Preliminary investigation of the effects of long-term dietary intake of genistein and daidzein on hepatic histopathology and biochemistry in domestic cats (Felis catus)

Dietary isoflavones have been hypothesised to play a role in hepatic veno-occlusive disease in captive exotic felids, although empirical evidence is lacking. This study aimed to investigate the effect of long-term (>1 year) dietary genistein and daidzein exposure on the hepatic biochemistry and histology of domestic cats. Individual cats were assessed for hepatic enzyme and bile acid production before and after the removal of isoflavones from their diet in the treatment group (n=4), and at the same times in unexposed control animals (n=7). No significant differences were detectable in hepatic biochemistry between treatment and control groups, and all serum values were within the normal reference ranges for domestic cats. Additionally, treatment animals demonstrated slightly greater areas of fibrosis surrounding hepatic venules than control animals, but this difference was not statistically significant. On the basis of the results presented, dietary isoflavones, at the current dose and duration of exposure do not appear to modulate hepatic enzyme production or histological parameters

Preliminary investigation of the influence of long-term dietary isoflavone intake on reproductive tract histology and sex steroid receptor expression in female domestic cats (Felis catus)

Genistein and daidzein are isoflavones which are reported to influence the reproductive system in a variety of mammalian species. This pilot study aimed to determine if dietary isoflavones could potentially influence reproductive tract histology or morphology in domestic cats, when consumed during the postnatal development period. Cats were maintained on either treatment (150 µg/g DM genistein and 150 µg/g DM daidzein, n=4) or control (isoflavone free, n=8) diets from weaning, up to 414 (±17.2) days post-weaning. Reproductive tissues were collected during routine ovario-hysterectomy and examined for histology and sex steroid receptor expression. Findings indicate that these dietary isoflavones influenced the expression of oestrogen receptor α (ERα) and oestrogen receptor β (ERβ), and progesterone receptor in feline reproductive tissues. One cat in the treatment group developed suppurative endometritis, but no evidence of uterotrophic or histological changes were found in any other cats. The potential to alter expression of hormone receptors in the reproductive tract of domestic cats exposed to genistein and daidzein warrants further investigation

Parathyroid hormone secretion is controlled by both ionised calcium and phosphate during exercise and recovery in men

The mechanism by which PTH is controlled during and after exercise is poorly understood due to insufficient temporal frequency of measurements. Objective: To examine the temporal pattern of PTH, PO4, ACa and Ca2+ during and after exercise. Design and setting: A laboratory-based study with a cross-over design, comparing 30 min of running at 55%, 65% and 75%VO2max, followed by 2.5-h of recovery. Blood was obtained at baseline, after 2.5, 5, 7.5, 10, 15, 20, 25 and 30 min of exercise and after 2.5, 5, 7.5, 10, 15, 20, 25, 30, 60, 90 and 150 min of recovery. Participants: Ten men (age 23±1 y, height 1.82±0.07 m, body mass 77.0±7.5 kg) participated. Main Outcome Measures: PTH, PO4, ACa and Ca2+ Results: Independent of intensity, PTH concentrations decreased with the onset of exercise (-21 to -33%; P≤0.001), increased thereafter and were higher than baseline by the end of exercise at 75%VO2max (+52%; P≤0.001). PTH peaked transiently after 5–7.5 min of recovery (+73 to +110%; P≤0.001). PO4 followed a similar temporal pattern to PTH and Ca2+ followed a similar but inverse pattern to PTH. PTH was negatively correlated with Ca2+ across all intensities (r=-0.739 to -0.790; P≤0.001). When PTH was increasing, the strongest cross-correlation was with Ca2+ at 0 lags (3.5 min) (r=-0.902 to -0.950); during recovery, the strongest cross-correlation was with PO4 at 0 lags (8 min) (r=0.987 to 0.995). Conclusions: PTH secretion during exercise and recovery is controlled by a combination of changes in Ca2+ and PO4 in men

The intestinal virome in children with cystic fibrosis differs from healthy controls.

