77,639 research outputs found

    Application of lactic acid bacteria for the biopreservation of meat products: A systematic review

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    .The increasing concern of consumers about food quality and safety and their rejection of chemical additives has promoted the breakthrough of the biopreservation field and the development of studies on the use of beneficial bacteria and their metabolites as potential natural antimicrobials for shelf life extension and enhanced food safety. Control of foodborne pathogens in meat and meat products represents a serious challenge for the food industry which can be addressed through the intelligent use of bio-compounds or biopreservatives. This article aims to systematically review the available knowledge about biological strategies based on the use of lactic acid bacteria to control the proliferation of undesirable microorganisms in different meat products. The outcome of the literature search evidenced the potential of several strains of lactic acid bacteria and their purified or semi-purified antimicrobial metabolites as biopreservatives in meat products for achieving longer shelf life or inhibiting spoilage and pathogenic bacteria, especially when combined with other technologies to achieve a synergistic effect.S

    Uso de las histonas circulantes y sus modificaciones post-traduccionales como biomarcadores en sepsis y shock s茅ptico

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    La sepsis es una afecci贸n potencialmente mortal causada por una respuesta anormal del hu茅sped a una infecci贸n, produciendo respuestas fisiol贸gicas alteradas que da帽an los propios tejidos del paciente y pueden provocar disfunci贸n org谩nica e incluso la muerte. Asimismo, algunos pacientes s茅pticos progresan a shock s茅ptico, caracterizado por alteraciones circulatorias, celulares y metab贸licas sustanciales que aumentan el riesgo de mortalidad. A pesar de que la sepsis se caracteriza por un mal funcionamiento del sistema inmunol贸gico, lo que a su vez conduce a una respuesta inmune alterada e inmunosupresi贸n, la alta complejidad de la fisiopatolog铆a de la sepsis requiere una mayor investigaci贸n para comprender las respuestas inmunes que ocurren durante la sepsis. Asimismo, las histonas extracelulares circulantes han ganado relevancia como mediadores citot贸xicos en la sepsis, ya que act煤an como patrones moleculares asociados a da帽o, que inducen estr茅s oxidativo y activan el inflamasoma NLRP3. Estos mecanismos median la activaci贸n de la piroptosis, un mecanismo de muerte celular programada que produce inflamaci贸n mediante la expresi贸n de IL-18, IL-1尾 and IL-1伪. Sin embargo, a pesar de la evidencia de activaci贸n del inflamasoma en las c茅lulas inmunes durante la sepsis, se desconoce si las histonas extracelulares son capaces de activar los inflamasomas endoteliales y sus consecuencias. En este trabajo destacamos el papel previamente desconocido de las histonas extracelulares, mediando la activaci贸n del inflamasoma NLRP3 y la piroptosis en las c茅lulas endoteliales, contribuyendo a la disfunci贸n endotelial y la desregulaci贸n de la respuesta inmune mediada por el endotelio. Asimismo, tambi茅n demostramos c贸mo la acetilaci贸n de histonas disminuye la activaci贸n de la piroptosis. Adem谩s, demostramos que la piroptosis se produce en pacientes con shock s茅ptico y los niveles de histonas circulantes se correlacionan con la expresi贸n de citoquinas proinflamatorias y citoquinas piropt贸ticas, la liberaci贸n de factores de adhesi贸n endotelial y la gravedad de la enfermedad. Proponemos la piroptosis mediada por histonas como un nuevo objetivo para desarrollar intervenciones cl铆nicas. De manera similar, hemos analizado las respuestas inmunorelacionadas que ocurren durante las primeras etapas de la sepsis con el objetivo de proporcionar nuevos datos comparando las cantidades de citoquinas, inmunomoduladores y otros mediadores endoteliales en pacientes cr铆ticamente enfermos no s茅pticos, s茅pticos y de shock s茅ptico. Nuestro enfoque ayudar谩 a caracterizar r谩pidamente las respuestas inmunes alteradas en pacientes s茅pticos y de shock s茅ptico ingresados en la Unidad de Cuidados Intensivos. Finalmente analizamos el papel de la metilaci贸n del ADN en el control del sistema inmune s茅ptico. Nuestros resultados demostraron el papel central de la metilaci贸n del ADN modulando la respuesta molecular en los pacientes de shock s茅ptico y contribuyendo a la inmunosupresi贸n, a trav茅s de la alteraci贸n de los patrones de metilaci贸n de los promotores de IL-10 y TREM-2.Sepsis is a life-threatening condition caused by an abnormal host response to an infection that produce altered physiological responses which damages own tissues of the patient and can result in organ dysfunction and in some cases death. Likewise, a subset of septic patients progresses to septic shock, characterized by substantial circulatory, cellular and metabolic abnormalities, which substantially increase the risk of mortality. Sepsis is characterized by a malfunction of the immune system and it can lead to an altered immune response and immunosuppression. Moreover, the high complexity of the pathophysiology of sepsis requires of further investigation to characterize the immune responses in sepsis and septic shock. Likewise, circulating extracellular histones have gained relevance as cytotoxic mediators in sepsis pathophysiology, since they act as damage-associated molecular patterns, which induce oxidative stress and activate NLRP3 inflammasome. Subsequently, inflammasome mediates pyroptosis activation, a programmed cell death mechanism that produces inflammation through the release of IL-18, IL-1尾 and IL-1伪. However, despite inflammasome activation may occur in immune cells during sepsis, it is unknown if this process also takes place in endothelial cells and particularly whether extracellular histones are capable of activating endothelial inflammasomes and their consequences. In this work we highlight a previously unknown role for extracellular histones, that mediates the activation of NLRP3 inflammasome and pyroptosis in endothelial cells by contributing to endothelial dysfunction and the dysregulation of the immune response mediated by endothelium. Likewise, we demonstrated how histone acetylation decreases pyroptosis activation. Furthermore, we show how pyroptosis occurs in septic shock patients and how circulating histone levels correlate with the expression of pro-inflammatory and pyroptotic cytokines, the release of endothelial adhesion factors and septic shock severity. We propose histone-mediated pyroptosis as a new target to develop clinical interventions. Similarly, we have analyzed the immune-related responses occurring during the early stages of sepsis with the aim of providing new data by comparing the amounts of cytokines, immune modulators and other endothelial mediators in critically-ill non-septic patients, septic and septic shock patients. Our approach will help to rapidly characterize the altered immune responses in septic and septic shock patients admitted in the Intensive Care Unit. Finally, we also analyzed the role of DNA methylation in the control of septic immune system. Our results demonstrated the central role of DNA methylation modulating the molecular response in septic shock patients and contributing to immunosuppression, through the alteration of DNA methylation patterns of IL-10 and TREM2 promoters

