Rift Valley fever surveillance in mobile sheep flocks in the Nile Delta

Rift Valley fever (RVF) surveillance was carried out in the Nile Delta by monitoring mobile and stationary sheep flocks for antibodies to RVF virus. Sheep are known to be susceptible to RVF virus infection and experienced severe morbidity in 1977 and 1978 when RVF was epidemic in Egypt. Four hundred six sheep in 32 flocks were surveyed during 1984. Twenty-four sheep from 7 flocks had antibodies to RVF virus detected by hemagglutination inhibition and plaque reduction neutralization tests. Antibodies were found primarily in sheep greater than 3 years of age, although 1- and 2-year-old sheep were included in the sample. No seroconversion was observed among 177 seronegative sheep that were bled successively for a period of 10 months. These results indicate that epizootic RVF was probably not present in the Nile Delta during 1984.     

Epithelial NAIPs protect against colonic tumorigenesis

NLR family apoptosis inhibitory proteins (NAIPs) belong to both the Nod-like receptor (NLR) and the inhibitor of apoptosis (IAP) families. NAIPs are known to form an inflammasome with NLRC4, but other in vivo functions remain unexplored. Using mice deficient for all NAIP paralogs (Naip1-6^Δ/Δ), we show that NAIPs are key regulators of colorectal tumorigenesis. Naip1-6^Δ/Δ mice developed increased colorectal tumors, in an epithelial-intrinsic manner, in a model of colitis-associated cancer. Increased tumorigenesis, however, was not driven by an exacerbated inflammatory response. Instead, Naip1-6^Δ/Δ mice were protected from severe colitis and displayed increased antiapoptotic and proliferation-related gene expression. Naip1-6^Δ/Δ mice also displayed increased tumorigenesis in an inflammation-independent model of colorectal cancer. Moreover, Naip1-6^Δ/Δ mice, but not Nlrc4-null mice, displayed hyper-activation of STAT3 and failed to activate p53 18 h after carcinogen exposure. This suggests that NAIPs protect against tumor initiation in the colon by promoting the removal of carcinogen-elicited epithelium, likely in a NLRC4 inflammasome-independent manner. Collectively, we demonstrate a novel epithelial-intrinsic function of NAIPs in protecting the colonic epithelium against tumorigenesis.Inflammatory bowel disease (IBD) is an important risk factor that favors the development and progression of colitis-associated cancer (CAC; Eaden et al., 2001; Terzić et al., 2010; Rubin et al., 2013). Even in the absence of overt inflammatory disease in colorectal cancer (CRC), loss of barrier function in the tumor epithelium enables translocation of microbial products into tumor tissue. This triggers the activation of lamina propria immunocytes and colonic epithelial cells via pattern-recognition receptors (PRRs) to produce cytokines and chemokines. Those factors then promote tumor growth and mediate recruitment of further immune cells (Grivennikov et al., 2012; Mueller, 2012). Alternatively, epithelial innate immune components could be subverted during tumorigenesis and influence tumor growth independently. Although cytokine/chemokine-mediated modulation of tumor growth has been described, the role of epithelial-intrinsic, innate immune components still remains elusive.Several Nod-like receptors (NLRs) have previously been implicated in colon inflammation and tumorigenesis, mostly in protective roles (Allen et al., 2010; Hu et al., 2010; Chen et al., 2011; Elinav et al., 2011; Zaki et al., 2011; Carvalho et al., 2012). In some cases, this has been attributed to reduced inflammasome-mediated release of IL-18, which is protective for the colonic epithelium (Allen et al., 2010; Dupaul-Chicoine et al., 2010). In other cases, noninflammasome-mediated factors were found to protect mice against CAC development. For example, NLRP12 was protective against colonic inflammation and tumorigenesis by dampening NF-κB and ERK activation in macrophages (Zaki et al., 2011). However, several discrepancies also exist, as illustrated by Caspase-1–deficient mice, which display increased colon tumorigenesis. In one study, this was dependent on NLRC4 and was epithelial intrinsic rather than inflammation mediated (Hu et al., 2010), whereas, in another study, increased tumorigenesis involved NLRP3 and was inflammation and hematopoietic cell–dependent (Allen et al., 2010). Such discrepancies are suggested to arise from differences in microbiota between facilities or use of WT mice from external sources (Ubeda et al., 2012), but could also arise from opposing functions of inflammasome components in different tissues, which has been demonstrated in a skin tumorigenesis model (Drexler et al., 2012).The physiological function of the NLR protein NAIP (NLR family apoptosis inhibitory protein, previously known as neuronal apoptosis inhibitory protein) is not fully characterized, mainly because mice have several possibly redundant Naip paralogs (e.g., 4 functional and 2 noncoding Naip genes in the C57BL/6 genome; Yaraghi et al., 1998; Endrizzi et al., 2000; Growney and Dietrich, 2000). Humans also have several NAIP genes, only one of which is full length (Schmutz et al., 2004; Romanish et al., 2009). NAIPs are intracellular, cytosolic proteins with a tripartite structure; three N-terminal baculovirus inhibitor of apoptosis (IAP) protein repeat (BIR) domains, a central NACHT domain and C-terminal leucine rich-repeat (LRR) domains. The latter two domains group NAIPs to the NLR family of proteins. Indeed, NAIPs are best characterized for their inflammasome function. Mouse and human NAIPs are involved in the detection of intracellular pathogens, such as Salmonella, and activation of the NLRC4 inflammasome, inducing pyroptosis and caspase-1–mediated cleavage of IL-1β and IL-18 (Kofoed and Vance, 2011; Zhao et al., 2011; Rayamajhi et al., 2013; Yang et al., 2013). In mice, NAIP paralogs provide specificity to different bacterial components (Kofoed and Vance, 2011; Zhao et al., 2011). In vivo, the NAIP5-NLRC4 inflammasome was required for sepsis-induced mortality by an Escherichia coli pathobiont or by systemic delivery of intracellular-targeted flagellin, although partial redundancy to other Naip paralogs was apparent (Ayres et al., 2012; von Moltke et al., 2012).NAIPs also belong to the IAP family due to three N-terminal BIR domains; but whether they actually function as inhibitors of apoptosis is controversial. Some studies show direct binding and inhibition of caspase-3 and -9 (Maier et al., 2002; Davoodi et al., 2004, 2010), but others do not (Roy et al., 1997). Also, NAIPs lack certain caspase-interaction residues within the BIR domains that would be necessary for direct inhibition of caspases, raising concern about whether NAIP can inhibit caspases in physiological settings (Scott et al., 2005; Eckelman and Salvesen, 2006; Eckelman et al., 2006). Additionally, NAIPs mediate inflammasome-induced caspase-1 activation and induction of pyroptosis via NLRC4, which is contrary to the suggested inhibitor of apoptosis function (Kofoed and Vance, 2012). BIR domains, however, can mediate a broad range of protein–protein interactions and therefore could be implicated in diverse cellular functions in addition to inhibition of caspases. In NAIPs, the BIR domains appeared to be necessary for NLRC4 inflammasome formation and activation of caspase-1 (Kofoed and Vance, 2011).A mouse model lacking all Naip paralogs has not been available, preventing definitive analysis of NAIPs physiological function. In this study, we describe the first complete Naip1-6 knockout mice and demonstrate a crucial role for NAIPs in preventing colonic tumor initiation and progression.     

