Tau-dependent suppression of adult neurogenesis in the stressed hippocampus.

Stress, a well-known sculptor of brain plasticity, is shown to suppress hippocampal neurogenesis in the adult brain; yet, the underlying cellular mechanisms are poorly investigated. Previous studies have shown that chronic stress triggers hyperphosphorylation and accumulation of the cytoskeletal protein Tau, a process that may impair the cytoskeleton-regulating role(s) of this protein with impact on neuronal function. Here, we analyzed the role of Tau on stress-driven suppression of neurogenesis in the adult dentate gyrus (DG) using animals lacking Tau (Tau-knockout; Tau-KO) and wild-type (WT) littermates. Unlike WTs, Tau-KO animals exposed to chronic stress did not exhibit reduction in DG proliferating cells, neuroblasts and newborn neurons; however, newborn astrocytes were similarly decreased in both Tau-KO and WT mice. In addition, chronic stress reduced phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)/glycogen synthase kinase-3ß (GSK3ß)/ß-catenin signaling, known to regulate cell survival and proliferation, in the DG of WT, but not Tau-KO, animals. These data establish Tau as a critical regulator of the cellular cascades underlying stress deficits on hippocampal neurogenesis in the adult brain.

Physicochemical and Microbiological Quality of Dietetic Functional Mixed Cerrado Fruit Jam during Storage.

The objective of the research was to evaluate changes of dietetic functional mixed cerrado fruit jam (marolo, sweet passion fruit, and soursop) processed in a vacuum pot and stored for 180 days in BODs at 25°C and 35°C. The parameters evaluated were pH, soluble solids (SS), titratable acidity (TA), total sugars (TS), total carotenoids (TC), total phenolics (TP), vitamin C, antioxidant activity (DPPH), and microbiological analysis. There was a significant effect of storage time on pH, SS, TA, TC, TS, and TP. Vitamin C and DPPH showed an effect for the temperature x storage time interaction. Statistical models are not adjusted for pH and SS, presenting an average of 4.15 and 61%, respectively. Carotenoids decreased up to105 days; total sugars increased up to 105 days. The TP, vitamin C, and DPPH, at the temperatures evaluated, showed a decrease up to 105 days. Yeasts and filamentous fungi were not detected.

Further evidence of a cumulative effect of social disadvantage on risk of psychosis.

BACKGROUND: A growing body of evidence suggests that indicators of social disadvantage are associated with an increased risk of psychosis. However, only a few studies have specifically looked at cumulative effects and long-term associations. The aims of this study are: To compare the prevalence of specific indicators of social disadvantage at, and prior to, first contact with psychiatric services in patients suffering their first episode of psychosis and in a control sample. To explore long-term associations, cumulative effects, and direction of effects. METHOD: We collected information on social disadvantage from 332 patients and from 301 controls recruited from the local population in South London. Three indicators of social disadvantage in childhood and six indicators of social disadvantage in adulthood were analysed. RESULTS: Across all the domains considered, cases were more likely to report social disadvantage than were controls. Compared with controls, cases were approximately two times more likely to have had a parent die and approximately three times more likely to have experienced a long-term separation from one parent before the age of 17 years. Cases were also more likely than controls to report two or more indicators of adult social disadvantage, not only at first contact with psychiatric services [odds ratio (OR) 9.5], but also at onset of psychosis (OR 8.5), 1 year pre-onset (OR 4.5), and 5 years pre-onset (OR 2.9). CONCLUSIONS: Greater numbers of indicators of current and long-term exposure are associated with progressively greater odds of psychosis. There is some evidence that social disadvantage tends to cluster and accumulate.

Synthesis of 3 H, 2 H4 , and 14 C-MK 3814 (preladenant).

