Survey of Citrus tristeza virus (CTV) diversity in pigmented Citrus x paradisi (Macfad.) (Grapefruit) trees in north-western Argentina

Citrus tristeza virus (CTV) is the most severe viral pathogen of citrus and elicits a wide range of devastating disease symptoms. Grapefruit cultivars (Citrus x paradisi) are the most sensitive among citrus to the effects of CTV infections. Grapefruit is an important crop within the north-western Argentine citrus industry; however, production has been affected by CTV stem-pitting. In general, CTV diversity within South America is poorly studied, with data on grapefruit CTV populations being particularly limited. In this study, 50 samples were collected from Star Ruby, Henninger’s Ruby and Ruben Pink cultivars, within the provinces of Tucumán, Salta and Jujuy in north-western Argentina. The CTV p33 gene was PCR amplified and the resulting amplicons sequenced with Sanger sequencing. A subset of these amplicons was sequenced with Illumina MiSeq sequencing. AT-1-like sequences were dominant within the majority of populations, as determined by Sanger sequencing, followed by sequences clustering within the unresolved Kpg3/SP/T3 and RB clades. Sequencing by Illumina MiSeq confirmed this, as well as detecting minor sequence types within the HA 16–5, VT, B165 and A18 clades.The National Research Foundation (South Africa) and Ministerio de Ciencia, Tecnologia e Innovación Productiva (Argentina) via the South Africa-Argentina Bilateral agreement programme.http://link.springer.com/journal/106582019-06-01hj2017Microbiology and Plant Patholog

Survey of citrus tristeza virus (CTV) strains in Citrus x limon (L) Burm f. (lemon) in Tucumán Province, Argentina

Citrus tristeza virus (CTV) causes various syndromes of citrus and consists of diverse strains which may cause symptoms of differing severity. Lemon is the most important citrus crop produced in Tucumán province, Argentina, but the diversity of CTV strains within this region has been poorly studied. In this study we identified strains of CTV in lemons in 29 trees of five commonly planted lemon cultivars from this area using direct Sanger and next generation sequencing (NGS) of amplicons derived from the CTV p33 gene. The Kpg3/SP/T3 genotype was dominant in 28 of the 29 samples analysed, with one sample being dominant for a genotype of RB. This was confirmed with NGS in all but one instance. In addition, all thirteen samples tested by NGS were infected with RB, Kpg3/SP/T3 and HA 16–5 genotypes. One sample also had a minor VT component, while a further two samples also had a minor AT-1 component.The National Research Foundation (South Africa) and Ministerio de Ciencia, Tecnologia e Innovación Productiva (Argentina) via the South Africa-Argentina Bilateral agreement programme.http://link.springer.com/journal/106582018-12-01hj2018Microbiology and Plant Patholog

Differential influences of early growth and social factors on young children's cognitive performance in four low-and-middle-income birth cohorts (Brazil, Guatemala, Philippines, and South Africa)

Background: Studies relating childhood cognitive development to poor linear growth seldom take adequate account of social conditions related to both, leading to a focus on nutrition interventions. We aimed to assess the roles of both biological and social conditions in determining early childhood cognition, mediated by birthweight and early linear growth. Methods: After exploratory structural equation modelling to identify determining factors, we tested direct and indirect paths to cognitive performance through birthweight and child height-for-age at 2 years, assessed between 4 and 8.5 years of age among 2448 children in four birth cohort studies in low-and-middle-income countries (Brazil, Guatemala, Philippines and South Africa). Determinants were compared across the cohorts. Findings: Three factors yielded excellent fit, comprising birth endowment (primarily maternal age and birth order), household resources (crowding, dependency) and parental capacity (parental education). We estimated their strength together with maternal height in determining cognitive performance. Percentage shares of total effects of the four determinants show a marked transition from mainly biological determinants of birth weight (birth endowment 34%) and maternal height (30%) compared to household resources (25%) and parental capacity (11%), through largely economic determinants of height at 2 years (household resources (60%) to cognitive performance being predominantly determined by parental capacity (64%) followed by household resources (29%). The largely biological factor, birth endowment (maternal age and birth order) contributed only 7% to childhood cognitive performance and maternal height was insignificant. In summary, the combined share of social total effects (household resources and parental capacity) rises from 36∙2% on birth weight, to 78∙2% on height for age at 24 m, and 93∙4% on cognitive functioning. Interpretation: Across four low- and middle-income contexts, cognition in childhood is influenced more by the parental capacity of families and their economic resources than by birth weight and early linear growth. Improving children's cognitive functioning requires multi-sectoral interventions to improve parental education and enhance their economic wellbeing, interventions that are known to improve also early childhood growth

Vaccination with nanoparticles combined with micro-adjuvants protects against cancer.