Measuring resistant-genotype transmission of malaria parasites: challenges and prospects

Increased gametocytemia in infections with resistant strains of Plasmodium species and their enhanced transmissibility are a matter of concern in planning and evaluating the impact of malaria control strategies. Various studies have determined weekly gametocyte carriage in response to antimalarial drugs in clinical trials. The advent of molecular biology techniques makes it easy to detect and quantify gametocytes, the stages responsible for transmission, and to detect resistant genotypes of the parasite. With the validation of molecular markers of resistance to certain antimalarial drugs, there is a need to devise a simpler formula that could be used with these epidemiological antimalarial resistance tools. Theoretical models for transmission of resistant malaria parasites are difficult to deploy in epidemiological studies. Therefore, devising a simple formula that determines the potential resistant-genotype transmission of malaria parasites should provide further insights into understanding the spread of drug resistance. The present perspective discusses gametocytogenesis in the context of antimalarial treatment and drug resistance. It also highlights the difficulties in applying the available theoretical models of drug resistance transmission and suggests Rashad’s devised formula that could perhaps be used in determining potentially transmissible resistant genotypes as well as in mapping areas with high potential risk for the transmission of drug-resistant malaria. The suggested formula makes use of the data on gametocytes and resistant genotypes of malaria parasites, detected by molecular techniques in a certain geographical area within a particular point in time, to calculate the potential risk of resistant genotype transmission.     

