and has the potential to avoid cryopreservation and its associated cold-chain issues. Here, we demonstrate that "freezing cells in amorphous silica" is a powerful technique for long-term preservation of whole mammalian cell proteomic structure and function at room temperature. Biomimetic silicification employs the crowded protein microenvironment of mammalian cells as a catalytic framework to proximally transform monomeric silicic acid into silicates forming a nanoscopic silica shell over all biomolecular interfaces. Silicification followed by dehydration preserves and passivates proteomic information within a nanoscale thin silica coating that exhibits size selective permeability (<3.6 nm), preventing protein leaching and protease degradation of cellular contents, while providing access of small molecular constituents for cellular enzymatic reaction. Exposure of dehydrated silicified cells to mild etchant or prolonged hydrolysis removes the silica, completely rerevealing biomolecular components and restoring their accessibility and functionality