Cyanobacteria possess the unique capacity to naturally produce hydrocarbons from fatty acids. Hydrocarbon compositions of thirty-two strains of cyanobacteria were characterized to reveal novel structural features and insights into hydrocarbon biosynthesis in cyanobacteria. This investigation revealed new double bond (2- and 3-heptadecene) and methyl group positions (3-, 4- and 5-methylheptadecane) for a variety of strains. Additionally, results from this study and literature reports indicate that hydrocarbon production is a universal phenomenon in cyanobacteria. All cyanobacteria possess the capacity to produce hydrocarbons from fatty acids yet not all accomplish this through the same metabolic pathway. One pathway comprises a two-step conversion of fatty acids first to fatty aldehydes and then alkanes that involves a fatty acyl ACP reductase (FAAR) and aldehyde deformylating oxygenase (ADO). The second involves a polyketide synthase (PKS) pathway that first elongates the acyl chain followed by decarboxylation to produce a terminal alkene (olefin synthase, OLS). Sixty-one strains possessing the FAAR/ADO pathway and twelve strains possessing the OLS pathway were newly identified through bioinformatic analyses. Strains possessing the OLS pathway formed a cohesive phylogenetic clade with the exception of three Moorea strains and Leptolyngbya sp. PCC 6406 which may have acquired the OLS pathway via horizontal gene transfer. Hydrocarbon pathways were identified in one-hundred-forty-two strains of cyanobacteria over a broad phylogenetic range and there were no instances where both the FAAR/ADO and the OLS pathways were found together in the same genome, suggesting an unknown selective pressure maintains one or the other pathway, but not both.

Neurological diseases and trauma often cause demyelination, resulting in the disruption of axonal function and integrity. Endogenous remyelination promotes recovery, but the process is not well understood because no method exists to definitively distinguish regenerated from preexisting myelin. To date, remyelinated segments have been defined as anything abnormally short and thin, without empirical data to corroborate these morphological assumptions. To definitively identify regenerated myelin, we used a transgenic mouse with an inducible membrane-bound reporter and targeted Cre recombinase expression to a subset of glial progenitor cells after spinal cord injury, yielding remarkably clear visualization of spontaneously regenerated myelin in vivo. Early after injury, the mean length of sheaths regenerated by Schwann cells and oligodendrocytes (OLs) was significantly shorter than control, uninjured myelin, confirming past assumptions. However, OL-regenerated sheaths elongated progressively over 6 mo to approach control values. Moreover, OL-regenerated myelin thickness was not significantly different from control myelin at most time points after injury. Thus, many newly formed OL sheaths were neither thinner nor shorter than control myelin, vitiating accepted dogmas of what constitutes regenerated myelin. We conclude that remyelination, once thought to be static, is dynamic and elongates independently of axonal growth, in contrast to stretch-based mechanisms proposed in development. Further, without clear identification, past assessments have underestimated the extent and quality of regenerated myelin.

Reactive nitrogen species are thought to be involved in both hypoxic-ischemic and cytokine-induced brain injury, including periventricular leukomalacia (PVL), the major pathological substrate of cerebral palsy in premature infants. PVL appears to be the result of perinatal inflammatory events and hypoxic-ischemic injury to the cerebral white matter. The chronic disturbance of myelination resulting from PVL suggests that developing oligodendrocytes (OLs) are involved in its pathogenesis. We hypothesized that nitric oxide (NO) could participate in the pathogenesis of PVL through a toxic effect on developing OLs. Using primary cultures of highly enriched OLs we found that NO is toxic to developing OLs (O4+, O1-, MBP-), with an EC50 value of 236 +/- 125 microm of DETANOnoate. Peroxynitrite formation does not appear to be involved in NO toxicity in developing OLs, as determined by the failure of peroxynitrite scavengers as well as superoxide dismutase overexpression to prevent NO-induced toxicity. Similarly, several pathways involving PARP, excitotoxicity, guanylyl cyclase and caspase activation were not related to NO toxicity to developing OLs. NO toxicity to OLs resulted in ATP depletion and loss of mitochondrial membrane potential (DeltaPsi) in developing OLs. Apoptosis-inducing factor (AIF) has been shown to be involved in caspase-independent cell death, and we found that AIF translocated from mitochondria into the nucleus upon NO exposure. In conclusion, we suggest that the vulnerability of developing OLs to NO involves mitochondrial dysfunction and translocation of AIF from mitochondria to nuclei.