Immunomodulatory effect of gelatin-coated silver nanoparticles in mice: Ultrastructural evaluation

Silver nanoparticles (SNP) are used in many pharmaceutical, cosmetic, and industrial products already available in the market. Although they are considered relatively safe, many toxic and pathological alterations in different organs including immune organs were reported after SNP administration. In this study, 10-week-old male mice (n = 20) were divided into two groups. Ten mice received greenly synthesized gelatin-coated silver nanoparticles in a dose of 10 mg/kg body weight for five consecutive days while the other 10 received 0.5 ml of distilled water daily for 5 days and kept as control. At the sixth day, all mice were sacrificed; blood and tissue samples were collected and prepared for pathological analysis. Liver and kidney lesions were in the form of degenerative and inflammatory changes. Interestingly, the immune organs were drastically affected by SNP treatment. Severe hyperplasia of the Peyer’s patches was noticed in the intestines of intoxicated animals both in gross and microscopic examination. Spleen was enlarged and showed large number of megakaryocytes. The particles were encountered in membrane-bound phagosomes inside macrophages in different organs like lungs and spleen. Blood picture complied to morphological findings with an increase in monocytes and eosinophils accompanied by drop in the platelets count in the intoxicated animals.     

Unbiased spontaneous solar hydrogen production using stable TiO2–CuO composite nanofiber photocatalysts

We report on the optimization of electrospun TiO₂–CuO composite nanofibers as low-cost and stable photocatalysts for visible-light photocatalytic water splitting. The effect of different annealing atmospheres on the crystal structure of the fabricated nanofibers was investigated and correlated to the photocatalytic activity of the material. The presence of CuO resulted in narrowing the bandgap of TiO₂ and shifting the absorption edge into the visible region of the light spectrum. The effect of incorporating CuO within TiO₂ nanofibers on the crystal structure and composition was also investigated using X-ray diffraction (XRD), electron paramagnetic resonance (EPR), and X-ray photoelectron spectroscopy (XPS) techniques. The fabricated TiO₂–CuO composite nanofibers showed 117% enhancement in the amount of hydrogen evolved during the photocatalytic water splitting process compared to pure TiO₂. This enhancement was related to the created shallow defect states that facilitate charge transfer from TiO₂ to CuO and distinct characteristics of the composite nanofibers, such as the high surface area and directional charge transfer. The study showed that Cu is a promising alternative to noble metals as a catalyst in photocatalytic water splitting, with the advantage of being an Earth abundant element and a relatively cheap material.

We report on the optimization of electrospun TiO₂–CuO composite nanofibers as low-cost and stable photocatalysts for visible-light photocatalytic water splitting.     

Application of DFT-based machine learning for developing molecular electrode materials in Li-ion batteries

In this study, we utilize a density functional theory-machine learning framework to develop a high-throughput screening method for designing new molecular electrode materials. For this purpose, a density functional theory modeling approach is employed to predict basic quantum mechanical quantities such as redox potentials, and electronic properties such as electron affinity, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), for a selected set of organic materials. Both the electronic properties and structural information, such as the numbers of oxygen atoms, lithium atoms, boron atoms, carbon atoms, hydrogen atoms, and aromatic rings, are considered as input variables for the machine learning-based prediction of redox potentials. The large-set of input variables are further downsized using a linear correlation analysis to have six core input variables, namely electron affinity, HOMO, LUMO, HOMO–LUMO gap, the number of oxygen atoms and the number of lithium atoms. The artificial neural network trained using the quasi-Newton method demonstrates a capability for accurately estimating the redox potentials. From the contribution analysis, in which the influence of each input on the target are accessed, we highlight that the electron affinity has the highest contribution to redox potential, followed by the number of oxygen atoms, HOMO–LUMO gap, the number of lithium atoms, LUMO, and HOMO, in order.

In this study, we utilize a density functional theory-machine learning framework to develop a high-throughput screening method for designing new molecular electrode materials.     

Hypercalcaemia in rheumatoid arthritis: investigation of its causes and implications.

When correction was made for hypoalbuminaemia, 23 of 50 ambulant patients with definite or classical rheumatoid arthritis were found to have hypercalcaemia. When these 23 patients were studied 6 months later, 7 had hypercalcaemia as defined by the correction factor for a low serum albumin level, and 6 of these patients had raised serum ionised calcium concentrations. Biochemical studies in the 23 patients indicated evidence of hyperparathyroidism, namely, hypophosphataemia, increased serum alkaline phosphatase, hyperchloraemia, and reduced tubular reabsorption of calcium. However, serum immunoreactive parathyroid hormone concentrations were normal. Only one patient had an abnormally low serum 25-hydroxy-vitamin D result: this patient had a high level of urinary D-glucaric acid and was receiving phenobarbitone for treatment of epilepsy. The biochemical features suggestive of parathyroid overactivity were particularly found in patients with raised serum calcium levels. The cause of hypercalcaemia in rheumatoid arthritis remains to be explained.