Role of microbes in the Ria Formosa lagoon

With the development of epifluorescence microscopy and sensitive radioisotope techniques, high abundance and activity of microorganisms was observed in marine waters since 1970s and 1980s. These observations resulted in a new concept of rapid turn-over and recycling of organic matter through a ‘microbial loop’ (Azam et al., 1983; Azam, 1998). Figure 5.1 illustrates fluxes of material through the marine microbial loop. Main processes are C fixation by photosynthetic microorganisms (prokaryotic and eukaryotic) with exudation losses of Dissolved Organic Matter (DOM), which is incorporated by heterotrophic bacteria. Phagotrophic protists in turn graze both autotrophs and bacteria producing ‘sloppy feeding’ loss of DOM, which returns to the loop. DOM is remineralized by all microorganisms into Dissolved Inorganic Nutrients (DIN), which are taken up by autotrophic and heterotrophic microorganisms.EU contract EVK3-CT1999-00002info:eu-repo/semantics/publishedVersio

Zika Virus Prevention Behaviors and Knowledge Among Male Partners of Pregnant People and Lack of Condom Use as a Prevention Behavior From the Zika en Embarazadas Y Niños (Zen) Prospective Cohort Study, Colombia

Objective: Zika virus (ZIKV) infection in pregnancy can cause brain and eye abnormalities and neurodevelopmental sequelae. In the absence of medical countermeasures, behavioral interventions were recommended to prevent mosquito bites and sexual transmission of ZIKV. This report uses data from the Zika en Embarazadas y Niños (ZEN) prospective cohort study in Colombia to describe the knowledge, attitudes, and behaviors (KAB) related to ZIKV prevention in male partners compared to those of their pregnant partners at study enrollment during February 2017-2018. Results: Most male partners reported wearing protective clothing such as long pants (97.6%) and long sleeves (72.8%), as well as covering ankles and feet (89.1%) to prevent ZIKV infection. When comparing the preventive behavior of condom use between male and pregnant partners, 26 pairs (10.0%) both responded that they performed the behavior. Overall, 25.1% of male partners and 18.9% of pregnant people reported any condom use during the three months before enrolling in ZEN. When comparing other preventive behaviors between male and pregnant partners, the behavior which was most frequently reported by both partners was wearing long pants (85.4%), and the least frequently reported by both partners was using condoms after finding out about a partner\u27s pregnancy (3.4%)

Genetic determination of the effect of post-translational modification on the innate immune response to the 19 kDa lipoprotein of Mycobacterium tuberculosis

<p>Abstract</p> <p>Background</p> <p>The 19 kDa lipoprotein of <it>Mycobacterium tuberculosis </it>(MTB) is an important target of the innate immune response. To investigate the effect of post-translation modification of this protein on innate recognition in the context of the whole bacillus, we derived a recombinant <it>M. tuberculosis </it>H37Rv that lacked the 19 kDa gene (Δ19) and complemented this strain by reintroduction of the 19 kDa gene into the chromosome as a single copy to produce Δ19::19. We also reintroduced the 19 kDa gene in two modified forms that lacked motifs for acylation (Δ19::19NA) and <it>O</it>-glycosylation (Δ19::19NOG).</p> <p>Results</p> <p>Both acylation and <it>O</it>-glycosylation were necessary for the protein to remain within the cell. IL-1 Beta secretion from human monocytes was significantly reduced by deletion of the 19 kDa gene (p < 0.02). Complementation by the wild type, but not the mutagenised gene reversed this phenotype. The effect of deletion and complementation on IL-12p40 and TNF secretion was less marked with no statistically significant differences between strains. Although deletion of the 19 kDa reduced apoptosis, an effect that could also only be reversed by complementation with the wild type gene, the results were variable between donors and did not achieve statistical significance.</p> <p>Conclusion</p> <p>These results confirm in the context of the whole bacillus an important role for post-translational modification of the 19 kDa on both the cellular location and immune response to this protein.</p

An ecotoxicological analysis of the sediment quality in a European Atlantic harbor emphasizes the current limitations of the Water Framework Directive