BACKGROUND

The present study was undertaken to determine whether laparoscopic live donor left lateral sectionectomy (LLS) in paediatric liver transplantation is a feasible, safe and reproducible procedure, compared with open live donor left lateral sectionectomy (OLS).

METHODS

A retrospective review was conducted of all consecutive live donor procedures for paediatric liver transplantation performed between May 2008 and October 2009. All live donor hepatectomies were carried out by a single surgeon.

RESULTS

A total of 26 live donor procedures for paediatric liver transplantation were performed, of which 11 were LLS and 11 OLS; four left hepatectomies were excluded. The LLS group had a significantly shorter hospital stay (mean(s.d.) 6·9(0·3) versus 9·8(0·9) days; P = 0·001) and time to oral diet (2·1(0·3) versus 2·7(0·4) days; P = 0·012). Duration of operation, blood loss, warm ischaemia time and out-of-pocket medical costs were comparable between groups. There was no death in either donor group and only one complication, a wound seroma, in the OLS group.

CONCLUSIONS

LLS seemed to be a safe, feasible and reproducible procedure, and was associated with reduced hospital stay.

OBJECTIVE

The prevalence of obesity and associated cardiometabolic risk factors such as diabetes, hyperlipidemia and hypertension is increasing significantly for all demographic groups.

METHODS

The 2000 and 2002 Medical Expenditure Panel Survey (MEPS), a nationally representative survey of the U.S. population, was used to estimate the marginal impact of obesity on health function, perception, and preferences for individuals with diabetes, hyperlipidemia, and hypertension using multivariate regression methods controlling for age, sex, race, ethnicity, education, income, insurance, smoking status, comorbidity, and proxy response. Three different instruments were used: SF-12 physical component scale (PCS-12) and mental component scale (MCS-12); EQ-5D index and visual analogue scale (VAS). Censored least absolute deviation was used for the EQ-5D and VAS (due to censoring) and ordinary least squares (OLS) was used for the PCS-12 and MCS-12.

RESULTS

After controlling for sociodemographic characteristics, diabetes, hyperlipidemia, and hypertension were associated with significantly lower scores compared to normal weight individuals without the condition for all four instruments. Obesity significantly exacerbated this association. Controlling for comorbidity attenuated the negative association of obesity and cardiometabolic risk factors on instrument scores. In addition, scores decreased for increasing weight and number of risk factors.

CONCLUSIONS

Obesity significantly exacerbates the deleterious association between diabetes, hyperlipidemia, and hypertension, and health function, health perception, and preference-based scores in the United States.

The presence of beta-amyloid plaques in brain is a hallmark of Alzheimer's disease (AD) and serves as a biomarker for confirmation of diagnosis postmortem. Positron emission tomography (PET) radioligands such as Pittsburgh compound B ([(11)C]-2-(3-fluoro-4-methylamino-phenyl)-benzothiazol-6-ol) (PIB) binds selectively to beta-amyloid and are promising new tools supporting the clinical diagnoses of AD. In addition, such methodology may be useful for evaluation of new drugs aiming at reduction of amyloid plaque load. The objective of this study is to develop a new amyloid selective PET radioligand with higher signal-to-background ratio when compared with existing amyloid PET ligands. The lead compound, AZD2184, (2-[6-(methylamino)pyridin-3-yl]-1,3-benzothiazol-6-ol) was found to have high affinity for amyloid fibrils in vitro (K(d): 8.4 +/- 1.0 nM). Two minutes after i.v. administration in rats, about 1% of the dose was in brain. In vitro autoradiography on cortical brain sections from amyloid-beta precursor protein/presenilin 1 (APP/PS1) mice and AD patients showed that while [(3)H]AZD2184 and [(3)H]PIB are mutually displaceable, [(3)H]AZD2184 displays a higher signal-to-background ratio primarily by virtue of lower background binding levels. The ratio of binding ability in prefrontal cortex (high plaque load) to subcortical white matter (background) was 4.5 for [(3)H]AZD2184 and 0.8 for [(3)H]PIB at 1 nM. In adjacent cortical sections from APP/PS1 mouse as well as from AD cortical tissue, [(3)H]AZD2184 and antibodies to human beta-amyloid labeled identical structures. In vivo administration of [(3)H]AZD2184 to APP/PS1 mice further showed that [(3)H]AZD2184 labels amyloid deposits with low non-specific background binding. Taken together, the pre-clinical profile of AZD2184 in relation to the reference ligand PIB, suggests that (11)C-labeled AZD2184 is a potential radioligand for PET-visualization of beta-amyloid deposits in the living human brain.

