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Rethinking the Niche of Upper-Atmosphere Bacteria: Draft Genome Sequences of Bacillus aryabhattai C765 and Bacillus aerophilus C772, Isolated from Rice Fields
Get PDFHere, we report two genome sequences of endospore-forming bacteria isolated from the rice fields of Comporta, Portugal, identified as Bacillus aryabhattai C765 and Bacillus aerophilus C772. Both species were previously identified in air samples from the upper atmosphere, but our findings suggest their presence in a wider range of environmental niches.FCT grant: (PEST-E/EQB/LA0004/2011), FCT contracts: (IF/00268/2013/CP1173/CT00061, SFRH/BPD/89907/2012)
Determinants of the Sympatric Host-Pathogen Relationship in Tuberculosis
Get PDFMajor contributions from pathogen genome analysis and host genetics have equated the possibility of Mycobacterium tuberculosis co-evolution with its human host leading to more stable sympatric host-pathogen relationships. However, the attribution to either sympatric or allopatric categories depends on the resolution or grain of genotypic characterization. We explored the influence on the sympatric host-pathogen relationship of clinical (HIV infection and multidrug-resistant tuberculosis [MDRTB]) and demographic (gender and age) factors in regards to the genotypic grain by using spacer oligonucleotide typing (spoligotyping) for classification of M. tuberculosis strains within the Euro-American lineage. We analyzed a total of 547 tuberculosis (TB) cases, from six year consecutive sampling in a setting with high TB-HIV coinfection (32.0%). Of these, 62.0% were caused by major circulating pathogen genotypes. The sympatric relationship was defined according to spoligotype in comparison to the international spoligotype database SpolDB4. While no significant association with Euro-American lineage was observed with any of the factors analyzed, increasing the resolution with spoligotyping evidenced a significant association of MDRTB with sympatric strains, regardless of the HIV status. Furthermore, distribution curves of the prevalence of sympatric and allopatric TB in relation to patients' age showed an accentuation of the relevance of the age of onset in the allopatric relationship, as reflected in the trimodal distribution. On the contrary, sympatric TB was characterized by the tendency towards a typical (standard) distribution curve. Our results suggest that within the Euro-American lineage a greater degree of genotyping fine-tuning is necessary in modeling the biological processes behind the host-pathogen interplay. Furthermore, prevalence distribution of sympatric TB to age was suggestive of host genetic determinisms driven by more common variants.Luso-American Development Foundation: (LACR Award program - 2007), European Community fund: (FEDER)
Genetic association of CD247 (CD3ζ) with SLE in a large-scale multiethnic study
Get PDFA classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multiethnic population. We typed 44 contiguous CD247 single-nucleotide polymorphisms (SNPs) in 8922 SLE patients and 8077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99 × 10(-4) < P < 4.15 × 10(-2)), where we further identified a five-marker haplotype (rs12141731-rs2949655-rs16859085-rs12144621-rs858554; G-G-A-G-A; P(hap) = 2.12 × 10(-5)) that exceeded the most associated single SNP rs858554 (minor allele frequency in controls = 13%; P = 4.99 × 10(-4), odds ratio = 1.32) in significance. Imputation and subsequent association analysis showed evidence of association (P < 0.05) at 27 additional SNPs within intron 1. Cross-ethnic meta-analysis, assuming an additive genetic model adjusted for population proportions, showed five SNPs with significant P-values (1.40 × 10(-3) < P< 3.97 × 10(-2)), with one (rs704848) remaining significant after Bonferroni correction (P(meta) = 2.66 × 10(-2)). Our study independently confirms and extends the association of SLE with CD247, which is shared by various autoimmune disorders and supports a common T-cell-mediated mechanism.National Institutes of Health grants: (UL1RR025741, K24AR002138, P602AR30692, P01AR49084, UL1TR000165, P01AI083194, RO1AR43814, P60AR053308, UL1TR000004, AR43727, R21AI070304, RO1AR057172, UL1RR025014, R01AR051545-03, UL1RR029882, P60AR062755, P30AR53483, U19AI082714, P30GM103510, U01AI101934, AI063274, AR056360, AI083194, R37AI024717,
P01083194, P01AR049084, PR094002); Northwestern University Feinberg School of Medicine; University
