Loss of Y-chromosome does not correlate with age at onset of head and neck carcinoma: a case-control study

Loss of Y-chromosome has been correlated with older age in males. Furthermore, current evidence indicates that Y-chromosome loss also occurs in several human tumors, including head and neck carcinomas. However, the association between Y nullisomy and the occurrence of neoplasias in elderly men has not been well established. In the present study, the association between Y-chromosome loss and head and neck carcinomas was evaluated by comparison to cells from peripheral blood lymphocytes and normal mucosa of cancer-free individuals matched for age using dual-color fluorescence in situ hybridization. Twenty-one patients ranging in age from 28 to 68 years were divided into five-year groups for comparison with 16 cancer-free individuals matched for age. The medical records of all patients were examined to obtain clinical and histopathological data. None of the patients had undergone radiotherapy or chemotherapy before surgery. In all groups, the frequency of Y-chromosome loss was higher among patients than among normal reference subjects (P < 0.0001) and was not age-dependent. These data suggest that Y-chromosome loss is a tumor-specific alteration not associated with advanced age in head and neck carcinomas.

Clinico-genetic aspects of a pediatric non-neurofibromatosis type 1 malignant triton tumor with loss of chromosome X

Malignant triton tumor (MTT) is an aggressive peripheral nerve sheath tumor with rhabdomyoblastic differentiation. Less than 100 cases have been described, being mostly male children with type 1 neurofibromatosis. We report a 6-year-old female with MTT and no diagnostic criteria for neurofibromatosis type 1. Cytogenetic analysis showed a 46,X,-X[4]/46,XX[16] karyotype. She underwent a transfemoral amputation and chemotherapy and is free of disease 15 months after diagnosis. The few cytogenetic studies of MTT described in the literature have been inconclusive. Further cytogenetic analyses are needed to understand the role of chromosome X monosomy in the pathogenesis of this rare tumor. Pediatr Blood Cancer 2012; 59: 13201323. (C) 2012 Wiley Periodicals, Inc.

Loss of male secondary sexual structures in allopatry in the Neotropical butterfly genus Arcas (Lycaenidae: Iheclinae: Eumaeini)

Male secondary sexual characters in Lepidoptera may be present or absent in species that otherwise appear to be closely related, an observation that has led to differences of opinion over the taxonomic usefulness of these structures above the species level. An evolutionary issue raised by this debate is whether male secondary sexual characters (1) can be regained after being lost evolutionarily, (2) are not lost after being evolved, or (3) are 'switched on and off' by genes that regulate development. A second evolutionary issue is the conditions under which male secondary sexual characters might be lost or gained evolutionarily. Because these structures are thought to promote species recognition, theory predicts evolutionary losses to be most likely in allopatry; evolutionary gains to be most likely during the process of secondarily establishing sympatry or during sympatric speciation. We updated the species-level taxonomy of the brilliant emerald winged Neotropical lycaenid butterfly genus Arcas and performed an analysis of phylogenetic relations among species to assess these evolutionary issues. We morphologically detail a scent pouch on the ventral hindwing of Areas and report that six species possess the pouch with androconia, one possesses the pouch without androconia, and the remaining two species have neither pouch nor androconia. In addition, eight Areas species have a morphologically species-specific male forewing scent pad, and one lacks a scent pad. This variation appears to be the result of three evolutionary losses and no gains of male secondary sexual organs. The four Areas species lacking a scent pouch or a scent pad are allopatric with their closest phylogenetic relatives while four of five with both of these structures are sympatric. Although Arcas is a small genus, these results are significantly more extreme than predicted by chance. For taxonomy, this study provides a rationale for the evolutionary loss of male secondary sexual structures and suggests that their absence, but itself, does not indicate a lack of relationship above the species level.

