Generation and Biological Properties of a Recombinant Dodecahedron Containing the Short Fiber Protein of the Human Adenovirus 41

Objective: In order to gain further insight into the function of the enteric adenovirus short fiber (SF), we have constructed a recombinant dodecahedron containing the SF protein of HAdV-41 and the HAdV-3 penton base. Methods: Recombinant baculoviruses expressing the HAdV-41 SF protein and HAdV-3 penton base were cloned and amplified in Sf9 insect cells. Recombinant dodecahedra were expressed by coinfection of High Five (TM) cells with both baculoviruses, 72 h post-infection. Cell lysate was centrifuged on sucrose density gradient and the purified recombinant dodecahedra were recovered. Results: Analysis by negative staining electron microscopy demonstrated that chimeric dodecahedra made of the HAdV-3 penton base and decorated with the HAdV-41 SF were successfully generated. Next, recombinant dodecahedra were digested with pepsin and analyzed by Western blot. A 'site-specific' proteolysis of the HAdV-41 SF was observed, while the HAdV-3 penton base core was completely digested. Conclusion: These results show that, in vitro, the HAdV-41 SF likely undergoes proteolysis in the gastrointestinal tract, its natural environment, which may facilitate the recognition of receptors in intestinal cells. The results obtained in the present study may be the basis for the development of gene therapy vectors towards the intestinal epithelium, as well as orally administered vaccine vectors, but also for the HAdV-41 SF partner identification. Copyright (C) 2011 S. Karger AG, Basel

In situ Evaluation of the Erosive Potential of Orange Juice Modified by Food Additives

The aim of this study was to evaluate the erosive potential of orange juice modified with food-approved additives: 0.4 g/l of calcium (Ca) from calcium lactate pentahydrate, 0.2 g/l of linear sodium polyphosphate (LPP) or their combination (Ca+LPP) were added to a commercially available orange juice (negative control, C-). A commercially available calcium-modified orange juice (1.6 g/l of calcium) was the positive control (C+). These juices were tested using a short-term erosion in situ model, consisting of a five-phase, single-blind crossover clinical trial involving 10 subjects. In each phase, subjects inserted custom-made palatal appliances containing 8 bovine enamel specimens in the mouth and performed erosive challenges for a total of 0 (control), 10, 20, and 30 min. Two specimens were randomly removed from the appliances after each challenge period. Enamel surface microhardness was measured before and after the clinical phase and the percentage of surface microhardness change (%SMC) was determined. Before the procedures, in each phase, the subjects performed a taste test, where the juice assigned to that phase was blindly compared to C-. Overall, C+ showed the lowest %SMC, being the least erosive solution (p < 0.05), followed by Ca+LPP and Ca, which did not differ from each other (p > 0.05). LPP and C- were the most erosive solutions (p <0.05). Taste differences were higher for C+ (5/10 subjects) and Ca (4/10 subjects), but detectable in all groups, including C- (2/10 subjects). Calcium reduced the erosive potential of the orange juice, while no protection was observed for LPP. Copyright (C) 2012 S. Karger AG, Basel

Early IL-10 production is essential for syngeneic graft acceptance

We performed a comparative study and evaluated cellular infiltrates and anti-inflammatory cytokine production at different time-points after syngeneic or allogeneic skin transplantation. We observed an early IL-10 production in syngeneic grafts compared with allografts. This observation prompted us to investigate the role of IL-10 in isograft acceptance. For this, we used IL-10 KO and WT mice to perform syngeneic transplantation, where IL-10 was absent in the graft or in the recipient. The majority of syngeneic grafts derived from IL-10 KO donors did not engraft or was only partially accepted, whereas IL-10 KO mice transplanted with skin from WT donors accepted the graft. We evaluated IL-10 producers in the transplanted skin and observed that epithelial cells were the major source. Taken together, our data show that production of IL-10 by donor cells, but not by the recipient, is determinant for graft acceptance and strongly suggest that production of this cytokine by keratinocytes immediately upon transplantation is necessary for isograft survival. J. Leukoc. Biol. 92: 259-264; 2012.

