A pelagic thresher shark (Alopias pelagicus) gives birth at a cleaning station in the Philippines

The final publication is available at Springer via http://dx.doi.org/10.1007/s00338-014-1249-8This article discusses photographic evidence captured on April 4, 2013, as the first record of a thresher shark giving birth

TCF7L2 polymorphisms and inflammatory markers before and after treatment with fenofibrate

<p>Abstract</p> <p>Background</p> <p>Inflammation is implicated in causing diabetes. We tested whether transcription factor 7 like-2 (TCF7L2) gene polymorphisms (rs12255372 and rs7903146), consistently associated with type 2 diabetes, are associated with plasma concentrations of inflammatory markers before and after three weeks of daily treatment with fenofibrate.</p> <p>Methods</p> <p>Men and women in the Genetics of Lipid-Lowering Drugs and Diet Network study (n = 1025, age 49 ± 16 y) were included. All participants suspended use of lipid-lowering drugs for three weeks and were then given 160 mg/day of fenofibrate for three weeks. Inflammatory markers and lipids were measured before and after fenofibrate. ANOVA was used to test for differences across TCF7L2 genotypes.</p> <p>Results</p> <p>Under the additive or dominant model, there were no significant differences (<it>P </it>> 0.05) in the concentrations of inflammatory markers (hsCRP, IL-2, IL-6, TNF-α and MCP-1) across TCF7L2 genotypes in the period before or after treatment. For both rs12255372 and rs7903146, homozygote T-allele carriers had significantly higher (<it>P </it>< 0.05) post-fenofibrate concentrations of MCP-1 in the recessive model. No other significant associations were detected.</p> <p>Conclusion</p> <p>Overall these data show no association between TCF7L2 polymorphisms and the inflammatory markers suggesting that the effects of TCF7L2 on diabetes may not be via inflammation.</p

The Dog Mite, Demodex canis: Prevalence, Fungal Co-Infection, Reactions to Light, and Hair Follicle Apoptosis

Infection rate, reaction to light, and hair follicle apoptosis are examined in the dogmite, Demodex canis Leydig (Prostigmata: Demodicidae), in dogs from the northern area of Taiwan. An analysis of relevant samples revealed 7.2% (73/1013) prevalence of D. canis infection. Infection during the investigation peaked each winter, with an average prevalence of 12.5% (32/255). The infection rates significantly varied in accordance with month, sex, age, and breed (p < 0.05). Most of the lesions were discovered on the backs of the infected animals, where the infection rate was 52.1% (38/73) (P < 0.05). The epidemiologic analysis of infection based on landscape area factor, found that employing a map-overlapping method showed a higher infection rate in the eastern distribution of Taiwan's northern area than other areas. Isolation tests for Microsporum canis Bodin (Onygenales: Arthrodermataceae) and Trichophyton mentagrophyte Robin (Blanchard) on the D. canis infected dogs revealed prevalence rates of 4.4% (2/45) and 2.2% (1/45), respectively. Observations demonstrated that D. canis slowly moved from a light area to a dark area. Skin samples were examined for cellular apoptosis by activated caspase3 immunohistochemical staining. Cells that surrounded the infected hair follicles were activated caspase3-positive, revealing cell apoptosis in infected follicles via the activation of caspase3

Immunomodulatory Effects of Bone Marrow-Derived Mesenchymal Stem Cells in a Swine Hemi-Facial Allotransplantation Model