Intestinal bacterial dysbiosis is evident in children with cystic fibrosis (CF) and intestinal viruses may be contributory, given their influence on bacterial species diversity and biochemical cycles. We performed a prospective, case-control study on children with CF and age and gender matched healthy controls (HC), to investigate the composition and function of intestinal viral communities. Stool samples were enriched for viral DNA and RNA by viral extraction, random amplification and purification before sequencing (Illumina MiSeq). Taxonomic assignment of viruses was performed using Vipie. Functional annotation was performed using Virsorter. Inflammation was measured by calprotectin and M2-pyruvate kinase (M2-PK). Eight CF and eight HC subjects were included (50% male, mean age 6.9 ± 3.0 and 6.4 ± 5.3 years, respectively, p = 0.8). All CF subjects were pancreatic insufficient. Regarding the intestinal virome, no difference in Shannon index between CF and HC was identified. Taxonomy-based beta-diversity (presence-absence Bray-Curtis dissimilarity) was significantly different between CF and HC (R2 = 0.12, p = 0.001). Myoviridae, Faecalibacterium phage FP Taranis and unclassified Gokushovirinae were significantly decreased in CF compared with HC (q<0.05). In children with CF (compared to HC), the relative abundance of genes annotated to (i) a peptidoglycan-binding domain of the peptidoglycan hydrolases (COG3409) was significantly increased (q<0.05) and (ii) capsid protein (F protein) (PF02305.16) was significantly decreased (q<0.05). Picornavirales, Picornaviridae, and Enterovirus were found to positively correlate with weight and BMI (r = 0.84, q = 0.01). Single-stranded DNA viruses negatively correlated with M2-PK (r = -0.86, q = 0.048). Children with CF have an altered intestinal virome compared to well-matched HC, with both taxonomic and predicted functional changes. Further exploration of Faecalibacterium phages, Gokushovirinae and phage lysins are warranted. Intestinal viruses and their functions may have important clinical implications for intestinal inflammation and growth in children with CF, potentially providing novel therapeutic targets

Lorentz Violation in Warped Extra Dimensions

Higher dimensional theories which address some of the problematic issues of the Standard Model(SM) naturally involve some form of $D=4+n$-dimensional Lorentz invariance violation (LIV). In such models the fundamental physics which leads to, e.g., field localization, orbifolding, the existence of brane terms and the compactification process all can introduce LIV in the higher dimensional theory while still preserving 4-d Lorentz invariance. In this paper, attempting to capture some of this physics, we extend our previous analysis of LIV in 5-d UED-type models to those with 5-d warped extra dimensions. To be specific, we employ the 5-d analog of the SM Extension of Kostelecky et. al. ~which incorporates a complete set of operators arising from spontaneous LIV. We show that while the response of the bulk scalar, fermion and gauge fields to the addition of LIV operators in warped models is qualitatively similar to what happens in the flat 5-d UED case, the gravity sector of these models reacts very differently than in flat space. Specifically, we show that LIV in this warped case leads to a non-zero bulk mass for the 5-d graviton and so the would-be zero mode, which we identify as the usual 4-d graviton, must necessarily become massive. The origin of this mass term is the simultaneous existence of the constant non-zero $AdS_5$ curvature and the loss of general co-ordinate invariance via LIV in the 5-d theory. Thus warped 5-d models with LIV in the gravity sector are not phenomenologically viable.Comment: 14 pages, 4 figs; discussion added, algebra repaire

Enhanced cosmic-ray flux toward zeta Persei inferred from laboratory study of H3+ - e- recombination rate

