205 research outputs found
Autoimmune neurological conditions associated with Zika virus infection
Zika virus (ZIKV) is an emerging flavivirus rapidly spreading throughout the tropical Americas. mosquitoes is the principal way of transmission of the virus to humans. ZIKV can be spread by transplacental, perinatal, and body fluids. ZIKV infection is often asymptomatic and those with symptoms present minor illness after 3 to 12 days of incubation, characterized by a mild and self-limiting disease with low-grade fever, conjunctivitis, widespread pruritic maculopapular rash, arthralgia and myalgia. ZIKV has been linked to a number of central and peripheral nervous system injuries such as Guillain-Barré syndrome (GBS), transverse myelitis (TM), meningoencephalitis, ophthalmological manifestations, and other neurological complications. Nevertheless, mechanisms of host-pathogen neuro-immune interactions remain incompletely elucidated. This review provides a critical discussion about the possible mechanisms underlying the development of autoimmune neurological conditions associated with Zika virus infection
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Fucose Sensing Regulates Bacterial Intestinal Colonization
The mammalian gastrointestinal (GI) tract provides a complex and competitive environment for the microbiota1. Successful colonization by pathogens depends on scavenging nutrients, sensing chemical signals, competing with the resident bacteria, and precisely regulating expression of virulence genes2. The GI pathogen enterohemorrhagic E.coli (EHEC) relies on inter-kingdom chemical sensing systems to regulate virulence gene expression3–4. Here we show that these systems control the expression of a novel two-component signal transduction system, named FusKR, where FusK is the histidine sensor kinase (HK), and FusR the response regulator (RR). FusK senses fucose and controls expression of virulence and metabolic genes. This fucose-sensing system is required for robust EHEC colonization of the mammalian intestine. Fucose is highly abundant in the intestine5. Bacteroides thetaiotaomicron (B.theta) produces multiple fucosidases that cleave fucose from host glycans, resulting in high fucose availability in the gut lumen6. During growth in mucin, B.theta contributes to EHEC virulence by cleaving fucose from mucin, thereby activating the FusKR signaling cascade, modulating EHEC’s virulence gene expression. Our findings suggest that EHEC uses fucose, a host-derived signal made available by the microbiota, to modulate EHEC pathogenicity and metabolism
Single loss of a Trp53 allele triggers an increased oxidative, DNA damage and cytokine inflammatory responses through deregulation of IκBα expression
Dose of Trp53, the main keeper of genome stability, influences tumorigenesis; however, the causes underlying and driving tumorigenesis over time by the loss of a single p53 allele are still poorly characterized. Here, we found that single p53 allele loss specifically impacted the oxidative, DNA damage and inflammatory status of hematopoietic lineages. In particular, single Trp53 allele loss in mice triggered oxidative stress in peripheral blood granulocytes and spleenocytes, whereas lack of two Trp53 alleles produced enhanced oxidative stress in thymus cells, resulting in a higher incidence of lymphomas in the Trp53 knockout (KO) mice compared with hemizygous (HEM). In addition, single or complete loss of Trp53 alleles, as well as p53 downregulation, led to a differential increase in basal, LPS- and UVB-induced expression of a plethora of pro-inflammatory cytokine, such as interleukin-12 (Il-12a), TNFα (Tnfa) and interleukin (Il-23a) in bone marrow-derived macrophage cells (BMDMs) compared to WT cells. Interestingly, p53-dependent increased inflammatory gene expression correlated with deregulated expression of the NF-κB pathway inhibitor IκBα. Chromatin immunoprecipitation data revealed decreased p65 binding to Nfkbia in the absence of p53 and p53 binding to Nfkbia promoter, uncovering a novel crosstalk mechanism between p53 and NF-κB transcription factors. Overall, our data suggest that single Trp53 allele loss can drive a sustained inflammatory, DNA damage and oxidative stress response that, over time, facilitate and support carcinogenesis
Clinical improvement following therapy for periodontitis: Association with a decrease in IL-1 and IL-6
Although a number of inflammatory cytokines have been shown to be associated with periodontal pathogenesis, it is important to investigate further whether these biomarkers are associated with the degree of success in nonsurgical treatment of chronic periodontitis. The aim of the present study was to quantify the total levels of interleukin (IL)‑1α, ‑1β, ‑6, ‑10 and tumour necrosis factor (TNF)‑α in gingival crevicular fluid (GCF) of chronic periodontitis patients prior to and following nonsurgical periodontal therapy. In total, 52 GCF samples from disease sites of patients with chronic periodontitis, prior to and following periodontal therapy, and ten non‑disease sites from non‑periodontitis subjects, were collected and cytokine concentrations were determined using a multiplex method. Periodontal parameters, including bleeding on probing, probing pocket depth and the clinical attachment level, in all the sites were recorded. Untreated disease sites exhibited higher cytokine levels in the GCF when compared with the non‑disease sites. Nonsurgical periodontal therapy resulted in a statistically significant decrease in the total levels of IL‑1α, ‑1β and ‑6 in the GCF, but not in IL‑10 or TNF‑α. The results support the hypothesis that proinflammatory cytokines, including IL‑1α, IL‑1β and IL‑6, are likely to be involved in the pathogenesis of periodontitis and are good markers to evaluate the success of nonsurgical therapy in disease sites of patients with periodontitis.The study was supported by a grant from the Cooperativa de
Ensino Superior, Politécnico e Universitário (CESPU), Portugal
(no. 06‑GCD‑CICS‑09)
Transferencia de conocimiento y los retos de la formación de ingenieros ante la globalización.