The "PortoNovo" project was developed to standardize the methodologies for water quality management in the port areas of coastal Atlantic regions to improve the Water Frame Directive (WFD) for these specific water bodies. Under this scope, water and sediment samples were collected from five sites within the Port of Aveiro, Portugal. According to the physical and chemical parameters that were analyzed (i.e., metals, total organic carbon, polychlorinated biphenyls and polycyclic aromatic hydrocarbons), the sediments were not considered at risk based on European sediment quality laws. However, the bioassays that were performed on the sediment samples (Microtox®) and the standardized acute toxicity test using the marine rotifer, Brachionus plicatilis, on sediment elutriates revealed higher toxicity levels. The use of bioassays to assess sediment quality clearly complements more conservative approaches and highlights current gaps within the WFD. The approach presented here can be easily transferred to other port areas for more reliable water quality management

Dorsal Periaqueductal gray ensembles represent approach and avoidance states

Animals must balance needs to approach threats for risk assessment and to avoid danger. The dorsal periaqueductal gray (dPAG) controls defensive behaviors, but it is unknown how it represents states associated with threat approach and avoidance. We identified a dPAG threatavoidance ensemble in mice that showed higher activity farther from threats such as the open arms of the elevated plus maze and a predator. These cells were also more active during threat avoidance behaviors such as escape and freezing, even though these behaviors have antagonistic motor output. Conversely, the threat approach ensemble was more active during risk assessment behaviors and near threats. Furthermore, unsupervised methods showed that avoidance/approach states were encoded with shared activity patterns across threats. Lastly, the relative number of cells in each ensemble predicted threat avoidance across mice. Thus, dPAG ensembles dynamically encode threat approach and avoidance states, providing a flexible mechanism to balance risk assessment and danger avoidance

Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion.

Mycobacterium tuberculosis (MTB) remains a major challenge to global health made worse by the spread of multidrug resistance. We therefore examined whether stimulating intracellular killing of mycobacteria through pharmacological enhancement of macroautophagy might provide a novel therapeutic strategy. Despite the resistance of MTB to killing by basal autophagy, cell-based screening of FDA-approved drugs revealed two anticonvulsants, carbamazepine and valproic acid, that were able to stimulate autophagic killing of intracellular M. tuberculosis within primary human macrophages at concentrations achievable in humans. Using a zebrafish model, we show that carbamazepine can stimulate autophagy in vivo and enhance clearance of M. marinum, while in mice infected with a highly virulent multidrug-resistant MTB strain, carbamazepine treatment reduced bacterial burden, improved lung pathology and stimulated adaptive immunity. We show that carbamazepine induces antimicrobial autophagy through a novel, evolutionarily conserved, mTOR-independent pathway controlled by cellular depletion of myo-inositol. While strain-specific differences in susceptibility to in vivo carbamazepine treatment may exist, autophagy enhancement by repurposed drugs provides an easily implementable potential therapy for the treatment of multidrug-resistant mycobacterial infection

Childhood tuberculosis is associated with decreased abundance of T cell gene transcripts and impaired T cell function

The WHO estimates around a million children contract tuberculosis (TB) annually with over 80 000 deaths from dissemination of infection outside of the lungs. The insidious onset and association with skin test anergy suggests failure of the immune system to both recognise and respond to infection. To understand the immune mechanisms, we studied genome-wide whole blood RNA expression in children with TB meningitis (TBM). Findings were validated in a second cohort of children with TBM and pulmonary TB (PTB), and functional T-cell responses studied in a third cohort of children with TBM, other extrapulmonary TB (EPTB) and PTB. The predominant RNA transcriptional response in children with TBM was decreased abundance of multiple genes, with 140/204 (68%) of all differentially regulated genes showing reduced abundance compared to healthy controls. Findings were validated in a second cohort with concordance of the direction of differential expression in both TBM (r2 = 0.78 p = 2x10-16) and PTB patients (r2 = 0.71 p = 2x10-16) when compared to a second group of healthy controls. Although the direction of expression of these significant genes was similar in the PTB patients, the magnitude of differential transcript abundance was less in PTB than in TBM. The majority of genes were involved in activation of leucocytes (p = 2.67E-11) and T-cell receptor signalling (p = 6.56E-07). Less abundant gene expression in immune cells was associated with a functional defect in T-cell proliferation that recovered after full TB treatment (p<0.0003). Multiple genes involved in T-cell activation show decreased abundance in children with acute TB, who also have impaired functional T-cell responses. Our data suggest that childhood TB is associated with an acquired immune defect, potentially resulting in failure to contain the pathogen. Elucidation of the mechanism causing the immune paresis may identify new treatment and prevention strategies

Symptom increase following a functional capacity evaluation in patients with chronic low back pain:An explorative study of safety