Assessment of the high-dose concept and level of control provided by MON 87701 x MON 89788 soybean against Anticarsia gemmatalis and Pseudoplusia includens (Lepidoptera: Noctuidae) in Brazil

BACKGROUND: Genetically modified MON 87701 X MON 89788 soybean (Glycine max), which expresses the Cry1Ac and EPSP-synthase proteins, has been registered for commercial use in Brazil. To develop an Insect Resistance Management (IRM) program for this event, laboratory and field studies were conducted to assess the high-dose concept and level of control it provides against Anticarsia gemmatalis and Pseudoplusia includens. RESULTS: The purified Cry1Ac protein was more active against A. gemmatalis [LC50 (FL 95%) = 0.23 (0.150.34) mu g Cry1Ac mL-1 diet] than P. includens [LC50 (FL 95%) = 3.72 (2.654.86) mu g Cry1Ac mL-1 diet]. In bioassays with freeze-dried MON 87701X MON 89788 soybean tissue diluted 25 times in an artificial diet, there was 100% mortality of A. gemmatalis and up to 95.79% mortality for P. includens. In leaf-disc bioassays and under conditions of high artificial infestation in the greenhouse and natural infestation in the field, MON 87701X MON 89788 soybean showed a high level of efficacy against both target pests. CONCLUSIONS: The MON 87701X MON 89788 soybean provides a high level of control against A. gemmatalis and P. includes, but a high-dose event only to A. gemmatalis. Copyright (c) 2012 Society of Chemical Industry

Loss of Interleukin-10 Signaling and Infantile Inflammatory Bowel Disease: Implications for Diagnosis and Therapy

BACKGROUND & AIMS: Homozygous loss of function mutations in interleukin-10 (IL10) and interleukin-10 receptors (IL10R) cause severe infantile (very early onset) inflammatory bowel disease (IBD). Allogeneic hematopoietic stem cell transplantation (HSCT) was reported to induce sustained remission in 1 patient with IL-10R deficiency. We investigated heterogeneity among patients with very early onset IBD, its mechanisms, and the use of allogeneic HSCT to treat this disorder. METHODS: We analyzed 66 patients with early onset IBD (younger than 5 years of age) for mutations in the genes encoding IL-10, IL-10R1, and IL-10R2. IL-10R deficiency was confirmed by functional assays on patients' peripheral blood mononuclear cells (immunoblot and enzyme-linked immunosorbent assay analyses). We assessed the therapeutic effects of standardized allogeneic HSCT. RESULTS: Using a candidate gene sequencing approach, we identified 16 patients with IL-10 or IL-10R deficiency: 3 patients had mutations in IL-10, 5 had mutations in IL-10R1, and 8 had mutations in IL-10R2. Refractory colitis became manifest in all patients within the first 3 months of life and was associated with perianal disease (16 of 16 patients). Extraintestinal symptoms included folliculitis (11 of 16) and arthritis (4 of 16). Allogeneic HSCT was performed in 5 patients and induced sustained clinical remission with a median follow-up time of 2 years. In vitro experiments confirmed reconstitution of IL-10R-mediated signaling in all patients who received the transplant. CONCLUSIONS: We identified loss of function mutations in IL-10 and IL-10R in patients with very early onset IBD. These findings indicate that infantile IBD patients with perianal disease should be screened for IL-10 and IL-10R deficiency and that allogeneic HSCT can induce remission in those with IL-10R deficiency.

Representation and analysis of control surface freeplay nonlinearity

Different representations for a control surface freeplay nonlinearity in a three degree of freedom aeroelastic system are assessed. These are the discontinuous, polynomial and hyperbolic tangent representations. The Duhamel formulation is used to model the aerodynamic loads. Assessment of the validity of these representations is performed through comparison with previous experimental observations. The results show that the instability and nonlinear response characteristics are accurately predicted when using the discontinuous and hyperbolic tangent representations. On the other hand, the polynomial representation fails to predict chaotic motions observed in the experiments. (c) 2012 Elsevier Ltd. All rights reserved.

