H2S biosynthesis and catabolism: new insights from molecular studies

Hydrogen sulfide (H2S) has profound biological effects within living organisms and is now increasingly being considered alongside other gaseous signalling molecules, such as nitric oxide (NO) and carbon monoxide (CO). Conventional use of pharmacological and molecular approaches has spawned a rapidly growing research field that has identified H2S as playing a functional role in cell-signalling and post-translational modifications. Recently, a number of laboratories have reported the use of siRNA methodologies and genetic mouse models to mimic the loss of function of genes involved in the biosynthesis and degradation of H2S within tissues. Studies utilising these systems are revealing new insights into the biology of H2S within the cardiovascular system, inflammatory disease, and in cell signalling. In light of this work, the current review will describe recent advances in H2S research made possible by the use of molecular approaches and genetic mouse models with perturbed capacities to generate or detoxify physiological levels of H2S gas within tissue

Aβ efflux impairment and inflammation linked to cerebrovascular accumulation of amyloid-forming amylin secreted from pancreas

Impairment of vascular pathways of cerebral β-amyloid (Aβ) elimination contributes to Alzheimer disease (AD). Vascular damage is commonly associated with diabetes. Here we show in human tissues and AD-model rats that bloodborne islet amyloid polypeptide (amylin) secreted from the pancreas perturbs cerebral Aβ clearance. Blood amylin concentrations are higher in AD than in cognitively unaffected persons. Amyloid-forming amylin accumulates in circulating monocytes and co-deposits with Aβ within the brain microvasculature, possibly involving inflammation. In rats, pancreatic expression of amyloid-forming human amylin indeed induces cerebrovascular inflammation and amylin-Aβ co-deposits. LRP1-mediated Aβ transport across the blood-brain barrier and Aβ clearance through interstitial fluid drainage along vascular walls are impaired, as indicated by Aβ deposition in perivascular spaces. At the molecular level, cerebrovascular amylin deposits alter immune and hypoxia-related brain gene expression. These converging data from humans and laboratory animals suggest that altering bloodborne amylin could potentially reduce cerebrovascular amylin deposits and Aβ pathology

Genotyping of Toxoplasma gondii and Sarcocystis spp. in road-killed wild mammals from the Central Western Region of the State of São Paulo, Brazil

Abstract INTRODUCTION: Road-killed wild animals host zoonotic pathogens such as Toxoplasma gondii, offering a new opportunity for the epidemiological study of these infectious organisms. METHODS This investigation aimed to determine the presence of T. gondii and other apicomplexan parasites in tissue samples of 64 road-killed wild animals, using polymerase chain reaction (PCR). Positive samples were then typed by PCR-restriction fragment length polymorphism (RFLP) using 7 markers: SAG1, 5′-3′SAG2, SAG3, BTUB, c29-6, PK1, and Apico. PCR-RFLP targeting 18S ribosomal RNA (rRNA) genes was also performed on all samples to detect other apicomplexan parasites. RESULTS T. gondii DNA was detected in 16 tissue samples from 8 individual animals, as follows: 1 Cerdocyon thous (crab-eating fox), 1 Didelphis albiventris (white-eared opossum), 1 Lutreolina crassicaudata (lutrine opossum), 2 Myrmecophaga tridactyla (giant anteater), 1 Procyon cancrivorus (crab-eating raccoon), and 2 Sphiggurus spinosus (Paraguay hairy dwarf porcupine). Seven different T. gondii genotypes were identified, 6 of which were novel. Typing by 18S rRNA verified these 16 T. gondii-infected samples, and identified 1 Sarcocystis spp.-infected animal [Dasypus novemcinctus (nine-banded armadillo)]. The amplified T. gondii (GenBank accession No. L37415.1) and Sarcocystis spp. 18S rRNA products were confirmed by sequencing. CONCLUSIONS Our results indicate that T. gondii is commonly present in wild mammals, which act as sources of infection for humans and animals, including other wild species. The approach employed herein proved useful for detecting T. gondii and Sarcocystis spp. in the environment and identifying their natural reservoirs, contributing to our understanding of host-parasite interactions

Additional Haplogroups of Toxoplasma gondii out of Africa: Population Structure and Mouse-Virulence of Strains from Gabon

Prevalence of human toxoplasmosis in tropical African countries usually exceeds 50%. Its role as a major opportunistic infection of AIDS patients is regularly described. Due to the lack of investigation, congenital infection is certainly underestimated in Africa. Incidence of Toxoplasma ocular disease is higher in Africa and South America than in Europe. Severe cases in immunocompetent patients were described after infection acquired in Amazonia, but nothing is known about such cases in Africa. Several studies argued for a role of genotypes in the clinical expression of human toxoplasmosis, and for a geographical structuration of Toxoplasma across continents. Genetic data concerning isolates from Africa are scarce. Here, apart from the worldwide Type III, we described two main haplogroups, Africa 1 and 3. We detected genetic exchanges between urban centers favored by trade exchange and transportation. It shows how important human influence is, even in shaping the genetic structure of a zoonotic disease agent. Finding of identical haplogroups in South America suggested that these African and American strains share a common ancestor. As a higher pathogenicity in human of South American genotypes has been described, this similarity of genotypes should encourage further clinical studies with genotype analysis in Africa