BACKGROUND: In this study, we investigated whether the infusion of bone marrow-derived mesenchymal stem cells (MSCs), combined with transient immunosuppressant treatment, could suppress allograft rejection and modulate T-cell regulation in a swine orthotopic hemi-facial composite tissue allotransplantation (CTA) model. METHODOLOGY/PRINCIPAL FINDINGS: Outbred miniature swine underwent hemi-facial allotransplantation (day 0). Group-I (n = 5) consisted of untreated control animals. Group-II (n = 3) animals received MSCs alone (given on days -1, +1, +3, +7, +14, and +21). Group-III (n = 3) animals received CsA (days 0 to +28). Group-IV (n = 5) animals received CsA (days 0 to +28) and MSCs (days -1, +1, +3, +7, +14, and +21). The transplanted face tissue was observed daily for signs of rejection. Biopsies of donor tissues and recipient blood sample were obtained at specified predetermined times (per 2 weeks post-transplant) or at the time of clinically evident rejection. Our results indicated that the MSC-CsA group had significantly prolonged allograft survival compared to the other groups (P<0.001). Histological examination of the MSC-CsA group displayed the lowest degree of rejection in alloskin and lymphoid gland tissues. TNF-α expression in circulating blood revealed significant suppression in the MSC and MSC-CsA treatment groups, as compared to that in controls. IHC staining showed CD45 and IL-6 expression were significantly decreased in MSC-CsA treatment groups compared to controls. The number of CD4+/CD25+ regulatory T-cells and IL-10 expressions in the circulating blood significantly increased in the MSC-CsA group compared to the other groups. IHC staining of alloskin tissue biopsies revealed a significant increase in the numbers of foxp3(+)T-cells and TGF-β1 positive cells in the MSC-CsA group compared to the other groups. CONCLUSIONS: These results demonstrate that MSCs significantly prolong hemifacial CTA survival. Our data indicate the MSCs did not only suppress inflammation and acute rejection of CTA, but also modulate T-cell regulation and related cytokines expression

Azithromycin attenuates airway inflammation in a mouse model of viral bronchiolitis

<p>Abstract</p> <p>Background</p> <p>Viral bronchiolitis is the leading cause of hospitalization in young infants. It is associated with the development of childhood asthma and contributes to morbidity and mortality in the elderly. Currently no therapies effectively attenuate inflammation during the acute viral infection, or prevent the risk of post-viral asthma. We hypothesized that early treatment of a paramyxoviral bronchiolitis with azithromycin would attenuate acute and chronic airway inflammation.</p> <p>Methods</p> <p>Mice were inoculated with parainfluenza type 1, Sendai Virus (SeV), and treated daily with PBS or azithromycin for 7 days post-inoculation. On day 8 and 21 we assessed airway inflammation in lung tissue, and quantified immune cells and inflammatory mediators in bronchoalveolar lavage (BAL).</p> <p>Results</p> <p>Compared to treatment with PBS, azithromycin significantly attenuated post-viral weight loss. During the peak of acute inflammation (day 8), azithromycin decreased total leukocyte accumulation in the lung tissue and BAL, with the largest fold-reduction in BAL neutrophils. This decreased inflammation was independent of changes in viral load. Azithromycin significantly attenuated the concentration of BAL inflammatory mediators and enhanced resolution of chronic airway inflammation evident by decreased BAL inflammatory mediators on day 21.</p> <p>Conclusions</p> <p>In this mouse model of paramyxoviral bronchiolitis, azithromycin attenuated acute and chronic airway inflammation. These findings demonstrate anti-inflammatory effects of azithromycin that are not related to anti-viral activity. Our findings support the rationale for future prospective randomized clinical trials that will evaluate the effects of macrolides on acute viral bronchiolitis and their long-term consequences.</p

Transcription Factor Binding Site Polymorphism in the Motilin Gene Associated with Left-Sided Displacement of the Abomasum in German Holstein Cattle

Left-sided displacement of the abomasum (LDA) is a common disease in many dairy cattle breeds. A genome-wide screen for QTL for LDA in German Holstein (GH) cows indicated motilin (MLN) as a candidate gene on bovine chromosome 23. Genomic DNA sequence analysis of MLN revealed a total of 32 polymorphisms. All informative polymorphisms used for association analyses in a random sample of 1,136 GH cows confirmed MLN as a candidate for LDA. A single nucleotide polymorphism (FN298674:g.90T>C) located within the first non-coding exon of bovine MLN affects a NKX2-5 transcription factor binding site and showed significant associations (ORallele = 0.64; −log10Pallele = 6.8, −log10Pgenotype = 7.0) with LDA. An expression study gave evidence of a significantly decreased MLN expression in cows carrying the mutant allele (C). In individuals heterozygous or homozygous for the mutation, MLN expression was decreased by 89% relative to the wildtype. FN298674:g.90T>C may therefore play a role in bovine LDA via the motility of the abomasum. This MLN SNP appears useful to reduce the incidence of LDA in German Holstein cattle and provides a first step towards a deeper understanding of the genetics of LDA

In vivo multiphoton imaging reveals gradual growth of newborn amyloid plaques over weeks

