Assessing the effect of zooprophylaxis on zoonotic cutaneous leishmaniasis transmission: A system dynamics approach

Capturing or diverting the disease carrying vector from humans can reduce the transmission of vector borne diseases such as leishmaniasis. The use of animals that act as dead-end hosts to relieve the vector (sandfly) bites on humans is called zooprophylaxis. However, as the number of blood meal providers especially domestic animals increases, the sandflies enhanced availability of blood meals will improve its number and survival, thereby countering the impact of diverting bites from humans. Thus, the transmission model exhibits the structure of a feedback loop characterizing complex dynamic systems. In order to rigorously assess the effect of zooprophylaxis, we propose a system dynamic model for zoonotic cutaneous leishmaniasis transmission with 3 blood-meal hosts: domestic animals, humans, and a reservoir (rodents). In this context, a simulation study of the proposed model with a follow-up period of 1000 days was performed.     

Messinian Lago-Mare mollusc fauna from the Gorgona Island slope, Tyrrhenian Sea

Late Miocene Lago-Mare macrofossiliferous sediments were recovered in the northeastern Tyrrhenian Sea by dredging the continental slope off Gorgona Island, Tuscan Archipelago, at 300-470 m depth. The fossil assemblage consists of a rich lymnocardiid bivalve fauna dominated by Pontalmyra ex gr. P. incerta (Deshayes), associated with Dreissena ex gr. D. rostriformis (Deshayes), Pontalmyra cf. partschi (Mayer), “Limnocardium” sp., the gastropods Melanopsis narzolina (D’Archiac), Melanopsis sp. and cf. Saccoia sp. All bivalve taxa recognized at species level are of Paratethyan (Pontian) affinity and widespread in the Late Miocene of the Mediterranean Basin while M. narzolina has so far only recorded from the Mediterranean Basin. This finding represents the most diverse Lago-Mare macrofauna reported thus far from any submerged location in the Mediterranean Basin and documents that the post-evaporitic Cusercoli Formation contributes to the syn-rift neoautochthonous units of this sector of the Northern Tyrrhenian Sea.     

Intraindividual validation of heart rate variability indexes to measure vagal effects on hearts

Heart rate variability (HRV) has been widely used as a measure of vagal activation in physiological, psychological, and clinical examinations. We studied the within-subject quantitative relationship between HRV and vagal effects on the heart in different body postures during a gradually decreasing vagal blockade. Electrocardiogram and respiratory frequency were measured in subjects (8 endurance athletes and 10 participants of nonendurance sports) in supine, sitting, and standing postures before the blockade, under vagal blockade (atropine sulfate, 0.04 mg/kg), and four times during a 150-min recovery from the blockade. Fast Fourier transform was used to calculate low-frequency power (LFP, 0.04-0.15 Hz), high-frequency power (HFP, 0.15-0.40 Hz), and total power (TP, 0.04-0.40 Hz). A within-subject linear regression analysis of recovery time on each HRV index was conducted. Complete vagal blockade decreased all HRV significantly, particularly HFP (P < 0.001). A linear fit explained a large portion of the within-subject variance between recovery time and natural log-transformed (ln) HRV indexes in every posture, with coefficients of determination (R2) in the supine posture [means (SD)]: 98 (SD 2)% for mean R-R interval, 87 (SD 10)% for lnLFP, 87 (SD 13)% for lnHFP, and 91 (SD 10)% for lnTP. Neither body posture nor endurance-training background had an impact on R2 values. There was marked between-subject variation in the R2 values, slopes, and intercepts. In conclusion, all HRV, particularly HFP, is predominantly under vagal control. Within subjects, lnLFP, lnHFP, and lnTP increased linearly with the gradually decreasing vagal blockade in all postures.     

Formulation and Stability Testing of Itraconazole Crystalline Nanoparticles

Itraconazole (ITZ) crystalline nanoparticles were prepared using relatively simple, low-cost sonoprecipitation technique, in which both the solvent and antisolvent were organic in nature. The effect of stabilizer type (hydroxypropyl methylcellulose, hydroxypropyl cellulose, Inutec SP1®, and pluronic F127), drying method (oven and freeze drying) and matrix former used (Avicel PH101, and Aerosil®200) on the dissolution performance as a key characteristic of nanocrystals was evaluated. In 10 min, all of the prepared nanocrystals showed 3.77−8.59 times improvement in percent drug dissolved compared to pure ITZ. Concerning the effect of stabilizer type, the following rank order can be given: pluronic F127 ≥ hydroxypropyl cellulose ≥ hydroxypropyl methylcellulose (HPMC) > inutec SP1. Freeze-dried ITZ nanocrystals containing Avicel PH 101 showed better dissolution rate compared to other nanocrystals. The chemical structure of itraconazole nanocrystals was not changed as revealed by Fourier transform infrared. Stability study of selected nanocrystals (F5, F7, and F8) revealed physical and chemical stability of F7 and F8, while a decrease in dissolution rate of F5 was observed (although being chemically stable) when stored under high relative humidity conditions. Although inutec is less potent than pluronic F127 and HPMC regarding their effect on dissolution rate enhancement, it is equipotent to pluronic F127 in preserving the rapid drug dissolution.Key words: itraconazole, nanocrystals, nanoparticles, stability study     

