Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.

A naturally occurring strain (Anga-Mali) was identified in mosquitoes of the complex collected in the Malian villages of Dangassa and Kenieroba. Phylogenetic analysis of the nucleotide sequence of two 16S rRNA regions showed thatAnga-Mali clusters with strains from supergroup A and has the highest homology to a strain isolated from cat fleas (). Anga-Mali is different from two strains previously reported in from Burkina Faso (Anga_VK5_STP and Anga_VK5_3.1a). Quantitative analysis of and sporozoite infection in field-collected mosquitoes indicates that the prevalence and intensity of sporozoite infection is significantly lower in -infected females. The presence of in females from a laboratory (, M form) colony experimentally infected with (NF54 strain) gametocyte cultures slightly enhanced oocyst infection. However, infection significantly reduced the prevalence and intensity of sporozoite infection, as observed in the field. This indicates that Anga-Mali infection does not limit early stages of infection in the mosquito, but it has a strong deleterious effect on sporozoites and reduces malaria transmission.

In recent years Venezuela has faced a severe economic crisis precipitated by political instability and a significant reduction in oil revenue. Public health provision has suffered particularly. Long-term shortages of medicines and medical supplies and an exodus of trained personnel have occurred against the backdrop of a surge in vector-borne parasitic and arboviral infections. Herein, we aim to assess comprehensively the impact of Venezuela's healthcare crisis on vectorborne diseases and the spillover to neighbouring countries. Methods Alongside the ongoing challenges affecting the healthcare system, health-indicator statistics have become increasingly scarce. Official data from the Ministry of Health, for example, are no longer available. To provide and update on vector-borne disease in Venezuela, this study used individualized data from nongovernmental organizations, academic institutions and professional colleges, various local health authorities and epidemiological surveillance programs from neighbouring countries, as well as data available through international agencies. Findings Between 2000-2015 Venezuela witnessed a 365% increase malaria cases followed by a 68% increase (319,765 cases) in late 2017. Neighbouring countries such as Brazil have reported an escalating trend of imported cases from Venezuelan from 1,538 (2014) to 3,129 (2017). Active Chagas disease transmission is reported with seroprevalence in children (<10 years) as high as 12.5% in one community tested (N=64). There has been a nine-fold rise in the mean incidence of dengue between 1990 to 2016. Estimated rates of chikungunya and Zika are 6,975 and 2,057 cases per 100,000 population, respectively, during their epidemic peaks. Interpretation The re-emergence of many arthropod-borne endemic diseases has set in place an epidemic of unprecedented proportions, not only in Venezuela but in the region. Data presented here demonstrates the complex determinants of this situation. National, regional and global authorities must take action to address these worsening epidemics and prevent their expansion beyond Venezuelan borders.

Arsenic ions, frequently present as environmental pollutants, are very toxic for most microorganisms. Some microbial strains possess genetic determinants that confer resistance. In bacteria, these determinants are often found on plasmids, which has facilitated their study at the molecular level. Bacterial plasmids conferring arsenic resistance encode specific efflux pumps able to extrude arsenic from the cell cytoplasm thus lowering the intracellular concentration of the toxic ions. In Gram-negative bacteria, the efflux pump consists of a two-component ATPase complex. ArsA is the ATPase subunit and is associated with an integral membrane subunit, ArsB. Arsenate is enzymatically reduced to arsenite (the substrate of ArsB and the activator of ArsA) by the small cytoplasmic ArsC polypeptide. In Gram-positive bacteria, comparable arsB and arsC genes (and proteins) are found, but arsA is missing. In addition to the wide spread plasmid arsenic resistance determinant, a few bacteria confer resistance to arsenite with a separate determinant for enzymatic oxidation of more-toxic arsenite to less-toxic arsenate. In contrast to the detailed information on the mechanisms of arsenic resistance in bacteria, little work has been reported on this subject in algae and fungi.

