PO and ID BCG vaccination in humans induce distinct mucosal and systemic immune responses and CD4(+) T cell transcriptomal molecular signatures.

Protective efficacy of Bacillus Calmette-Guérin (BCG) may be affected by the methods and routes of vaccine administration. We have studied the safety and immunogenicity of oral (PO) and/or intradermal (ID) administration of BCG in healthy human subjects. No major safety concerns were detected in the 68 healthy adults vaccinated with PO and/or ID BCG. Although both PO and ID BCG could induce systemic Th1 responses capable of IFN-γ production, ID BCG more strongly induced systemic Th1 responses. In contrast, stronger mucosal responses (TB-specific secretory IgA and bronchoalveolar lavage T cells) were induced by PO BCG vaccination. To generate preliminary data comparing the early gene signatures induced by mucosal and systemic BCG vaccination, CD4(+) memory T cells were isolated from subsets of BCG vaccinated subjects pre- (Day 0) and post-vaccination (Days 7 and 56), rested or stimulated with BCG infected dendritic cells, and then studied by Illumina BeadArray transcriptomal analysis. Notably, distinct gene expression profiles were identified both on Day 7 and Day 56 comparing the PO and ID BCG vaccinated groups by GSEA analysis. Future correlation analyses between specific gene expression patterns and distinct mucosal and systemic immune responses induced will be highly informative for TB vaccine development.Mucosal Immunology advance online publication 30 August 2017; doi:10.1038/mi.2017.67

Tomato breeding in sub-Saharan Africa - Challenges and opportunities: A review

Successful tomato ( Solanum lycopersicum ) production depends on availability of improved cultivars that can withstand biotic and abiotic pressures inflicted by the environment. This paper explores the challenges in tomato breeding and identifies opportunities that can be explored to improve tomato breeding initiatives in Africa. The review focuses on primary sources of information and notes that few existing tomato breeding institutions in Africa can drive a vibrant tomato industry and its downstream enterprises. This is coupled with inadequate breeding policies regarding varietal release and protection, negative effects of climate change, emergence of pests and diseases that impact negatively on tomato production efforts in Africa. There is a chance to tap in the diversity currently existing in wild tomato relatives, and to introduce and strengthen tomato breeding at various research institutes, through capacity building. Furthermore, there is need for Africa to embrace long term breeding strategies such as pre-breeding and the use of modern breeding technologies, if tomato production is to be sustained. Key production challenges in Africa include high incidences of fungal diseases and pests, low soil fertility, limited tomato breeding, climate change induced stresses and lack of adequate inputs due to prohibitive costs. Tomato production opportunities arise as a result of increase in human populations and consequently mounting consumer demands for nutrition and potential use of improved technologies such as CRISPR and gene sequence technologies to produce novel genotypes.La r\ue9ussite de la production de tomates ( Solanum lycopersicum ) d\ue9pend de la disponibilit\ue9 de cultivars am\ue9lior\ue9s qui peuvent r\ue9sister aux pressions biotiques et abiotiques inflig\ue9es par l\u2019environnement. Cet article scientifique explore les d\ue9fis de la s\ue9lection des tomates et identifie les opportunit\ue9s qui peuvent \ueatre explor\ue9es pour am\ue9liorer les initiatives de s\ue9lection des tomates en Afrique. La revue scientifique se concentre sur les principales sources d\u2019information et note que peu d\u2019institutions de s\ue9lection de tomates en Afrique peuvent stimuler une industrie de la tomate dynamique et ses entreprises en aval. Ceci est coupl\ue9 \ue0 des politiques de s\ue9lection inad\ue9quates concernant la lib\ue9ration et la protection vari\ue9tales, les effets n\ue9gatifs du changement climatique, l\u2019\ue9mergence de ravageurs et de maladies qui ont un impact n\ue9gatif sur les efforts de production de tomates en Afrique. Il est possible d\u2019exploiter la diversit\ue9 qui existe actuellement chez les parents de tomates sauvages et d\u2019introduire et de renforcer la s\ue9lection des tomates dans divers instituts de recherche, gr\ue2ce au renforcement des capacit\ue9s. En outre, l\u2019Afrique doit adopter des strat\ue9gies de s\ue9lection \ue0 long terme telles que la pr\ue9-s\ue9lection et l\u2019utilisation de technologies de s\ue9lection modernes, si la production de tomates doit \ueatre maintenue. Les principaux d\ue9fis de production en Afrique comprennent une incidence \ue9lev\ue9e de maladies fongiques et de ravageurs, une faible fertilit\ue9 des sols, une reproduction limit\ue9e des tomates, des stress induits par le changement climatique et le manque d\u2019intrants ad\ue9quats en raison de co\ufbts prohibitifs. Les opportunit\ue9s de production de tomates r\ue9sultent de l\u2019augmentation des populations humaines et par cons\ue9quent de la demande croissante des consommateurs pour la nutrition et l\u2019utilisation potentielle de technologies am\ue9lior\ue9es telles que CRISPR et les technologies de s\ue9quence de g\ue8nes pour produire de nouveaux g\ue9notypes