MK 3814 is a potent and selective antagonist of the A2a receptor. A2a receptor antagonists have the potential for the treatment of Parkinson disease. Three distinct isotopically labelled forms of MK 3814 were synthesized. [3 H]MK 3814 was prepared for a preliminary absorption, distribution, metabolism, and excretion data (ADME) evaluation of the compound and [14 C]MK 3814 for more definitive ADME work, including an absorption, metabolism, and excretion study in man. In addition, [2 H4 ]MK 3814 was prepared as an internal standard for a liquid chromatography mass spectrometry bioanalytical method. This paper discusses the synthesis of 3 isotopically labelled forms of MK 3814.

Association of ADAMTS7 gene polymorphism with cardiovascular survival in coronary artery disease.

Recent genetic studies have revealed an association between polymorphisms at the ADAMTS7 gene locus and coronary artery disease (CAD) risk. Functional studies have shown that a CAD-associated polymorphism (rs3825807) affects ADAMTS7 maturation and vascular smooth muscular cell (VSMC) migration. Here, we tested whether ADAMTS7 (A/G) SNP is associated with cardiovascular (CV) survival in patients with established CAD. A cohort of 1,128 patients with angiographic proven CAD, who were followed up prospectively for a mean follow-up period of 63 (range 6-182) mo, were genotyped for rs3825807 A/G. Survival statistics (Cox regression) compared heterozygous (AG) and wild-type (AA) with the reference homozygous GG. Kaplan-Meier (K-M) survival curves were performed according to ADAMTS7 genotypes for CV mortality. Results showed that 47.3% of patients were heterozygous (AG), 36.5% were homozygous for the wild-type allele (AA) and only 16.2% were homozygous for the GG genotype. During the follow-up period, 109 (9.7%) patients died, 77 (6.8%) of CV causes. Survival analysis showed that AA genotype was an independent risk factor for CV mortality compared with reference genotype GG (HR = 2.7, P = 0.025). At the end of follow-up, the estimated survival probability (K-M) was 89.8% for GG genotype, 82.2% for AG and 72.3% for AA genotype (P = 0.039). Carriage of the mutant G allele of the ADAMTS7 gene was associated with improved CV survival in patients with documented CAD. The native overfunctional ADAMTS7 allele (A) may accelerate VSMC migration and lead to neointimal thickening, atherosclerosis progression and acute plaque events. ADAMTS7 gene should be further explored in CAD for risk prediction, mechanistic and therapeutic goals.

Synthesis of (3) H, (2) H4 and (14) C-SCH 417690 (Vicriviroc).

Vicriviroc or SCH 417690 is a potent and selective antagonist of the CCR5 receptor. CCR5 receptor antagonists have the potential for the treatment of HIV infections. Four distinct isotopically labelled forms of SCH 417690 were synthesized. Low specific activity [(3) H]SCH 417690 was prepared for a preliminary absorption, distribution, metabolism and excretion evaluation of the compound and [(14) C]SCH 417690 for more definitive absorption, distribution, metabolism and excretion work, including an absorption, metabolism and excretion study in man. In addition, high specific activity [(3) H]SCH 417690 was prepared for CCR5 receptor binding work and [(2) H4 ]SCH 417690 was prepared as an internal standard for a liquid chromatography-mass spectrometry bioanalytical method. The paper discusses the synthesis of four isotopically labelled forms of SCH 417690.

Influence of sub-lethal stresses on the survival of lactic acid bacteria after spray-drying in orange juice.

The demand for new functional non-dairy based products makes the production of a probiotic orange juice powder an encouraging challenge. However, during drying process and storage, loss of viability of the dried probiotic cultures can occur, since the cells are exposed to various stresses. The influence of sub-lethal conditions of temperature, acidic pH and hydrogen peroxide on the viability of Pediococcus acidilactici HA-6111-2 and Lactobacillus plantarum 299v during spray drying in orange juice and subsequent storage under different conditions was investigated. At the end of storage, the survival of both microorganisms through simulated gastro-intestinal tract (GIT) conditions was also determined. The viability of cells previously exposed to each stress was not affected by the drying process. However, during 180 days of storage at room temperature, unlike P. acidilactici HA-6111-2, survival of L. plantarum 299v was enhanced by prior exposure to sub-lethal conditions. Previous exposure to sub-lethal stresses of each microorganism did not improve their viability after passage through simulated GIT. Nevertheless, as cellular inactivation during 180 days of storage was low, both microorganisms were present in numbers of ca. 10(7) cfu/mL at the end of GIT. This is an indication that both bacteria are good candidates for use in the development of an orange juice powder with functional characteristics.

