Mathematical modelling of competitive LDL/VLDL binding and uptake by hepatocytes

Elevated levels of low-density-lipoprotein cholesterol (LDL-C) in the plasma are a well-established risk factor for the development of coronary heart disease. Plasma LDL-C levels are in part determined by the rate at which LDL particles are removed from the bloodstream by hepatic uptake. The uptake of LDL by mammalian liver cells occurs mainly via receptor-mediated endocytosis, a process which entails the binding of these particles to specific receptors in specialised areas of the cell surface, the subsequent internalization of the receptor-lipoprotein complex, and ultimately the degradation and release of the ingested lipoproteins' constituent parts. We formulate a mathematical model to study the binding and internalization (endocytosis) of LDL and VLDL particles by hepatocytes in culture. The system of ordinary differential equations, which includes a cholesterol-dependent pit production term representing feedback regulation of surface receptors in response to intracellular cholesterol levels, is analysed using numerical simulations and steady-state analysis. Our numerical results show good agreement with in vitro experimental data describing LDL uptake by cultured hepatocytes following delivery of a single bolus of lipoprotein. Our model is adapted in order to reflect the in vivo situation, in which lipoproteins are continuously delivered to the hepatocyte. In this case, our model suggests that the competition between the LDL and VLDL particles for binding to the pits on the cell surface affects the intracellular cholesterol concentration. In particular, we predict that when there is continuous delivery of low levels of lipoproteins to the cell surface, more VLDL than LDL occupies the pit, since VLDL are better competitors for receptor binding. VLDL have a cholesterol content comparable to LDL particles; however, due to the larger size of VLDL, one pit-bound VLDL particle blocks binding of several LDLs, and there is a resultant drop in the intracellular cholesterol level. When there is continuous delivery of lipoprotein at high levels to the hepatocytes, VLDL particles still out-compete LDL particles for receptor binding, and consequently more VLDL than LDL particles occupy the pit. Although the maximum intracellular cholesterol level is similar for high and low levels of lipoprotein delivery, the maximum is reached more rapidly when the lipoprotein delivery rates are high. The implications of these results for the design of in vitro experiments is discussed.

Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002). INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

Centennial changes in solar activity and the response of galactic cosmic rays

There is a growing consensus that the eleven year modulation of galactic cosmic rays (GCRs) resulting from solar activity is related to interplanetary propagating diffusive barriers (PDBs). The source of these PDBs is not well understood and numerical models describing GCR modulation simulate their effect by scaling the diffusion tensor to the interplanetary magnetic field strength (IMF). The implications of a century-scale change in solar wind speed and open solar flux, for numerical modelling of GCR modulation and the reconstruction of GCR variations over the last hundred years are discussed. The dominant role of the solar non-axisymmetric magnetic field in both forcing longitudinal solar wind speed fluctuations at solar maximum and in increasing the IMF is discussed in the context of a long-term rise in the open solar magnetic flux.

Striatum brain-derived neurotrophic factor levels are decreased in dystrophin-deficient mice

Brain dystrophin is enriched in the postsynaptic densities of pyramidal neurons specialized regions of the subsynaptic cytoskeletal network, which are critical for synaptic transmission and plasticity. Lack of dystrophin in brain structures have been involved with impaired cognitive functions. The brain-derived neurotrophic factor (BDNF) is a regulator of neuronal survival, fast synaptic transmission, and activity-dependent synaptic plasticity. The present study investigated BDNF protein levels by Elisa analysis in prefrontal cortex, cerebellum, hippocampus, striatum and cortex tissues from male dystrophic mdx (n = 5) and normal C57BL10 mouse (n = 5). We observed that the mdx mouse display diminution in BDNF levels in striatum (t = 6.073; df = 6; p = 0.001), while a tendency of decrease in BDNF levels was observed in the prefrontal cortex region (t = 1.962; df = 6; p = 0.096). The cerebellum (t = 1.258; df = 7; p = 0.249), hippocampus (t = 0.631; df = 7; p = 0.548) and cortex (t = 0.572; df = 7; p = 0.586) showed no significant alterations as compared to wt mouse. In conclusion, we demonstrate that only striatum decreased BDNF levels compared with wild-type (wt) mouse, differently to the other areas of the brain. This dystrophin deficiency may be affecting BDNF levels in striatum and contributing, in part, in memory storage and restoring. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