To develop regression models for outcomes with truncated supports, such as health-related quality of life (HRQoL) data, and account for features typical of such data such as a skewed distribution, spikes at 1 or 0, and heteroskedasticity.

Regression estimators based on features of the Beta distribution. First, both a single equation and a 2-part model are presented, along with estimation algorithms based on maximum-likelihood, quasi-likelihood, and Bayesian Markov-chain Monte Carlo methods. A novel Bayesian quasi-likelihood estimator is proposed. Second, a simulation exercise is presented to assess the performance of the proposed estimators against ordinary least squares (OLS) regression for a variety of HRQoL distributions that are encountered in practice. Finally, the performance of the proposed estimators is assessed by using them to quantify the treatment effect on QALYs in the EVALUATE hysterectomy trial. Overall model fit is studied using several goodness-of-fit tests such as Pearson's correlation test, link and reset tests, and a modified Hosmer-Lemeshow test.

The simulation results indicate that the proposed methods are more robust in estimating covariate effects than OLS, especially when the effects are large or the HRQoL distribution has a large spike at 1. Quasi-likelihood techniques are more robust than maximum likelihood estimators. When applied to the EVALUATE trial, all but the maximum likelihood estimators produce unbiased estimates of the treatment effect.

One and 2-part Beta regression models provide flexible approaches to regress the outcomes with truncated supports, such as HRQoL, on covariates, after accounting for many idiosyncratic features of the outcomes distribution. This work will provide applied researchers with a practical set of tools to model outcomes in cost-effectiveness analysis.

The identification of the CB2 cannabinoid receptor has provided a novel target for the development of therapeutically useful cannabinergic molecules. We have synthesized benzo[ c]chromen-6-one analogs possessing high affinity and selectivity for this receptor. These novel compounds are structurally related to cannabinol (6,6,9-trimethyl-3-pentyl-6 H-benzo[ c]chromen-1-ol), a natural constituent of cannabis with modest CB2 selectivity. Key pharmacophoric features of the new selective agonists include a 3-(1',1'-dimethylheptyl) side chain and a 6-oxo group on the cannabinoid tricyclic structure that characterizes this class of compounds as "cannabilactones." Our results suggest that the six-membered lactone pharmacophore is critical for CB2 receptor selectivity. Optimal receptor subtype selectivity of 490-fold and subnanomolar affinity for the CB2 receptor is exhibited by a 9-hydroxyl analog 5 (AM1714), while the 9-methoxy analog 4b (AM1710) had a 54-fold CB2 selectivity. X-ray crystallography and molecular modeling show the cannabilactones to have a planar ring conformation. In vitro testing revealed that the novel compounds are CB2 agonists, while in vivo testing of cannabilactones 4b and 5 found them to possess potent peripheral analgesic activity.

Diets that are rich in plant foods have been associated with a decreased risk for specific disease processes and certain chronic diseases. In addition to essential macronutrients and micronutrients, the flavonoids in a variety of plant foods may have health-enhancing properties. Chocolate is a food that is known to be rich in the flavan-3-ol epicatechin and procyanidin oligomers. However, the bioavailability and the biological effects of the chocolate flavonoids are poorly understood. To begin to address these issues, we developed a method based on HPLC coupled with electrochemical (coulometric) detection to determine the physiological levels of epicatechin, catechin and epicatechin dimers. This method allows for the determination of 20 pg (69 fmol) of epicatechin, which translates to plasma concentrations as low as 1 nmol/L. We next evaluated the absorption of epicatechin, from an 80-g semisweet chocolate (procyanidin-rich chocolate) bolus. By 2 h after ingestion, there was a 12-fold increase in plasma epicatechin, from 22 to 257 nmol/L (P < 0.01). Consistent with the antioxidant properties of epicatechin, within the same 2-h period, there was a significant increase of 31% in plasma total antioxidant capacity (P < 0.04) and a decrease of 40% in plasma 2-thiobarbituric acid reactive substances (P < 0.01). Plasma epicatechin and plasma antioxidant capacity approached baseline values by 6 h after ingestion. These results show that it is possible to determine basal levels of epicatechin in plasma. The data support the concept that the consumption of chocolate can result in significant increases in plasma epicatechin concentrations and decreases in plasma baseline oxidation products.