Vascular smooth muscle cells exhibit a progressive loss of rigidity with serial culture passaging

One drawback of in vitro cell culturing is the dedifferentiation process that cells experience. Smooth muscle cells (SMC) also change molecularly and morphologically with long term culture. The main objective of this study was to evaluate if culture passages interfere in vascular SMC mechanical behavior. SMC were obtained from five different porcine arterial beds. Optical magnetic twisting cytometry (OMTC) was used to characterize mechanically vascular SMC from different cultures in distinct passages and confocal microscopy/western blotting, to evaluate cytoskeleton and extracellular matrix proteins. We found that vascular SMC rigidity or viscoelastic complex modulus (G) decreases with progression of passages. A statistically significant negative correlation between G and passage was found in four of our five cultures studied. Phalloidin-stained SMC from higher passages exhibited lower mean signal intensity per cell (confocal microscopy) and quantitative western blotting analysis showed a decrease in collagen I content throughout passages. We concluded that vascular SMC progressively lose their stiffness with serial culture passaging. Thus, limiting the number of passages is essential for any experiment measuring viscoelastic properties of SMC in culture.

Effect of Plastic Deformation on the Excess Loss of Electrical Steel

The interpretation of the effect of plastic deformation on the calculated excess loss component (anomalous-loss) supports the concept of loss separation. Magnetic losses and Barkhausen noise of nonoriented electrical steel sheets were measured on Epstein strips taken from a single coil of 0.8% Si nonoriented electrical steel. Sheets were extracted in the annealed condition, without any skin pass and with a grain size of 18 mu m. This material was cold rolled in order to obtain sets of samples with true strain from 2% up to 29%. X-ray diffraction was used to estimate the dislocation density. The analysis of magnetic properties was performed by Barkhausen noise measurements and also by analyzing the hysteresis loops obtained from Epstein frame measurements for different inductions and different frequencies (including the quasi-static regime for hysteresis loss measurements). These data allowed us to observe that most of the well known total loss increase with plastic deformation is due to an increase in the hysteresis loss component, while excess loss decreases to become negligible. This behavior can be explained if it is assumed that the plastic deformation lead to an increase in the number of domain walls per unit volume, thereby decreasing the excess loss. Barkhausen peak area increases with plastic deformation, reproducing results taken from samples of different silicon content.

Dynamic symmetry loss of high-frequency hysteresis loops in single-domain particles with uniaxial anisotropy

Understanding how magnetic materials respond to rapidly varying magnetic fields, as in dynamic hysteresis loops, constitutes a complex and physically interesting problem. But in order to accomplish a thorough investigation, one must necessarily consider the effects of thermal fluctuations. Albeit being present in all real systems, these are seldom included in numerical studies. The notable exceptions are the Ising systems, which have been extensively studied in the past, but describe only one of the many mechanisms of magnetization reversal known to occur. In this paper we employ the Stochastic Landau-Lifshitz formalism to study high-frequency hysteresis loops of single-domain particles with uniaxial anisotropy at an arbitrary temperature. We show that in certain conditions the magnetic response may become predominantly out-of-phase and the loops may undergo a dynamic symmetry loss. This is found to be a direct consequence of the competing responses due to the thermal fluctuations and the gyroscopic motion of the magnetization. We have also found the magnetic behavior to be exceedingly sensitive to temperature variations, not only within the superparamagnetic-ferromagnetic transition range usually considered, but specially at even lower temperatures, where the bulk of interesting phenomena is seen to take place. (C) 2011 Elsevier B.V. All rights reserved.

The association between coronary artery calcification progression and loss of bone density in non-dialyzed CKD patients

Background: Coronary artery calcification (CAC) and low bone density are coexisting deleterious conditions commonly shared by chronic kidney disease (CKD) patients. In the present study, we aimed to investigate whether the progression of CAC was associated with overtime reduction in bone density in non-dialyzed CKD patients. Methods: This is a prospective study of 24 months including 72 non-dialyzed CKD patients Stages 2 - 4 (age 57.6 +/- 10.3 years, 62% male, 22% diabetics). CAC and vertebral bone density (VBD) were measured by computed tomography. Results: At baseline, 46% of the patients had CAC (calcified group) and calcification was not identified in 54% of the patients (non-calcified group). The calcified group was older, predominantly male, and had lower VBD in comparison to non-calcified group. CAC progression was observed only in the calcified group (91% of the patients increased calcium score). The multiple regression analysis revealed loss of VBD as the independent determinant of CAC progression in these patients. Conclusion: CAC progression was associated with loss of VBD in non-dialyzed CKD patients.

