The phylogeographic history of Megistostegium (Malvaceae) in the dry,spiny thickets of southwestern Madagascar using RAD‐seq data and ecological niche modeling

The spiny thicket of southwestern Madagascar represents an extreme and ancient landscape with extraordinary levels of biodiversity and endemism. Few hypotheses exist for explaining speciation in the region and few plant studies have explored hypotheses for species diversification. Here, we investigate three species in the endemic genus Megistostegium (Malvaceae) to evaluate phylogeographic structure and explore the roles of climate, soil, and paleoclimate oscillations on population divergence and speciation throughout the region. We combine phylogenetic and phylogeographic inference of RADseq data with ecological niche modeling across space and time. Population structure is concurrent with major rivers in the region and we identify a new, potentially important biogeographic break coincident with several landscape features. Our data further suggests that niches occupied by species and populations differ substantially across their distribution. Paleodistribution modeling provide evidence that past climatic change could be responsible for the current distribution, population structure, and maintenance of species in Megistostegium.     

The burden of T. solium cysticercosis and selected neuropsychiatric disorders in Mocuba district,Zambézia province,Mozambique

BackgroundTaenia solium (neuro-)cysticercosis, a neglected tropical disease, can be associated with epileptic seizures and other neuropsychiatric (= neurological and psychiatric) disorders. This study aimed to evaluate the association of T. solium cysticercosis with selected neuropsychiatric disorders and/or symptoms (chronic headache, epileptic seizures/epilepsy and psychosis) in Mocuba district, Mozambique.MethodologyBetween March and May 2018, a cross-sectional study was conducted among 1,086 participants aged 2 years or above in Mocuba district, Zambézia province, central Mozambique, to assess the seroprevalence of human cysticercosis and risk factors for infection, as well as to explore its relation to selected neuropsychiatric disorders. Socio-demographic and clinical data were collected from each participant using a modified questionnaire designed by the Cysticercosis Working Group for Eastern and Southern Africa. Additionally, neuropsychiatric disorders, such as chronic headache, epileptic seizures/epilepsy and psychosis were assessed using four vignettes. T. solium antigen and cysticercosis IgG in serum were detected using both T. solium antigen B158/B60 enzyme linked immunosorbent assay (ELISA) and LDBIO Cysticercosis Western Blot, respectively.Principal findingsOverall, 112/1,086 participants (10.3%) were sero-positive for T. solium antigen or antibodies. Prevalence of antibodies (6.6%; n = 72) was higher than of antigens (4.9%; n = 54). In the questionnaires, 530 (49.5%) of participants reported chronic headache, 293 (27%) had generalized epileptic seizures, 188 (18%) focal seizures and 183 (18.3%) psychosis. We found a statistically significant association between seropositivity for T. solium and chronic headache (p = 0.013). Additionally, increasing age (p = 0.03) was associated with Ag-ELISA seropositivity.ConclusionsOur study revealed that in Mocuba, T. solium cysticercosis is prevalent and associated with self-reported chronic headache. Additionally, in the study setting, the seroprevalence of cysticercosis increased with age. However, it is not associated with other neuropsychiatric disorders such epileptic seizures/epilepsy and psychosis. Future studies are needed to confirm the high burden of neuropsychiatric disorders and their possible etiology, including neurocysticercosis, using additional serological, molecular biological and radiological diagnostic tools, as well as in-depth clinical examinations.     

Mapping the lithic colonization at the boundaries of life in Northern Victoria Land,Antarctica

The endolithic microbial communities of the Antarctic represent a borderline lifestyle in the most hostile ice-free areas of the continent. The extreme adaptation of microbes in these communities renders them very sensitive to environmental changes. To date, the actual distribution of these communities has never been investigated; yet, this information would define the geographic limits for life at present and supply a useful tool for monitoring any possible future variation related to climate change. In this study, most of the outcrops of Northern and of one site in Southern Victoria Land were recorded by altitudinal and sea distance gradients. The presence of endolithic life was determined by in situ observation, by microscopic observation of rock fragments in the laboratory, and, for doubtful samples, by culture experiment. Colonizers were present in more than 87 % of the visited sites. The presence of lithic life in Victoria Land appears to be wider than that reported 14 years earlier. The colonization trend follows climatic variation, with epiliths prevailing in coastal sites and decreasing towards the interior, while chasmoendoliths and cryptoendoliths increase and become predominant from the coast towards the inland sites. Typical cryptoendolithic colonization was exclusive on porous rocks as sandstone, chasmoendolithic colonization occurred even in less porous but translucent rocks as granite and quartz. Multivariate analysis of the combined results clearly indicates the pivotal role of the rock type in the colonization of endolithic micro-organisms; sandstone allows lithobionts to push themselves towards areas characterized by harsher conditions.     