    Metabolic phenotyping of opioid and psychostimulant addiction: A novel approach for biomarker discovery and biochemical understanding of the disorder.

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    Despite the progress in characterising the pharmacological profile of drugs of abuse, their precise biochemical impact remains unclear. The metabolome reflects the multifaceted biochemical processes occurring within a biological system. This includes those encoded in the genome but also those arising from environmental/exogenous exposures and interactions between the two. Using metabolomics, the biochemical derangements associated with substance abuse can be determined as the individual transitions from recreational drug to chronic use (dependence). By understanding the biomolecular perturbations along this time course and how they vary across individuals, metabolomics can elucidate biochemical mechanisms of the addiction cycle (dependence/withdrawal/relapse) and predict prognosis (recovery/relapse). In this review, we summarise human and animal metabolomic studies in the field of opioid and psychostimulant addiction. We highlight the importance of metabolomics as a powerful approach for biomarker discovery and its potential to guide personalised pharmacotherapeutic strategies for addiction targeted towards the individual's metabolome

    Genome-wide identification of the genetic basis of amyotrophic lateral sclerosis

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    Amyotrophic lateral sclerosis (ALS) is a complex disease that leads to motor neuron death. Despite heritability estimates of 52%, genome-wide association studies (GWASs) have discovered relatively few loci. We developed a machine learning approach called RefMap, which integrates functional genomics with GWAS summary statistics for gene discovery. With transcriptomic and epigenetic profiling of motor neurons derived from induced pluripotent stem cells (iPSCs), RefMap identified 690 ALS-associated genes that represent a 5-fold increase in recovered heritability. Extensive conservation, transcriptome, network, and rare variant analyses demonstrated the functional significance of candidate genes in healthy and diseased motor neurons and brain tissues. Genetic convergence between common and rare variation highlighted KANK1 as a new ALS gene. Reproducing KANK1 patient mutations in human neurons led to neurotoxicity and demonstrated that TDP-43 mislocalization, a hallmark pathology of ALS, is downstream of axonal dysfunction. RefMap can be readily applied to other complex diseases