Introduction: This study was performed to study intensity and duration of symptom increase following an FCE and to explore safety of an FCE. Methods: Included were 92 patients with chronic low back pain (CLBP), mean age 38.5 years, mean self-reported disability 12.5 (Roland Morris Disability Questionnaire). All patients underwent an FCE. Symptom increase was measured with a 2-item questionnaire. Operational definition for safety: no formal complaint filed and symptom increase to occur only temporarily. Results: No formal complaints were filed (n=92). In total, 54 patients returned the questionnaire (59%; 'responders'). Of the responders, 76% reported increased symptom intensity after an FCE, ranging from 'little increase' to 'severe increase'. Symptoms of all responders returned to pre-FCE level. Duration of symptom increase of the responders ranged from 1 day to 3 weeks. Symptom increase resided to pre-FCE level within 1 week in 93% of the responders. Symptom increase was weakly related to self-reported disability (r=0.38, p <0.05). Except for gender, differences between responders and non-responders were non-significant. Conclusion: A temporary increase in symptom intensity following an FCE is common. Within the operational definitions of safety used in this study, assessment of functional capacity of patients with CLBP appears safe

The association between clinical integration of care and transfer of veterans with acute coronary syndromes from primary care VHA hospitals

BACKGROUND: Few studies report on the effect of organizational factors facilitating transfer between primary and tertiary care hospitals either within an integrated health care system or outside it. In this paper, we report on the relationship between degree of clinical integration of cardiology services and transfer rates of acute coronary syndrome (ACS) patients from primary to tertiary hospitals within and outside the Veterans Health Administration (VHA) system. METHODS: Prospective cohort study. Transfer rates were obtained for all patients with ACS diagnoses admitted to 12 primary VHA hospitals between 1998 and 1999. Binary variables measuring clinical integration were constructed for each primary VHA hospital reflecting: presence of on-site VHA cardiologist; referral coordinator at the associated tertiary VHA hospital; and/or referral coordinator at the primary VHA hospital. We assessed the association between the integration variables and overall transfer from primary to tertiary hospitals, using random effects logistic regression, controlling for clustering at two levels and adjusting for patient characteristics. RESULTS: Three of twelve hospitals had a VHA cardiologist on site, six had a referral coordinator at the tertiary VHA hospital, and four had a referral coordinator at the primary hospital. Presence of a VHA staff cardiologist on site and a referral coordinator at the tertiary VHA hospital decreased the likelihood of any transfer (OR 0.45, 95% CI 0.27–0.77, and 0.46, p = 0.002, CI 0.27–0.78). Conversely, having a referral coordinator at the primary VHA hospital increased the likelihood of transfer (OR 6.28, CI 2.92–13.48). CONCLUSIONS: Elements of clinical integration are associated with transfer, an important process in the care of ACS patients. In promoting optimal patient care, clinical integration factors should be considered in addition to patient characteristics

USP18-Based Negative Feedback Control Is Induced by Type I and Type III Interferons and Specifically Inactivates Interferon α Response

Type I interferons (IFN) are cytokines that are rapidly secreted upon microbial infections and regulate all aspects of the immune response. In humans 15 type I IFN subtypes exist, of which IFN α2 and IFN β are used in the clinic for treatment of different pathologies. IFN α2 and IFN β are non redundant in their expression and in their potency to exert specific bioactivities. The more recently identified type III IFNs (3 IFN λ or IL-28/IL-29) bind an unrelated cell-type restricted receptor. Downstream of these two receptor complexes is a shared Jak/Stat pathway. Several mechanisms that contribute to the shut down of the IFN-induced signaling have been described at the molecular level. In particular, it has long been known that type I IFN induces the establishment of a desensitized state. In this work we asked how the IFN-induced desensitization integrates into the network built by the multiple type I IFN subtypes and type III IFNs. We show that priming of cells with either type I IFN or type III IFN interferes with the cell's ability to further respond to all IFN α subtypes. Importantly, primed cells are differentially desensitized in that they retain sensitivity to IFN β. We show that USP18 is necessary and sufficient to induce differential desensitization, by impairing the formation of functional binding sites for IFN α2. Our data highlight a new type of differential between IFNs α and IFN β and underline a cross-talk between type I and type III IFN. This cross-talk could shed light on the reported genetic variation in the IFN λ loci, which has been associated with persistence of hepatitis C virus and patient's response to IFN α2 therapy