Sequential actions of 17beta-estradiol (E(2)) and progesterone (P(4)) in the hypothalamus and the P(4) metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), in the midbrain ventral tegmental area (VTA) respectively mediate the initiation and intensity of lordosis of female rats and may also modulate anxiety and social behaviors, through actions in these, and/or other brain regions. Biosynthesis of E(2), P(4), and 3alpha,5alpha-THP can also occur in brain, independent of peripheral gland secretion, in response to environmental/behavioral stimuli. The extent to which engaging in tasks related to reproductive behaviors and/or mating increased E(2) or progestin concentrations in brain was investigated. In Experiment 1, proestrous rats were randomly assigned to be tested in individual tasks, including the open field, elevated plus maze, partner preference, social interaction, or no test control, in conjunction with paced mating or no mating. Engaging in paced mating, but not other behaviors, significantly increased dihydroprogesterone (DHP) and 3alpha,5alpha-THP levels in midbrain, hippocampus, striatum, and cortex. In Experiment 2, proestrous rats were tested in the combinations of the above tasks (open field and elevated plus maze, partner preference, and social interaction) with or without paced mating. As in Experiment 1, only engaging in paced mating increased DHP and 3alpha,5alpha-THP concentrations in midbrain, hippocampus, striatum, and cortex. Thus, paced mating enhances concentrations of 5alpha-reduced progestins in brain areas associated with reproduction (midbrain), as well as exploration/anxiety (hippocampus and striatum) and social behavior (cortex).

Enantiomers differ only in the left or right handedness (chirality) of their orientations and exhibit identical chemical and physical properties. In chemical communication systems, enantiomers can be differentially active at the physiological and behavioral levels. Only recently were enantioselective odorant receptors demonstrated in mammals while their existence in insects has remained hypothetical. Using the two-microelectrode voltage clamp of Xenopus oocytes, we show that the yellow fever mosquito, Aedes aegypti, odorant receptor 8 (AaOR8) acts as a chiral selective receptor for the (R)-(-)-enantiomer of 1-octen-3-ol, which in the presence of other kairomones is an attractant used by blood-sucking insects to locate their hosts. In addition to steric constraints, chain length and degree of unsaturation play important roles in this recognition process. This is the first characterization of an enantioselective odorant receptor in insects and the results demonstrate that an OR alone, without helper proteins, can account for chiral specificity exhibited by olfactory sensory neurons (OSNs).

Field studies were done of the responses of Glossina palpalis palpalis in Côte d'Ivoire, and G. p. gambiensis and G. tachinoides in Burkina Faso, to odours from humans, cattle and pigs. Responses were measured either by baiting (1.) biconical traps or (2.) electrocuting black targets with natural host odours. The catch of G. tachinoides from traps was significantly enhanced ( approximately 5x) by odour from cattle but not humans. In contrast, catches from electric targets showed inconsistent results. For G. p. gambiensis both human and cattle odour increased (>2x) the trap catch significantly but not the catch from electric targets. For G. p. palpalis, odours from pigs and humans increased (approximately 5x) the numbers of tsetse attracted to the vicinity of the odour source but had little effect on landing or trap-entry. For G. tachinoides a blend of POCA (P = 3-n-propylphenol; O = 1-octen-3-ol; C = 4-methylphenol; A = acetone) alone or synthetic cattle odour (acetone, 1-octen-3-ol, 4-methylphenol and 3-n-propylphenol with carbon dioxide) consistently caught more tsetse than natural cattle odour. For G. p. gambiensis, POCA consistently increased catches from both traps and targets. For G. p. palpalis, doses of carbon dioxide similar to those produced by a host resulted in similar increases in attraction. Baiting traps with super-normal (approximately 500 mg/h) doses of acetone also consistently produced significant but slight (approximately 1.6x) increases in catches of male flies. The results suggest that odour-baited traps and insecticide-treated targets could assist the AU-Pan African Tsetse and Trypanosomiasis Eradication Campaign (PATTEC) in its current efforts to monitor and control Palpalis group tsetse in West Africa. For all three species, only approximately 50% of the flies attracted to the vicinity of the trap were actually caught by it, suggesting that better traps might be developed by an analysis of the visual responses and identification of any semiochemicals involved in short-range interaction.

