Genome-wide gene expression profiling analysis of Leishmania major and Leishmania infantum developmental stages reveals substantial differences between the two species

<p>Abstract</p> <p>Background</p> <p><it>Leishmania </it>parasites cause a diverse spectrum of diseases in humans ranging from spontaneously healing skin lesions (e.g., <it>L. major</it>) to life-threatening visceral diseases (e.g., <it>L. infantum</it>). The high conservation in gene content and genome organization between <it>Leishmania major </it>and <it>Leishmania infantum </it>contrasts their distinct pathophysiologies, suggesting that highly regulated hierarchical and temporal changes in gene expression may be involved.</p> <p>Results</p> <p>We used a multispecies DNA oligonucleotide microarray to compare whole-genome expression patterns of promastigote (sandfly vector) and amastigote (mammalian macrophages) developmental stages between <it>L. major </it>and <it>L. infantum</it>. Seven per cent of the total <it>L. infantum </it>genome and 9.3% of the <it>L. major </it>genome were differentially expressed at the RNA level throughout development. The main variations were found in genes involved in metabolism, cellular organization and biogenesis, transport and genes encoding unknown function. Remarkably, this comparative global interspecies analysis demonstrated that only 10–12% of the differentially expressed genes were common to <it>L. major </it>and <it>L. infantum</it>. Differentially expressed genes are randomly distributed across chromosomes further supporting a posttranscriptional control, which is likely to involve a variety of 3'UTR elements.</p> <p>Conclusion</p> <p>This study highlighted substantial differences in gene expression patterns between <it>L. major </it>and <it>L. infantum</it>. These important species-specific differences in stage-regulated gene expression may contribute to the disease tropism that distinguishes <it>L. major </it>from <it>L. infantum.</it></p

HSAF-induced antifungal effects in Candida albicans through ROS-mediated apoptosis

Heat-stable antifungal factor (HSAF) belongs to polycyclic tetramate macrolactams (PTMs), which inhibits many fungal pathogens and is effective in inhibiting Candida albicans (C. albicans). In this study, we found that HSAF induced the apoptosis of C. albicans SC5314 through inducing the production of reactive oxygen species (ROS). Nevertheless, we validated the efficacy of HSAF against candidiasis caused by C. albicans in a murine model in vivo,and HSAF significantly improved survival and reduced fungal burden compared to vehicles. A molecular dynamics (MD) simulation was also investigated, revealing the theoretical binding mode of HSAF to the β-tubulin of C. albicans. This study first found PTMs-induced fungal apoptosis through ROS accumulation in C. albicans and its potential as a novel agent for fungicides

Infantile Convulsions with Paroxysmal Dyskinesia (ICCA Syndrome) and Copy Number Variation at Human Chromosome 16p11

BACKGROUND: Benign infantile convulsions and paroxysmal dyskinesia are episodic cerebral disorders that can share common genetic bases. They can be co-inherited as one single autosomal dominant trait (ICCA syndrome); the disease ICCA gene maps at chromosome 16p12-q12. Despite intensive and conventional mutation screening, the ICCA gene remains unknown to date. The critical area displays highly complicated genomic architecture and is the site of deletions and duplications associated with various diseases. The possibility that the ICCA syndrome is related to the existence of large-scale genomic alterations was addressed in the present study. METHODOLOGY/PRINCIPAL FINDINGS: A combination of whole genome and dedicated oligonucleotide array comparative genomic hybridization coupled with quantitative polymerase chain reaction was used. Low copy number of a region corresponding to a genomic variant (Variation_7105) located at 16p11 nearby the centromere was detected with statistical significance at much higher frequency in patients from ICCA families than in ethnically matched controls. The genomic variant showed no apparent difference in size and copy number between patients and controls, making it very unlikely that the genomic alteration detected here is ICCA-specific. Furthermore, no other genomic alteration that would directly cause the ICCA syndrome in those nine families was detected in the ICCA critical area. CONCLUSIONS/SIGNIFICANCE: Our data excluded that inherited genomic deletion or duplication events directly cause the ICCA syndrome; rather, they help narrowing down the critical ICCA region dramatically and indicate that the disease ICCA genetic defect lies very close to or within Variation_7105 and hence should now be searched in the corresponding genomic area and its surrounding regions

Genome sequencing of the lizard parasite Leishmania tarentolae reveals loss of genes associated to the intracellular stage of human pathogenic species

The Leishmania tarentolae Parrot-TarII strain genome sequence was resolved to an average 16-fold mean coverage by next-generation DNA sequencing technologies. This is the first non-pathogenic to humans kinetoplastid protozoan genome to be described thus providing an opportunity for comparison with the completed genomes of pathogenic Leishmania species. A high synteny was observed between all sequenced Leishmania species. A limited number of chromosomal regions diverged between L. tarentolae and L. infantum, while remaining syntenic to L. major. Globally, >90% of the L. tarentolae gene content was shared with the other Leishmania species. We identified 95 predicted coding sequences unique to L. tarentolae and 250 genes that were absent from L. tarentolae. Interestingly, many of the latter genes were expressed in the intracellular amastigote stage of pathogenic species. In addition, genes coding for products involved in antioxidant defence or participating in vesicular-mediated protein transport were underrepresented in L. tarentolae. In contrast to other Leishmania genomes, two gene families were expanded in L. tarentolae, namely the zinc metallo-peptidase surface glycoprotein GP63 and the promastigote surface antigen PSA31C. Overall, L. tarentolae's gene content appears better adapted to the promastigote insect stage rather than the amastigote mammalian stage

PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine.