Synthesis of 3H, 13C,2H3,15N and 14C-labelled SCH 466036, a histamine 3 receptor antagonist.

The synthesis of [(3)H]SCH 466036, [Me-(3)H3]SCH 466036, [(13)C,(2)H3,(15)N]SCH 466036 and [(14)C]SCH 466036 is described. [(3)H]SCH 466036 was prepared in two steps via Raney Ni-catalysed exchange with tritiated water. [Me-(3)H3]SCH 466036 was prepared in a single step from [(3)H]methyl iodide in 45% yield. [(13)C,(2)H3,(15)N]SCH 466036 was prepared in two steps from [(15)N]hydroxylamine and [(13)C,(2)H3]methyl iodide with an overall yield of 16%. [(14)C]SCH 466036 was prepared in seven steps from [(14)C]potassium cyanide in an overall yield of 13%.

Process and quality parameters of convective dried yacon: Influence of ethanol treatment.

Yacon is a highly perishable tuberous root, rich in fructooligosaccharides (FOS). Convective drying preceded by ethanol treatment (ET) is an alternative for increasing shelf life in a shorter process. The aim of this study was to investigate the impact of ET and temperature (50 °C and 70 °C) on quality parameters (fructan retention, total phenolic content, antioxidant capacity, shrinkage, color and microstructural parameters) and process parameters (drying time, drying kinetics, and energy consumption) in the convective drying of yacon slices. The ET induced structural alterations in the tissues and cells that aids in the reduction of drying time up to 28.00 %. ET resulted in an increase in effective diffusivity and leaded to noteworthy reduction in energy consumption (up to 22.72 %). The quality parameters such as color, shrinkage, and total phenolic content showed no significant differences among the treatments. The use of ethanol promoted highest preservation of antioxidant activity; however, it caused degradation of FOS. The ethanol pretreated drying at 50 °C was the better condition for lower consumption and preservation of quality parameters as total phenolic content, antioxidant capacity and fructan retention, but the samples dried at 50 °C were the ones with the highest fructan retention (55.11 ± 2.19 %).

The physiological quality of Vigna unguiculata L. seeds shows tolerance to salinity.

Salinity reduces feijão-caupi production, and the search for tolerant varieties becomes important within the agricultural context, as, in addition to being used in the field, they can be used in genetic improvement. The objective was to for a identify variety that is tolerant to salinity considering the physiological quality of seeds and seedling growth. A 2 × 4 factorial scheme was used, referring to the varieties Pingo-de-ouro and Coruja, and four electrical conductivities of water (0; 3.3; 6.6 and 9.9 dS m-1). The physiological quality of seeds and the growth of seedlings were analyzed, in addition to the cumulative germination. The Pingo-de-ouro variety showed no germination, length of the shoot and root, dry mass of the shoot and root compromised up to electrical conductivity of 6 dS m-1 in relation to 0.0 dS m-1. On the other hand, the Coruja variety showed reduced germination, increased shoot and root length. The creole variety Pingo-de-ouro proved to be tolerant to salinity.

Evaluation of characteristics of Pediococcus spp. to be used as a vaginal probiotic.

