Evaluation of the mouse eye as a model for recurrent herpetic infection

Thesis (D.Sc.D.)--Boston University, Henry M. Goldman School of Graduate Dentistry, 1982 (Oral biology)Bibliography: leaves 102-114.The eyes, the trigeminal ganglia and the superior cervical ganglia of CD-1 mice were studied as a model for recurrent herpetic infections. Animals were corneally infected with Type 1 herpes simplex virus (HSV-1). During the period of acute infection, both gnaglionic tissues were demonstrated to have almost 100% infection with herpes virus. Following recovery from the acute infection, HSV was shown to be latent in both ganglionic tissues; the HSV could be demonstrated in over 75% of trigeminal ganglia and approximately 20% of superior cervical ganglia by explantation of gnaglia. During t he latent phase, spontaneous reactivation in both ocular and ganglionic t issues were uncommon in our animals. Different stimuli, including fever, thermal burn, mechanical trauma, treatment with cyclophosphamide (CPA), an immunosuppressant, and physical stress were employed in attempts to induce recurrent infection. Daily cultures of eye swabbings and cultures of homogenates of the ganglia were used to sutdy effects of these stimuli on virus reactivation. A low incidence of reactivation (approximately 10%) was demonstrated in eyes and trigeminal gnaglia following CPA trea t men~ of these mice. The other stimuli apparently p~oduced no reactivation of infection in our animals. This mouse eye model may still prove to be useful for studying the mechaniams of viral latency and reactivation in herpetic infection, and thus warrants investigation

Bifid mandibular canals and their cortex thicknesses: A comparison study on images obtained from cone-beam and multislice computed tomography

AbstractBackground/purposeHigh prevalence of bifid mandibular canals has been visualized with various types of computerized tomography (CT). Along the canals, a various ranged corticalization was recently reported. The depiction of the fine anatomic structures on multislice and cone-beam CT images was compared.Material and methodsThe presence or absence of the bifid canal was assessed on 327 images obtained by multislice CT (MSCT; n = 173) or by cone-beam CT (CBCT; n = 154), according to the configuration. The cortex thickness and distribution were also assessed.ResultsThe prevalence of bifid canal detected by CBCT was significantly greater than that detected by MSCT (42.2% vs. 18.7% for hemi-mandibles and 58.4% vs. 30.6% for patients). Cortical thickness recorded by CBCT was significantly thinner than that recorded by MSCT (0.48 mm vs. 0.65 mm, P < 0.001); however, the distributions of corticalization detected by the two tomography methods were similar. There was a significant association of cortex thickness with CT type and corticalization degree (R2 = 0.530, P < 0.001).ConclusionThinner cortices, but greater prevalence of bifid canals recorded by CBCT, compared to MSCT, suggests that clinicians should be cautious when using CT to interpret this fine anatomic structure

Prognostic Value of Choline and Betaine Depends on Intestinal Microbiota-Generated Metabolite Trimethylamine-N-Oxide

Aims: Recent metabolomics and animal model studies show trimethylamine-N-oxide (TMAO), an intestinal microbiota-dependent metabolite formed from dietary trimethylamine-containing nutrients such as phosphatidylcholine (PC), choline, and carnitine, is linked to coronary artery disease pathogenesis. Our aim was to examine the prognostic value of systemic choline and betaine levels in stable cardiac patients. Methods and Results: We examined the relationship between fasting plasma choline and betaine levels and risk of major adverse cardiac events (MACE = death, myocardial infraction, stroke) in relation to TMAO over 3 years of follow-up in 3903 sequential stable subjects undergoing elective diagnostic coronary angiography. In our study cohort, median (IQR) TMAO, choline, and betaine levels were 3.7 (2.4–6.2)μM, 9.8 (7.9–12.2)μM, and 41.1 (32.5–52.1)μM, respectively. Modest but statistically significant correlations were noted between TMAO and choline (r = 0.33, P \u3c 0.001) and less between TMAO and betaine (r = 0.09, P \u3c 0.001). Higher plasma choline and betaine levels were associated with a 1.9-fold and 1.4-fold increased risk of MACE, respectively (Quartiles 4 vs. 1; P \u3c 0.01, each). Following adjustments for traditional cardiovascular risk factors and high-sensitivity C-reactive protein, elevated choline [1.34 (1.03–1.74), P \u3c 0.05], and betaine levels [1.33 (1.03–1.73), P \u3c 0.05] each predicted increased MACE risk. Neither choline nor betaine predicted MACE risk when TMAO was added to the adjustment model, and choline and betaine predicted future risk for MACE only when TMAO was elevated. Conclusion: Elevated plasma levels of choline and betaine are each associated with incident MACE risk independent of traditional risk factors. However, high choline and betaine levels are only associated with higher risk of future MACE with concomitant increase in TMAO