M-ficolin and leukosialin (CD43): new partners in neutrophil adhesion

M-ficolin specificity for sialylated ligands prompted us to investigate its interactions with the main membrane sialoprotein of human neutrophils, CD43. rM-ficolin bound CD43 and prevented the access of anti-CD43 mAb. Moreover, rM-ficolin reacted exclusively with CD43 on Western blots of neutrophil lysate. We confirmed that M-ficolin is secreted by fMLP-activated neutrophils, and this endogenous M-ficolin also binds to CD43 and competes with anti-CD43 mAb. Anti-CD43 antibody cross-linking or fMLP resulted in M-ficolin and CD43 colocalization on polarized neutrophils. The binding of rM-ficolin to resting neutrophils induced cell polarization, adhesion, and homotypic aggregation as anti-CD43 mAb. The M-ficolin Y271F mutant, unable to bind sialic acid, neither reacted with neutrophils nor modulated their functions. Finally, rM-ficolin activated the lectin complement pathway on neutrophils. These results emphasize a new function of M-ficolin, different from ficolin pathogen recognition, i.e., a participation to neutrophil adhesion potentially important in early inflammation, as nanomolar agonist concentrations are sufficient to mobilize M-ficolin to the neutrophil surface. This multivalent lectin could then endow the antiadhesive CD43, essentially designed to prevent leukocyte aggregation in the blood flow, with new adhesive properties and explain, at least in part, dual-adhesive/antiadhesive roles of CD43 in neutrophil recruitment. J. Leukoc. Biol. 91: 469-474; 2012.

Previous Exposure to Cigarette Smoke Aggravates Experimental Cyclosporine-Induced Nephrotoxicity

Background/Aims: The effects of cigarette smoke (CS) on cyclosporine (CsA)-induced nephrotoxicity are poorly studied. This study aims to assess the effects of previous exposure to CS on CsA nephrotoxicity. Methods: Rats were either exposed to CS or sham (S) procedures for 10 min twice a day for 20 weeks. From the 16th to the 20th week, they received a low-salt diet. Beginning with the 17th week, they were given 2.5 mg/day CsA or vehicle (VH) for 3 weeks. The final groups were VH/CS, CsA/CS, VH/S, and CsA/S. On day 141, glomerular filtration rate (GFR), renal blood flow (RBF), renal vascular resistance (RVR), tubulointerstitial fibrosis, and CsA blood levels were measured and immunohistochemistry was analyzed for renal alpha-smooth muscle actin (SMA), nitrotyrosine, and vimentin. Results: CsA decrease in GFR was enhanced by CS exposure. CsA associated with CS induced higher periglomerular alpha-SMA and renal nitrotyrosine expression. CsA decreased RBF, but increased RVR, tubulointerstitial fibrosis, and alpha-SMA and renal vimentin expression. These changes and the CsA blood levels were not affected by CS exposure. Conclusion: CS aggravated the CsA-induced impairment of GFR and CS associated with CsA caused the development of periglomerular structural lesions and oxidative stress in a rat model of CsA nephrotoxicity. Copyright (C) 2012 S. Karger AG, Basel

Decreased Reelin Expression in the Left Prefrontal Cortex (BA9) in Chronic Schizophrenia Patients

Background: Reelin is under epigenetic control and has been reported to be decreased in cortical regions in schizophrenia. Methods: To establish if expression of reelin is altered in specific cortical, hippocampal or thalamic regions of schizophrenia patients, we measured gene expression of reelin in a postmortem study of elderly patients with schizophrenia and non-affected controls in both hemispheres differentiating between gray and white matter. We compared cerebral postmortem samples (dorsolateral prefrontal cortex BA9 and BA46, superior temporal cortex BA22, entorhinal cortex BA28, sensoric cortex BA1-3, hippocampus, CA4, mediodorsal nucleus of the thalamus) from 12 schizophrenia patients with 13 normal subjects investigating gene expression of reelin in the gray and white matter of both hemispheres by in situ-hybridization. Results: The left prefrontal area (BA9) of schizophrenia patients revealed a decreased expression of reelin-mRNA of 29.1% in the white (p = 0.022) and 13.6% in the gray matter (p = 0.007) compared to the control group. None of the other regions examined showed any statistically significant differences. Conclusion: Since reelin is responsible for migration and synapse formation, the decreased gene expression of reelin in the left prefrontal area of schizophrenia patients points to neurodevelopmental deficits in neuronal migration and synaptic plasticity. However, our study group was small, and results should be verified using larger samples. Copyright (C) 2012 S. Karger AG, Basel

Expansion of a subset of CD14(high)CD16(neg)CCR2(low/neg) monocytes functionally similar to myeloid-derived suppressor cells during SIV and HIV infection