Loss of interest, depressed mood and impact on the quality of life: Cross-sectional survey

Abstract Background Depressive symptoms and chronic disease have adverse effects on patients' health-related quality of life (H-RQOL). However, little is known about this effect on H-RQOL when only the two core depressive symptoms - loss of interest and depressed mood - are considered. The objective of this study is to investigate H-RQOL in the presence of loss of interest and depressed mood at a general medical outpatient unit. Methods We evaluated 553 patients at their first attendance at a general medical outpatient unit of a teaching hospital. H-RQOL was assessed with the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). Depressed mood and loss of interest were assessed by the Primary Care Evaluation of Mental Disorders (PRIME-MD)-Patient Questionnaire. A physician performed the diagnosis of chronic diseases by clinical judgment and classified them in 13 possible pre-defined categories. We used multiple linear regression to investigate associations between each domain of H-RQOL and our two core depression symptoms. The presence of chronic diseases and demographic variables were included in the models as covariates. Results Among the 553 patients, 70.5% were women with a mean age of 41.0 years (range 18-85, SD ± 15.4). Loss of interest was reported by 54.6%, and depressed mood by 59.7% of the patients. At least one chronic disease was diagnosed in 59.5% of patients; cardiovascular disease was the most prevalent, affecting 20.6% of our patients. Loss of interest and depressed mood was significantly associated with decreased scores in all domains of H-RQOL after adjustment for possible confounders. The presence of any chronic disease was associated with a decrease in the domain of vitality. The analysis of each individual chronic disease category revealed that no category was associated with a decrease in more than one domain of H-RQOL. Conclusion Loss of interest and depressed mood were associated with significant decreases in H-RQOL. We recommend these simple tests for screening in general practice.

Loss of the anorexic response to systemic 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside administration despite reducing hypothalamic AMP-activated protein kinase phosphorylation in insulin-deficient rats

This study tested whether chronic systemic administration of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) could attenuate hyperphagia, reduce lean and fat mass losses, and improve whole-body energy homeostasis in insulin-deficient rats. Male Wistar rats were first rendered diabetic through streptozotocin (STZ) administration and then intraperitoneally injected with AICAR for 7 consecutive days. Food and water intake, ambulatory activity, and energy expenditure were assessed at the end of the AICAR-treatment period. Blood was collected for circulating leptin measurement and the hypothalami were extracted for the determination of suppressor of cytokine signaling 3 (SOCS3) content, as well as the content and phosphorylation of AMP-kinase (AMPK), acetyl-CoA carboxylase (ACC), and the signal transducer and activator of transcription 3 (STAT3). Rats were thoroughly dissected for adiposity and lean body mass (LBM) determinations. In non-diabetic rats, despite reducing adiposity, AICAR increased (∼1.7-fold) circulating leptin and reduced hypothalamic SOCS3 content and food intake by 67% and 25%, respectively. The anorexic effect of AICAR was lost in diabetic rats, even though hypothalamic AMPK and ACC phosphorylation markedly decreased in these animals. Importantly, hypothalamic SOCS3 and STAT3 levels remained elevated and reduced, respectively, after treatment of insulin-deficient rats with AICAR. Diabetic rats were lethargic and displayed marked losses of fat and LBM. AICAR treatment increased ambulatory activity and whole-body energy expenditure while also attenuating diabetes-induced fat and LBM losses. In conclusion, AICAR did not reverse hyperphagia, but it promoted anti-catabolic effects on skeletal muscle and fat, enhanced spontaneous physical activity, and improved the ability of rats to cope with the diabetes-induced dysfunctional alterations in glucose metabolism and whole-body energy homeostasis.