AIMS: The aim of our research was to select, identify and characterize an isolate of lactic acid bacteria to be considered as a vaginal probiotic. METHODS AND RESULTS: Thirty-five isolates of Pediococcus spp. showed bacteriocinogenic activity against Listeria monocytogenes and the ability to survive in simulated vaginal fluid (SVF) at pH 4.2. One isolate of Pediococcus spp. was selected and characterized to evaluate its safety before the use as vaginal probiotic. Pediococcus pentosaceus SB83 did not show the presence of virulence factors such as the production of gelatinase, lipase and DNase, haemolytic activity, nor the presence of virulence genes (genes esp, agg, gelE, efaAfm, efaAfs, cylA, cylB and cylM). Pediococcus pentosaceus SB83 was considered sensitive to chloramphenicol, gentamicin, streptomycin, kanamycin, erythromycin and ampicillin. This strain was considered resistant to tetracycline and vancomycin. Pediococcus pentosaceus SB83 was a biofilm producer at different pH values (4.2, 5.5 and 6.5) in SVF and in de Man, Rogosa and Sharpe medium. CONCLUSIONS: The in vitro results provide a basis for the use of P. pentosaceus SB83 as a vaginal probiotic, to prevent colonization by L. monocytogenes in pregnant women. SIGNIFICANCE AND IMPACT OF STUDY: The application of vaginal probiotics could have the potential for preventing vaginal infections and consequently reduce abortion and neonatal infections.

Behaviour of Listeria monocytogenes isolates through gastro-intestinal tract passage simulation, before and after two sub-lethal stresses.

The effects of previous exposure to sub-lethal acidic and osmotic stresses on the survival of Listeria monocytogenes during exposure to gastro-intestinal (GI) tract simulation, was investigated. Six L. monocytogenes strains isolated from cheeses were selected and exposed to high salt concentrations or acidic conditions and their viability compared in quick and slow digestions. The results demonstrated that (i) all isolates were more sensitive to the exposure to acidic than to osmotic sub-lethal conditions (ii) significant differences (p < 0.05) between the two types of digestion were observed; in slow digestion, the log reduction was higher for all the tested isolates (iii) all isolates were inhibited in the presence of bile salts for both types of digestion (iv) differences between quick and slow digestion were not observed (p > 0.05) after exposure to either osmotic or acidic stress (v) a higher cellular inactivation (p < 0.001) was observed during the passage through the GI tract simulation after exposure to osmotic than to acidic stresses and (vi) neither osmotic nor acidic sub-lethal stresses conferred resistance to simulated GI tract conditions.

Quality evaluation of banana skin extract jellies.

Due to the great volume of banana skin resulting from the industrialization of banana and to their high pectin content, the objectives of the present study were to evaluate the effect of the following factors: extract/sugar, pectin and citric acid on the chemical, physical and sensory qualities of the jellies obtained. A complete factorial experimental design was used (2(3)) with 3 central points to evaluate the influence of the factors on the dependent variables, testing the linear models. The chemical properties underwent few alterations and the instrumental and sensory texture attributes were mainly affected by the extract/sugar ratio and the pectin level. The brittleness, elasticity and gumminess increased with increases in the extract/ sugar ratio and pectin level. According to the sensory analysis and the purchasing intention, the best formulations were those obtained using a higher extract/sugar ratio (60/40) and lower pectin level (0.5 g/ 100), combined with the highest (20 mL) or lowest volumes of citric acid (15 mL), with scores for all the attributes in the range from 'I liked slightly' to 'I liked moderately'.

Control of transmitter release from retinal amacrine cells by Ca2+ influx and efflux.

Cultured retinal amacrine cells show quantal GABAergic synaptic transmission. Voltage clamping pre- and post-synaptic cells of an isolated pair has allowed us to examine the entry and removal of Ca2+ at synaptic terminals. Brief presynaptic Ca2+ currents elicit an initial postsynaptic current that probably reflects the roughly synchronous exocytosis of docked vesicles. Prolonged Ca2+ currents elicit an additional second phase of release whose time course can greatly exceed that of the presynaptic voltage step. The time course of this second phase reflects a sustained increase in cytosolic Ca2+ and is matched closely by the activity of the presynaptic Na-Ca exchanger, as revealed by an exchange current. Eliminating the activity of the exchanger by removal of external Na+ prolongs this second phase of transmission greatly. Because transmitter release at these synapses outlasts Ca+ channel opening, Na-Ca exchange plays a significant role in shaping transmission.