of Alabama Birmingham; National Institute of Arthritis and Musculoskeletal and Skin Diseases; University of California Los Angeles; University of California San Francisco; Hopkins University; University of Colorado School of Medicine; University of Southern California; Seattle Children's Research Institute Arthritis Foundation; Medical University of South Carolina; Oklahoma Medical Research Foundation; Cincinnati Children's Hospital Medical Center; US Departments of Defense grant: (PR094002); Veterans Affairs; Alliance for Lupus Research; Kirkland Scholar Award; Korea Healthcare technology R & D project: (A121983); Ministry for Health and Welfare; Republic of Korea; Swedish Research Council; Instituto de Salud Carlos III grant: (PS09/00129); European Union FEDER funds; Fundação para a Ciência e Tecnologia fellowships: (SFRH/BPD/29354/2006, SFRH/BPD/34648/2007)
Potential for adaptation overrides cost of resistance
Get PDFThe deposited article is a post-print version and has been submitted to peer review.This deposit is composed by the main article plus the supplementary materials of the publication.This work is licensed under the Creative Commons Attribution-NonCommercial 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/To investigate the cost of antibiotic resistance versus the potential for resistant clones to adapt in maintaining polymorphism for resistance. Materials & methods: Experimental evolution of Escherichia coli carrying different resistance alleles was performed under an environment devoid of antibiotics and evolutionary parameters estimated from their frequencies along time. Results & conclusion: Costly resistance mutations were found to coexist with lower cost resistances for hundreds of generations, contrary to the hypothesis that the cost of a resistance dictates its extinction. Estimated evolutionary parameters for the different resistance backgrounds suggest a higher adaptive potential of clones with costly antibiotic resistance mutations, overriding their initial cost of resistance and allowing their maintenance in the absence of drugs.The research leading to these results has received funding from the European Research Council under the European Community's Seventh Framework Programme (FP7/2007–2013)/ERC grant agreement no 260421 – ECOADAPT, and PTDC/BIA-EVF/114622/2009, financed by Fundação para a Ciência e Tecnologia (FCT). I Gordo acknowledges the salary support of LAO/ITQB & FCT. JM de Sousa acknowledges the scholarship SFRH/BD/89151/2012, from FCT.info:eu-repo/semantics/publishedVersio
Mutualism Breakdown by Amplification of Wolbachia Genes
Get PDFMost insect species are associated with vertically transmitted endosymbionts. Because of the mode of transmission, the fitness of these symbionts is dependent on the fitness of the hosts. Therefore, these endosymbionts need to control their proliferation in order to minimize their cost for the host. The genetic bases and mechanisms of this regulation remain largely undetermined. The maternally inherited bacteria of the genus Wolbachia are the most common endosymbionts of insects, providing some of them with fitness benefits. In Drosophila melanogaster, Wolbachia wMelPop is a unique virulent variant that proliferates massively in the hosts and shortens their lifespan. The genetic bases of wMelPop virulence are unknown, and their identification would allow a better understanding of how Wolbachia levels are regulated. Here we show that amplification of a region containing eight Wolbachia genes, called Octomom, is responsible for wMelPop virulence. Using Drosophila lines selected for carrying Wolbachia with different Octomom copy numbers, we demonstrate that the number of Octomom copies determines Wolbachia titers and the strength of the lethal phenotype. Octomom amplification is unstable, and reversion of copy number to one reverts all the phenotypes. Our results provide a link between genotype and phenotype in Wolbachia and identify a genomic region regulating Wolbachia proliferation. We also prove that these bacteria can evolve rapidly. Rapid evolution by changes in gene copy number may be common in endosymbionts with a high number of mobile elements and other repeated regions. Understanding wMelPop pathogenicity and variability also allows researchers to better control and predict the outcome of releasing mosquitoes transinfected with this variant to block human vector-borne diseases. Our results show that transition from a mutualist to a pathogen may occur because of a single genomic change in the endosymbiont. This implies that there must be constant selection on endosymbionts to control their densities.FCT PhD fellowship: (SFRH/BD/51625/2011)
The ecdysteroidome of Drosophila: influence of diet and development