Numerical analysis of control surface effects on AUV

Computational fluid dynamics, CFD, is becoming an essential tool in the prediction of the hydrodynamic efforts and flow characteristics of underwater vehicles for manoeuvring studies. However, when applied to the manoeuvrability of autonomous underwater vehicles, AUVs, most studies have focused on the de- termination of static coefficients without considering the effects of the vehicle control surface deflection. This paper analyses the hydrodynamic efforts generated on an AUV considering the combined effects of the control surface deflection and the angle of attack using CFD software based on the Reynolds-averaged Navier–Stokes formulations. The CFD simulations are also independently conducted for the AUV bare hull and control surface to better identify their individual and interference efforts and to validate the simulations by comparing the experimental results obtained in a towing tank. Several simulations of the bare hull case were conducted to select the k –ω SST turbulent model with the viscosity approach that best predicts its hydrodynamic efforts. Mesh sensitivity analyses were conducted for all simulations. For the flow around the control surfaces, the CFD results were analysed according to two different methodologies, standard and nonlinear. The nonlinear regression methodology provides better results than the standard methodology does for predicting the stall at the control surface. The flow simulations have shown that the occurrence of the control surface stall depends on a linear relationship between the angle of attack and the control surface deflection. This type of information can be used in designing the vehicle’s autopilot system.

High-fat diet causes an imbalance in the colonic serotonergic system promoting adipose tissue enlargement and dysplasia in rats

A high-fat (HF) diet, the serotonergic system and stromal elements have all been implicated in colon carcinogenesis. We investigated whether the colonic serotonergic system could play a main role in the development of colonic dysplasia and stromal reactivity in carcinogen-treated rats under HF diet. For this, dimethylhydrazine-treated rats were fed with standard diet and a HF diet. Fat distribution was quantified by computerized tomography exam, serotonergic activity was analyzed by high-performance liquid chromatography, gene expression, and immunohistochemistry, which along with histopathological technique enabled us to enumerate dysplasia, microvessels density, cell proliferation and COX-2 expression. We found that the HF diet induced an increase in the amount of viscera! adipose tissue, even without expressive changes in the average body weight. This was correlated with a loss of serotonergic balance in colon tissue. Moreover, the HF diet promoted dysplasia and microvessel density in association with increased proliferation and COX-2 expression within pericryptal colonic stroma. Our current findings suggest that a HF diet promotes the enlargement of adipose tissue via loss of control in colon serotonergic activity, which enhances colonic dysplasia by supporting microvessel development. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

GABA(B) receptor agonist only reduces ethanol drinking in light-drinking mice

Baclofen, a GABA(B) agonist, reduces ethanol intake in animals and humans, but the contrary or no effect was also reported. Our previous study demonstrated that mice characterized as "loss of control over ethanol intake" had different Gabbr1 and Gabbr2 transcription levels, which express, respectively, the GABA(B1) and GABA(B2) subunits in brain areas related to addictive behavior. In the present study, we tested baclofen on ethanol intake in mice exposed to the free-choice paradigm. Adult male Swiss mice, individually housed, had free access to three bottles: ethanol (5% and 10%) and water. The protocol had four phases: acquisition (AC, 10 weeks), withdrawal (W, 4 cycles during 2 weeks of 2 day-free-choice and 2 day-only-water), reexposure (RE, 2 weeks), and adulteration of ethanol solutions with quinine (AD, 2 weeks). Mice characterized as "loss of control" (A, n = 11, preference for ethanol in AC and maintenance of ethanol intake levels in AD), heavy (H, n = 11, preference for ethanol in AC and reduction of ethanol intake levels in AD), and light (L n = 16, preference for water in all phases) drinkers were randomly distributed into two subgroups receiving either intraperitoneal injections of all doses of baclofen (1.25, 2.5, and 5.0 mg/kg, given each dose twice in consecutive days) or saline, being exposed to free-choice. Fluid consumption was measured 24 h later. Baclofen reduced ethanol intake in group L In group H a reduction compared to AC was observed. Group A maintained their high ethanol intake even after baclofen treatment. Activation of the GABA(B) receptor depends on the precise balance between the GABA(B1) and GABA(B2) subunits, so the disproportionate transcription levels, we reported in group A, could explain this lack of response to baclofen. These data highlight the importance to test baclofen in individuals with different ethanol drinking profiles, including humans. (C) 2012 Elsevier Inc. All rights reserved.