Induction of strong T cell responses, in particular cytotoxic T cells, is a key for the generation of efficacious therapeutic cancer vaccines which yet, remains a major challenge for the vaccine developing world. Here we demonstrate that it is possible to harness the physiological properties of the lymphatic system to optimize the induction of a protective T cell response. Indeed, the lymphatic system sharply distinguishes between nanoscale and microscale particles. The former reaches the fenestrated lymphatic system via diffusion, while the latter either need to be transported by dendritic cells or form a local depot. Our previously developed cucumber-mosaic virus-derived nanoparticles termed (CuMV <sub>TT</sub> -VLPs) incorporating a universal Tetanus toxoid epitope TT830-843 were assessed for their draining kinetics using stereomicroscopic imaging. A nano-vaccine has been generated by coupling p33 epitope as a model antigen to CuMV <sub>TT</sub> -VLPs using bio-orthogonal Cu-free click chemistry. The CuMV <sub>TT</sub> -p33 nano-sized vaccine has been next formulated with the micron-sized microcrystalline tyrosine (MCT) adjuvant and the formed depot effect was studied using confocal microscopy and trafficking experiments. The immunogenicity of the nanoparticles combined with the micron-sized adjuvant was next assessed in an aggressive transplanted murine melanoma model. The obtained results were compared to other commonly used adjuvants such as B type CpGs and Alum. Our results showed that CuMV <sub>TT</sub> -VLPs can efficiently and rapidly drain into the lymphatic system due to their nano-size of ~ 30 nm. However, formulating the nanoparticles with the micron-sized MCT adjuvant of ~ 5 μM resulted in a local depot for the nanoparticles and a longer exposure time for the immune system. The preclinical nano-vaccine CuMV <sub>TT</sub> -p33 formulated with the micron-sized MCT adjuvant has enhanced the specific T cell response in the stringent B16F10p33 murine melanoma model. Furthermore, the micron-sized MCT adjuvant was as potent as B type CpGs and clearly superior to the commonly used Alum adjuvant when total CD8 <sup>+</sup> , specific p33 T cell response or tumour protection were assessed. The combination of nano- and micro-particles may optimally harness the physiological properties of the lymphatic system. Since the nanoparticles are well defined virus-like particles and the micron-sized adjuvant MCT has been used for decades in allergen-specific desensitization, this approach may readily be translated to the clinic

Influence of green tea consumption on endoxifen steady-state concentration in breast cancer patients treated with tamoxifen

Background: Many cancer patients use additional herbs or supplements in combination with their anti-cancer therapy. Green tea—active ingredient epigallocatechin-3-gallate (EGCG)—is one of the most commonly used dietary supplements among breast cancer patients. EGCG may alter the metabolism of tamoxifen. Therefore, the aim of this study was to investigate the influence of green tea supplements on the pharmacokinetics of endoxifen; the most relevant active metabolite of tamoxifen. Methods: In this single-center, randomized cross-over trial, effects of green tea capsules on endoxifen levels were evaluated. Patients treated with tamoxifen for at least 3 months were eligible for this study. After inclusion, patients were consecutively treated with tamoxifen monotherapy for 28 days and in combination with green tea supplements (1 g twice daily; containing 300 mg EGCG) for 14 days (or vice versa). Blood samples were collected on the last day of monotherapy or combination therapy. Area under the curve (AUC0–24h), maximum concentration (Cmax) and minimum concentration (Ctrough) were obtained from individual plasma concentration–time curves. Results: No difference was found in geometric mean endoxifen AUC0–24h in the period with green tea versus tamoxifen monotherapy (− 0.4%; 95% CI − 8.6 to 8.5%; p = 0.92). Furthermore, no differences in Cmax (− 2.8%; − 10.6 to 5.6%; p = 0.47) nor Ctrough (1.2%; − 7.3 to 10.5%; p = 0.77) were found. Moreover, no severe toxicity was reported during the whole study period. Conclusions: This study demonstrated the absence of a pharmacokinetic interaction between green tea supplements and tamoxifen. Therefore, the use of green tea by patients with tamoxifen does not have to be discouraged

Subsurface Supergranular Vertical Flows as Measured Using Large Distance Separations in Time-Distance Helioseismology

As large--distance rays (say, 10\,-\,$24 ^\circ$) approach the solar surface approximately vertically, travel times measured from surface pairs for these large separations are mostly sensitive to vertical flows, at least for shallow flows within a few Mm of the solar surface. All previous analyses of supergranulation have used smaller separations and have been hampered by the difficulty of separating the horizontal and vertical flow components. We find that the large separation travel times associated with supergranulation cannot be studied using the standard phase-speed filters of time-distance helioseismology. These filters, whose use is based upon a refractive model of the perturbations, reduce the resultant travel time signal by at least an order of magnitude at some distances. More effective filters are derived. Modeling suggests that the center--annulus travel time difference $[\delta t_{\rm{oi}}]$ in the separation range $\Delta=10$\,-\,$24 ^\circ$ is insensitive to the horizontally diverging flow from the centers of the supergranules and should lead to a constant signal from the vertical flow. Our measurement of this quantity, 5.1 \pm 0.1\secs, is constant over the distance range. This magnitude of signal cannot be caused by the level of upflow at cell centers seen at the photosphere of 10\ms extended in depth. It requires the vertical flow to increase with depth. A simple Gaussian model of the increase with depth implies a peak upward flow of 240\ms at a depth of 2.3\Mm and a peak horizontal flow of 700\ms at a depth of 1.6\Mm.Comment: Solar Physics; 15 pages, 6 figure

Recent Developments in Helioseismic Analysis Methods and Solar Data Assimilation

MR and AS have received funding from the European Research Council under the European Union’s Seventh Framework Program (FP/2007-2013)/ERC Grant Agreement no. 307117

Mega-analysis of association between obesity and cortical morphology in bipolar disorders:ENIGMA study in 2832 participants

Background: Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact. Methods: We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations. Results: BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI. Conclusions: We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.</p