The postnatal development of IPSPs and response to locally applied GABA were examined using intracellular recording techniques in region CA1 of rabbit hippocampal slices maintained in vitro. Pyramidal neurons in slices from mature rabbits demonstrated an EPSP-IPSP sequence following stimulation of stratum radiatum. In these same slices, pressure application of GABA into stratum pyramidale and stratum radiatum produced membrane hyperpolarization and depolarization, respectively. Pyramidal neurons in slices from immature rabbits (age 6 to 10 days) responded differently. Stimulation of stratum radiatum produced a prolonged depolarizing postsynaptic potential; few IPSPs were observed. Ejection of GABA into either stratum pyramidale or stratum radiatum evoked a depolarizing response. The GABA agonist, 4,5,6,7-tetrahydroisoxazolo [5,4-c] pyridine-3-ol (THIP), which has been reported to activate "hyperpolarizing" GABA receptors selectively, primarily produced membrane hyperpolarization when applied to the somata of mature neurons, but it evoked a depolarization when applied to immature neurons. Bicuculline, a GABA antagonist which may have a preferential selectivity for "depolarizing" GABA receptors, was somewhat more efficacious (at 50 microM concentration) at antagonizing GABA-evoked depolarization in immature cells than GABA-evoked hyperpolarization in mature cells. This same concentration of bicuculline partially antagonized IPSPs in mature cells, and it markedly potentiated depolarizing PSPs in immature cells. Taken together, these results suggest that the late development of synaptic inhibition in rabbit hippocampus is due, at least in part, to an immaturity in the GABAergic system.

The aroma of roses (Rosa hybrida) is due to more than 400 volatile compounds including terpenes, esters, and phenolic derivatives. 2-Phenylethyl acetate, cis-3-hexenyl acetate, geranyl acetate, and citronellyl acetate were identified as the main volatile esters emitted by the flowers of the scented rose var. "Fragrant Cloud." Cell-free extracts of petals acetylated several alcohols, utilizing acetyl-coenzyme A, to produce the corresponding acetate esters. Screening for genes similar to known plant alcohol acetyltransferases in a rose expressed sequence tag database yielded a cDNA (RhAAT1) encoding a protein with high similarity to several members of the BAHD family of acyltransferases. This cDNA was functionally expressed in Escherichia coli, and its gene product displayed acetyl-coenzyme A:geraniol acetyltransferase enzymatic activity in vitro. The RhAAT1 protein accepted other alcohols such as citronellol and 1-octanol as substrates, but 2-phenylethyl alcohol and cis-3-hexen-1-ol were poor substrates, suggesting that additional acetyltransferases are present in rose petals. The RhAAT1 protein is a polypeptide of 458 amino acids, with a calculated molecular mass of 51.8 kD, pI of 5.45, and is active as a monomer. The RhAAT1 gene was expressed exclusively in floral tissue with maximum transcript levels occurring at stage 4 of flower development, where scent emission is at its peak.

The aim of this study was to screen for the anti-inflammatory activity of fractions and compounds from Atractylodes macrocephala Koidz. The rhizomes of Atractylodes macrocephala were treated with supercritical CO(2) fluid and the extract was separated by normal-phase and reverse-phase column chromatography. The separated samples were screened with white blood cell membrane (WBCM) chromatography (WBCM-C). The anti-inflammatory effects of these fractions and components were tested pharmacologically in vivo. The results indicated that the retention characteristics of the petrol-ether (1:1, v/v) fraction (BZC-2) of the supercritical CO(2) extract, the atractylenolide I and 14-acetoxy-12-senecioyloxytetradeca-2E,8E,10E-trien-4, 6-diyn-1-ol isolated from BZC-2 as active fractions and components were similar to that of dexamethasone in WBCM-C. Therefore, they may act on WBCM and its receptors. BZC-2 has shown anti-inflammatory effects in acute and chronic inflammation models in rats and mice. Oral administration of atractylenolide I and 14-acetoxy-12-senecioyloxytetradeca-2E,8E,10E-trien-4,6-diyn-1-ol produced significant anti-inflammatory effects in acute and chronic inflammation models in mice. The screening results with WBCM-C were correlated significantly with pharmacological effects in vivo. Atractylenolide I and 14-acetoxy-12-senecioyloxytetradeca-2E,8E,10E-trien-4,6-diyn-1-ol were the main components of Atractylodes macrocephala that were effective as anti-inflammatory agents.

