Biology subjects

Schneider, P.

Publications and source records attributed to Schneider, P..

21 records · Page 2Linked to original sources

bioRxiv2018

Adaptive periodicity in the infectivity of malaria gametocytes to mosquitoes

That periodicity in the biting activity of mosquito vectors explains why malaria parasites have evolved rhythms in cycles of asexual replication in the hosts blood was proposed almost 50 years ago. Yet, tests of this hypothesis have proved inconclusive. Using the rodent malaria Plasmodium chabaudi, we examine rhythms in the density and infectivity of transmission forms (gametocytes) in the hosts blood, parasite development inside mosquitoes, and onwards transmission.Moreover, we control for the confounding effects of rhythms in mosquito susceptibility. We reveal that at night, gametocytes are twice as infective to mosquitoes, despite being less numerous in the blood. This enhanced infectiousness at night interacts with mosquito rhythms to increase sporozoite burdens by almost four-fold when mosquitoes feed during their day. Thus, daytime blood-feeding (e.g. driven by the use of bed nets) may render gametocytes less infective, but this is compensated for by the greater susceptibility of mosquitoes.

microbiology↗

bioRxiv2017

Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo

Epigenetic mechanisms and transcription factor networks essential for differentiation of cardiac myocytes have been uncovered. However, reshaping of the epigenome of these terminally differentiated cells during fetal development, postnatal maturation and in disease remains unknown. Thus, the aim of this study was to determine the dynamics of the cardiac myocyte epigenome during development and in chronic heart failure. Prenatal development and postnatal maturation are characterized by a cooperation of active CpG methylation and histone marks at cis-regulatory and genic regions to shape the cardiac myocyte transcriptome. In contrast, pathological gene expression in terminal heart failure is accompanied by changes in active histone marks without major alterations in CpG methylation and repressive chromatin marks. Notably, cis-regulatory regions in cardiac myocytes are significantly enriched for cardiovascular disease-associated variants. This study uncovers distinct layers of epigenetic regulation not only during prenatal development and postnatal maturation but also in diseased human cardiac myocytes.

genomics↗

bioRxiv2017

The Pax9/Wnt pathway regulates secondary palate formation in mice

Clefts of the palate and/or lip arise in about 1/700 human live births and are caused by multiple genetic and environmental factors. Studies of mouse knockout models of cleft palate have improved our understanding of the molecular control of palatogenesis. While it is known that Pax9 regulates palatogenesis through Bmp, Fgf and Shh signaling, there is still much to learn about its precise relationship with other pathways. Here we show that alterations of Wnt expression and decreased Wnt activity in Pax9-/- palatal shelves are a result of Pax9s ability to directly bind and repress the promoters of Dkk1 and Dkk2, proteins that antagonize Wnt signaling. The delivery of small-molecule Dkk inhibitors (Wnt agonists) into the tail-veins of pregnant Pax9+/- mice from E10.5 to E14.5 restored Wnt signaling, promoted cell proliferation, bone formation and restored the fusion of palatal shelves in Pax9-/- embryos. In contrast, other organ defects in Pax9 mutants were not corrected. These data uncover a unique molecular relationship between Pax9 and Wnt genes in palatogenesis and offer a new approach for treating cleft palates in humans.\n\nSummary StatementThese studies demonstrate that the Pax9/Wnt genes regulate murine palatogenesis. This unique molecular relationship is proven by the correction of cleft defects in Pax9-deficient mice through Wnt agonist therapies.

developmental biology↗