La transferencia de conocimiento es una máxima en la sociedad contemporánea. Ante este fenómeno, impulsado por la globalización neoliberal, se le impone a las instituciones de educación universitaria cambios radicales que apuntan a adecuar los planes de estudio a los requerimientos de la aldea global. La formación de ingenieros no puede situarse al margen de estas perspectivas curriculares, pero ha de imponer una visión humanista al quehacer cientÃfico y tecnológico. El presente trabajo se inscribe en la ruta de fortalecer la ética y la crÃtica en la formación de ingenieros
Perspectives in anaerobic digestion of lipid-rich wastewater
Lipid-rich wastewaters are ideal sources for methane production, but lipids are generally separated
and removed prior to anaerobic treatment to avoid sludge flotation and microbial inhibition. In this
work, we review the major technological and microbiological advances in the anaerobic digestion
(AD) of lipids, while highlighting the most important breakthroughs in the field and identifying the
future perspectives. In the past decades, several treatment processes have been developed for lipidrich
wastewaters, moving from the upflow granular sludge based reactor designs to anaerobic
membrane bioreactors and in situ flotation based bioreactors all now commercially available.
Knowledge on the complexity of microbial communities and microbial interactions has increased
greatly, allowing a better interpretation of lipids anaerobic biodegradation. However, there are still
knowledge gaps and bottlenecks in lipids AD that need to be overcome to improve industrial
applications. A multi-faceted approach with industrial and academic partners will provide a unique
strategy for future widespread usage of waste-lipids as valuable resource for AD.The authors acknowledge the funding from EPA Research (Ireland), the Irish Dairy Processing Technology Centre, The Irish
Research Council (EBPS2012) and the Microbiology Society; the Portuguese Foundation for Science and Technology (FCT) under the
scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684), of Project
RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462), POCI-01-0145-FEDER-007679 (UID/CTM/50011/2013), and by
BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of
Norte2020 - Programa Operacional Regional do Norte. The authors also acknowledge the financial support of the European Research
Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement no. 323009 and the
funding of ANII-Uruguay, UNESCO-IHE and LATU (Uruguay).info:eu-repo/semantics/publishedVersio
The Glycobiome of the Rumen Bacterium Butyrivibrio proteoclasticus B316T Highlights Adaptation to a Polysaccharide-Rich Environment
Determining the role of rumen microbes and their enzymes in plant polysaccharide breakdown is fundamental to understanding digestion and maximising productivity in ruminant animals. Butyrivibrio proteoclasticus B316T is a Gram-positive, butyrate-forming rumen bacterium with a key role in plant polysaccharide degradation. The 4.4Mb genome consists of 4 replicons; a chromosome, a chromid and two megaplasmids. The chromid is the smallest reported for all bacteria, and the first identified from the phylum Firmicutes. B316 devotes a large proportion of its genome to the breakdown and reassembly of complex polysaccharides and has a highly developed glycobiome when compared to other sequenced bacteria. The secretion of a range of polysaccharide-degrading enzymes which initiate the breakdown of pectin, starch and xylan, a subtilisin family protease active against plant proteins, and diverse intracellular enzymes to break down oligosaccharides constitute the degradative capability of this organism. A prominent feature of the genome is the presence of multiple gene clusters predicted to be involved in polysaccharide biosynthesis. Metabolic reconstruction reveals the absence of an identifiable gene for enolase, a conserved enzyme of the glycolytic pathway. To our knowledge this is the first report of an organism lacking an enolase. Our analysis of the B316 genome shows how one organism can contribute to the multi-organism complex that rapidly breaks down plant material in the rumen. It can be concluded that B316, and similar organisms with broad polysaccharide-degrading capability, are well suited to being early colonizers and degraders of plant polysaccharides in the rumen environment