Because of their several biological activities, flavonoids may have an important role in explaining the protective effects of vegetables, fruit, and, possibly, tea against cancer. The potential relation between flavonoids and colorectal cancer risk was investigated using data from a multicentric Italian case-control study, including 1,953 cases of colorectal cancers (1,225 colon cancers and 728 rectal cancers) and 4,154 hospital controls admitted for acute nonneoplastic diseases. We have applied recently published data on the composition of foods and beverages, in terms of six principal classes of flavonoids, on dietary information collected through a validated food-frequency questionnaire. Odds ratios (OR) were estimated by multiple logistic regression models, including terms for sex, age, study center, family history of colorectal cancer, education, alcohol consumption, body mass index, physical activity, and energy intake. A reduced risk of colorectal cancer was found for increasing intake of isoflavones (OR, 0.76, for the highest versus the lowest quintile, P(trend) = 0.001), anthocyanidins (OR, 0.67, P(trend) < 0.001), flavones (OR, 0.78, P(trend) = 0.004), and flavonols (OR, 0.64, P(trend) < 0.001). No significant association was found for flavan-3-ols (OR, 0.98), flavanones (OR, 0.96), and total flavonoids (OR, 0.97). The estimates did not substantially differ for colon and rectal cancers, as well as in strata of sex, age, and body mass index. The findings of this large study provide support for an inverse association of selected classes of flavonoids with colorectal cancer risk.

The function of fungal volatiles in fungal-plant interactions is poorly understood. The aim here was to address this lack of knowledge, focusing on truffles, ectomycorrhizal fungi that are highly appreciated for their aroma. The effect of volatiles released by truffles was tested on Arabidopsis thaliana in a closed chamber bioassay. The volatiles produced by Tuber melanosporum, Tuber indicum and Tuber borchii fruiting bodies inhibited A. thaliana in terms of root length and cotyledon leaf size, and in some cases induced a bleaching of the seedlings, thus indicating toxicity. Ten synthetic volatiles were tested in a similar way. The strongest inhibitory effect was observed with C(8) molecules such as 1-octen-3-ol, an alcohol with a typical 'fungal smell'. Two of these C(8) compounds were further tested to investigate their mechanism of action. 1-Octen-3-ol and trans-2-octenal induced an oxidative burst (hydrogen peroxide, H(2)O(2)) in the A. thaliana leaves as well as a strong increase in the activities of three reactive oxygen species (ROS)-scavenging enzymes. These results demonstrate that fungal volatiles inhibit the development of A. thaliana and modify its oxidative metabolism. Even though limited to laboratory observations, these results indicate the presence of a hitherto unknown function of fungal volatiles as molecules that mediate fungal-plant interactions.

Oligodendrocytes (OL), cells that myelinate axons in the CNS, differentiate from early to late oligodendrocyte progenitor cells (OPC) to become mature OL. Unlike the case in the rodent brain, myelin formation starts prenatally in the human brain, but the sequence of OL development and the onset of myelination are not well understood. We studied the human fetal forebrain at midgestation (17-23 gestational weeks, g.w.) using OL lineage-specific antibodies and mRNA probes. Early OPC were present in a gradient from the subventricular zone to the cortical plate. Their close apposition to radial glia fibers suggests a possible role of these fibers in OPC migration. Late OPC reached peak density in the subplate layer, whereas multipolar cells with the morphology of mature OL were restricted to the emerging white matter. At 20 g.w., myelinated axons were observed in the diencephalon, but not in the telencephalon, consistent with caudal-to-rostral progression of myelination. Interestingly, in organotypic slice cultures of the same gestational ages, the subventricular zone contained a considerably greater number of the mature OL cells, suggesting the presence of inhibitory signals in vivo. Overall, in addition to considerable similarities with rodents, important differences in temporal and spatial distribution and regulatory signals for OL differentiation exist in the human brain.

