Transcriptional memory emerges from cooperative histone modifications

Background
Transcriptional regulation in cells makes use of diverse mechanisms to ensure that functional states can be maintained and adapted to variable environments; among them are chromatin-related mechanisms. While mathematical models of transcription factor networks controlling development are well established, models of transcriptional regulation by chromatin states are rather rare despite they appear to be a powerful regulatory mechanism.
Results
We here introduce a mathematical model of transcriptional regulation governed by histone modifications. This model describes binding of protein complexes to chromatin which are capable of reading and writing histone marks. Molecular interactions between these complexes and DNA or histones create a regulatory switch of transcriptional activity possessing a regulatory memory. The regulatory states of the switch depend on the activity of histone (de-) methylases, the structure of the DNA-binding regions of the complexes, and the number of histones contributing to binding. 
We apply our model to transcriptional regulation by trithorax- and polycomb- complex binding. By analyzing data on pluripotent and lineage-committed cells we verify basic model assumptions and provide evidence for a positive effect of the length of the modified regions on the stability of the induced regulatory states and thus on the transcriptional memory.
Conclusions
Our results provide new insights into epigenetic modes of transcriptional regulation. Moreover, they implicate well-founded hypotheses on cooperative histone modifications, proliferation induced epigenetic changes and higher order folding of chromatin which await experimental validation. Our approach represents a basic step towards multi-scale models of transcriptional control during development and lineage specification. 
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Cholestyramine treatment in two dogs with presumptive bile acid diarrhoea: a case report

Background: In people, bile acid diarrhoea is a prevalent complication of Crohn’s disease and diarrhoea- associated irritable bowel syndrome. Affected patients typically respond to bile acid sequestrants, such as cholestyramine, but human gastroenterologists often fail to recognize bile acid diarrhoea. Consequently, bile acid diarrhoea is regarded as an underrecognized and undertreated condition in human medicine. Due to lack of diagnostic tools, clinical response to bile acid sequestrants is often used to confirm a diagnosis of bile acid diarrhoea in people. Several recent studies have shown that bile acid dysmetabolism also occurs in dogs with chronic enteropathies. It has further been shown that dogs with chronic enteropathies have significantly decreased expression of a bile acid transport protein in the ileum compared to healthy dogs, which correlates with faecal bile acid dysmetabolism. Consequently, in spite of the lack of reports in the literature, bile acid diarrhoea is likely to exist in dogs as well. Case descriptions: Two dogs, an 8-year old Rottweiler and a 4.5-year old Siberian Husky were evaluated for chronic watery diarrhoea. Neither dog responded to dietary trials, probiotics, cyclosporine, faecal microbial transplantations or metronidazole. One of the dogs responded to high daily doses of corticosteroids, which were however associated with unacceptable side effects. The other dog was refractory to all standard treatment protocols, including cyclosporine and corticosteroids. Since none of the dogs responded satisfactorily to standard treatment or modulation of the intestinal microbiome, a suspicion of possible bile acid diarrhoea was raised. Treatment with cholestyramine, a bile acid sequestrant was initiated and resulted in marked improvement of faecal consistency, frequency of defecation and activity level in both dogs. Conclusion: This report presents two dogs with presumed bile acid diarrhoea that were successfully treated with cholestyramine. Therefore, bile acid diarrhoea should be considered as a possible diagnosis in dogs with treatment-refractory chronic diarrhoea. Keywords: Bile acids, Diarrhoea, Dog, CholestyraminePeer reviewe

A thyroid hormone receptor-dependent glucocorticoid induction.

Glucocorticoid and thyroid hormones exert their effects in many body tissues by binding to their respective receptors. The search for possible cross-talking mechanisms in overlapping target cells led to the discovery of synergism between a thyroid hormone receptor-binding site and a cryptic glucocorticoid-responsive element. Glucocorticoid responsiveness could only be detected in the presence of thyroid hormone and its receptor. This synergism requires the glucocorticoid receptor (GR) DNA-binding domain and is mediated by the transactivation domains. We found that synergism also occurs when the thyroid hormone receptor is replaced by the retinoic acid receptor or the GR is replaced by the progesterone receptor. Synergism is qualitatively independent of the type of thyroid hormone receptor-binding site and promoter. In several combinations of promoter and response elements, including a retinoic acid response element, T3 induction was only seen in the presence of the cryptic glucocorticoid-responsive element, GR, and glucocorticoids

Whole carcass diets: a role for fibre in gastrointestinal health of cheetahs?

This study was undertaken to test the hypothesis that altered podocyte slit protein nephrin distribution is associated with disturbed polarity protein expressions in podocytes from preeclampsia (PE). We examined expressions and distributions of nephrin, podoplanin, polarity protein partitioning defective-3 (PARD-3), and PARD-6 in podocytes from PE. Podocyte cell line (AB 8/13 cells) was used as control. Podocytes were found in all severe PE cases. In contrast, no podocyte was found in the samples from normal pregnancies and mild PE. Compared to control cells, nephrin, PARD-3 and PARD-6 expressions were reduced or lost in podocytes from severe PE. Podoplanin was expressed in podocyte surface membrane on control cells but reduced in podocytes from PE. These findings indicate that loss of slit protein nephrin and polarity protein PARD-3 and PARD-6 on foot processes could explain for podocyte detachment from glomerular basement membrane and lead to podocyte shedding in PE. © The Author(s) 2011.link_to_subscribed_fulltex

Une étude pilote sur le congé parental de pères au Tirol

La présente étude porte sur les pères en congé parental au Tirol. Les auteurs constatent que les réflexions systématiques à propos des pères en congé sont rares. Les auteurs tentent de répondre à la question suivante : le congé parental a-t-il des implications sur l'attachement père-enfant ? L'étude pilote porte sur un échantillon de 15 dyades père-enfant. La description et l'analyse du comportement d'interaction père-enfant ont été effectuées à l'aide du Child Adult Relationship Index (CARE-Index) élaboré par Crittenden (1988, 2000).A pilot study of fathers on parental leave in Tirol The current study examines fathers in parental leave in Tirol. The authors have come to realise that systematic reflections concerning fathers on leave of their work are rare. The authors attempt to answer the following question: does parental leave have implications on child/father attachment? The pilot study examines a small sample of 15 father/child couples. The description and analysis of father/child interactions was elaborated with the Child Adult Relationship Index (CARE-Index) designed by Crittenden (1988, 2000).Un proyecto piloto sobre el permiso parental en Tirol El estudio trata de los padres en permiso parental en Tirol. Los autores constatan que son muy pocas las reflexiones systématicas sobre los padres en permiso. ¿Tiene el permiso parental implicaciones sobre el apego padre-hijo? Los autores tratan de responder a esta pregunta en un estudio piloto con una muestra de 15 dyadas padre-hijo. La descripción y el analisis del comportamiento de la interaccion padre-hijo han sido realisadas con la ayuda del Child Adult Relationship Index (CARE-Index) elaborado por Crittenden (1988, 2000)

Characterization of the fecal microbiome in cats with inflammatory bowel disease or alimentary small cell lymphoma.

Feline chronic enteropathy (CE) is a common gastrointestinal disorder in cats and mainly comprises inflammatory bowel disease (IBD) and small cell lymphoma (SCL). Both IBD and SCL in cats share features with chronic enteropathies such as IBD and monomorphic epitheliotropic intestinal T-cell lymphoma in humans. The aim of this study was to characterize the fecal microbiome of 38 healthy cats and 27 cats with CE (13 cats with IBD and 14 cats with SCL). Alpha diversity indices were significantly decreased in cats with CE (OTU p = 0.003, Shannon Index p = 0.008, Phylogenetic Diversity p = 0.019). ANOSIM showed a significant difference in bacterial communities, albeit with a small effect size (P = 0.023, R = 0.073). Univariate analysis and LEfSE showed a lower abundance of facultative anaerobic taxa of the phyla Firmicutes (families Ruminococcaceae and Turicibacteraceae), Actinobacteria (genus Bifidobacterium) and Bacteroidetes (i.a. Bacteroides plebeius) in cats with CE. The facultative anaerobic taxa Enterobacteriaceae and Streptococcaceae were increased in cats with CE. No significant difference between the microbiome of cats with IBD and those with SCL was found. Cats with CE showed patterns of dysbiosis similar to those in found people with IBD

