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The dnt pathway of Burkholderia sp. R34 is in the midst of an evolutionary journey from its ancestral, natural substrate (naphthalene) towards a new xenobiotic one [2,4-dinitrotoluene (DNT)]. The gene cluster encoding the leading multicomponent ring dioxygenase (DntA) has activity on the old and the new substrate, but it is induced by neither. Instead, the transcriptional factor encoded by the adjacent gene (dntR) activates expression of the dnt cluster upon addition of salicylate, one degradation intermediate of the ancestral naphthalene route but not any longer a substrate/product of the evolved DntA enzyme. Fluorescence of cells bearing dntA-gfp fusions revealed that induction of the dnt genes by salicylate was enhanced upon exposure to bona fide DntA substrates, i.e., naphthalene or DNT. Such amplification was dependent on effective dioxygenation of these pathway-specific head compounds, which thereby fostered expression of the cognate catabolic operon. The phenomenon seems to happen not through direct binding to a cognate transcriptional factor but through the interplay of a non-specific regulator with a substrate-specific enzyme. This regulatory scenario may ease transition of complete catabolic operons (i.e. enzymes plus regulatory devices) from one substrate to another without loss of fitness during the evolutionary roadmap between two optimal specificities.In recent years, multicomponent reactions with inorganic and organic sulfur compounds as one of reactants have achieved a remarkable development. In this review, we summarize recent advances in the multicomponent reactions involving sulfur components, which include elemental sulfur, sodium metabisulfite, sodium hyposulfite, potassium pyrosulfite, DABSO, sodium sulfide, thiocyanate, sulfur dioxide, carbon disulfide and other divalent, tetravalent and hexavalent organosulfur compounds.Senescence phenotypes and mitochondrial dysfunction are implicated in aging and in premature aging diseases, including ataxia telangiectasia (A-T). Loss of mitochondrial function can drive age-related decline in the brain, but little is known about whether improving mitochondrial homeostasis alleviates senescence phenotypes. We demonstrate here that mitochondrial dysfunction and cellular senescence with a senescence-associated secretory phenotype (SASP) occur in A-T patient fibroblasts, and in ATM-deficient cells and mice. Senescence is mediated by stimulator of interferon genes (STING) and involves ectopic cytoplasmic DNA. learn more We further show that boosting intracellular NAD+ levels with nicotinamide riboside (NR) prevents senescence and SASP by promoting mitophagy in a PINK1-dependent manner. NR treatment also prevents neurodegeneration, suppresses senescence and neuroinflammation, and improves motor function in Atm-/- mice. Our findings suggest a central role for mitochondrial dysfunction-induced senescence in A-T pathogenesis, and that enhancing mitophagy as a potential therapeutic intervention.Forest-to-pasture conversion is known to cause global losses in plant and animal diversity, yet impacts of livestock management after such conversion on vital microbial communities in adjoining natural ecosystems remain poorly understood. We examined how pastoral land management practices impact soil microorganisms in adjacent native forest fragments, by comparing bacterial communities sampled along 21 transects bisecting pasture-forest boundaries. Our results revealed greater bacterial taxon richness in grazed pasture soils and the reduced dispersal of pasture-associated taxa into adjacent forest soils when land uses were separated by a boundary fence. Relative abundance distributions of forest-associated taxa (i.e., Proteobacteria and Nitrospirae) and a pasture-associated taxon (i.e., Firmicutes) also suggest a greater impact of pastoral land uses on forest fragment soil bacterial communities when no fence is present. Bacterial community richness and composition were most related to changes in soil physicochemical variables commonly associated with agricultural fertilization, including concentrations of Olsen P, total P, total Cd, delta 15 N and the ratio of CP and NP. Overall, our findings demonstrate clear, and potentially detrimental effects of agricultural disturbance on bacterial communities in forest soils adjacent to pastoral land. We provide evidence that simple land management decisions, such as livestock exclusion, can mitigate the effects of agriculture on adjacent soil microbial communities.Microbial communities exhibit spatial structure at different scales, due to constant interactions with their environment and dispersal limitation. While this spatial structure is often considered in studies focusing on free-living environmental communities, it has received less attention in the context of host-associated microbial communities or microbiota. The wider adoption of methods accounting for spatial variation in these communities will help to address open questions in basic microbial ecology as well as realize the full potential of microbiome-aided medicine. Here, we first overview known factors affecting the composition of microbiota across diverse host types and at different scales, with a focus on the human gut as one of the most actively studied microbiota. We outline a number of topical open questions in the field related to spatial variation and patterns. We then review the existing methodology for the spatial modelling of microbiota. We suggest that methodology from related fields, such as systems biology and macro-organismal ecology, could be adapted to obtain more accurate models of spatial structure. We further posit that methodological developments in the spatial modelling and analysis of microbiota could in turn broadly benefit theoretical and applied ecology and contribute to the development of novel industrial and clinical applications.

Rotator cuff related shoulder pain (RCRSP) knowledge is an important contributor to compliance with clinical practice guidelines and providing best practice care. However, there are no validated instruments for measuring health literacy levels among people with RCRSP. This study aimed to design a valid and reliable instrument to measure RCRSP health literacy and use it to evaluate an education intervention for people with RCRSP.

Development of the patient knowledge questionnaire (PKQ-RCRSP) included three phases. Phase 1 was developed based on available literature and input from expert clinicians, researchers and patients. Face validity, pilot testing andreadability assessment were also undertaken. In Phase 2, internal consistency and predictive validity were assessed in people with RCRSP and other shoulder pain diagnoses. In Phase 3, RCRSP health literacy was assessed.

Face validity was acceptable and pilot testing identified minor accuracy issues that were corrected. Literacy level was rated as 'difficult to read' which reflects the medical terminology within the questionnaire.

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