FTO influences adipogenesis by regulating mitotic clonal expansion

The fat mass and obesity-associated (FTO) gene plays a pivotal role in regulating body weight and fat mass; however, the underlying mechanisms are poorly understood. Here we show that primary adipocytes and mouse embryonic fibroblasts (MEFs) derived from FTO overexpression (FTO-4) mice exhibit increased potential for adipogenic differentiation, while MEFs derived from FTO knockout (FTO-KO) mice show reduced adipogenesis. As predicted from these findings, fat pads from FTO-4 mice fed a high-fat diet show more numerous adipocytes. FTO influences adipogenesis by regulating events early in adipogenesis, during the process of mitotic clonal expansion. The effect of FTO on adipogenesis appears to be mediated via enhanced expression of the pro-adipogenic short isoform of RUNX1T1, which enhanced adipocyte proliferation, and is increased in FTO-4 MEFs and reduced in FTO-KO MEFs. Our findings provide novel mechanistic insight into how upregulation of FTO leads to obesity

Biomagnetic of Apatite-Coated Cobalt Ferrite: A Core–Shell Particle for Protein Adsorption and pH-Controlled Release

Magnetic nanoparticle composite with a cobalt ferrite (CoFe2O4, (CF)) core and an apatite (Ap) coating was synthesized using a biomineralization process in which a modified simulated body fluid (1.5SBF) solution is the source of the calcium phosphate for the apatite formation. The core–shell structure formed after the citric acid–stabilized cobalt ferrite (CFCA) particles were incubated in the 1.5 SBF solution for 1 week. The mean particle size of CFCA-Ap is about 750 nm. A saturation magnetization of 15.56 emug-1 and a coercivity of 1808.5 Oe were observed for the CFCA-Ap obtained. Bovine serum albumin (BSA) was used as the model protein to study the adsorption and release of the proteins by the CFCA-Ap particles. The protein adsorption by the CFCA-Ap particles followed a more typical Freundlich than Langmuir adsorption isotherm. The BSA release as a function of time became less rapid as the CFCA-Ap particles were immersed in higher pH solution, thus indicating that the BSA release is dependent on the local pH

Assessment of optimal strategies in a two-patch dengue transmission model with seasonality

Emerging and re-emerging dengue fever has posed serious problems to public health officials in many tropical and subtropical countries. Continuous traveling in seasonally varying areas makes it more difficult to control the spread of dengue fever. In this work, we consider a two-patch dengue model that can capture the movement of host individuals between and within patches using a residence-time matrix. A previous two-patch dengue model without seasonality is extended by adding host demographics and seasonal forcing in the transmission rates. We investigate the effects of human movement and seasonality on the two-patch dengue transmission dynamics. Motivated by the recent Peruvian dengue data in jungle/rural areas and coast/urban areas, our model mimics the seasonal patterns of dengue outbreaks in two patches. The roles of seasonality and residence-time configurations are highlighted in terms of the seasonal reproduction number and cumulative incidence. Moreover, optimal control theory is employed to identify and evaluate patch-specific control measures aimed at reducing dengue prevalence in the presence of seasonality. Our findings demonstrate that optimal patch-specific control strategies are sensitive to seasonality and residence-time scenarios. Targeting only the jungle (or endemic) is as effective as controlling both patches under weak coupling or symmetric mobility. However, focusing on intervention for the city (or high density areas) turns out to be optimal when two patches are strongly coupled with asymmetric mobility.ope

Transmission Selects for HIV-1 Strains of Intermediate Virulence: A Modelling Approach

Recent data shows that HIV-1 is characterised by variation in viral virulence factors that is heritable between infections, which suggests that viral virulence can be naturally selected at the population level. A trade-off between transmissibility and duration of infection appears to favour viruses of intermediate virulence. We developed a mathematical model to simulate the dynamics of putative viral genotypes that differ in their virulence. As a proxy for virulence, we use set-point viral load (SPVL), which is the steady density of viral particles in blood during asymptomatic infection. Mutation, the dependency of survival and transmissibility on SPVL, and host effects were incorporated into the model. The model was fitted to data to estimate unknown parameters, and was found to fit existing data well. The maximum likelihood estimates of the parameters produced a model in which SPVL converged from any initial conditions to observed values within 100–150 years of first emergence of HIV-1. We estimated the 1) host effect and 2) the extent to which the viral virulence genotype mutates from one infection to the next, and found a trade-off between these two parameters in explaining the variation in SPVL. The model confirms that evolution of virulence towards intermediate levels is sufficiently rapid for it to have happened in the early stages of the HIV epidemic, and confirms that existing viral loads are nearly optimal given the assumed constraints on evolution. The model provides a useful framework under which to examine the future evolution of HIV-1 virulence

Characterization of barley (Hordeum vulgare L.) NAC transcription factors suggests conserved functions compared to both monocots and dicots