Variation in GABA mini amplitude is the consequence of variation in transmitter concentration.

Miniature postsynaptic currents (minis) in cultured retinal amacrine cells, as in other central neurons, show large variations in amplitude. To understand the origin of this variability, we have exploited a novel form of synapse in which pre- and postsynaptic receptors sample the same quantum of transmitter. At these synapses, mini amplitudes measured simultaneously in the 2 cells show a strong correlation, accounting for, on average, more than half of the variance in amplitude. Two pieces of evidence support the conclusion that variations in the amount of transmitter in different quanta underlie this correlation. First, diazepam, which enhances GABA binding, increases mini amplitude, implying therefore that transmitter concentration is not saturating. Second, we show that amplitude distributions from all cells, even those with a small number of release sites, have the same shape, implying that most or all variance is intrinsic to each release site.

Toxoplasma gondii promotes changes in VIPergic submucosal neurons, mucosal intraepithelial lymphocytes, and goblet cells during acute infection in the ileum of rats.

BACKGROUND: The intestinal mucosa plays an important role in the mechanical barrier against pathogens. During Toxoplasma gondii infection, however, the parasites invade the epithelial cells of the small intestine and initiate a local immune response. In the submucosal plexus, this response promotes an imbalance of neurotransmitters and induces neuroplasticity, which can change the integrity of the epithelium and its secretory function. This study evaluated the submucosal neurons throughout acute T. gondii infection and the relationship between possible alterations and the epithelial and immune defense cells of the mucosa. METHODS: Forty Wistar rats were randomly assigned to 8 groups (n = 5): 1 control group, uninfected, and 7 groups infected with an inoculation of 5000 sporulated T. gondii oocysts (ME-49 strain, genotype II). Segments of the ileum were collected for standard histological processing, histochemical techniques, and immunofluorescence. KEY RESULTS: The infection caused progressive neuronal loss in the submucosal general population and changed the proportion of VIPergic neurons throughout the infection periods. These changes may be related to the observed reduction in goblet cells that secret sialomucins and increase in intraepithelial lymphocytes after 24 hours, and the increase in immune cells in the lamina propria after 10 days of infection. The submucosa also presented fibrogenesis, characterizing injury and tissue repair. CONCLUSIONS AND INFERENCES: The acute T. gondii infection in the ileum of rats changes the proportion of VIPergic neurons and the epithelial cells, which can compromise the mucosal defense during infection.

Radial scar of the breast: Is it possible to avoid surgery?

INTRODUCTION: Breast radial scar (RS) management remains controversial. The need for surgical excision is supported by the concern of an associated high-grade lesion missed in the biopsy. The aim of this study was to assess histologic upgrade rate after a percutaneous biopsy, to determine if vacuum assisted biopsy prevents the need for subsequent RS surgical resection and to evaluate the upgrade risk factors. PATIENTS AND METHODS: This was a uni-institutional retrospective study of consecutive patients with RS histologically diagnosed from January 2010 to December 2015. RESULTS: A total of 113 cases of RS were diagnosed. We verify that there was a histologic upgrade in 22 (19.5%) cases. The upgrade risk factors were the type of biopsy performed, the presence of atypia, the presence of calcifications and the number of fragments obtained in the biopsy (p < 0.05). The biopsy type was vacuum assisted in 25 (22.1%). The upgrade rate in the vacuum assisted biopsy group was 4.0%, whereas in the standard core needle biopsy group was 23,9% (p = 0.041). DISCUSSION AND CONCLUSION: We demonstrated that the risk of upgrade after a RS diagnosis depends on the type of biopsy performed, the presence of atypia, the presence of calcifications and the number of fragments obtained. When a standard core biopsy is performed the risk of upgrade and malignancy is not negligible, and surgery is indicated. When the biopsy is vacuum assisted, the risk of upgrade and malignancy is significantly decreased and so the indication for excisional biopsy seems not to be so imperative.