A Mathematical Model for Dengue Fever in a Virgin Environment

Dengue is a mosquito-borne viral infection found in tropical and subtropical regions around the world. The disease was named in 1779 and the first recorded epidemic of it occurred simultaneously on three continents within the following decade. Dengue is characterized by flu-like symptoms and, while its symptoms are generally reported as quite unpleasant, is rarely fatal. However, in some cases patients can contract a more serious form of the disease, known as Dengue Hemorrhagic Fever, which is far more dangerous. The World Health Organization estimates that today over 2.5 billion people are at risk for Dengue (over 40% of the world’s population). Between 50 and 100 million cases of traditional Dengue occur globally per year, with an estimated additional 500,000 cases of the hemorrhagic variation. Four decades ago, the disease was endemic in only nine countries. Currently it is endemic in more than 100 countries, and is spreading. A variety of characteristics complicate any attempt to study or model the Dengue virus. Foremost among these is that the virus exists in four serotypes. Infection from one serotype grants life-long immunity, but makes the patient more susceptible to the other three forms. There is also an elevated risk of contracting Dengue Hemorrhagic Fever from a secondary infection. Furthermore, endemic Dengue tends to appear cyclically, with each outbreak separated by several years. Thus, populations where Dengue is endemic (such as many parts of Asia and Latin America) and several serotypes exist are exceedingly difficult to accurately represent with a single mathematical model. In this paper, a system of differential equations is used as a virus dynamics model, based off a Dengue epidemics model proposed by Pinho et. al (2010). A 2009 Cape Verde epidemic, the first in that country’s history, is chosen as the outbreak for this study because of its unique characteristics: a virgin environment with no immunities or increased susceptibilities to the various Dengue serotypes, and the existence of a single serotype through-out the epidemic. Due to this novel incidence of Dengue in Cape Verde and to minimal reporting, the data set for the epidemic is sparse. However, this shortcoming is dealt with by using an extended logistic model-fitting technique. Certain key parameter values in the differential equations model can then be found based on this fitting. Other parameters are taken from previous studies in similar environments. With these, the basic reproductive rate (R0) can be calculated, giving a numerical measure of this particular epidemic\u27s infectiousness. The validity of this differential equation model is then tested by comparing generated values to the fitted data. The Cape Verde epidemic presents a valuable opportunity to study the behavior of the Dengue virus without the added complexity of immunity, increased susceptibility, or multiple serotypes. Furthermore, this simplified population is natural, and not the result of human data selection or manipulation. This paper represents the first attempt in existing literature to carefully apply existing Dengue models and theory to such a virgin environment

Ultrafine hydrogen storage powders

A method of making hydrogen storage powder resistant to fracture in service involves forming a melt having the appropriate composition for the hydrogen storage material, such, for example, LaNi5 and other AB5 type materials and AB5+x materials, where x is from about -2.5 to about +2.5, including x=0, and the melt is gas atomized under conditions of melt temperature and atomizing gas pressure to form generally spherical powder particles. The hydrogen storage powder exhibits improved chemcial homogeneity as a result of rapid solidfication from the melt and small particle size that is more resistant to microcracking during hydrogen absorption/desorption cycling. A hydrogen storage component, such as an electrode for a battery or electrochemical fuel cell, made from the gas atomized hydrogen storage material is resistant to hydrogen degradation upon hydrogen absorption/desorption that occurs for example, during charging/discharging of a battery. Such hydrogen storage components can be made by consolidating and optionally sintering the gas atomized hydrogen storage powder or alternately by shaping the gas atomized powder and a suitable binder to a desired configuration in a mold or die

Topology and Ground State Control In Open-Shell Donor-Acceptor Conjugated Polymers

Donor-acceptor (DA) conjugated polymers (CPs) with narrow bandgaps and open-shell (diradical) character represent an emerging class of materials whose rich behavior emanates from their collective electronic properties and diminished electron pairing. However, the structural and electronic heterogeneities that define these materials complicate bandgap control at low energies and connections linking topology, exchange interactions, and (opto)electronic functionality remain nascent. To address these challenges, we demonstrate structurally rigid and strongly π-conjugated copolymers comprised of a solubilizing thiadiazoloquinoxaline acceptor and cyclopenta[2,1-b:3,4-b′]dithiophene or dithieno[3,2-b:2′,3′-d]thiophene donors. Atom-specific substitution modulates local aromatic character within the donor resulting in dramatic differences in structural, physicochemical, electronic, and magnetic properties of the polymers. These long-range π-mediated interactions facilitate control between low-spin aromatic and high-spin quinoidal forms. This work provides a strategy to understand the evolution of the electronic structure within DA CPs, control the ground state spin multiplicity, tune spin-spin interactions, and articulate the emergence of their novel properties