The Changes of Nutrition Labeling of Packaged Food in Hangzhou in China during 2008∼2010

OBJECTIVE: To understand the changes of the nutrition labeling of packaged food in China two years after the promulgation of the Regulation for Food Nutrition Labeling, which encourages food manufacturers to identify nutrition labeling. METHODS: Investigators copied out the nutrition information panel, nutrition claim and nutrient function claim of packaged food in a supermarket with prepared questionnaire and finished normative judgment in 2008 and 2010. RESULTS: 4693 and 5526 kinds of packaged food were investigated separately. Nutrition information panel, nutrition claim and nutrient function claim were found on the food label of 27.6%, 13.0% and 1.9% of packaged food respectively in 2008, while 35.1%, 7.7% and 2.3% in 2010. The nutrition information panel which labeled energy, protein, fat, carbohydrate and sodium was 597 (43.8%) and 1661 (85.9%) in 2008 and 2010, only 134 (9.8%) and 985 (51.0%) nutrition information panel were totally normalized. Nutrition claim and nutrient function claim focused on vitamin, mineral and dietary fiber. The total qualified proportions for nutrition claim were increased significantly for most of the nutrients, except for cholesterol. There were 6 (6.4%) and 5 (3.9%) nutrient function claims with hinting of therapeutic effects on diseases separately. CONCLUSION: Although the voluntary regulation remarkably improved the level of normalization for nutrition labeling, its role on the prevalence was minus. It's imperative to enforce nutrition labeling for not only China but also other countries, and furthermore, health education on nutrition labeling should be initiated to support the policy

A Novel Replication-Competent Vaccinia Vector MVTT Is Superior to MVA for Inducing High Levels of Neutralizing Antibody via Mucosal Vaccination

Mucosal vaccination offers great advantage for inducing protective immune response to prevent viral transmission and dissemination. Here, we report our findings of a head-to-head comparison of two viral vectors modified vaccinia Ankara (MVA) and a novel replication-competent modified vaccinia Tian Tan (MVTT) for inducing neutralizing antibodies (Nabs) via intramuscular and mucosal vaccinations in mice. MVTT is an attenuated variant of the wild-type VTT, which was historically used as a smallpox vaccine for millions of Chinese people. The spike glycoprotein (S) of SARS-CoV was used as the test antigen after the S gene was constructed in the identical genomic location of two vectors to generate vaccine candidates MVTT-S and MVA-S. Using identical doses, MVTT-S induced lower levels (∼2-3-fold) of anti- SARS-CoV neutralizing antibodies (Nabs) than MVA-S through intramuscular inoculation. MVTT-S, however, was capable of inducing consistently 20-to-100-fold higher levels of Nabs than MVA-S when inoculated via either intranasal or intraoral routes. These levels of MVTT-S-induced Nab responses were substantially (∼10-fold) higher than that induced via the intramuscular route in the same experiments. Moreover, pre-exposure to the wild-type VTT via intranasal or intraoral route impaired the Nab response via the same routes of MVTT-S vaccination probably due to the pre-existing anti-VTT Nab response. The efficacy of intranasal or intraoral vaccination, however, was still 20-to-50-fold better than intramuscular inoculation despite the subcutaneous pre-exposure to wild-type VTT. Our data have implications for people who maintain low levels of anti-VTT Nabs after historical smallpox vaccination. MVTT is therefore an attractive live viral vector for mucosal vaccination

Blinded by the bright: A lack of congruence between colour morphs, phylogeography and taxonomy for a cosmopolitan Indo-Pacific butterflyfish, Chaetodon auriga