Metabolic engineering of Vibrio natriegens for anaerobic succinate production

The biotechnological production of succinate bears serious potential to fully replace existing petrochemical approaches in the future. In order to establish an economically viable bioprocess, obtaining high titre, yield and productivity is of central importance. In this study, we present a straightforward engineering approach for anaerobic succinate production with Vibrio natriegens, consisting of essential metabolic engineering and optimization of process conditions. The final producer strain V. natriegens Δlldh Δdldh Δpfl Δald Δdns::pyc_Cg (Succ1) yielded 1.46 mol of succinate per mol of glucose under anaerobic conditions (85% of the theoretical maximum) and revealed a particularly high biomass-specific succinate production rate of 1.33 g_Succ g_CDW⁻¹ h⁻¹ compared with well-established production systems. By applying carbon and redox balancing, we determined the intracellular flux distribution and show that under the tested conditions the reductive TCA as well as the oxidative TCA/glyoxylate pathway contributed to succinate formation. In a zero-growth bioprocess using minimal medium devoid of complex additives and expensive supplements, we obtained a final titre of 60.4 g_Succ l⁻¹ with a maximum productivity of 20.8 g_Succ l⁻¹ h⁻¹ and an overall volumetric productivity of 8.6 g_Succ l⁻¹ h⁻¹ during the 7 h fermentation. The key performance indicators (titre, yield and productivity) of this first engineering approach in V. natriegens are encouraging and compete with costly tailored microbial production systems.     

Novel,potent, selective,and brain penetrant phosphodiesterase 10A inhibitors

Herein we report the discovery of a novel series of phosphodiesterase 10A inhibitors. Optimization of a HTS hit (17) resulted in potent, selective, and brain penetrant 23 and 26; both exhibited much lower clearance in vivo and decreased volume of distribution (rat PK) and have thus the potential to inhibit the PDE10A target in vivo at a lower efficacious dose than the reference compound WEB-3.     

5-Azacytidine combined with 2,4-D improves somatic embryogenesis of Acca sellowiana (O. Berg) Burret by means of changes in global DNA methylation levels

DNA methylation is an epigenetic regulatory mechanism of gene expression which can be associated with developmental phases and in vitro morphogenetic competence in plants. The present work evaluated the effects of 5-azacytidine (AzaC) and 2,4-dichlorophenoxyacetic acid (2,4-D) on Acca sellowiana somatic embryogenesis (SE) and global DNA methylation levels by high-performance liquid chromatography mass spectrometry (HPLC/MS/MS). 2,4-D-free treatments revealed no somatic embryo formation in both accessions tested. Treatments supplemented with 2,4-D pulse plus AzaC in the culture medium resulted in increased embryo formation. In AzaC-free treatment, HPLC/MS/MS analysis showed a gradual increase in methylation levels in cultures of both accessions tested during SE induction. Treatment with AzaC and 2,4-D-free resulted in a marked decrease in methylation for both accessions, ranging from 37.6 to 20.8?%. In treatment with 2,4-D and AzaC combined, the 85 accession showed increasing global methylation levels. Otherwise, the 101X458 accession, in the same treatment, showed a decrease between 10 and 20?days, followed by an increase after 30?days (39.5, 36.2 and 41.6?%). These results indicate that 2,4-D pulse combined with AzaC improves SE induction. However, the conversion phase showed that although positively influencing SE induction, AzaC had a dysregulatory effect on the stage of autotrophic plant formation, resulting in significantly lower conversion rates. The results suggest that DNA methylation dramatically influences SE in Acca sellowiana, and global DNA methylation dynamics are related to morphogenetic response. Key message 5-Azacytidine combined with 2,4-D increases the number of Acca sellowiana somatic embryos. Global DNA methylation is directly affected by these compounds.