Towards deracemization in the absence of grinding through crystal transformation, ripening, and racemization

New insights into the obscure mechanisms of solid-state deracemization phenomena are obtained by crystal ripening experiments that, contrary to standard techniques, exclude attrition enhancement (grinding). The results point out that small particles and an initial size imbalance between the two enantiomeric crystal populations can intensify the rate of solidstate enantiomeric enrichment even in the absence of intermediate actions (e.g., grinding or thermal cycling). On this ground, a new process that creates such initial conditions is designed and exemplified for the proteinogenic glutamic acid. As a first step, racemic compound solvate (DL-glutamic acid monohydrate) crystals are completely converted to small-sized conglomerate anhydrate crystals, in the presence of larger seeds of a single chirality. After the transformation is complete and the racemization catalyst is added, the suspension contains an equal number of small-sized conglomerate crystals of both enantiomers together with the larger seeds of the preferred enantiomer. Over time, the large crystals of the preferred enantiomer tend to grow at the expense of smaller ones, which dissolve. This, combined with the fast racemization, leads to enantiomeric enrichment. The possible occurrence of enantioselective agglomeration between small and seed crystals speeds up this process by removing small crystals of the preferred enantiomer. Since most amino acids and several other pharmaceutical compounds are known to form metastable racemic hydrate crystals, it is expected that this new method is readily applicable to a variety of compounds. In addition, the process provides a technically simpler and more scalable route to enantiomeric enrichment compared to attritionenhanced deracemization, and its applicability extends to the wider pool of compounds that crystallize as racemic crystals

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Bacterial toxins from Staphylococcus aureus and Bordetella bronchiseptica predispose the horse’s respiratory tract to equine herpesvirus type 1 infection

Respiratory disease in horses is caused by a multifactorial complex of infectious agents and environmental factors. An important pathogen in horses is equine herpesvirus type 1 (EHV-1). During co-evolution with this ancient alphaherpesvirus, the horse’s respiratory tract has developed multiple antiviral barriers. However, these barriers can become compromised by environmental threats. Pollens and mycotoxins enhance mucosal susceptibility to EHV-1 by interrupting cell junctions, allowing the virus to reach its basolateral receptor. Whether bacterial toxins also play a role in this impairment has not been studied yet. Here, we evaluated the role of α-hemolysin (Hla) and adenylate cyclase (ACT), toxins derived from the facultative pathogenic bacterium Staphylococcus aureus (S. aureus) and the primary pathogen Bordetella bronchiseptica (B. bronchiseptica), respectively. Equine respiratory mucosal explants were cultured at an air–liquid interface and pretreated with these toxins, prior to EHV-1 inoculation. Morphological analysis of hematoxylin–eosin (HE)-stained sections of the explants revealed a decreased epithelial thickness upon treatment with both toxins. Additionally, the Hla toxin induced detachment of epithelial cells and a partial loss of cilia. These morphological changes were correlated with increased EHV-1 replication in the epithelium, as assessed by immunofluorescent stainings and confocal microscopy. In view of these results, we argue that the ACT and Hla toxins increase the susceptibility of the epithelium to EHV-1 by disrupting the epithelial barrier function. In conclusion, this study is the first to report that bacterial exotoxins increase the horse’s sensitivity to EHV-1 infection. Therefore, we propose that horses suffering from infection by S. aureus or B. bronchiseptica may be more susceptible to EHV-1 infection.</jats:p

Towards deracemization in the absence of grinding through crystal transformation, ripening and racemization

©2016 American Chemical Society. New insights into the obscure mechanisms of solid-state deracemization phenomena are obtained by crystal ripening experiments that, contrary to standard techniques, exclude attrition enhancement (grinding). The results point out that small particles and an initial size imbalance between the two enantiomeric crystal populations can intensify the rate of solidstate enantiomeric enrichment even in the absence of intermediate actions (e.g., grinding or thermal cycling). On this ground, a new process that creates such initial conditions is designed and exemplified for the proteinogenic glutamic acid. As a first step, racemic compound solvate (DL-glutamic acid monohydrate) crystals are completely converted to small-sized conglomerate anhydrate crystals, in the presence of larger seeds of a single chirality. After the transformation is complete and the racemization catalyst is added, the suspension contains an equal number of small-sized conglomerate crystals of both enantiomers together with the larger seeds of the preferred enantiomer. Over time, the large crystals of the preferred enantiomer tend to grow at the expense of smaller ones, which dissolve. This, combined with the fast racemization, leads to enantiomeric enrichment. The possible occurrence of enantioselective agglomeration between small and seed crystals speeds up this process by removing small crystals of the preferred enantiomer. Since most amino acids and several other pharmaceutical compounds are known to form metastable racemic hydrate crystals, it is expected that this new method is readily applicable to a variety of compounds. In addition, the process provides a technically simpler and more scalable route to enantiomeric enrichment compared to attritionenhanced deracemization, and its applicability extends to the wider pool of compounds that crystallize as racemic crystals.status: publishe

Can community-based peer support promote health literacy and reduce inequalities? A realist review

Background: Community-based peer support (CBPS) has been proposed as a potentially promising approach to improve health literacy (HL) and reduce health inequalities. Peer support, however, is described as a public health intervention in search of a theory, and as yet there are no systematic reviews exploring why or how peer support works to improve HL. Objective: To undertake a participatory realist synthesis to develop a better understanding of the potential for CBPS to promote better HL and reduce health inequalities. Data sources: Qualitative evidence syntheses, conceptual reviews and primary studies evaluating peer-support programmes; related studies that informed theoretical or contextual elements of the studies of interest were included. We conducted searches covering 1975 to October 2011 across Scopus, Global Health (including MEDLINE), ProQuest Dissertations & Theses database (PQDT) [including the Education Resources Information Center (ERIC) and Social Work Abstracts], The King’s Fund Database and Web of Knowledge, and the Institute of Development Studies supplementary strategies were used for the identification of grey literature. We developed a new approach to searching called ‘cluster searching’, which uses a variety of search techniques to identify papers or other research outputs that relate to a single study. Study eligibility criteria: Studies written in English describing CBPS research/evaluation, and related papers describing theory, were included. Study appraisal and synthesis methods: Studies were selected on the basis of relevance in the first instance. We first analysed within-programme articulation of theory and appraised for coherence. Cross-programme analysis was used to configure relationships among context, mechanisms and outcomes. Patterns were then identified and compared with theories relevant to HL and health inequalities to produce a middle-range theory. Results: The synthesis indicated that organisations, researchers and health professionals that adopt an authoritarian design for peer-support programmes risk limiting the ability of peer supporters (PSs) to exercise autonomy and use their experiential knowledge to deliver culturally tailored support. Conversely, when organisations take a negotiated approach to codesigning programmes, PSs are enabled to establish meaningful relationships with people in socially vulnerable groups. CBPS is facilitated when organisations prioritise the importance of assessing community needs; investigate root causes of poor health and well-being; allow adequate time for development of relationships and connections; value experiential cultural knowledge; and share power and control during all stages of design and implementation. The theory now needs to be empirically tested via further primary research. Limitations: Analysis and synthesis were challenged by a lack of explicit links between peer support for marginalised groups and health inequalities; explicitly stated programme theory; inconsistent reporting of context and mechanism; poor reporting of intermediate process outcomes; and the use of theories aimed at individual-level behaviour change for community-based interventions. Conclusions: Peer-support programmes have the potential to improve HL and reduce health inequalities but potential is dependent upon the surrounding equity context. More explicit empirical research is needed, which establishes clearer links between peer-supported HL and health inequalities. Study registration: This study is registered as PROSPERO CRD42012002297. Funding: The National Institute for Health Research Public Health Research programme

Myofibroblast Phenotype and Reversibility of Fibrosis in Patients With End-Stage Heart Failure

International audienc

Myofibroblast Phenotype and Reversibility of Fibrosis in Patients With End-Stage Heart Failure

BACKGROUND: Interstitial fibrosis is an important component of diastolic, and systolic, dysfunction in heart failure (HF) and depends on activation and differentiation of fibroblasts into myofibroblasts (MyoFb). Recent clinical evidence suggests that in late-stage HF, fibrosis is not reversible. OBJECTIVES: The study aims to examine the degree of differentiation of cardiac MyoFb in end-stage HF and the potential for their phenotypic reversibility. METHODS: Fibroblasts were isolated from the left ventricle of the explanted hearts of transplant recipients (ischemic and dilated cardiomyopathy), and from nonused donor hearts. Fibroblasts were maintained in culture without passaging for 4 or 8 days (treatment studies). Phenotyping included functional testing, immunostaining, and expression studies for markers of differentiation. These data were complemented with immunohistology and expression studies in tissue samples. RESULTS: Interstitial fibrosis with cross-linked collagen is prominent in HF hearts, with presence of activated MyoFbs. Tissue levels of transforming growth factor (TGF)-β1, lysyl oxidase, periostin, and osteopontin are elevated. Fibroblastic cells isolated from HF hearts are predominantly MyoFb, proliferative or nonproliferative, with mature α-smooth muscle actin stress fibers. HF MyoFb express high levels of profibrotic cytokines and the TGF-β1 pathway is activated. Inhibition of TGF-β1 receptor kinase in HF MyoFb promotes dedifferentiation of MyoFb with loss of α-smooth muscle actin and depolymerization of stress fibers, and reduces the expression of profibrotic genes and cytokines levels to non-HF levels. CONCLUSION: MyoFb in end-stage HF have a variable degree of differentiation and retain the capacity to return to a less activated state, validating the potential for developing antifibrotic therapy targeting MyoFb.status: publishe

TRY plant trait database - enhanced coverage and open access

10.1111/gcb.14904GLOBAL CHANGE BIOLOGY261119-18