Activity-dependent heteromerization of the hyperpolarization-activated, cyclic-nucleotide gated (HCN) channels: role of N-linked glycosylation.

Formation of heteromeric complexes of ion channels via co-assembly of different subunit isoforms provides an important mechanism for enhanced channel diversity. We have previously demonstrated co-association of the hyperpolarization activated cyclic-nucleotide gated (HCN1/HCN2) channel isoforms that was regulated by network (seizure) activity in developing hippocampus. However, the mechanisms that underlie this augmented expression of heteromeric complexes have remained unknown. Glycosylation of the HCN channels has been implicated in the stabilization and membrane expression of heteromeric HCN1/HCN2 constructs in heterologous systems. Therefore, we used in vivo and in vitro systems to test the hypothesis that activity modifies HCN1/HCN2 heteromerization in neurons by modulating the glycosylation state of the channel molecules. Seizure-like activity (SA) increased HCN1/HCN2 heteromerization in hippocampus in vivo as well as in hippocampal organotypic slice cultures. This activity increased the abundance of glycosylated HCN1 but not HCN2-channel molecules. In addition, glycosylated HCN1 channels were preferentially co-immunoprecipitated with the HCN2 isoforms. Provoking SA in vitro in the presence of the N-linked glycosylation blocker tunicamycin abrogated the activity-dependent increase of HCN1/HCN2 heteromerization. Thus, hippocampal HCN1 molecules have a significantly higher probability of being glycosylated after SA, and this might promote a stable heteromerization with HCN2

Anthelmintic activity and cytotoxic effects of compounds isolated from the fruits of Ozoroa insignis del. (Anacardiaceae)

Ozoroa insignis Del. is an ethnobotanical plant widely used in traditional medicine for various ailments, including schistosomiasis, tapeworm, and hookworm infections. From the so far not investigated fruits of Ozoroa insignis, the anthelmintic principles could be isolated through bioassay-guided isolation using Caenorhabditis elegans and identified by NMR spectroscopic analysis and mass spectrometric studies. Isolated 6-[8(Z)-pentadecenyl] anacardic (1), 6-[10(Z)-heptadecenyl] anacardic acid (2), and 3-[7(Z)-pentadecenyl] phenol (3) were evaluated against the 5 parasitic organisms Schistosoma mansoni (adult and newly transformed schistosomula), Strongyloides ratti, Heligmosomoides polygyrus, Necator americanus, and Ancylostoma ceylanicum, which mainly infect humans and other mammals. Compounds 1-3 showed good activity against Schistosoma mansoni, with compound 1 showing the best activity against newly transformed schistosomula with 50% activity at 1microM. The isolated compounds were also evaluated for their cytotoxic properties against PC-3 (human prostate adenocarcinoma) and HT-29 (human colorectal adenocarcinoma) cell lines, whereby compounds 2 and 3 showed antiproliferative activity in both cancer cell lines, while compound 1 exhibited antiproliferative activity only on PC-3 cells. With an IC50 value of 43.2 microM, compound 3 was found to be the most active of the 3 investigated compounds

Macroscopic Quantum Coherence in a Magnetic Nanoparticle Above the Surface of a Superconductor

We study macroscopic quantum tunneling of the magnetic moment in a single-domain particle placed above the surface of a superconductor. Such a setup allows one to manipulate the height of the energy barrier, preserving the degeneracy of the ground state. The tunneling amplitude and the effect of the dissipation in the superconductor are computed.Comment: RevTeX, 4 pages, 1 figure. Submitted to Phys. Rev. Let