Monocytes have been categorized in three main subpopulations based on CD14 and CD16 surface expression. Classical monocytes express the CD14(++)CD16(-) CCR2(+) phenotype and migrate to inflammatory sites by quickly responding to CCL2 signaling. Here, we identified and characterized the expansion of a novel monocyte subset during HIV and SIV infection, which were undistinguishable from classical monocytes, based on CD14 and CD16 expression, but expressed significantly lower surface CCR2. Transcriptome analysis of sorted cells demonstrated that the CCR2(low/neg) cells are a distinct subpopulation and express lower levels of inflammatory cytokines and activation markers than their CCR2(high) counterparts. They exhibited impaired phagocytosis and greatly diminished chemotaxis in response to CCL2 and CCL7. In addition, these monocytes are refractory to SIV infection and suppress CD8(+) T cell proliferation in vitro. These cells express higher levels of STAT3 and NOS2, suggesting a phenotype similar to monocytic myeloid-derived cells, which suppress expansion of CD8(+) T cells in vivo. They may reflect an antiproliferative response against the extreme immune activation observed during HIV and SIV infections. In addition, they may suppress antiviral responses and thus, have a role in AIDS pathogenesis. Antiretroviral therapy in infected macaque and human subjects caused this population to decline, suggesting that this atypical phenotype is linked to viral replication. J. Leukoc. Biol. 91: 803-816; 2012.

Using exercise training to counterbalance chronotropic incompetence and delayed heart rate recovery in systemic lupus erythematosus: a randomized trial

Objective. To evaluate the efficacy of a 3-month exercise training program in counteracting the chronotropic incompetence and delayed heart rate recovery in patients with systemic lupus erythematosus (SLE). Methods. A 12-week randomized trial was conducted. Twenty-four inactive SLE patients were randomly assigned into 2 groups: trained (T; n = 15, 3-month exercise program) and nontrained (NT; n = 13). A sex-, body mass index-, and age-matched healthy control (C) group (n = 8) also underwent the exercise program. Subjects were assessed at baseline and at 12 weeks after training. Main measurements included the chronotropic reserve (CR) and the heart rate (HR) recovery (Delta HRR) as defined by the difference between HR at peak exercise and at both the first (Delta HRR1) and second (Delta HRR2) minutes after the exercise test. Results. Neither the NT SLE patients nor the C group presented any change in the CR or in Delta HRR1 and Delta HRR2 (P > 0.05). The exercise training program was effective in promoting significant increases in CR (P = 0.007, effect size [ES] 1.15) and in Delta HRR1 and Delta HRR2 (P = 0.009, ES 1.12 and P = 0.002, ES 1.11, respectively) in the SLE T group when compared with the NT group. Moreover, the HR response in SLE patients after training achieved parameters comparable to the C group, as evidenced by the analysis of variance and by the Z score analysis (P > 0.05, T versus C). Systemic Lupus Erythematosus Disease Activity Index scores remained stable throughout the study. Conclusion. A 3-month exercise training program was safe and capable of reducing the chronotropic incompetence and the delayed Delta HRR observed in physically inactive SLE patients.

High Cholesterol Feeding May Induce Tubular Dysfunction Resulting in Hypomagnesemia

Background/Aims: Hypomagnesemia may induce hypercholesterolemia, but the contrary has not been described yet. Thus, magnesium homeostasis was evaluated in rats fed a cholesterol-enriched diet for 8 days. This study has a relevant clinical application if hypomagnesemia, due to hypercholesterolemia, is confirmed in patients with long-term hypercholesterolemia. Methods: Both hypercholesterolemic (HC) and normocholesterolemic rats (NC) were divided into sets of experiments to measure hemodynamic parameters, physiological data, maximum capacity to dilute urine (C-H2O), variations (Delta) in [Ca2+](i) and the expression of transporter proteins. Results: HC developed hypomagnesemia and showed high magnesuria in the absence of hemodynamic abnormalities. However, the urinary sodium excretion and C-H2O in HC was similar to NC. On the other hand, the responses to angiotensin II by measuring Delta [Ca2+](i) were higher in the thick ascending limb of Henle's loop (TAL) of HC than NC. Moreover, high expression of the cotransporter NKCC2 was found in renal outer medulla fractions of HC. Taken together, the hypothesis of impairment in TAL was excluded. Actually, the expression of the epithelial Mg2+ channel in renal cortical membrane fractions was reduced in HC. Conclusion: Impairment in distal convoluted tubule induced by hypercholesterolemia explains high magnesuria and hypomagnesemia observed in HC. Copyright (C) 2011 S. Karger AG, Basel

