Host carbon sources modulate cell wall architecture, drug resistance and virulence in a fungal pathogen

The survival of all microbes depends upon their ability to respond to environmental challenges. To establish infection, pathogens such as Candida albicans must mount effective stress responses to counter host defences while adapting to dynamic changes in nutrient status within host niches. Studies of C. albicans stress adaptation have generally been performed on glucose-grown cells, leaving the effects of alternative carbon sources upon stress resistance largely unexplored. We have shown that growth on alternative carbon sources, such as lactate, strongly influence the resistance of C. albicans to antifungal drugs, osmotic and cell wall stresses. Similar trends were observed in clinical isolates and other pathogenic Candida species. The increased stress resistance of C. albicans was not dependent on key stress (Hog1) and cell integrity (Mkc1) signalling pathways. Instead, increased stress resistance was promoted by major changes in the architecture and biophysical properties of the cell wall. Glucose- and lactate-grown cells displayed significant differences in cell wall mass, ultrastructure, elasticity and adhesion. Changes in carbon source also altered the virulence of C. albicans in models of systemic candidiasis and vaginitis, confirming the importance of alternative carbon sources within host niches during C. albicans infection

Lactate signalling regulates fungal β-glucan masking and immune evasion

AJPB: This work was supported by the European Research Council (STRIFE, ERC- 2009-AdG-249793), The UK Medical Research Council (MR/M026663/1), the UK Biotechnology and Biological Research Council (BB/K017365/1), the Wellcome Trust (080088; 097377). ERB: This work was supported by the UK Biotechnology and Biological Research Council (BB/M014525/1). GMA: Supported by the CNPq-Brazil (Science without Borders fellowship 202976/2014-9). GDB: Wellcome Trust (102705). CAM: This work was supported by the UK Medical Research Council (G0400284). DMM: This work was supported by UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/K000306/1). NARG/JW: Wellcome Trust (086827, 075470,101873) and Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377). ALL: This work was supported by the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).Peer reviewedPostprin

Tectonic and stratigraphic evolution based on seismic sequence stratigraphy: Central rift section of the campos basin, offshore brazil

The rift section of the Brazilian basins represent the sedimentary record associated with the first stages of Gondwana break‐up in the Early Cretaceous phase (Berriasian to Aptian). The rift succession of the Campos Basin constitutes one of the main petroleum systems of Brazil’s marginal basins. This interval contains the main source rock and important reservoirs in the Lagoa Feia Group deposits. The Lagoa Feia Group is characterized by siliciclastic, carbonate and evaporite sediments deposited during the rift and post‐rift phases. Despite the economic relevance, little is known in stratigraphic terms regarding this rift interval. To date, most studies of the Lagoa Feia Group have adopted a lithostratigraphic approach, while this study proposes a tectonostrati-graphic framework for the deep‐rift succession of the Campos Basin (Lagoa Feia Group), using the fundamentals of seismic sequence stratigraphy. This work also aims to establish a methodological and practical procedure for the stratigraphic analysis of rift basins, using seismic data and seismofacies, and focusing on tectonicstratigraphic analysis. The dataset comprised 2D seismic lines, core and lithological logs from exploration wells. Three seismic facies were identified based on reflector patterns and lithologic data from well cores, providing an improved subdivision of the pre‐, syn‐ and post‐rift stages. The syn‐rift stage was further subdivided based on the geometric patterns of the reflectors. Tectonics was the main controlling factor in the sedimentary succession, and the pattern and geometry of the seismic reflectors of the syn‐rift interval in the Campos Basin allowed the identification of three tectonic systems tracts: (i) a Rift Initiation Systems Tract; (ii) a High Tectonic Activity Systems Tract and (iii) a Low Tectonic Activity Systems Tract

Selfing revealed potential for higher yield performance than backcrossing among tomato segregating populations of Solanum lycopersicum × S. pimpinellifolium crosses under tropical humid climate

