Tuberculous dilated cardiomyopathy: an under-recognized entity?

BACKGROUND: Tuberculosis (TB) is a common public health problem in many parts of the world. TB is generally believed to spare these four organs-heart, skeletal muscle, thyroid and pancreas. We describe a rare case of myocardial TB diagnosed on a post-mortem cardiac biopsy. CASE PRESENTATION: Patient presented with history suggestive of congestive heart failure. We describe the clinical presentation, investigations and outcome of this case, and review the literature on the involvement of myocardium by TB. CONCLUSION: Involvement of myocardium by TB is rare. However it should be suspected as a cause of congestive heart failure in any patient with features suggestive of TB. Increasing recognition of the entity and the use of endomyocardial biopsy may help us detect more cases of this "curable" form of cardiomyopathy

Making Free Trade Fair

Philosophers have done very little work on what makes trade fair. Perhaps the most extensive discussion is Malgorzata Kurjanska and Mathias Risse’s article, “Fairness in Trade II: export subsidies and the fair trade movement.”2 In their article, Kurjanska and Risse consider the case for trade subsidies and the Fair Trade movement. They suggest that it is not permissible for developed countries to give their producers subsidies because doing so does not strike an appropriate balance between meeting the needs of the global poor and protecting domestic workers (Kurjanska and Risse, 2008: 34). Kurjanska and Risse also argue that the case for Fair Trade hinges, primarily, on whether or not it is part of the best development strategy for poor countries. They do not think Fair Trade is part of the best development strategy and, so, they believe purchasing Fair Trade certified goods is only acceptable because doing so does not constitute a large share of the market in traded goods. This chapter argues that the case against subsidies and Fair Trade Kurjanska and Risse present is much weaker than they make out. To the contrary, it argues that giving some subsidies and purchasing some Fair Trade certified goods may even be necessary to make trade fair. Section 11.2 starts by saying a few words about the normative framework Kurjanska and Risse adopt

Toward International Animal Rights

The chapter starts from the observation that while animal welfare is increasingly protected in domestic jurisdictions, animal rights are still hardly recognised, although they would serve animals better. It argues that animal rights would need to be universalised in order to deploy effects in a globalised setting. The international legal order is flexible and receptive to non-human personhood which goes with rights. Also, the historical experience with international human rights encourages the animal rights project, because it shows how similar conceptual and normative difficulties have been overcome. Animal rights would complement human rights not the least because the entrenchment of the species hierarchy as manifest in the denial of animal rights in the extreme case condones disrespect for the rights of humans themselves

Thin, fine and with sensitivity: a metamethodology of intuitions

Do philosophers use intuitions? Should philosophers use intuitions? Can philosophical methods (where intuitions are concerned) be improved upon? In order to answer these questions we need to have some idea of how we should go about answering them. I defend a way of going about methodology of intuitions: a metamethodology. I claim the following: (i) we should approach methodological questions about intuitions with a thin conception of intuitions in mind; (ii) we should carve intuitions finely; and, (iii) we should carve to a grain to which we are sensitive in our everyday philosophising. The reason is that, unless we do so, we don’t get what we want from philosophical methodology. I argue that what we want is information that will aid us in formulating practical advice concerning how to do philosophy responsibly/well/better

PCR-TTGE Analysis of 16S rRNA from Rainbow Trout (Oncorhynchus mykiss) Gut Microbiota Reveals Host-Specific Communities of Active Bacteria

This study assessed the relative contributions of host genetics and diet in shaping the gut microbiota of rainbow trout. Full sibling fish from four unrelated families, each consisting of individuals derived from the mating of one male and one female belonging to a breeding program, were fed diets containing either vegetable proteins or vegetable oils for two months in comparison to a control diet consisting of only fish protein and fish oil. Two parallel approaches were applied on the same samples: transcriptionally active bacterial populations were examined based on RNA analysis and were compared with bacterial populations obtained from DNA analysis. Comparison of temporal temperature gradient gel electrophoresis (TTGE) profiles from DNA and RNA showed important differences, indicating that active bacterial populations were better described by RNA analysis. Results showed that some bacterial groups were significantly (P<0.05) associated with specific families, indicating that microbiota composition may be influenced by the host. In addition, the effect of diet on microbiota composition was dependent on the trout family

Intronic Cis-Regulatory Modules Mediate Tissue-Specific and Microbial Control of angptl4/fiaf Transcription