The Genome Sequence of the Rumen Methanogen Methanobrevibacter ruminantium Reveals New Possibilities for Controlling Ruminant Methane Emissions
BACKGROUND: Methane (CH(4)) is a potent greenhouse gas (GHG), having a global warming potential 21 times that of carbon dioxide (CO(2)). Methane emissions from agriculture represent around 40% of the emissions produced by human-related activities, the single largest source being enteric fermentation, mainly in ruminant livestock. Technologies to reduce these emissions are lacking. Ruminant methane is formed by the action of methanogenic archaea typified by Methanobrevibacter ruminantium, which is present in ruminants fed a wide variety of diets worldwide. To gain more insight into the lifestyle of a rumen methanogen, and to identify genes and proteins that can be targeted to reduce methane production, we have sequenced the 2.93 Mb genome of M. ruminantium M1, the first rumen methanogen genome to be completed. METHODOLOGY/PRINCIPAL FINDINGS: The M1 genome was sequenced, annotated and subjected to comparative genomic and metabolic pathway analyses. Conserved and methanogen-specific gene sets suitable as targets for vaccine development or chemogenomic-based inhibition of rumen methanogens were identified. The feasibility of using a synthetic peptide-directed vaccinology approach to target epitopes of methanogen surface proteins was demonstrated. A prophage genome was described and its lytic enzyme, endoisopeptidase PeiR, was shown to lyse M1 cells in pure culture. A predicted stimulation of M1 growth by alcohols was demonstrated and microarray analyses indicated up-regulation of methanogenesis genes during co-culture with a hydrogen (H(2)) producing rumen bacterium. We also report the discovery of non-ribosomal peptide synthetases in M. ruminantium M1, the first reported in archaeal species. CONCLUSIONS/SIGNIFICANCE: The M1 genome sequence provides new insights into the lifestyle and cellular processes of this important rumen methanogen. It also defines vaccine and chemogenomic targets for broad inhibition of rumen methanogens and represents a significant contribution to worldwide efforts to mitigate ruminant methane emissions and reduce production of anthropogenic greenhouse gases
Cytokines and Inflammatory Mediators in Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by a breakdown in immune tolerance that induces an attack on normal tissues by the immune system. The dysfunction within both the innate and adaptive immune systems increases cytokine production, B lymphocytic overproduction of autoantibodies, and T lymphocyte activity. Cytokines and inflammatory mediators have been associated with several clinical endpoints, including the activity of disease and outcomes. In fact, some of them have been associated with different clinical subphenotypes (e.g., lupus nephritis), suggesting their role as biomarkers, and, in some cases, therapeutic targets. Thus, knowledge of the pathophysiological processes associated with the development of SLE could aid in setting up better diagnostic and therapeutic approaches to reduce the high burden of disease, and thus improve quality of life and outcomes. Herein, the authors have compiled a concise review of the clinically relevant cytokines and inflammatory mediators associated with SLE and its manifestations
Convenient genotyping of nine bovine K-casein variants
K-casein gene polymorphisms are of major importance in the dairy
industry due to their association with different quality and productive
traits (i.e., milk protein). Several methods for genotyping this gene
have been proposed; however, none are focused on the simultaneous
discrimination of nine K-casein variants. A strategy based on PCR-RFLP
was designed to characterize nine K-casein variants (A, B, C, E, F2, G,
H, I and J) and used to genotype three cattle populations: Gyrholando
(3/8 Gyr x 5/8 Holstein), Charolais and Carora. The B variant was the
most frequent in the Charolais and Carora breeds, with allelic
frequencies of 0.60 and 0.59, respectively. In the Gyrholando breed,
four variants were found, with the A variant being the most frequent
and E and H the least. The genotyping strategy was effective in
detection and differentiation of K-casein variants, and it is proposed
for use in laboratories with minimal molecular biology equipment for
genotyping and evaluation of the phenotypic effects of nine K-casein
variants on milk production and quality
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