The kinetics of amyloid plaque formation and growth as one of the characteristic hallmarks of Alzheimer’s disease (AD) are fundamental issues in AD research. Especially the question how fast amyloid plaques grow to their final size after they are born remains controversial. By long-term two-photon in vivo imaging we monitored individual methoxy-X04-stained amyloid plaques over 6 weeks in 12 and 18 months old Tg2576 mice. We found that in 12 months old mice, newly appearing amyloid plaques were initially small in volume and subsequently grew over time. The growth rate of plaques was inversely proportional to their volume; thus amyloid plaques that were already present at the first imaging time point grew over time but slower compared to new plaques. Additionally, we analyzed 18 months old Tg2576 mice in which we neither found newly appearing plaques nor a significant growth of pre-existing plaques over 6 weeks of imaging. In conclusion, newly appearing amyloid plaques are initially small in size but grow over time until plaque growth can not be detected anymore in aged mice. These results suggest that drugs that target plaque formation should be most effective early in the disease, when plaques are growing

Lysosomotropic agents as HCV entry inhibitors

HCV has two envelop proteins named as E1 and E2 which play an important role in cell entry through two main pathways: direct fusion at the plasma membrane and receptor-mediated endocytosis. Fusion of the HCV envelope proteins is triggered by low pH within the endosome. Lysosomotropic agents (LA) such as Chloroquine and Ammonium chloride (NH4Cl) are the weak bases and penetrate in lysosome as protonated form and increase the intracellular pH. To investigate the antiviral effect of LA (Chloroquine and NH4Cl) on pH dependent endocytosis, HCV pseudoparticles (HCVpp) of 1a and 3a genotype were produced and used to infect liver cells. The toxicological effects of Chloroquine and NH4Cl were tested in liver cells through MTT cell proliferation assay. For antiviral screening of Chloroquine and NH4Cl, liver cells were infected with HCVpp of 3a and 1a genotype in the presence or absence of different concentrations of Chloroquine and NH4Cl and there luciferase activity was determined by using a luminometer. The results demonstrated that Chloroquine and NH4Cl showed more than 50% reduction of virus infectivity at 50 μM and 10 mM concentrations respectively. These results suggest that inhibition of HCV at fusion step by increasing the lysosomal pH will be better option to treat chronic HCV

Does long-term care use within primary health care reduce hospital use among older people in Norway? A national five-year population-based observational study

<p>Abstract</p> <p>Background</p> <p>Population ageing may threaten the sustainability of future health care systems. Strengthening primary health care, including long-term care, is one of several measures being taken to handle future health care needs and budgets. There is limited and inconsistent evidence on the effect of long-term care on hospital use. We explored the relationship between the total use of long-term care within public primary health care in Norway and the use of hospital beds when adjusting for various effect modifiers and confounders.</p> <p>Methods</p> <p>This national population-based observational study consists of all Norwegians (59% women) older than 66 years (N = 605676) (13.2% of total population) in 2002-2006. The unit of analysis was defined by municipality, age and sex. The association between total number of recipients of long-term care per 1000 inhabitants (LTC-rate) and hospital days per 1000 inhabitants (HD-rate) was analysed in a linear regression model. Modifying and confounding effects of socioeconomic, demographic and geographic variables were included in the final model. We defined a difference in hospitalization rates of more than 1000 days per 1000 inhabitants as clinically important.</p> <p>Results</p> <p>Thirty-one percent of women and eighteen percent of men were long-term care users. Men had higher HD-rates than women. The crude association between LTC-rate and HD-rate was weakly negative. We identified two effect modifiers (age and sex) and two strong confounders (travel time to hospital and mortality). Age and sex stratification and adjustments for confounders revealed a positive statistically significant but not clinically important relationship between LTC-rates and hospitalization for women aged 67-79 years and all men. For women 80 years and over there was a weak but negative relationship which was neither statistically significant nor clinically important.</p> <p>Conclusions</p> <p>We found a weak positive adjusted association between LTC-rates and HD-rates. Opposite to common belief, we found that increased volume of LTC by itself did not reduce pressure on hospitals. There still is a need to study integrated care models for the elderly in the Norwegian setting and to explore further why municipalities far away from hospital achieve lower use of hospital beds.</p