Effects of oral cobalamin supplementation on serum cobalamin concentrations in dogs with exocrine pancreatic insufficiency: A pilot study

The objective of this retrospective study was to evaluate serum cobalamin concentrations before and after oral cobalamin supplementation in dogs with low serum cobalamin concentrations and exocrine pancreatic insufficiency (EPI). Eighteen dogs with serum trypsin-like immunoreactivities between <1.0-2.7 μg/L (reference interval, 5.2-35 μg/L) and serum cobalamin concentrations ≤350 ng/L (reference interval, 244-959 ng/L) were enrolled. All dogs were treated with oral cyanocobalamin according to a previously described protocol (0.25-1.0 mg daily, depending on bodyweight). Median (range) serum cobalamin concentrations at inclusion was 188 ng/L (<111-350 ng/L), which increased significantly to 1000 ng/L (794-2385 ng/L; P < 0.001) after cobalamin supplementation for 19-199 days (median, 41 days). Oral cobalamin supplementation is a potential alternative to parenteral supplementation in dogs with EPI.The objective of this retrospective study was to evaluate serum cobalamin concentrations before and after oral cobalamin supplementation in dogs with low serum cobalamin concentrations and exocrine pancreatic insufficiency (EPI). Eighteen dogs with serum trypsin-like immunoreactivities between < 1.0-2.7 mu g/L (reference interval, 5.2-35 mu g/L) and serum cobalamin concentrations < 350 ng/L (reference interval, 244-959 ng/L) were enrolled. All dogs were treated with oral cyanocobalamin according to a previously described protocol (0.25-1.0 mg daily, depending on bodyweight). Median (range) serum cobalamin concentrations at inclusion was 188 ng/L (< 111-350 ng/L), which increased significantly to 1000 ng/L (794-2385 ng/L; P < 0.001) after cobalamin supplementation for 19-199 days (median, 41 days). Oral cobalamin supplementation is a potential alternative to parenteral supplementation in dogs with EPI.Peer reviewe

Bacterial fecal microbiota is only minimally affected by a standardized weight loss plan in obese cats

Background: Research in humans and mice suggests that obesity influences the abundance and diversity of gastrointestinal (GI) microbiota, and that an "obese microbiome" influences energy metabolism and fat storage in the host. Microbiota membership and composition have been previously assessed in healthy cats. However, research investigating the effects of obesity and weight loss on the cat's fecal microbiota is limited. Therefore, this study's objective was to evaluate differences in fecal microbial abundance and biodiversity, as well as serum cobalamin and folate concentrations in obese cats, before and after weight loss, and compare to lean cats. Fourteen lean and 17 obese healthy client-owned cats were fed a veterinary therapeutic weight loss food at maintenance energy requirement for 4 weeks. At the end of week 4, lean cats finished the study, whereas obese cats continued with a 10-week weight loss period on the same food, fed at individually-tailored weight loss energy requirements. Body weight and body condition score were recorded every 2 weeks throughout the study. At the end of each period, a fecal sample and food-consumption records were obtained from the owners, and serum cobalamin and folate concentrations were analysed. DNA was extracted from fecal samples, polymerase chain reaction (PCR) was performed, and products were sequenced using next-generation sequencing (Illumina MiSeq). Results: No significant differences in the relative abundance of taxa and in biodiversity indices were observed between cats in either group (P > 0.05 for all tests). Nevertheless, some significantly enriched taxa, mainly belonging to Firmicutes, were noted in linear discriminant analysis effect size test in obese cats before weight loss compared to lean cats. Serum cobalamin concentrations were significantly higher in lean compared to obese cats both before and after weight loss. Serum folate concentrations were higher in obese cats before weight loss compared to after. Conclusions: The association between feline obesity and the fecal bacterial microbiota was demonstrated in enriched taxa in obese cats compared to lean cats, which may be related to enhanced efficiency of energy-harvesting. However, in obese cats, the fecal microbial abundance and biodiversity were only minimally affected during the early phase of a standardized weight loss plan