The gut microbiome plays a critical role in regulating host immunity and can no longer be regarded as a bystander in human health and disease. In recent years, circadian (24 h) oscillations have been identified in the composition of the microbiota, its biophysical localization within the intestinal tract and its metabolic outputs. The gut microbiome and its key metabolic outputs, such as short chain fatty acids and tryptophan metabolites contribute to maintenance of intestinal immunity by promoting barrier function, regulating the host mucosal immune system and maintaining the function of gut-associated immune cell populations. Loss of rhythmic host-microbiome interactions disrupts host immunity and increases risk of inflammation and metabolic complications. Here we review factors that drive circadian variation in the microbiome, including meal timing, dietary composition and host circadian clocks. We also consider how host-microbiome interactions impact the core molecular clock and its rhythmic outputs in addition to the potential impact of this relationship on circadian control of immunity.

Nutrient deficiency causes growth failure and decreases serum insulin-like growth factor-I (IGF-I) concentrations. Because IGFBPs modulate the concentrations and availability of IGFs in serum, IGF-binding proteins (IGFBPs) were measured along with IGF-I and IGF-II before and after 21 days of refeeding in 22 undernourished Bangladeshi children (2-4 yr of age) with shigellosis. The effects of a 150 Cal/kg.day diet with a normal protein (6%; n = 10) or high protein (15%; n = 12) content were studied. The results were compared with those of 25 age-matched healthy American children (controls). Body weight gain was better in patients receiving the high protein diet than in those receiving the normal protein diet. In both groups, initial IGF-I (32 +/- 6 and 24 +/- 7 ng/mL; mean +/- SD) and IGF-II (177 +/- 15, 174 +/- 45 ng/mL) concentrations were low compared to controls (100 +/- 12 and 542 +/- 29 ng/mL, respectively; P < 0.007). After refeeding, IGF-I increased to 160 +/- 26 ng/mL on the normal protein diet and to 322 +/- 41 ng/mL on the high protein diet, exceeding values in controls (P < 0.007). IGF-II increased more than 2-fold on each diet (P < 0.007), reaching control values. IGFBP-2 concentrations before refeeding were twice those in controls (750 +/- 200 vs. 317 +/- 33 ng/mL; P < 0.007) and normalized after refeeding in the high protein group (288 +/- 32 ng/mL; P = NS), but remained elevated in the normal protein group (526 +/- 77 ng/mL; P < 0.007). IGFBP-3 levels before refeeding were low and returned to normal on each diet. IGFBP-3 proteolytic activity in serum was initially increased and declined on the high protein diet. In conclusion, protein content in the refeeding diet differentially affects IGFs and IGFBPs in young undernourished children with infection. IGF-I and IGFBP-2 seem to be particularly sensitive to dietary protein alterations. We speculate that an increase in IGF-I concentrations, normalization of IGFBP levels, and a decrease in IGFBP-3 proteolytic activity in serum may all be involved in the improved recovery and catch-up growth observed with the high protein diet.

Background: Dermoscopy is a useful tool to aid diagnosis of pigmented and non-pigmented skin lesions, as well as many other dermatological conditions. Use of dermoscopy is increasing worldwide, but to date, there are no reported data on attitudes of dermatologists in the United Kingdom (UK) towards dermoscopy. Objective: To determine current attitudes of UK dermatologists towards dermoscopy and assess how these attitudes have changed over the last decade. Methods: In October 2012, an online survey was sent to members of British Association of Dermatologists over a 12-week period. Data were subsequently compared with data from a similar UK nationwide paper questionnaire distributed to members in 2003. Results: The 2003 survey collected 292 responses (uptake 42%), and in 2012 there were 209 responses (22%), predominantly from consultants and registrars. In 2012, 86% respondents reported increased use of dermoscopy over the previous decade with 98.5% of respondents reporting regular clinical use of dermoscopy, compared with 54% in 2003. Overall, 81% respondents in 2012 had received dermoscopy training, mainly from UK-based courses (62% of respondents) but increasingly via Internet-based resources (30% vs. 7% in 2003). However, 39% respondents lacked confidence when making a diagnosis based on their interpretation of dermoscopy findings.  Conclusions: Over the last decade, use of dermoscopy has increased amongst UK dermatologists and the majority of respondents now employ dermoscopy in daily clinical practice. However, the use of dermoscopy in the dermatology community overall is not known and for those individuals there is a continued need for education.

The normal genomic stability of human cells is reversed during neoplastic transformation. The SV40 large T antigen alters the DNA content in human endometrial stromal cells in a manner that relates to neoplastic progression. Human endometrial stromal cells were transfected with a plasmid containing the A209 temperature-sensitive mutant of SV40 (tsSV40), which is also defective in the viral origin of replication. Ninety-seven clonal transfectants from seven different primary cell strains were isolated. Initial analysis revealed that 20% of the clonal populations (19/97) had an apparent diploid DNA content, 35% (34/97) had an apparent tetraploid DNA content, and the remainder were mixed populations of diploid and tetraploid cells. No aneuploid populations were observed. Diploid tsSV40 transformed cells always give rise to a population of cells with a tetraploid DNA content when continuously cultured at the permissive temperature. The doubling of DNA content can be vastly accelerated by the sudden reintroduction of large T antigen activity following a shift from non-permissive to permissive temperature. Tetraploid tsSV40 transfected cells have a lower capacity for anchorage-independent growth and earlier entry into 'crisis' than diploid cells. These results indicate that during the pre-crisis, extended lifespan phase of growth, the SV40 large T antigen causes a doubling of DNA content. This apparent doubling of DNA content does not confer growth advantage during the extended lifespan that precedes 'crisis'.

Human endometrial stromal cells transfected with an origin-defective, temperature-sensitive simian virus 40 recombinant plasmid are dependent on T-antigen function for proliferation and at the permissive temperature have an extended life span in culture. Southern blot analysis indicates that the transfected gene is present in low copy number, possibly at a single integration site. Normal stromal cells are capable of 10 to 20 population doublings in culture. Transfected cultures have been carried at the permissive temperature to 80 population doublings before crisis. In the multistep model of malignant transformation of human cells, these cells represent one of the earliest stages: extended but finite life span. We have used these cells to investigate alterations in signal transduction that may be responsible for this early stage of transformation caused by the large T antigen. Temperature shift experiments indicate that the expression of ornithine decarboxylase (ODC) but not of c-fos is altered by the large T antigen. Induction of c-fos by serum or 12-O-tetradecanoylphorbol-13-acetate is independent of temperature. However, in the transfected cells, the induction of ODC by asparagine or serum is greatly enhanced at the permissive temperature. This result indicates that the large T antigen acts downstream of c-fos but upstream of ODC expression in the signal-transducing cascade.