DAF-16/FOXO employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity

Organisms are constantly challenged by stresses and privations and require adaptive responses for their survival. The transcription factor DAF-16/FOXO is central nexus in these responses, but despite its importance little is known about how it regulates its target genes. Proteomic identification of DAF-16/FOXO binding partners in Caenorhabditis elegans and their subsequent functional evaluation by RNA interference (RNAi) revealed several candidate DAF-16/FOXO cofactors, most notably the chromatin remodeller SWI/SNF. DAF-16/FOXO and SWI/SNF form a complex and globally colocalize at DAF-16/FOXO target promoters. We show that specifically for gene-activation, DAF-16/FOXO depends on SWI/SNF, facilitating SWI/SNF recruitment to target promoters, in order to activate transcription by presumed remodelling of local chromatin. For the animal, this translates into an essential role of SWI/SNF for DAF-16/FOXO-mediated processes, i.e. dauer formation, stress resistance, and the promotion of longevity. Thus we give insight into the mechanisms of DAF-16/FOXO-mediated transcriptional regulation and establish a critical link between ATP-dependent chromatin remodelling and lifespan regulation

Shallow water marine sediment bacterial community shifts along a natural CO2 gradient in the Mediterranean Sea off Vulcano, Italy.

The effects of increasing atmospheric CO(2) on ocean ecosystems are a major environmental concern, as rapid shoaling of the carbonate saturation horizon is exposing vast areas of marine sediments to corrosive waters worldwide. Natural CO(2) gradients off Vulcano, Italy, have revealed profound ecosystem changes along rocky shore habitats as carbonate saturation levels decrease, but no investigations have yet been made of the sedimentary habitat. Here, we sampled the upper 2 cm of volcanic sand in three zones, ambient (median pCO(2) 419 μatm, minimum Ω(arag) 3.77), moderately CO(2)-enriched (median pCO(2) 592 μatm, minimum Ω(arag) 2.96), and highly CO(2)-enriched (median pCO(2) 1611 μatm, minimum Ω(arag) 0.35). We tested the hypothesis that increasing levels of seawater pCO(2) would cause significant shifts in sediment bacterial community composition, as shown recently in epilithic biofilms at the study site. In this study, 454 pyrosequencing of the V1 to V3 region of the 16S rRNA gene revealed a shift in community composition with increasing pCO(2). The relative abundances of most of the dominant genera were unaffected by the pCO(2) gradient, although there were significant differences for some 5 % of the genera present (viz. Georgenia, Lutibacter, Photobacterium, Acinetobacter, and Paenibacillus), and Shannon Diversity was greatest in sediments subject to long-term acidification (>100 years). Overall, this supports the view that globally increased ocean pCO(2) will be associated with changes in sediment bacterial community composition but that most of these organisms are resilient. However, further work is required to assess whether these results apply to other types of coastal sediments and whether the changes in relative abundance of bacterial taxa that we observed can significantly alter the biogeochemical functions of marine sediments

IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2–dependent mechanisms with implications for psoriasis pathogenesis

Aberrant cytokine expression has been proposed as an underlying cause of psoriasis, although it is unclear which cytokines play critical roles. Interleukin (IL)-23 is expressed in human psoriasis and may be a master regulator cytokine. Direct intradermal administration of IL-23 in mouse skin, but not IL-12, initiates a tumor necrosis factor–dependent, but IL-17A–independent, cascade of events resulting in erythema, mixed dermal infiltrate, and epidermal hyperplasia associated with parakeratosis. IL-23 induced IL-19 and IL-24 expression in mouse skin, and both genes were also elevated in human psoriasis. IL-23–dependent epidermal hyperplasia was observed in IL-19−/− and IL-24−/− mice, but was inhibited in IL-20R2−/− mice. These data implicate IL-23 in the pathogenesis of psoriasis and support IL-20R2 as a novel therapeutic target

The mitochondrial Ca2+ channel MCU is critical for tumor growth by supporting cell cycle progression and proliferation