Aim: We assess genetic differentiation among biogeographical provinces and colour morphs of the threadfin butterflyfish, Chaetodon auriga. This species is among the most broadly distributed butterflyfishes in the world, occurring on reefs from the Red Sea and western Indian Ocean to French Polynesia and Hawai'i. The Red Sea form lacks a conspicuous 'eye-spot' on the dorsal fin, which may indicate an evolutionary distinction. Location: Red Sea, Indian Ocean and Pacific Ocean. Methods: Specimens were obtained at 17 locations (n = 358) spanning the entire range of this species. The genetic data included 669 base pairs of mitochondrial DNA (mtDNA) cytochrome b and allele frequencies at six microsatellite loci. Analysis of molecular variance, structure plots, haplotype networks and estimates of population expansion time were used to assess phylogeographical patterns. Results: Population structure was low overall, but significant and concordant between molecular markers (mtDNA: ΦST = 0.027, P < 0.001; microsatellites: F ST = 0.023, P < 0.001). Significant population-level partitions were only detected at peripheral locations including the Red Sea and Hawai'i. Population expansion events in the Red Sea and Socotra are older (111,940-223,881 years) relative to all other sites (16,343-87,910 years). Main conclusions: We find little genetic evidence to support an evolutionary partition of a previously proposed Red Sea subspecies. The oldest estimate of population expansion in the Red Sea and adjacent Gulf of Aden indicates a putative refuge in this region during Pleistocene glacial cycles. The finding of population separations at the limits of the range, in the Red Sea and Hawai'i, is consistent with peripheral speciation

The malarial exported PFA0660w is an Hsp40 co-chaperone of PfHsp70-x

Plasmodium falciparum, the human pathogen responsible for the most dangerous malaria infection, survives and develops in mature erythrocytes through the export of proteins needed for remodelling of the host cell. Molecular chaperones of the heat shock protein (Hsp) family are prominent members of the exportome, including a number of Hsp40s and a Hsp70. PFA0660w, a type II Hsp40, has been shown to be exported and possibly form a complex with PfHsp70-x in the infected erythrocyte cytosol. However, the chaperone properties of PFA0660w and its interaction with human and parasite Hsp70s are yet to be investigated. Recombinant PFA0660w was found to exist as a monomer in solution, and was able to significantly stimulate the ATPase activity of PfHsp70-x but not that of a second plasmodial Hsp70 (PfHsp70-1) or a human Hsp70 (HSPA1A), indicating a potential specific functional partnership with PfHsp70-x. Protein binding studies in the presence and absence of ATP suggested that the interaction of PFA0660w with PfHsp70-x most likely represented a co-chaperone/chaperone interaction. Also, PFA0660w alone produced a concentrationdependent suppression of rhodanese aggregation, demonstrating its chaperone properties. Overall, we have provided the first biochemical evidence for the possible role of PFA0660w as a chaperone and as co-chaperone of PfHsp70-x. We propose that these chaperones boost the chaperone power of the infected erythrocyte, enabling successful protein trafficking and folding, and thereby making a fundamental contribution to the pathology of malaria

Present and past climatic effects on the current distribution and genetic diversity of the Iberian spadefoot toad (Pelobates cultripes): an integrative approach

Aim: Predicting species responses to global change is one of the most pressing issues in Conservation Biogeography. A key part of the problem is understanding how organisms have reacted to climatic changes in the past. Here we use species distribution modelling to infer the effects of climate changes since the Last Interglacial (LIG, about 130,000 ybp) on patterns of genetic structure and diversity in the Western Spadefoot toad (Pelobates cultripes) in combination with spatially-explicit phylogeographic analyses. Location: Iberian Peninsula and mainland France. Methods: 524 individuals from 54 populations across the species range were sampled to document patterns of genetic diversity and infer their evolutionary history based on data from mtDNA and fourteen polymorphic microsatellites. Generalized linear models based on distribution data were used to infer climatic favourability for the species in the present and in projected scenarios for the LIG, the Mid Holocene and the last glacial maximum (LGM). Results: Estimates of genetic diversity show a decreasing trend from south to north, suggesting persistence of higher historical population sizes in the southern Iberian Peninsula. Species distribution models show differences in climatic favourability through time, with significant correlations between historically stable favourable areas and current patterns of genetic diversity. These results are corroborated by Bayesian Skyline Plots and continuous diffusion phylogeographic analyses. Main conclusions: The results indicate the presence of southern refugia, with moderate recent expansions at the northern end of the species’ range. Populations at the northern range margin exhibit the lowest genetic diversity and occupy historically unstable areas, classified as marginal in terms of favourability, rendering them most vulnerable to climate-mediated changes in the medium to long term