Wolbachia strain wAlbB shows favourable characteristics for dengue control use in Aedes aegypti from Burkina Faso

Dengue represents an increasing public health burden worldwide. In Africa, underreporting and misdiagnosis often mask its true epidemiology, and dengue is likely to be both more widespread than reported data suggest and increasing in incidence and distribution. Wolbachia-based dengue control is underway in Asia and the Americas but has not to date been deployed in Africa. Due to the genetic heterogeneity of African Aedes aegypti populations and the complexity of the host-symbiont interactions, characterization of key parameters of Wolbachia-carrying mosquitoes is paramount for determining the potential of the system as a control tool for dengue in Africa. The wAlbB Wolbachia strain was stably introduced into an African Ae. aegypti population by introgression, and showed high intracellular density in whole bodies and different mosquito tissues; high intracellular density was also maintained following larval rearing at high temperatures. No effect on the adult lifespan induced by Wolbachia presence was detected. Moreover, the ability of this strain to strongly inhibit DENV-2 dissemination and transmission in the host was also demonstrated in the African background. Our findings suggest the potential of harnessing Wolbachia for dengue control for African populations of Ae. aegypti.     

Effect of positive charge in VIP 16gamma-glutamyl diamino derivatives on hVPAC1 and hVPAC2 receptor function.

Increase of VPAC receptor s binding to the (16)gamma-glutamyl diaminopropane vasoactive intestinal peptide (VIP-DAP) agonist, a vasoactive intestinal polypeptide (VIP) structural analogue containing a positive charge at position 16, has confirmed the importance of a positive charge at this site. By investigating the effect of distance from the peptide backbone Calpha of a positive charge in position 16, data are reported here concerning: (i) a novel chemical method used for the synthesis of a new family of (16)gamma-glutamyl diamine VIP derivatives differing among them for single carbon atoms and including diaminoethane (VIP-DAE2), diaminopropane (VIP-DAP3), diaminobutane (VIP-DAB4), diaminopentane (VIP-DAP5), and diaminohexane (VIP-DAH6); (ii) functional characterization of these compounds on human VPAC1 and VPAC2 receptors. In more detail, the EC50 and IC50 values, when measured as a function of the alkylic chain length, show in more detail, that the use of VIP-DAB4 derivative changes the IC50 but not the EC50, thus indicating on hVPAC2 receptor an unexpected relationship between binding and activity that differs from that obtained on hVPAC1.     

Effect of temporal and geographical factors on fatty acid composition of M. galloprovincialis from the Adriatic sea

Soft body tissue and gill and mantle microsomal membranes of Mytilus galloprovincialis, were analyzed to assess geographical and temporal effects on fatty acid distribution with special focus on n-3 polyunsaturated fatty acid (PUFA) content. Mussels and plankton samples were collected in April and in October from three locations of the North Adriatic Sea. Plankton fatty acid composition apparently depended both on the sampling site and time and differences referable to temporal features prevailed on the geographical ones. Accordingly, also mussel fatty acid composition appeared to be more effectively modulated by sampling time rather than by sampling location. Membrane fatty acids showed high homeostatic capabilities to reduce effects of exogenous input on cellular organization. Selective capabilities apparently enable mussels to modulate their fatty acid composition combining plankton input, environmental effects on lipid metabolism and physiological requirements. The constantly higher n-3/n-6 ratio in April than in October, shared by fatty acids of plankton, soft tissues and microsomal membranes, confirms the influence of temporal factors in fatty acid modulation. On these bases, late spring is suggested to be the more suitable period for collecting mussels destined for healthy diet of humans or other animals.     

Autophagy in hematopoietic stem/progenitor cells exposed to heavy metals: Biological implications and toxicological relevance

The inherent toxicity of many metal compounds, together with their widespread environmental distribution, raises concerns of potential health hazards. Little is known about the impact of these important environmental toxicants on adult stem/progenitor cells, necessary for tissue homeostasis and repair. We recently reported that autophagy is implicated in the response of hematopoietic stem/progenitor cells to toxic concentrations of hexavalent chromium (Cr[VI]) and cadmium (Cd), two well known carcinogenic heavy metal cations. Autophagy may lead to cell death if carried out too extensively, but also acts as a survival pathway in cells under stress. In stem/progenitor cells, an autophagic phenotype could mitigate metal-induced toxicity, contributing to the conservation of tissue renewal capability. Given the key role of toxic damage to adult stem/progenitor cells in cancer, it is necessary to investigate whether autophagic responses modulate the carcinogenic potential of exposure to heavy metals during stem/progenitor cell differentiation.     

Nitrate in exhaled breath condensate of patients with different airway diseases.