The objectives of this study were to assess and identify new source of phenotypic variability among F3 and BC1F2 tomato populations, and apply genotype by yield*trait (GYT) biplots for population and line selection based on multiple traits. Four diverse cultivated parents (‘CLN2498D’ [D] and ‘CLN2417H’ [H] from Ethiopia; ‘UC Dan INDIA’ [U] and ‘Tima’ [T] from Nigeria), and wild parent ‘LA2093’ [W] were used to generate 276 potential breeding lines. The lines were categorized into eight populations (‘pop_1_W/H1’, ‘pop_2_W/H2’, ‘pop_3_W/D1’, ‘pop_4_W/D2’, ‘pop_5_W/T1’, ‘pop_6_W/T2’, ‘pop_7_W/U1’, and ‘pop_8_W/U2’), and evaluated twice in the field using 19 × 15 alpha-lattice design with two replicates. Significant differences were observed among lines and populations for all yield enhancing traits. ‘Pop_1_W/H1’, ‘pop_4_W/D2’ and ‘pop_6_W/T2’ expressed the highest genetic divergence for plant height, number of leaves, total flower and fruit number, and fruit weight. GYT biplots revealed that all yield*trait interactions had a positive correlation with each other. F3 populations, ‘pop_5_W/T1’ and ‘pop_1_W/H1’ exhibited the best performance for majority of the yield*trait combinations. Hierarchical clustering on principal components (HCPC) revealed overlapping lines (70.58% of Cluster D lines) and (54.05% of Cluster U lines) from the two F3 populations. In BC1F2 population, 32.35% of the 34 original lines of Cluster D and 48.48% of Cluster T lines overlapped between Clusters D and T, while 18.18% of Cluster T lines and 8.82% of Cluster H lines were transgressive between Clusters T and H. Transgressive segregants ‘0210U1’, ‘0211U1’, and ‘0171T1’ of selfed population using multivariate analysis were believed to represent potential sources of novel genetic variation for future tomato breeding

The Rewiring of Ubiquitination Targets in a Pathogenic Yeast Promotes Metabolic Flexibility, Host Colonization and Virulence

Funding: This work was funded by the European Research Council [http://erc.europa.eu/], AJPB (STRIFE Advanced Grant; C-2009-AdG-249793). The work was also supported by: the Wellcome Trust [www.wellcome.ac.uk], AJPB (080088, 097377); the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk], AJPB (BB/F00513X/1, BB/K017365/1); the CNPq-Brazil [http://cnpq.br], GMA (Science without Borders fellowship 202976/2014-9); and the National Centre for the Replacement, Refinement and Reduction of Animals in Research [www.nc3rs.org.uk], DMM (NC/K000306/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We thank Dr. Elizabeth Johnson (Mycology Reference Laboratory, Bristol) for providing strains, and the Aberdeen Proteomics facility for the biotyping of S. cerevisiae clinical isolates, and to Euroscarf for providing S. cerevisiae strains and plasmids. We are grateful to our Microscopy Facility in the Institute of Medical Sciences for their expert help with the electron microscopy, and to our friends in the Aberdeen Fungal Group for insightful discussions.Peer reviewedPublisher PD

Lactate Regulates Metabolic and Proinflammatory Circuits in Control of T Cell Migration and Effector Functions

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Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Uniparental Genetic Heritage of Belarusians: Encounter of Rare Middle Eastern Matrilineages with a Central European Mitochondrial DNA Pool

Ethnic Belarusians make up more than 80% of the nine and half million people inhabiting the Republic of Belarus. Belarusians together with Ukrainians and Russians represent the East Slavic linguistic group, largest both in numbers and territory, inhabiting East Europe alongside Baltic-, Finno-Permic- and Turkic-speaking people. Till date, only a limited number of low resolution genetic studies have been performed on this population. Therefore, with the phylogeographic analysis of 565 Y-chromosomes and 267 mitochondrial DNAs from six well covered geographic sub-regions of Belarus we strove to complement the existing genetic profile of eastern Europeans. Our results reveal that around 80% of the paternal Belarusian gene pool is composed of R1a, I2a and N1c Y-chromosome haplogroups – a profile which is very similar to the two other eastern European populations – Ukrainians and Russians. The maternal Belarusian gene pool encompasses a full range of West Eurasian haplogroups and agrees well with the genetic structure of central-east European populations. Our data attest that latitudinal gradients characterize the variation of the uniparentally transmitted gene pools of modern Belarusians. In particular, the Y-chromosome reflects movements of people in central-east Europe, starting probably as early as the beginning of the Holocene. Furthermore, the matrilineal legacy of Belarusians retains two rare mitochondrial DNA haplogroups, N1a3 and N3, whose phylogeographies were explored in detail after de novo sequencing of 20 and 13 complete mitogenomes, respectively, from all over Eurasia. Our phylogeographic analyses reveal that two mitochondrial DNA lineages, N3 and N1a3, both of Middle Eastern origin, might mark distinct events of matrilineal gene flow to Europe: during the mid-Holocene period and around the Pleistocene-Holocene transition, respectively

Observation of an Excited Bc+ State

Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+π+π- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2±0.6(stat)±0.1(syst)±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bc∗(2S31)+ state reconstructed without the low-energy photon from the Bc∗(1S31)+→Bc+γ decay following Bc∗(2S31)+→Bc∗(1S31)+π+π-. A second state is seen with a global (local) statistical significance of 2.2σ (3.2σ) and a mass of 6872.1±1.3(stat)±0.1(syst)±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date