IntroductionThe episodic release of growth hormone (GH) from pituitary somatotrophs results from a complex interplay primarily between two hypothalamic peptides, the stimulatory GH-releasing hormone (GHRH) and the inhibitory somatostatin (SST) (1). Activation of the GH secretagogue receptor (GHS-R) in hypothalamus and pituitary further modulates the actions of the two classically defined regulators of GH secretion (2). Direct measurement of GHRH and SST in hypophyseal-portal blood of male rats indicates a rhythmic pattern of release of these two neuropeptides at regular 3-to 4-hour intervals about 180°out of phase (3). In contrast, female rats appear to have a different release pattern of the two peptides characterized by continuous secretion of SST and episodic, rather than rhythmic bursts of GHRH. As a result, GH secretory profiles in females are distinct from males and may account for the striking sex difference in somatic growth (4). Male rats exhibit narrow GH pulses with a frequency of about one pulse every 3-4 hours and prolonged nadir values below 1-2 ng/ml. Female rats exhibit relatively broader pulses with an irregular frequency and nadir values of 5-20 ng/ml (4). In humans, a similar sexual diergism (functional dimorphism) of GH secretion exists between men and women, indicating phylogenetic conservation of neuroendocrine hormone rhythms (5).The underlying mechanisms for such a sharp sex-specific difference in GH secretion remain unclear. Periventricular hypothalamic SST peptide and mRNA levels are higher in male compared with female rats and mice (6, 7), leading to the suggestion that sex differences in hypothalamic SST signaling to pituitary somatotrophs play a key role in the sexually diergic GH responses (1). Ontogenic studies have demonstrated that these differences are first evident at postnatal day 5 and continue to develop in an orderly cascade through puberty into adulthood (8, 9). There are five known SST receptors (SSTRs) with distinct cellular distributions and Pulsatile growth hormone (GH) secretion differs between males and females and regulates the sexspecific expression of cytochrome P450s in liver. Sex steroids influence the secretory dynamics of GH, but the neuroendocrine mechanisms have not been conclusively established. Because periventricular hypothalamic somatostatin (SST) expression is greater in males than in females, we generated knockout (Smst -/-) mice to investigate whether SST peptides are necessary for sexually differentiated GH secretion and action. Despite marked increases in nadir and median plasma GH levels in both sexes of Smst -/-compared with Smst +/+ mice, the mutant mice had growth curves identical to their sibling controls and retained a normal sexual dimorphism in weight and length. In contrast, the liver of male Smst -/-mice was feminized, resulting in an identical profile of GH-regulated hepatic mRNAs between male and female mutants. Male Smst -/-mice show higher expression of two SST receptors in the hypothalamus and pituitary than do females. These data ind...

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Abstract. The persistence of Trypanosoma cruzi tissue forms was detected in the myocardium of seropositive individuals clinically diagnosed as chronic chagasic patients following endomyocardial biopsies (EMBs) processed by immunohistochemical (peroxidase-anti-peroxidase [PAP] staining) and molecular (polymerase chain reaction [PCR]) techniques. An indirect immunofluorescent technique revealed antigenic deposits in the cardiac tissue in 24 (88.9%) of 27 patients. Persistent T. cruzi amastigotes were detected by PAP staining in the myocardium of 22 (84.6%) of 26 patients. This finding was confirmed with a PCR assay specific for T. cruzi in 21 (91.3%) of 23 biopsy specimens from the same patients. Statistical analysis revealed substantial agreement between PCR and PAP techniques (k ϭ 0.68) and the PCR and any serologic test (k ϭ 0.77). The histopathologic study of EMB specimens from these patients revealed necrosis, inflammatory infiltrates, and fibrosis, and made it possible to detect heart abnormalities not detected by electrocardiogram and/or cineventriculogram. These indications of myocarditis were supported by the detection of T. cruzi amastigotes by the PAP technique or its genome by PCR. They suggest that although the number of parasites is low in patients with chronic Chagas' disease, their potential for heart damage may be comparable with those present during the acute phase. The urgent necessity for testing new drugs with long-term effects on T. cruzi is discussed in the context of the present results.

SummaryTrypanosoma cruzi isolates from 23 acute chagasic patients from localities of Western Venezuela (state of Barinas) where Chagas' disease is endemic were typed using ribosomal and mini-exon gene markers.Results showed that isolates of the two major phylogenetic lineages, T. cruzi I and T. cruzi II, were isolated from these patients. Six isolates (26%) were typed as T. cruzi II and 17 (74%) as belonging to T. cruzi lineage I. Analysis of random amplified polymorphic DNA (RAPD) patterns confirmed these two groups of isolates, but did not disclose significant genetic intra-lineage polymorphism. Patients infected by both T. cruzi I or T. cruzi II showed different clinical profiles presenting highly variable signs and symptoms of acute phase of Chagas' disease ranging from totally asymptomatic to severe heart failure. The predominance of T. cruzi I human isolates in Venezuela allied to the higher prevalence of severe symptoms of Chagas' disease (heart failure) in patients infected by this lineage do not corroborate an innocuousness of T. cruzi I infection to humans. To our knowledge, this is the first study describing predominance of T. cruzi lineage I in a large number of acute chagasic patients with distinct and wellcharacterized clinical profiles.