OBJECTIVE: Whole genome sequencing and the screening of 103 families recently led us to identify PRRT2 (proline-rich-transmembrane protein) as the gene causing infantile convulsions (IC) with paroxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerly ICCA). There is interfamilial and intrafamilial variability and the patients may have IC or PKD. Association of IC with hemiplegic migraine (HM) has also been reported. In order to explore the mutational and clinical spectra, we analyzed 34 additional families with either typical PKD/IC or PKD/IC with migraine. METHODS: We performed Sanger sequencing of all PRRT2 coding exons and of exon-intron boundaries in the probands and in their relatives whenever appropriate. RESULTS: Two known and 2 novel PRRT2 mutations were detected in 18 families. The p.R217Pfs*8 recurrent mutation was found in ≈50% of typical PKD/IC, and the unreported p.R145Gfs*31 in one more typical family. PRRT2 mutations were also found in PKD/IC with migraine: p.R217Pfs*8 cosegregated with PKD associated with HM in one family, and was also detected in one IC patient having migraine with aura, in related PKD/IC familial patients having migraine without aura, and in one sporadic migraineur with abnormal MRI. Previously reported p.R240X was found in one patient with PKD with migraine without aura. The novel frameshift p.S248Afs*65 was identified in a PKD/IC family member with IC and migraine with aura. CONCLUSIONS: We extend the spectrum of PRRT2 mutations and phenotypes to HM and to other types of migraine in the context of PKD/IC, and emphasize the phenotypic pleiotropy seen in patients with PRRT2 mutationsjournal articleresearch support, non-u.s. gov't2012 Nov 202012 10 17importedComment in : Paroxysmal disorders associated with PRRT2 mutations shake up expectations on ion channel genes. [Neurology. 2012

Gene Expression Profiling and Molecular Characterization of Antimony Resistance in Leishmania amazonensis

Leishmania are unicellular microorganisms that can be transmitted to humans by the bite of sandflies. They cause a spectrum of diseases called leishmaniasis, which are classified as neglected tropical diseases by the World Health Organization. The treatment of leishmaniasis is based on the administration of antimony-containing drugs. These drugs have been used since 1947 and still constitute the mainstay for leishmaniasis treatment in several countries. One of the problems with these compounds is the emergence of resistance. Our work seeks to understand how these parasites become resistant to the drug. We studied antimony-resistant Leishmania amazonensis mutants. We analyzed gene expression at the whole genome level in antimony-resistant parasites and identified mechanisms used by Leishmania for resistance. This work could help us in developing new strategies for treatment in endemic countries where people are unresponsive to antimony-based chemotherapy. The identification of common mechanisms among different species of resistant parasites may also contribute to the development of diagnostic kits to identify and monitor the spread of resistance

Culture-specific links between maternal executive function, parenting, and preschool children's executive function in South Korea.

BACKGROUND: Research on the relationships between parental factors and children's executive function (EF) has been conducted mainly in Western cultures. AIM: This study provides the first empirical test, in a non-Western context, of how maternal EF and parenting behaviours relate to child EF. SAMPLE: South Korean mothers and their preschool children (N = 95 dyads) completed EF tasks. METHOD: Two aspects of parental scaffolding were observed during a puzzle task: contingency (i.e., adjusting among levels of scaffolding according to the child's ongoing evidence of understanding) and intrusiveness (i.e., directive, mother-centred interactions). RESULTS AND CONCLUSIONS: Maternal EF and maternal contingency each accounted for unique variance in child EF, above and beyond child age, child language and maternal education. Maternal intrusiveness, however, was not significantly related to child EF. Additionally, no mediating role of parenting was found in the maternal and child EF link. However, child language was found to partially mediate the link between maternal contingency and child EF. These results complement prior findings by revealing distinctive patterns in the link between maternal EF, parenting behaviours, and child EF in the Korean context

The noise-lovers: cultures of speech and sound in second-century Rome

This chapter provides an examination of an ideal of the ‘deliberate speaker’, who aims to reflect time, thought, and study in his speech. In the Roman Empire, words became a vital tool for creating and defending in-groups, and orators and authors in both Latin and Greek alleged, by contrast, that their enemies produced babbling noise rather than articulate speech. In this chapter, the ideal of the deliberate speaker is explored through the works of two very different contemporaries: the African-born Roman orator Fronto and the Syrian Christian apologist Tatian. Despite moving in very different circles, Fronto and Tatian both express their identity and authority through an expertise in words, in strikingly similar ways. The chapter ends with a call for scholars of the Roman Empire to create categories of analysis that move across different cultural and linguistic groups. If we do not, we risk merely replicating the parochialism and insularity of our sources.Accepted manuscrip