    Facile cellulase immobilisation on bioinspired silica

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    Cellulases are enzymes with great potential for converting biomass to biofuels for sustainable energy. However, their commercial use is limited by their costs and low reusability. Therefore, the scientific and industrial sectors are focusing on finding better strategies to reuse enzymes and improve their performance. In this work, cellulase from Aspergillus niger was immobilised through in situ entrapment and adsorption on bio-inspired silica (BIS) supports. To the best of our knowledge, this green effect strategy has never been applied for cellulase into BIS. In situ entrapment was performed during support synthesis, applying a one-pot approach at mild conditions (room temperature, pH 7, and water solvent), while adsorption was performed after support formation. The loading efficiency was investigated on different immobilisation systems by Bradford assay and FTIR. Bovine serum albumin (BSA) was chosen as a control to optimize cellulase loading. The residual activity of cellulase was analysed by the dinitro salicylic acid (DNS) method. Activity of 90% was observed for the entrapped enzyme, while activity of ~55% was observed for the adsorbed enzyme. Moreover, the supported enzyme systems were recycled five times to evaluate their reuse potential. The thermal and pH stability tests suggested that both entrapment and adsorption strategies can increase enzyme activity. The results highlight that the entrapment in BIS is a potentially useful strategy to easily immobilise enzymes, while preserving their stability and recycle potential

    Investigating the potential role for RBMY in cancer

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    Introduction: Head and neck squamous cell carcinoma (HNSCC), is a major healthcare concern with a high male prevalence. We hypothesise that the testis specific mRNA splicing regulator, Y-linked RBMY gene, is aberrantly expressed in HNSCC in part promoting HNSCC through ZFY-short splicing. RBMY has been shown to enhance tumour development in male hepatocellular carcinoma (human tissue specimens and transgenic-mouse models) whilst ZFY-short is predicted to have anti-apoptotic properties and the deletion of RBMY locus on Y-chromosome resulted in lowered ZFY-short expression. Thus, we hypothesize that ZFY-short is generated by RBMY and exerts its anti-apoptotic effects to promote male HNSCC. Methods: Due to the coronavirus lockdown, bench work was restricted to 6 months, therefore, I conducted an extended analysis of RBMY expression in human cancer, including a computational analysis of RBMY gene expression with data from the cBioPortal database. In my bench-work, I attempted to establish GFP- RBMY expressing cell lines and conducted fluorescence microscopy, RT- PCR and qPCR to analyse RBMY expression in HNSCC cell lines and its impact on ZFY-short expression. Results: RBMY is expressed in several cancers, with no driver mutations. RBMY has nuclear localisation and is expressed in 93-UV-147T and UM-SCC-104 cell lines (both HPV16-positive HNSCC cell lines), with increased ZFY-short expression observed in UM- SCC-104. Discussion: Despite RBMY having been shown to be an oncogene in male liver cancer, our analysis of cBioPortal data suggests this activity may be restricted to the small minority of tumours of different cancer types that express RBMY. The paralleled expression of RBMY and ZFY-short in our cell lines indicate an association. UMSCC104 cell line originates from a highly an aggressive and recurrent tumour, RBMY is associated with tumour stemness, thus it is possible that via ZFY-short, RBMY could have promoted the aggressive phenotype in this, and in other HNSCCs

    Electromethanogenesis at medium-low temperatures: Impact on performance and sources of variability

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    .In this study we aimed to understand the impact of medium鈥搇ow temperatures on the two main steps that usually comprise the electromethanogenesis (EM) process: electrothrophic hydrogenesis and hydrogenothrophic methanogenesis. Results revealed that pure CO2 could effectively be converted into a high-purity biogas (鈭90:10 CH4/CO2) at 30 掳C. However, when temperature was reduced to 15 掳C, methane richness greatly decreased (鈭40:60 CH4/CO2). This deterioration in performance was mostly attributed to a decline in methanogenic activity (represented mainly by Methanobacterium and Methanobrevibacter). In contrast, the hydrogenic activity (mostly Desulfomicrobium) did not suffer any significant decay. Results also seemed to indicate that methanogenesis, rather than hydrogenesis, is the main source of variability in EM. Increasing the temperature again to 30 掳C restored previous performance, which highlights the resilience of EM to wide temperature fluctuations (from 30 to 15 and back 30 掳C).S
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