The H3+ molecular ion plays a fundamental role in interstellar chemistry, as it initiates a network of chemical reactions that produce many interstellar molecules. In dense clouds, the H3+ abundance is understood using a simple chemical model, from which observations of H3+ yield valuable estimates of cloud path length, density, and temperature. On the other hand, observations of diffuse clouds have suggested that H3+ is considerably more abundant than expected from the chemical models. However, diffuse cloud models have been hampered by the uncertain values of three key parameters: the rate of H3+ destruction by electrons, the electron fraction, and the cosmic-ray ionisation rate. Here we report a direct experimental measurement of the H3+ destruction rate under nearly interstellar conditions. We also report the observation of H3+ in a diffuse cloud (towards zeta Persei) where the electron fraction is already known. Taken together, these results allow us to derive the value of the third uncertain model parameter: we find that the cosmic-ray ionisation rate in this sightline is forty times faster than previously assumed. If such a high cosmic-ray flux is indeed ubiquitous in diffuse clouds, the discrepancy between chemical models and the previous observations of H3+ can be resolved.Comment: 6 pages, Nature, in pres

The Patients Assessment Chronic Illness Care (PACIC) questionnaire in The Netherlands: a validation study in rural general practice

BACKGROUND: Many patients with chronic illness receive health care in primary care settings, so a challenge is to provide well-structured chronic care in these settings. Our aim was to develop and test a Dutch version of the PACIC questionnaire, a measure for patient reported structured chronic care. METHODS: Observational study in 165 patients with diabetes or COPD from four general practices (72% response rate). Patients completed a written questionnaire, which included instruments for assessing chronic illness care (PACIC), evaluations of general practice (Europep), enablement (PEI), and individual characteristics. RESULTS: The patients had a mean age of 68.0 years and 47% comprised of women. Twenty-two to 35% of responding patients did not provide answers to specific items in the PACIC. In 11 items the lowest answering category was used by 30% or more of the responders and in 6 items the highest answering category was used by this number of responders. Principal factor analysis identified the previously defined five domains reasonably well. Cronbach's alpha per domain varied from 0.71 to 0.83, and the intraclass coefficient from 0.66 to 0.91. Diabetes patients reported higher presence of structured chronic care for 14 out of the 20 PACIC items. The effect of patient evaluations of general practice on the PACIC score was positive (b = 0.72, p < 0.004), but the effect of patient enablement on the PACIC score was negative (b = -1.13, p < 0.000). CONCLUSION: A translated and validated Dutch version of the PACIC questionnaire is now available. Further research on its validity is recommended

Evaluating the potential for the environmentally sustainable control of foot and mouth disease in Sub-Saharan Africa

Strategies to control transboundary diseases have in the past generated unintended negative consequences for both the environment and local human populations. Integrating perspectives from across disciplines, including livestock, veterinary and conservation sectors, is necessary for identifying disease control strategies that optimise environmental goods and services at the wildlife-livestock interface. Prompted by the recent development of a global strategy for the control and elimination of foot-and-mouth disease (FMD), this paper seeks insight into the consequences of, and rational options for potential FMD control measures in relation to environmental, conservation and human poverty considerations in Africa. We suggest a more environmentally nuanced process of FMD control that safe-guards the integrity of wild populations and the ecosystem dynamics on which human livelihoods depend while simultaneously improving socio-economic conditions of rural people. In particular, we outline five major issues that need to be considered: 1) improved understanding of the different FMD viral strains and how they circulate between domestic and wildlife populations; 2) an appreciation for the economic value of wildlife for many African countries whose presence might preclude the country from ever achieving an FMD-free status; 3) exploring ways in which livestock production can be improved without compromising wildlife such as implementing commodity-based trading schemes; 4) introducing a participatory approach involving local farmers and the national veterinary services in the control of FMD; and 5) finally the possibility that transfrontier conservation might offer new hope of integrating decision-making at the wildlife-livestock interface

Dynamic Carboniferous tropical forests: new views of plant function and potential for physiological forcing of climate

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138385/1/nph14700_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138385/2/nph14700.pd

Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus.

Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. Expression studies were performed by microarray analysis, quantitative PCR (qPCR), reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes), many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes). Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV