An unusual case of peripartum cardiomyopathy manifesting with multiple thrombo-embolic phenomena

Peripartum cardiomyopathy (PPCM) is a rare form of heart failure with a reported incidence of 1 per 3000 to 1 per 4000 live births and a fatality rate of 20%–50%. Onset is usually between the last month of pregnancy and up to 5 months postpartum in previously healthy women. Although viral, autoimmune and idiopathic factors may be contributory, its etiology remains unknown. PPCM initially presents with signs and symptoms of congestive heart failure and rarely with thrombo-embolic complications. We report an unusual case of PPCM in a previously healthy postpartum woman who presented with an acute abdomen due to unrecognized thromboemboli of the abdominal organs. This case illustrates that abdominal pain in PPCM may not always result from hepatic congestion as previously reported, but may occur as a result of thromboemboli to abdominal organs. Further research is needed to determine the true incidence of thromboemboli in PPCM

On the Quantum Theory of Molecules

Transition state theory was introduced in the 1930s to account for chemical reactions. Central to this theory is the idea of a potential energy surface (PES). It was assumed that such a surface could be constructed using eigensolutions of the Schr\"{o}dinger equation for the molecular (Coulomb) Hamiltonian but at that time such calculations were not possible. Nowadays quantum mechanical ab-initio electronic structure calculations are routine and from their results PESs can be constructed which are believed to approximate those assumed derivable from the eigensolutions. It is argued here that this belief is unfounded. It is suggested that the potential energy surface construction is more appropriately regarded as a legitimate and effective modification of quantum mechanics for chemical purpose

Integrating ecosystem markets to co-ordinate landscape-scale public benefits from nature

Ecosystem markets are proliferating around the world in response to increasing demand for climate change mitigation and provision of other public goods. However, this may lead to perverse outcomes, for example where public funding crowds out private investment or different schemes create trade-offs between the ecosystem services they each target. The integration of ecosystem markets could address some of these issues but to date there have been few attempts to do this, and there is limited understanding of either the opportunities or barriers to such integration. This paper reports on a comparative analysis of eleven ecosystem markets in operation or close to market in Europe, based on qualitative analysis of 25 interviews, scheme documentation and two focus groups. Our results indicate three distinct types of markets operating from the regional to national scale, with different modes of operation, funding and outcomes: regional ecosystem markets, national carbon markets and green finance. The typology provides new insights into the operation of ecosystem markets in practice, which may challenge traditionally held notions of Payment for Ecosystem Services. Regional ecosystem markets, in particular, represent a departure from traditional models, by using a risk-based funding model and aggregating both supply and demand to overcome issues of free-riding, ecosystem service trade-offs and land manager engagement. Central to all types of market were trusted intermediaries, brokers and platforms to aggregate supply and demand, build trust and lower transaction costs. The paper outlines six options for blending public and private funding for the provision of ecosystem services and proposes a framework for integrating national carbon markets and green finance with regional ecosystem markets. Such integration may significantly increase funding for regenerative agriculture and conservation across multiple habitats and services, whilst addressing issues of additionality and ecosystem service trade-offs between multiple schemes

A Lipid Based Antigen Delivery System Efficiently Facilitates MHC Class-I Antigen Presentation in Dendritic Cells to Stimulate CD8+ T Cells

The most effective strategy for protection against intracellular infections such as Leishmania is vaccination with live parasites. Use of recombinant proteins avoids the risks associated with live vaccines. However, due to low immunogenicity, they fail to trigger T cell responses particularly of CD8+cells requisite for persistent immunity. Previously we showed the importance of protein entrapment in cationic liposomes and MPL as adjuvant for elicitation of CD4+ and CD8+ T cell responses for longterm protection. In this study we investigated the role of cationic liposomes on maturation and antigen presentation capacity of dendritic cells (DCs). We observed that cationic liposomes were taken up very efficiently by DCs and transported to different cellular sites. DCs activated with liposomal rgp63 led to efficient presentation of antigen to specific CD4+ and CD8+ T cells. Furthermore, lymphoid CD8+ T cells from liposomal rgp63 immunized mice demonstrated better proliferative ability when co-cultured ex vivo with stimulated DCs. Addition of MPL to vaccine enhanced the antigen presentation by DCs and induced more efficient antigen specific CD8+ T cell responses when compared to free and liposomal ntigen. These liposomal formulations presented to CD8+ T cells through TAP-dependent MHC-I pathway offer new possibilities for a safe subunit vaccine

A community effort towards a knowledge-base and mathematical model of the human pathogen Salmonella Typhimurium LT2

<p>Abstract</p> <p>Background</p> <p>Metabolic reconstructions (MRs) are common denominators in systems biology and represent biochemical, genetic, and genomic (BiGG) knowledge-bases for target organisms by capturing currently available information in a consistent, structured manner. <it>Salmonella enterica </it>subspecies I serovar Typhimurium is a human pathogen, causes various diseases and its increasing antibiotic resistance poses a public health problem.</p> <p>Results</p> <p>Here, we describe a community-driven effort, in which more than 20 experts in <it>S</it>. Typhimurium biology and systems biology collaborated to reconcile and expand the <it>S</it>. Typhimurium BiGG knowledge-base. The consensus MR was obtained starting from two independently developed MRs for <it>S</it>. Typhimurium. Key results of this reconstruction jamboree include i) development and implementation of a community-based workflow for MR annotation and reconciliation; ii) incorporation of thermodynamic information; and iii) use of the consensus MR to identify potential multi-target drug therapy approaches.</p> <p>Conclusion</p> <p>Taken together, with the growing number of parallel MRs a structured, community-driven approach will be necessary to maximize quality while increasing adoption of MRs in experimental design and interpretation.</p

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

A constitutively active and uninhibitable caspase-3 zymogen efficiently induces apoptosis

The caspase-3 zymogen has essentially zero activity until it is cleaved by initiator caspases during apoptosis. However, a mutation of V266E in the dimer interface activates the protease in the absence of chain cleavage. We show that low concentrations of the pseudo-activated procaspase-3 kill mammalian cells rapidly and, importantly, this protein is not cleaved nor is it inhibited efficiently by the endogenous regulator XIAP (X-linked inhibitor of apoptosis). The 1.63 Å (1 Å = 0.1 nm) structure of the variant demonstrates that the mutation is accommodated at the dimer interface to generate an enzyme with substantially the same activity and specificity as wild-type caspase-3. Structural modelling predicts that the interface mutation prevents the intersubunit linker from binding in the dimer interface, allowing the active sites to form in the procaspase in the absence of cleavage. The direct activation of procaspase-3 through a conformational switch rather than by chain cleavage may lead to novel therapeutic strategies for inducing cell death