<p>Abstract</p> <p>Background</p> <p>The NAC transcription factor family is involved in the regulation of traits in both monocots and dicots of high agronomic importance. Understanding the precise functions of the NAC genes can be of utmost importance for the improvement of cereal crop plants through plant breeding. For the cereal crop plant barley (<it>Hordeum vulgare </it>L.) only a few <it>NAC </it>genes have so far been investigated.</p> <p>Results</p> <p>Through searches in publicly available barley sequence databases we have obtained a list of 48 barley <it>NAC </it>genes (<it>HvNACs</it>) with 43 of them representing full-length coding sequences. Phylogenetic comparisons to Brachypodium, rice, and Arabidopsis NAC proteins indicate that the barley NAC family includes members from all of the eight NAC subfamilies, although by comparison to these species a number of <it>HvNACs </it>still remains to be identified. Using qRT-PCR we investigated the expression profiles of 46 <it>HvNACs </it>across eight barley tissues (young flag leaf, senescing flag leaf, young ear, old ear, milk grain, late dough grain, roots, and developing stem) and two hormone treatments (abscisic acid and methyl jasmonate).</p> <p>Conclusions</p> <p>Comparisons of expression profiles of selected barley <it>NAC </it>genes with the published functions of closely related <it>NAC </it>genes from other plant species, including both monocots and dicots, suggest conserved functions in the areas of secondary cell wall biosynthesis, leaf senescence, root development, seed development, and hormone regulated stress responses.</p

Structure Activity Relationship of Dendrimer Microbicides with Dual Action Antiviral Activity

Topical microbicides, used by women to prevent the transmission of HIV and other sexually transmitted infections are urgently required. Dendrimers are highly branched nanoparticles being developed as microbicides. However, the anti-HIV and HSV structure-activity relationship of dendrimers comprising benzyhydryl amide cores and lysine branches, and a comprehensive analysis of their broad-spectrum anti-HIV activity and mechanism of action have not been published.Dendrimers with optimized activity against HIV-1 and HSV-2 were identified with respect to the number of lysine branches (generations) and surface groups. Antiviral activity was determined in cell culture assays. Time-of-addition assays were performed to determine dendrimer mechanism of action. In vivo toxicity and HSV-2 inhibitory activity were evaluated in the mouse HSV-2 susceptibility model. Surface groups imparting the most potent inhibitory activity against HIV-1 and HSV-2 were naphthalene disulfonic acid (DNAA) and 3,5-disulfobenzoic acid exhibiting the greatest anionic charge and hydrophobicity of the seven surface groups tested. Their anti-HIV-1 activity did not appreciably increase beyond a second-generation dendrimer while dendrimers larger than two generations were required for potent anti-HSV-2 activity. Second (SPL7115) and fourth generation (SPL7013) DNAA dendrimers demonstrated broad-spectrum anti-HIV activity. However, SPL7013 was more active against HSV and blocking HIV-1 envelope mediated cell-to-cell fusion. SPL7013 and SPL7115 inhibited viral entry with similar potency against CXCR4-(X4) and CCR5-using (R5) HIV-1 strains. SPL7013 was not toxic and provided at least 12 h protection against HSV-2 in the mouse vagina.Dendrimers can be engineered with optimized potency against HIV and HSV representing a unique platform for the controlled synthesis of chemically defined multivalent agents as viral entry inhibitors. SPL7013 is formulated as VivaGel(R) and is currently in clinical development to provide protection against HIV and HSV. SPL7013 could also be combined with other microbicides

Scientific, sustainability and regulatory challenges of cultured meat

Producing meat without the drawbacks of conventional animal agriculture would greatly contribute to future food and nutrition security. This Review Article covers biological, technological, regulatory and consumer acceptance challenges in this developing field of biotechnology. Cellular agriculture is an emerging branch of biotechnology that aims to address issues associated with the environmental impact, animal welfare and sustainability challenges of conventional animal farming for meat production. Cultured meat can be produced by applying current cell culture practices and biomanufacturing methods and utilizing mammalian cell lines and cell and gene therapy products to generate tissue or nutritional proteins for human consumption. However, significant improvements and modifications are needed for the process to be cost efficient and robust enough to be brought to production at scale for food supply. Here, we review the scientific and social challenges in transforming cultured meat into a viable commercial option, covering aspects from cell selection and medium optimization to biomaterials, tissue engineering, regulation and consumer acceptance

Measurement of the matrix element for the decay η′→ηπ +π -

The Dalitz plot of η⊃′→ηπ⊃+π⊃- decay is studied using (225.2±2.8)×106 J/ψ events collected with the BESIII detector at the BEPCII e⊃+e⊃- collider. With the largest sample of η⊃′ decays to date, the parameters of the Dalitz plot are determined in a generalized and a linear representation. Also, the branching fraction of J/ψ→γη⊃′ is determined to be (4.84±0.03±0.24)×10⊃-3, where the first error is statistical and the second systematic. © 2011 American Physical Society.published_or_final_versio