Rye-derived powdery mildew resistance gene <Emphasis Type="Italic">Pm8</Emphasis> in wheat is suppressed by the <Emphasis Type="Italic">Pm3</Emphasis> locus

Genetic suppression of disease resistance is occasionally observed in hexaploid wheat or in its interspecific crosses. The phenotypic effects of genes moved to wheat from relatives with lower ploidy are often smaller than in the original sources, suggesting the presence of modifiers or partial inhibitors in wheat, especially dilution effects caused by possible variation at orthologous loci. However, there is little current understanding of the underlying genetics of suppression. The discovery of suppression in some wheat genotypes of the cereal rye chromosome 1RS-derived gene Pm8 for powdery mildew resistance offered an opportunity for analysis. A single gene for suppression was identified at or near the closely linked storage protein genes Gli-A1 and Glu-A3, which are also closely associated with the Pm3 locus on chromosome 1AS. The Pm3 locus is a complex of expressed alleles and pseudogenes embedded among Glu-A3 repeats. In the current report, we explain why earlier work indicated that the mildew suppressor was closely associated with specific Gli-A1 and Glu-A3 alleles, and predict that suppression of Pm8 involves translated gene products from the Pm3 locus.     

Morphological variation of Echinococcus granulosus protoscoleces from hydatid cysts of human and various domestic animals in Jordan

, and 1988. Morphological variation of Echinococcus granulosus protoscoleces from hydatid cysts of human and various domestic animals in Jordan. International Journal for Parasitology 18: 1111–1114. Rostellar hook morphology of protoscoleces was employed to study the possible existence of Echinococcus granulosus strains in humans and various domestic animals in Jordan. A distinct form in the donkey was evident as the protoscoleces from this host did not share any characteristics with those from the other hosts examined. Sheep, goats and cattle appeared to be affected by another form since the protoscoleces from their hydatid cysts shared six out of nine characteristics studied. Protoscoleces of camel and human cysts shared seven out of nine characteristics studied and they were different in six characteristics from protoscoleces from other hosts. Differences observed among the three forms may reflect strain variation of E. granulosus in this country.     

Refolding of human beta-1-2 GlcNAc transferase (GnT1) and the role of its unpaired Cys 121

Human beta1-2N-acetylglucosaminyltransferase (hGnT1) lacking the first 103 amino acids was expressed as a maltose binding protein (MBP) fusion protein in inclusion bodies (IBs) in Escherichia coli and refolded using an oxido-shuffling method. GnT1 mutants were prepared by replacing a predicted unpaired cysteine (C121) with alanine (C121A), serine (C121S), threonine (C121T) or aspartic acid (C121D). A double mutant R120A/C121H, was generated to mimic Gly14, the Caenorhabditis elegans GnT1 counterpart to hGNT1. Each mutant hGnT1 was constructed as an MBP fusion protein and resultant IBs were isolated and refolded. Wild type hGnT1 and mutants C121A, C121S and R120A/C121H transferred UDP-GlcNAc to the glycoprotein acceptor Man(5)-RNAse B, whereas mutants C121T and C121D were inactive. These findings indicated that cysteine 121 has a structural role in maintaining active site geometry of hGnT1, rather than a catalytic role, and illustrates for the first time the potential utility of E. coli as an expression system for hGnT1.     

Determination of plasma microRNA for early detection of gastric cancer

Gastric cancer is the fourth most prevalent malignancy worldwide and remains the second most common cause of cancer-related death globally. Understanding the molecular structure of gastric carcinogenesis might identify new diagnostic and therapeutic strategies for this disease. Thus, early detection of gastric cancer is a key measure to reduce the mortality and improve the prognosis of gastric cancer. There have recently been several reports that microRNAs (miRNAs) circulate in highly stable, cell-free forms in blood. Because serum and plasma miRNAs are relatively easy to access, circulating miRNAs also have great potential to serve as non-invasive biomarkers. Although a number of miRNAs associated with gastric cancer have been identified, the underlying mechanism of these miRNAs in tumorigenesis and tumor progression remains to be investigated. The purpose of this study is to identify the potential of serum miRNAs as biomarkers for early detection of gastric cancer patients. RNA was isolated using the High Pure miRNA Isolation Kit (Roche) following the manufacturer’s protocol. cDNA and preamplification protocols were obtained from the isolated plasma miRNAs. The BioMark? 96.96 Dynamic Array (Fluidigm Corporation) for real-time qPCR was used to simultaneously quantite the expression of 740 miRNAs. All statistical analyses were performed using the Biogazelle’s qbase PLUS 2.0 software. In this study, among 740 miRNAs that we analyzed only miR-195-5p was significantly (p < 0.05, fold changes = 13, 3) down-regulated in gastric cancer patients compared with control. We demonstrated that miR-195-5p is a novel tumor suppressor miRNA and may contribute to gastric carcinogenesis. The miRNA expression profile described in this study should contribute to future studies on the role of miRNAs in gastric cancer.