Get PDFEcdysteroids are the hormones regulating development, physiology and fertility in arthropods, which synthesize them exclusively from dietary sterols. But how dietary sterol diversity influences the ecdysteroid profile, how animals ensure the production of desired hormones and whether there are functional differences between different ecdysteroids produced in vivo remains unknown. This is because currently there is no analytical technology for unbiased, comprehensive and quantitative assessment of the full complement of endogenous ecdysteroids. We developed a new LC-MS/MS method to screen the entire chemical space of ecdysteroid-related structures and to quantify known and newly discovered hormones and their catabolites. We quantified the ecdysteroidome in Drosophila melanogaster and investigated how the ecdysteroid profile varies with diet and development. We show that Drosophila can produce four different classes of ecdysteroids, which are obligatorily derived from four types of dietary sterol precursors. Drosophila makes makisterone A from plant sterols and epi-makisterone A from ergosterol, the major yeast sterol. However, they prefer to selectively utilize scarce ergosterol precursors to make a novel hormone 24,28-dehydromakisterone A and trace cholesterol to synthesize 20-hydroxyecdysone. Interestingly, epi-makisterone A supports only larval development, whereas all other ecdysteroids allow full adult development. We suggest that evolutionary pressure against producing epi-C-24 ecdysteroids might explain selective utilization of ergosterol precursors and the puzzling preference for cholesterol.Max Planck Geselleschaft, Deutsche Forschungsgemeinschaft (TRR 83, projects A17 and A19), European Molecular Biology Organization Long Term Fellowship, University Pierre and Marie Curie
How Inflammation Impinges on NAFLD: A Role for Kupffer Cells
Get PDFThis deposit is composed by the main article, and it hasn't any supplementary materials associated.This deposit is composed by a publication in which the IGC's authors have had the role of collaboration (it's a collaboration publication). This type of deposit in ARCA is in restrictedAccess (it can't be in open access to the public), and can only be accessed by two ways: either by requesting a legal copy from the author (the email contact present in this deposit) or by visiting the following link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450298/Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most prevalent cause of liver disease worldwide and afflicts adults and children as currently associated with obesity and insulin resistance. Even though lately some advances have been made to elucidate the mechanism and causes of the disease much remains unknown about NAFLD. The aim of this paper is to discuss the present knowledge regarding the pathogenesis of the disease aiming at the initial steps of NAFLD development, when inflammation impinges on fat liver deposition. At this stage, the Kupffer cells attain a prominent role. This knowledge becomes subsequently relevant for the development of future diagnostic, prevention, and therapeutic options for the management of NAFLD.FCT, Portuguese Diabetes Society (SPD)
STR-based genetic structure of the Berber population of Bejaia (Northern Algeria) and its relationships to various ethnic groups
Get PDFPatterns of genetic variation in human populations have been described for decades. However, North Africa has received little attention and Algeria, in particular, is poorly studied, Here we genotyped a Berber-speaking population from Algeria using 15 short tandem repeat (STR) loci D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA from the commercially available AmpF/STR Identifiler kit. Altogether 150 unrelated North Algerian individuals were sampled across 10 administrative regions or towns from the Bejaia Wilaya (administrative district). We found that all of the STR loci met Hardy-Weinberg equilibrium expectations, after Bonferroni correction and that the Berber-speaking population of Bejaia presented a high level of observed heterozygosity for the 15 STR system (>0.7). Genetic parameters of forensic interest such as combined power of discrimination (PD) and combined probability of exclusion (PE) showed values higher than 0.999, suggesting that this set of STRs can be used for forensic studies. Our results were also compared to those published for 42 other human populations analyzed with the same set. We found that the Bejaia sample clustered with several North African populations but that some geographically close populations, including the Berber-speaking Mozabite from Algeria were closer to Near-Eastern populations. While we were