Introduction: The mitochondrial uniporter (MCU) Ca2+ ion channel represents the primary means for Ca2+ uptake by mitochondria. Mitochondrial matrix Ca2+ plays critical roles in mitochondrial bioenergetics by impinging upon respiration, energy production and flux of biochemical intermediates through the TCA cycle. Inhibition of MCU in oncogenic cell lines results in an energetic crisis and reduced cell proliferation unless media is supplemented with nucleosides, pyruvate or α-KG. Nevertheless, the roles of MCU-mediated Ca2+ influx in cancer cells remain unclear, in part because of a lack of genetic models.Methods: MCU was genetically deleted in transformed murine fibroblasts for study in vitro and in vivo. Tumor formation and growth were studied in murine xenograft models. Proliferation, cell invasion, spheroid formation and cell cycle progression were measured in vitro. The effects of MCU deletion on survival and cell-death were determined by probing for live/death markers. Mitochondrial bioenergetics were studied by measuring mitochondrial matrix Ca2+ concentration, membrane potential, global dehydrogenase activity, respiration, ROS production and inactivating-phosphorylation of pyruvate dehydrogenase. The effects of MCU rescue on metabolism were examined by tracing of glucose and glutamine utilization for fueling of mitochondrial respiration.Results: Transformation of primary fibroblasts in vitro was associated with increased MCU expression, enhanced MCU-mediated Ca2+ uptake, altered mitochondrial matrix Ca2+ concentration responses to agonist stimulation, suppression of inactivating-phosphorylation of pyruvate dehydrogenase and a modest increase of mitochondrial respiration. Genetic MCU deletion inhibited growth of HEK293T cells and transformed fibroblasts in mouse xenograft models, associated with reduced proliferation and delayed cell-cycle progression. MCU deletion inhibited cancer stem cell-like spheroid formation and cell invasion in vitro, both predictors of metastatic potential. Surprisingly, mitochondrial matrix [Ca2+], membrane potential, global dehydrogenase activity, respiration and ROS production were unaffected. In contrast, MCU deletion elevated glycolysis and glutaminolysis, strongly sensitized cell proliferation to glucose and glutamine limitation, and altered agonist-induced cytoplasmic Ca2+ signals.Conclusion: Our results reveal a dependence of tumorigenesis on MCU, mediated by a reliance on MCU for cell metabolism and Ca2+ dynamics necessary for cell-cycle progression and cell proliferation

Forced Hepatic Overexpression of CEACAM1 Curtails Diet-Induced Insulin Resistance

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates insulin sensitivity by promoting hepatic insulin clearance. Liver-specific inactivation or global null-mutation of Ceacam1 impairs hepatic insulin extraction to cause chronic hyperinsulinemia, resulting in insulin resistance and visceral obesity. In this study we investigated whether diet-induced insulin resistance implicates changes in hepatic CEACAM1. We report that feeding C57/BL6J mice a high-fat diet reduced hepatic CEACAM1 levels by >50% beginning at 21 days, causing hyperinsulinemia, insulin resistance, and elevation in hepatic triacylglycerol content. Conversely, liver-specific inducible CEACAM1 expression prevented hyperinsulinemia and markedly limited insulin resistance and hepatic lipid accumulation that were induced by prolonged high-fat intake. This was partly mediated by increased hepatic β-fatty acid oxidation and energy expenditure. The data demonstrate that the high-fat diet reduced hepatic CEACAM1 expression and that overexpressing CEACAM1 in liver curtailed diet-induced metabolic abnormalities by protecting hepatic insulin clearance

Plasminogen Alleles Influence Susceptibility to Invasive Aspergillosis

Invasive aspergillosis (IA) is a common and life-threatening infection in immunocompromised individuals. A number of environmental and epidemiologic risk factors for developing IA have been identified. However, genetic factors that affect risk for developing IA have not been clearly identified. We report that host genetic differences influence outcome following establishment of pulmonary aspergillosis in an exogenously immune suppressed mouse model. Computational haplotype-based genetic analysis indicated that genetic variation within the biologically plausible positional candidate gene plasminogen (Plg; Gene ID 18855) correlated with murine outcome. There was a single nonsynonymous coding change (Gly110Ser) where the minor allele was found in all of the susceptible strains, but not in the resistant strains. A nonsynonymous single nucleotide polymorphism (Asp472Asn) was also identified in the human homolog (PLG; Gene ID 5340). An association study within a cohort of 236 allogeneic hematopoietic stem cell transplant (HSCT) recipients revealed that alleles at this SNP significantly affected the risk of developing IA after HSCT. Furthermore, we demonstrated that plasminogen directly binds to Aspergillus fumigatus. We propose that genetic variation within the plasminogen pathway influences the pathogenesis of this invasive fungal infection

Landscape Changes Influence the Occurrence of the Melioidosis Bacterium Burkholderia pseudomallei in Soil in Northern Australia

Melioidosis is a severe disease affecting humans and animals in the tropics. It is caused by the bacterium Burkholderia pseudomallei, which lives in tropical soil and especially occurs in southeast Asia and northern Australia. Despite the recognition that melioidosis is an emerging infectious disease, little is known about the habitat of B. pseudomallei in the environment. We performed a survey in the Darwin area in tropical Australia, screening 809 soil samples for the presence of these bacteria using molecular methods. We found that environmental factors describing the habitat of these bacteria differed between environmentally undisturbed and disturbed sites. At undisturbed sites, B. pseudomallei was primarily found in close proximity to streams and in grass- and roots-rich areas. In disturbed soil, B. pseudomallei was associated with the presence of animals, farming or irrigation. Highest B. pseudomallei counts were retrieved from paddocks, pens and kennels holding livestock and dogs. This study contributes to the elucidation of the habitat of B. pseudomallei in northern Australia. It also raises concerns that B. pseudomallei may spread due to changes in land management