Video Quality Assessments on Digital TV and Video Streaming Services Using Objective Metrics

There is a wide range of telecommunications services that transmit voice, video and data through complex transmission networks and in some cases, the service has not an acceptable quality level for the end user. In this sense the study of methods for assessing video quality and voice have a very important role. This paper presents a classification scheme, based on different criteria, of the methods and metrics that are being studied in recent years. This paper presents how the video quality is affected by degradation in the transmission channel in two kinds of services: Digital TV (ISDB-TB) due the fading in the air interface and video streaming service on an IP network due packet loss. For Digital TV tests was set up a scenario where the digital TV transmitter is connected to an RF channel emulator, where are inserted different fading models and at the end, the videos are saved in a mobile device. The tests of streaming video were performed in an isolated scenario of IP network, which are scheduled several network conditions, resulting in different qualities of video reception. The video quality assessment is performed using objective assessment methods: PSNR, SSIM and VQM. The results show how the losses in the transmission channel affects the quality of end-user experience on both services studied.

Mayaro Virus Infection in Amazonia: A Multimodel Inference Approach to Risk Factor Assessment

Background: Arboviral diseases are major global public health threats. Yet, our understanding of infection risk factors is, with a few exceptions, considerably limited. A crucial shortcoming is the widespread use of analytical methods generally not suited for observational data - particularly null hypothesis-testing (NHT) and step-wise regression (SWR). Using Mayaro virus (MAYV) as a case study, here we compare information theory-based multimodel inference (MMI) with conventional analyses for arboviral infection risk factor assessment. Methodology/Principal Findings: A cross-sectional survey of anti-MAYV antibodies revealed 44% prevalence (n = 270 subjects) in a central Amazon rural settlement. NHT suggested that residents of village-like household clusters and those using closed toilet/latrines were at higher risk, while living in non-village-like areas, using bednets, and owning fowl, pigs or dogs were protective. The "minimum adequate" SWR model retained only residence area and bednet use. Using MMI, we identified relevant covariates, quantified their relative importance, and estimated effect-sizes (beta +/- SE) on which to base inference. Residence area (beta(Village) = 2.93 +/- 0.41; beta(Upland) = -0.56 +/- 0.33, beta(Riverbanks) = -2.37 +/- 0.55) and bednet use (beta = -0.95 +/- 0.28) were the most important factors, followed by crop-plot ownership (beta = 0.39 +/- 0.22) and regular use of a closed toilet/latrine (beta = 0.19 +/- 0.13); domestic animals had insignificant protective effects and were relatively unimportant. The SWR model ranked fifth among the 128 models in the final MMI set. Conclusions/Significance: Our analyses illustrate how MMI can enhance inference on infection risk factors when compared with NHT or SWR. MMI indicates that forest crop-plot workers are likely exposed to typical MAYV cycles maintained by diurnal, forest dwelling vectors; however, MAYV might also be circulating in nocturnal, domestic-peridomestic cycles in village-like areas. This suggests either a vector shift (synanthropic mosquitoes vectoring MAYV) or a habitat/habits shift (classical MAYV vectors adapting to densely populated landscapes and nocturnal biting); any such ecological/adaptive novelty could increase the likelihood of MAYV emergence in Amazonia.

Optimal Timing for Assessment of Tumor Response to Neoadjuvant Chemoradiation in Patients With Rectal Cancer: Do All Patients Benefit From Waiting Longer Than 6 Weeks?

Purpose: To estimate the metabolic activity of rectal cancers at 6 and 12 weeks after completion of chemoradiation therapy (CRT) by 2-[fluorine-18] fluoro-2-deoxy-D-glucose-labeled positron emission tomography/computed tomography ([18 FDG] PET/CT) imaging and correlate with response to CRT. Methods and Materials: Patients with cT2-4N0-2M0 distal rectal adenocarcinoma treated with long-course neoadjuvant CRT (54 Gy, 5-fluouracil-based) were prospectively studied (ClinicalTrials. org identifier NCT00254683). All patients underwent 3 PET/CT studies (at baseline and 6 and 12 weeks fromCRT completion). Clinical assessment was at 12 weeks. Maximal standard uptakevalue (SUVmax) of the primary tumor wasmeasured and recorded at eachPET/CTstudy after 1 h (early) and3 h (late) from 18 FDGinjection. Patientswith an increase in early SUVmax between 6 and 12 weeks were considered " bad" responders and the others as "good" responders. Results: Ninety-one patients were included; 46 patients (51%) were "bad" responders, whereas 45 (49%) patients were " good" responders. " Bad" responders were less likely to develop complete clinical response (6.5% vs. 37.8%, respectively; PZ. 001), less likely to develop significant histological tumor regression (complete or near-complete pathological response; 16% vs. 45%, respectively; PZ. 008) and exhibited greater final tumor dimension (4.3cmvs. 3.3cm; PZ. 03). Decrease between early (1 h) and late (3 h) SUVmax at 6-week PET/CTwas a significant predictor of " good" response (accuracy of 67%). Conclusions: Patients who developed an increase in SUVmax after 6 weeks were less likely to develop significant tumor downstaging. Early-late SUVmax variation at 6-week PET/CT may help identify these patients and allow tailored selection of CRT-surgery intervals for individual patients. (C) 2012 Elsevier Inc.