There is an increasing interest in the measurement of nitric oxide (NO.) in the airways. NO. is a free radical that reacts rapidly with reactive oxygen species in aqueous solution to form peroxynitrite which can then break down to nitrite (NO(2)(-)) and nitrate (NO(3)(-)). NO(3)(-) is considered a stable oxidative end product of NO. metabolism. The aim of this study was to assay NO(3)(-) in exhaled breath condensate (EBC) of normal nonsmoking and smoking subjects, asthmatics, patients with obstructive pulmonary disease (COPD), and patients with community-acquired pneumonia (CAP). EBC was collected using a glass condenser and samples were assayed for NO(3)(-) by ion chromatography followed by conductivity measurement. NO(3)(-) was detectable in EBC of all subjects. NO(3)(-) was elevated in smokers [median (range)] [62.5 (9.6-158.0) microM] and in asthmatics [68.0 (25.8-194.6) microM] compared to controls [9.6 (2.6-119.4) microM; p=0.003 and p=0.006, respectively], whereas NO(3)(-) was not elevated in COPD patients [24.1 (1.9-337.0 microM]. The concentration of NO(3)(-) in patients with CAP [243.4 (26.1-584.5) microM] was higher than that in controls (p=0.002) and NO(3)(-) values decreased after treatment and recovery from illness [40.0 (4.1-167.0) microM, p=0.009]. This study shows that NO(3)(-) is detectable in EBC of healthy subjects and it varies in patients with inflammatory airway diseases.     

Tissue transglutaminase in celiac disease: role of autoantibodies

In celiac disease (CD), gluten, the disease-inducing toxic component in wheat, induces the secretion of IgA-class autoantibodies which target tissue transglutaminase (tTG). These autoantibodies are produced in the small-intestinal mucosa, and, during gluten consumption, they can also be detected in patients' serum but disappear slowly from the circulation on a gluten-free diet. Interestingly, after adoption of a gluten-free diet the serum autoantibodies disappear from the circulation more rapidly than the small-intestinal mucosal autoantibody deposits. The finding of IgA deposits on extracellular tTG in the liver, kidney, lymph nodes and muscles of patients with CD indicates that tTG is accessible to the gut-derived autoantibodies. Although the specific autoantibody response directed against tTG is very characteristic in celiac patients, their role in the immunopathology of the celiac mucosal lesion is a matter of debate. Here we report a brief summary of anti-tTG antibody effects demonstrating that these antibodies are functional and not mere bystanders in the disease pathogenesis. In fact, they inhibit intestinal epithelial cell differentiation, induce intestinal epithelial cell proliferation, increase epithelial permeability and activate monocytes and disturb angiogenesis.     

Cyclic glycopeptidomimetics through a versatile sugar-based scaffold

Cyclic peptidomimetics are attracting structures to obtain a distinct, bioactive conformation. Even more attractive are sugar-containing cyclic peptidomimetics which present turn structures induced by the pyranose ring when incorporated in cyclic peptides. The use of a new and versatile saccharidic scaffold to achieve sugar-based peptidomimetics is here reported together with the successful synthesis of diastereomerically pure cyclic SAA peptidomimetics 15 and 16.     

Novel potent and highly selective human A(3) adenosine receptor antagonists belonging to the 4-amido-2-arylpyrazolo[3,4-c]quinoline series: molecular docking analysis and pharmacological studies

The study of novel 2-arylpyrazolo[3,4-c]quinolin-4-(hetero)arylamides, designed as human (h) A(3) adenosine receptor antagonists, is reported. The new derivatives are endowed with nanomolar hA(3) receptor affinity and high selectivity versus hA(1), hA(2A) and hA(2B) receptors. Among the (hetero)aroyl residues introduced on the 4-amino group, the 2-furyl and 4-pyridyl rings turned out to be the most beneficial for hA(3) affinity (K(i)=3.4 and 5.0nM, respectively). An intensive molecular docking study to a rhodopsin-based homology model of the hA(3) receptor was carried out to obtain a 'structure-based pharmacophore model' that proved to be helpful for the interpretation of the observed affinities of the new hA(3) pyrazoloquinoline antagonists.     

Pathogenetic mechanisms in hereditary dysfunctions of complex I of the respiratory chain in neurological diseases

This paper covers genetic and biochemical aspects of mitochondrial bioenergetics dysfunction in hereditary neurological disorders associated with complex I defects. Three types of hereditary complex I dysfunction are dealt with: (i) homozygous mutations in the nuclear genes NDUFS1 and NDUFS4 of complex I, associated with mitochondrial encephalopathy; (ii) a recessive hereditary epileptic neurological disorder associated with enhanced proteolytic degradation of complex I; (iii) homoplasmic mutations in the ND5 and ND6 mitochondrial genes of the complex, cohexistent with mutation in the nuclear PINK1 gene in familial Parkinsonism. The genetic and biochemical data examined highlight different mechanisms by which mitochondrial bioenergetics is altered in these hereditary defects of complex I. This knowledge, besides clarifying molecular aspects of the pathogenesis of hereditary diseases, can also provide hints for understanding the involvement of complex I in sporadic neurological disorders and aging, as well as for developing therapeutical strategies.