The intestinal microbiota enhances dietary energy harvest leading to increased fat storage in adipose tissues. This effect is caused in part by the microbial suppression of intestinal epithelial expression of a circulating inhibitor of lipoprotein lipase called Angiopoietin-like 4 (Angptl4/Fiaf). To define the cis-regulatory mechanisms underlying intestine-specific and microbial control of Angptl4 transcription, we utilized the zebrafish system in which host regulatory DNA can be rapidly analyzed in a live, transparent, and gnotobiotic vertebrate. We found that zebrafish angptl4 is transcribed in multiple tissues including the liver, pancreatic islet, and intestinal epithelium, which is similar to its mammalian homologs. Zebrafish angptl4 is also specifically suppressed in the intestinal epithelium upon colonization with a microbiota. In vivo transgenic reporter assays identified discrete tissue-specific regulatory modules within angptl4 intron 3 sufficient to drive expression in the liver, pancreatic islet β-cells, or intestinal enterocytes. Comparative sequence analyses and heterologous functional assays of angptl4 intron 3 sequences from 12 teleost fish species revealed differential evolution of the islet and intestinal regulatory modules. High-resolution functional mapping and site-directed mutagenesis defined the minimal set of regulatory sequences required for intestinal activity. Strikingly, the microbiota suppressed the transcriptional activity of the intestine-specific regulatory module similar to the endogenous angptl4 gene. These results suggest that the microbiota might regulate host intestinal Angptl4 protein expression and peripheral fat storage by suppressing the activity of an intestine-specific transcriptional enhancer. This study provides a useful paradigm for understanding how microbial signals interact with tissue-specific regulatory networks to control the activity and evolution of host gene transcription

SBDS Expression and Localization at the Mitotic Spindle in Human Myeloid Progenitors

BACKGROUND: Shwachman-Diamond Syndrome (SDS) is a hereditary disease caused by mutations in the SBDS gene. SDS is clinically characterized by pancreatic insufficiency, skeletal abnormalities and bone marrow dysfunction. The hematologic abnormalities include neutropenia, neutrophil chemotaxis defects, and an increased risk of developing Acute Myeloid Leukemia (AML). Although several studies have suggested that SBDS as a protein plays a role in ribosome processing/maturation, its impact on human neutrophil development and function remains to be clarified. METHODOLOGY/PRINCIPAL FINDINGS: We observed that SBDS RNA and protein are expressed in the human myeloid leukemia PLB-985 cell line and in human hematopoietic progenitor cells by quantitative RT-PCR and Western blot analysis. SBDS expression is downregulated during neutrophil differentiation. Additionally, we observed that the differentiation and proliferation capacity of SDS-patient bone marrow hematopoietic progenitor cells in a liquid differentiation system was reduced as compared to control cultures. Immunofluorescence analysis showed that SBDS co-localizes with the mitotic spindle and in vitro binding studies reveal a direct interaction of SBDS with microtubules. In interphase cells a perinuclear enrichment of SBDS protein which co-localized with the microtubule organizing center (MTOC) was observed. Also, we observed that transiently expressed SDS patient-derived SBDS-K62 or SBDS-C84 mutant proteins could co-localize with the MTOC and mitotic spindle. CONCLUSIONS/SIGNIFICANCE: SBDS co-localizes with the mitotic spindle, suggesting a role for SBDS in the cell division process, which corresponds to the decreased proliferation capacity of SDS-patient bone marrow CD34(+) hematopoietic progenitor cells in our culture system and also to the neutropenia in SDS patients. A role in chromosome missegregation has not been clarified, since similar spatial and time-dependent localization is observed when patient-derived SBDS mutant proteins are studied. Thus, the increased risk of myeloid malignancy in SDS remains unexplained

Zebrafish Endzone Regulates Neural Crest-Derived Chromatophore Differentiation and Morphology

The development of neural crest-derived pigment cells has been studied extensively as a model for cellular differentiation, disease and environmental adaptation. Neural crest-derived chromatophores in the zebrafish (Danio rerio) consist of three types: melanophores, xanthophores and iridiphores. We have identified the zebrafish mutant endzone (enz), that was isolated in a screen for mutants with neural crest development phenotypes, based on an abnormal melanophore pattern. We have found that although wild-type numbers of chromatophore precursors are generated in the first day of development and migrate normally in enz mutants, the numbers of all three chromatophore cell types that ultimately develop are reduced. Further, differentiated melanophores and xanthophores subsequently lose dendricity, and iridiphores are reduced in size. We demonstrate that enz function is required cell autonomously by melanophores and that the enz locus is located on chromosome 7. In addition, zebrafish enz appears to selectively regulate chromatophore development within the neural crest lineage since all other major derivatives develop normally. Our results suggest that enz is required relatively late in the development of all three embryonic chromatophore types and is normally necessary for terminal differentiation and the maintenance of cell size and morphology. Thus, although developmental regulation of different chromatophore sublineages in zebrafish is in part genetically distinct, enz provides an example of a common regulator of neural crest-derived chromatophore differentiation and morphology