Validation of fingernail fluoride concentration as a predictor of risk for dental fluorosis

The aim of this study was to validate the use of fingernail fluoride concentrations at ages 2-7 years as predictors of the risk for developing dental fluorosis in the permanent dentition. Fifty-six children of both genders (10-15 years of age) had their incisors and premolars examined for dental fluorosis using the Thylstrup-Fejerskov index. Fingernail fluoride concentrations were obtained from previous studies when children were 2-7 years of age. Data were analyzed by unpaired t test, ANOVA, and Fisher's exact test when the fingernail fluoride concentrations were dichotomized (<= 2 or > 2 mu g/g). Children with dental fluorosis had significantly higher fingernail fluoride concentrations than those without the condition, and the concentrations tended to increase with the severity of fluorosis (r(2) = 0.47, p < 0.0001). Using a fingernail fluoride concentration of 2 mu g/g at ages 2-7 years as a threshold, this biomarker had high sensitivity (0.84) and moderate specificity (0.53) as a predictor for dental fluorosis. The high positive predictive value indicates that fingernail fluoride concentrations should be useful in public health research, since it has the potential to identify around 80% of children at risk of developing dental fluorosis. Copyright (C) 2012 S. Karger AG, Basel

Can Roads Be Used as Transects for Primate Population Surveys?

Line transect distance sampling (LTDS) can be applied to either trails or roads. However, it is likely that sampling along roads might result in biased density estimates. In this paper, we compared the results obtained with LTDS applied on trails and roads for two primate species (Callithrix penicillata and Callicebus nigrifrons) to clarify whether roads are appropriate transects to estimate densities. We performed standard LTDS surveys in two nature reserves in south-eastern Brazil. Effective strip width and population density were different between trails and roads for C. penicillata, but not for C. nigrifrons. The results suggest that roads are not appropriate for use as transects in primate surveys, at least for some species. Further work is required to fully understand this issue, but in the meantime we recommend that researchers avoid using roads as transects or treat roads and trails as covariates when sampling on roads is unavoidable. Copyright (C) 2012 S. Karger AG, Basel

Vitamin E Alters Inflammatory Gene Expression in Alcoholic Chronic Pancreatitis

Objective: To evaluate the effect of vitamin E supplementation on pancreatic gene expression of inflammatory markers in rats with alcoholic chronic pancreatitis. Methods: Wistar rats were divided into 3 groups: control (1), alcoholic chronic pancreatitis without (2) and with (3) vitamin E supplementation. Pancreatitis was induced by a liquid diet containing ethanol, cyclosporin A and cerulein. a-tocopherol content in plasma and liver and pancreas histopathology were analyzed. Gene expression of inflammatory biomarkers was analyzed by the quantitative real-time PCR technique. Results: The animals that received vitamin E supplementation had higher alpha-tocopherol amounts in plasma and liver. The pancreas in Group 1 showed normal histology, whereas in Groups 2 and 3, mild to moderate tissue destruction foci and mononuclear cell infiltration were detected. Real-time PCR analysis showed an increased expression of all genes in Groups 2 and 3 compared to Group 1. Vitamin E supplementation decreased the transcript number of 5 genes (alpha-SMA, COX-2, IL-6, MIP-3 alpha and TNF-alpha) and increased the transcript number of 1 gene (Pap). Conclusion: Vitamin E supplementation had anti-inflammatory and beneficial effects on the pancreatic gene expression of some inflammatory biomarkers in rats with alcoholic chronic pancreatitis, confirming its participation in the inflammatory response mechanisms in the pancreas. Copyright (c) 2012 S. Karger AG, Basel