able to detect some genetic structure among samples, we found that it was not correlated to language (Berber-speaking versus Arab-speaking) or to geography (east versus west). In other words, no significant genetic differences were found between the Berber-speaking and the Arab-speaking populations of North Africa. The genetic closeness of European, North African and Near-Eastern populations suggest that North Africa should be integrated in models aiming at reconstructing the demographic history of Europe. Similarly, the genetic proximity with sub-Saharan Africa is a reminder of the links that connect all African regions.Instituto Gulbenkian de Ciência, Laboratoire d'Excellence (LABEX) entitled TULIP: (ANR-10-LABX-41)
SUMOylation represses SnRK1 signaling in Arabidopsis
Get PDFThe SnRK1 protein kinase balances cellular energy levels in accordance with extracellular conditions and is thereby key for plant stress tolerance. In addition, SnRK1 has been implicated in numerous growth and developmental processes from seed filling and maturation to flowering and senescence. Despite its importance, the mechanisms that regulate SnRK1 activity are poorly understood. Here, we demonstrate that the SnRK1 complex is SUMOylated on multiple subunits and identify SIZ1 as the E3 Small Ubiquitin-like Modifier (SUMO) ligase responsible for this modification. We further show that SnRK1 is ubiquitinated in a SIZ1-dependent manner, causing its degradation through the proteasome. In consequence, SnRK1 degradation is deficient in siz1-2 mutants, leading to its accumulation and hyperactivation of SnRK1 signaling. Finally, SnRK1 degradation is strictly dependent on its activity, as inactive SnRK1 variants are aberrantly stable but recover normal degradation when expressed as SUMO mimetics. Altogether, our data suggest that active SnRK1 triggers its own SUMOylation and degradation, establishing a negative feedback loop that attenuates SnRK1 signaling and prevents detrimental hyperactivation of stress responses.Austrian Science Foundation FWF grant: (P25488, P23435); EMBO Installation program; FCT grants: (PTDC/BIA-PLA/3937/2012, SFRH/BD/51627/2011,SFRH/BPD/79255/2011); UID/Multi/04551/2013_Research unit GREEN-it_'Bioresources for Sustainability’
Serum Pantetheinase/Vanin Levels Regulate Erythrocyte Homeostasis and Severity of Malaria
No full textThis deposit is composed by a publication in which the IGC's authors have had the role of collaboration (it's a collaboration publication). This type of deposit in ARCA is in restrictedAccess (it can't be in open access to the public), and can only be accessed by two ways: either by requesting a legal copy from the author (the email contact present in this deposit) or by visiting the following link: https://www.sciencedirect.com/science/article/pii/S0002944015004393?via%3Dihub#ack0010This publication hasn't any creative commons license associated.This deposit is composed by the main article plus the supplementary materials of the publication.Tissue pantetheinase, encoded by the VNN1 gene, regulates response to stress, and previous studies have shown that VNN genes contribute to the susceptibility to malaria. Herein, we evaluated the role of pantetheinase on erythrocyte homeostasis and on the development of malaria in patients and in a new mouse model of pantetheinase insufficiency. Patients with cerebral malaria have significantly reduced levels of serum pantetheinase activity (PA). In mouse, we show that a reduction in serum PA predisposes to severe malaria, including cerebral malaria and severe anemia. Therefore, scoring pantetheinase in serum may serve as a severity marker in malaria infection. This disease triggers an acute stress in erythrocytes, which enhances cytoadherence and hemolysis. We speculated that serum pantetheinase might contribute to erythrocyte resistance to stress under homeostatic conditions. We show that mutant mice with a reduced serum PA are anemic and prone to phenylhydrazine-induced anemia. A cytofluorometric and spectroscopic analysis documented an increased frequency of erythrocytes with an autofluorescent aging phenotype. This is associated with an enhanced oxidative stress and shear stress-induced hemolysis. Red blood cell transfer and bone marrow chimera experiments show that the aging phenotype is not cell intrinsic but conferred by the environment, leading to a shortening of red blood cell half-life. Therefore, serum pantetheinase level regulates erythrocyte life span and modulates the risk of developing complicated malaria.There are no funders and sponsors indicated explicitly in the document.info:eu-repo/semantics/publishedVersio