A singular integro-differential equation model for dryout in LMFBR boiler tubes

A 2D steady model for the annular two-phase flow of water and steam in the steam-generating boiler pipes of a liquid metal fast breeder reactor is proposed The model is based on thin-layer lubrication theory and thin aerofoil theory. The exchange of mass between the vapour core and the liquid film due to evaporation of the liquid film is accounted for using some simple thermodynamics models, and the resultant change of phase is modelled by proposing a suitable Stefan problem Appropriate boundary conditions for the now are discussed The resulting non-lineal singular integro-differential equation for the shape of the liquid film free surface is solved both asymptotically and numerically (using some regularization techniques) Predictions for the length to the dryout point from the entry of the annular regime are made The influence of both the traction tau provided by the fast-flowing vapour core on the liquid layer and the mass transfer parameter eta on the dryout length is investigated

Household survey of hepatitis B vaccine coverage among Brazilian children

We conducted a multi-stage household cluster survey to calculate hepatitis B vaccine coverage among children 18-30 months of age in 27 Brazilian cities. Hepatitis B vaccine is administered at birth, 1 month and 6 months of age by Brazil`s national immunization program. Among 17,749 children surveyed, 40.2% received a birth dose within one day of birth, 94.8% received at least one dose of hepatitis B vaccine, and 86.7% completed the three-dose series by 12 months of age. Increased coverage with the birth dose and administration of hepatitis B in combination with diphtheria-tetanus-pertussis-Haemophilus influenzae type b antigens could improve protection against hepatitis B. (C) 2009 Elsevier Ltd. All rights reserved.

Synthesis and characterization of lanthanum- and yttrium-doped Fe2O3 pigments

MELO, D. M. A. et al. Synthesis and charactezarion of lanthanum and yttrium doped Fe2O3 pigments. Cerâmica, São Paulo, v. 53, p. 79-82, 2007.

Vicilina de sementes da leguminosa selvagem Anadenanthera macrocarpa (AmV): purificação, caracterização, efeito deletério e mecanismo de ação para bruquídeo callosobruchus maculatus

Grains and legume seeds are foods that form the basis of the diets of many cultures around the world, winch contritbute to the daily nutrient requirements of humans. Vicilins (7S globulin) are storage proteins found in legume seeds, and may have an additional function constitutive defense of the embryo against pests and pathogens. In this work the vicilin from Anadenanthera macrocarpa - AmV (red-angico), was purified and partially characterized, its effect on development and larval survival and adult emergence of Callosobruchus maculatus was evaluated by determination of LD50, WD50 and ED50 in system bioassay. Purification of vicilin was initiated by the chitin affinity chromatography and then gel filtration (Superdex 75 Tricorn 10x300 mm) FPLC system followed by reverse phase chromatography (C8 phenomenex) on HPLC system. Bioassays WD50 and LD50 for larvae were 0.32% and 0.33% (w:w) respectively, since the ED50 for adults was 0.096%. The probable mechanism of action was evaluated by testing digestibility of AmV in vitro, and observed for the involvement of two fragments vicilins immunoreactive against polyclonal Anti-vicilin from Erythrina velutina (Anti-EvV) about of 22 and 13 kDa chitin binding. The AmV in its native form has been recognized by the anti-EvV, indicating that there is a conserved region in the vicilin and is probably corresponding to the chitin binding domains. These results point to a new vicilin chitin binding that can subsequently be used as a possible biopesticide protein source, in order to control insect pest C. maculatus and confirm literature findings that demonstrate vicilin in the presence of different kinds of ligands to conserved regions chitin not yet characterized

Análise de cDNAs identificados em bibliotecas substrativas de cDNA para floração de variedades de cana-de-açúcar cultivadas no Rio Grande do Norte(RN): fator de transição NAC, Calmodulina e Fosfatidiltransferase

The flowering is a physiological process that it is vital for plants. This physiological process has been well studied in the plant model Arabidopsis, but in sugarcane this process is not well known. The transition of the shoot apical meristem from vegetative to flowering is a critical factor for plant development. At Brazil northeastern region, the transition to flowering in sugarcane has an important effect as it may reduce up to 60% its production. This is a consequence of the sugar translocation from stalks to the shoot apical meristem which is necessary during the flowering process. Therefore, the aim of this work was to explore and analyze cDNAs previously identified using subtractive cDNA libraries. The results showed that these cDNAs showed differential expression profile in varieties of sugarcane (early x late flowering). The in silico analysis suggested that these cDNAs had homology to calmodulin, NAC transcription factor and phosphatidylinositol, a SEC14, which were described in the literature as having a role in the process of floral development. To better understand the role of the cDNA homologous to calmodulin, tobacco plants were transformed with overexpression cassettes in sense and antissense orientation. Plants overexpressing the cassette in sense orientation did not flowered, while plants overexpressing the cassette in the antissense orientation produced flowers. The data obtained in this study suggested the possible role from CAM sequence, SEC14 and NAC in the induction/floral development pathway in sugarcane, this is the first study in order to analyze these genes in the sugarcane flowering process.

Representações sociais de discentes sobre universidade: um estudo psicossocial entre ingressantes do vestibular e da seleção ProUni

Demand for access to higher education to put in test the education Brazilian system in view of the surplus of selective processes of public universities, people without option to pay their studies at this education level. In this context, it has arisen the University for All(Universidade para Todos)Program, the ProUni, from Ministry of Education - MEC, created by the Federal Government in 2004, and that it aims the granting of full and partial scholarships in private higher education institutions, graduate courses in sequential specific training, low-income Brazilians students who do not have higher-level degree. Created by the Provisional Measure No 213/2004 and institutionalized by Law No. 11096 of January 13, 2005, the ProUni offers, however, the exemption of some taxes to those institutions that join the program. This is one of the privileged time for the study of Social Representations by offering the researcher, a living laboratory, natural environment, the confrontation between the established and new. In time like this people are challenged to incorporate the new system to the pre-existing one, aiming it through a strangeness of what was so familiar. It is through this game of social forces that we developed the present study with 196 entering higher education, of these are 116 of selective vestibular system and 80 of the ProUni selective system. We opt by the procedures for data collection in order to have access to the circulating senses, in addition to the streamlined responses. With foundation in Abric, we perform the test the Free Association of Words, then analysed by the software and by EVOC Content of the type theme as Bardin. Besides, we require of the subjects, a writing on the study object university later analysed by the software ALCESTE. The results point out to a representation strongly rooted in social factors such as more traditional socio-cultural elements: the beliefs, values, the symbols. It is unique in both groups of subjects: among those entering by the selective ProUni system, there was a stronger anchor in that it does not make inquiries about the program. At the same time, there is a stronger presence of objectivation, entering the selective vestibular system in order that they explained with a value judgement on the programme. It is suggested further studies considering the embryonic state of social representation, as recent as the social purpose that triggered. It would be relevant even the replication of the same research with other people in order to strengthen the power of the theorising of empiria available

Seletividade da soja transgênica tolerante ao glyphosate e eficácia de controle de Commelina benghalensis com herbicidas aplicados isolados e em misturas

O objetivo do trabalho foi avaliar os possíveis efeitos fitotóxicos de herbicidas aplicados em pós-emergência, isolados e em misturas, na soja transgênica (cv. M-SOY 8008 RR) tolerante ao glyphosate e no controle de plântulas de Commelina benghalensis. Os experimentos foram desenvolvidos no período de janeiro a maio de 2006, em vasos, mantidos em condições de ambiente não controlado, no Departamento de Fitossanidade, UNESP, Campus de Jaboticabal (SP). Os tratamentos avaliados foram: glyphosate (1,20 kg ha-1 e.a.), chlorimuron-ethyl (0,02 kg ha-1), lactofen (0,18 kg ha-1), fomesafen (0,25 kg ha-1), flumioxazin (0,025 kg ha-1), imazethapyr (0,10 kg ha-1), chlorimuron-ethyl (0,01 kg ha-1) mais lactofen (0,096 kg ha-1), chlorimuron-ethyl (0,01 kg ha-1) mais fomesafen (0,125 kg ha-1), lactofen (0,096kg ha-1) mais fomesafen (0,125 kg ha-1), as misturas de glyphosate (0,60kgha-1) com chlorimuron-ethyl (0,01 kg ha-1), lactofen (0,096 kg ha-1), fomesafen (0,125 kg ha-1), flumioxazin (0,0125 kg ha-1), imazethapyr (0,05 kg ha-1) e uma testemunha sem aplicação de herbicida. No experimento com C. benghalensis, testou-se também a aplicação seqüencial de glyphosate (0,96 mais 0,72 kg ha-1 e.a.). A associação de ghyphosate a herbicidas utilizados em soja convencional ocasionou danos visuais às plantas de soja. em alguns casos, como nas misturas de glyphosate com lactofen e glyphosate com flumioxazin, os sintomas foram severos, com necroses e pontos cloróticos nas folhas. Mesmo assim, essa fitointoxicação não influenciou no desenvolvimento vegetativo e reprodutivo da soja. A mistura de glyphosate a outros herbicidas, assim como a sua aplicação seqüencial, não foram eficazes no controle de C. benghalensis, nas doses testadas e quando as plantas estavam no estádio de 4 a 6 folhas totalmente expandidas.

Transplacental transmission of Toxoplasma gondii in reinfected pregnant female canines

Twelve pregnant female canines, naturally infected with Toxoplasma gondii, were reinfected with T. gondii: three (GI) received tachyzoites subcutaneously (1.0 x 107), three (GII) were orally inoculated with oocysts (1.5 x 104), and six (GIII) were kept as a nonreinfected control group. All the reinfected female canines (GI and GII) miscarried or presented fetal death, while only one GIII female presented a stillborn in a litter of four pups (P < 0.01). Fever, lymphoadenopathy, miscarriage, and fetal death were the main clinical alterations observed. The highest serological titers detected through the indirect fluorescence antibody test (IFAT) were 1,024 (GI) and 4,096 (GII). In group III, the titers ranged between 64 and 256. By bioassays in mice, T. gondii was isolated in 17 organs of the reinfected adult canines, in 11 of the control group, and in 20 of the neonates. Positive immunostaining of cysts and/or tachyzoites were observed in 26 canine tissues (14 from GI and GII and ten from GIII). The agent was detected by immunohistochemistry in the encephalon of a neonate and in the spinal cord of a stillborn, thus, confirming that T. gondii infected canine fetuses, provoking miscarriages, even in bitches that presented primoinfection.

Validação do questionário Internacional de Atividade Física (IPAQ) através da acelerometria em idosas

Physical activity is one of the main components of a healthy lifestyle, responsible for many health benefits. Despite being considered important for both disease prevention and health promotion there is high prevalence of sedentary behavior in the elderly population. Questionnaires are practical and feasible instruments for assessing levels of physical activity. However, they may have limitations in older age ranges. Accelerometers, movement sensors that make physical activity data more objective, emerge as reliable measuring devices. Aim: Determine the validity of the International Physical Activity Questionnaire (IPAQ) adapted for elderly with accelerometry in elderly women. Methods: 57 elderly women, with mean age of 66.05 ± 5.98 years who took part in hypertension control and physical activity incentive programs were assessed in relation to objective and subjective measures of physical activity. The accelerometer was used for 07 consecutive days, 24 hours per day before the IPAQ was applied. Data were analyzed using measures of central tendency and dispersion to characterize the sample according to variables collected. To check the validity of the data we used the Spearman correlation test, considering a significance level of p <0.05. Results: With respect to the categories of physical activity obtained by IPAQ, 46.4% developed moderate physical activity, followed by a high (30.3%) and low level (23.2%). There was a negative correlation only between self-reported time spent sitting and time spent on light activities as measured by accelerometry (r = - 0.408; p = 0.003) and mean activity level (counts/min) with physical activity levels evaluated by IPAQ (r = 0.297; p = 0.036). Conclusion: The IPAQ used in elderly women shows moderate to low validity levels according to accelerometry measures. Assessment of sedentary activities exhibited acceptable levels compared to accelerometry; however, moderate (r = 0.096; p > 0.05) to vigorous (r = 0.098; p > 0.05) activities were not correlated, demonstrating the inability of IPAQ to evaluate this type of activity in elderly women

Soroprevalência da arterite viral equina em mesorregiões paulistas entre 2007 e 2008

This study investigated the occurrence of equine arteritis virus antibodies using neutralization test in 1,400 horses from Campinas and macro metropolitan paulista mesoregions located at São Paulo State, between 2007 and 2008. Eighty (5.7%) samples showed antibodies to virus (titers from 4 to 4,096). Among the 42 cities, 15 (35.7%) presented at least one seropositive animal to equine arteritis virus. of the 238 farms analyzed 41 showed at least one seropositive animal. The occurrence was higher in sport horses like jumping horses, Quarter horses and was similar for female and male. The rate of seropositive was higher in animals older than 24 months of age. These results suggest the virus circulation among horse population in studied farms, and the need for continuing epidemiological surveillance studies.