Proanthocyanidins are condensed tannins with various pharmacological properties. These phytochemicals are considered as 'offense and defense molecules because of their human health benefits. The validation of their diverse health aspects, namely, antioxidant, anticancer, antidiabetic, neuroprotective, and antimicrobial has earned them repute in thermochemistry. Proanthocyanidins are oligo- or polymers of monomeric flavan-3-ols produced as an end product of flavonoid biosynthetic pathway. Agricultural wastes and food processing wastes contain immense amount of proanthocyanidins, exploitation of which can be a sustainable source of dietary supplements and functional ingredients. The current review article discusses recent developments in the health promoting properties of proanthocyanidins and the associated hurdles.

B cells are important in the pathogenesis of multiple sclerosis (MS) and some of the effects are not dependent on maturation of B cells into immunoglobulin (Ig) producing plasmablasts and plasma cells. B cells present antigen, activate T cells, and are involved in immunoregulation and cytokine secretion. To determine if B cells from MS patients secrete products that have deleterious effects on glial cells not mediated by Ig, and to compare effects with secretory products of normal controls (NC), we isolated B cells from 7 patients with relapsing remitting MS (RRMS) and 4 NC. B cells were cultured alone or after stimulation with CD40 ligand (CD40L), CD40L+cross-linking of the B cell antigen receptor (xBCR) and CD40L+xBCR+stimulation of toll like receptor 9 (TLR9). Supernatants were harvested and incubated with mixed central nervous system (CNS) neonatal rat glial cells. Supernatants from unstimulated NC B cells induced on average death of 7% (range 0-24%) of differentiated oligodendrocytes (OL); in contrast, supernatants from unstimulated B cells from RRMS patients induced death of 57% (range 35-74%) of OL. Supernatants of stimulated B cells from NC did not increase the minimal OL death whereas stimulation of B cells from RRMS had variable results compared to unstimulated B cells. Supernatants from both NC and RRMS induced microglial enlargement and loss of normal resting bipolar morphology. OL death did not correlate with levels of tumor necrosis alpha (TNF-α), lymphotoxin alpha (LT-α), interleukin 6 (IL-6), IL-10, transforming growth factor beta 1 (TGF-β1) or any combination or ratio of these cytokines. Analysis of 26 supernatants from NC and RRMS patients failed to detect IgM. There were very low levels of IgG in 8 of the 26 supernatants, and no correlation between of OL death and presence or absence of IgG. Sera used in both the B cell and glial cell cultures were heated, which inactivates complement. The effects of B cell supernatants on OL could be direct and/or indirect involving either microglia and/or astrocytes. The identity of the toxic factor(s) is as yet unknown. Thus we have demonstrated that B cells from patients with RRMS but not NC secrete one or more factors toxic to OL. It is possible that such factors produced by peripheral blood B cells when within the CNS could contribute to demyelination in MS patients.

Opioids are regarded to act via receptors interacting with heterotrimeric pertussis toxin (PTX)-sensitive G proteins. In membranes of SH-SY5Y cells, the mu-selective agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAGO) and the delta-selective agonist [D-Pen2,Pen5]-enkephalin (DPDPE) stimulated incorporation of the photoreactive GTP analog [alpha-32P]GTP azidoanilide into proteins comigrating with the alpha subunits of G(i1), G(i2), G(i3), G(o1), and another form of G(o), presumably G(o2). In membranes of PTX-treated cells, both agonists were ineffective. Subtype-specific immunoprecipitation of G protein alpha subunits photolabeled in the absence or presence of agonists revealed profound differences between mu and delta opioid receptors in coupling to PTX-sensitive G proteins. Whereas activated delta opioid receptors preferentially coupled to G(i1), activated mu opioid receptors more effectively coupled to G(i3). Additionally, we provide evidence that G(o) subtypes are also differentially activated by the two receptors. Thus, mu and delta opioid receptors appear to discriminate between PTX-sensitive G proteins and lead to activation of distinct G protein subtypes.

In a community-based sample of Hispanic women, this study examines differences in relation to level of acculturation in knowledge about the Pap examination, fear/fatalism towards cancer, and cervical cancer screening behaviors. Respondents were randomly chosen from 11 churches in the Phoenix metropolitan area (n = 566) and were categorized into three acculturation levels: low (35.2%), bicultural (26.3%), and high (38.5%). Interviews focused on family history of cancer as well as knowledge about cancer and utilization of screening techniques for breast and cervical cancers. OLS regression and probit analyses were conducted to examine the role of acculturation in differentiating. Hispanic subgroups in relation to knowledge, beliefs, and behaviors regarding cervical cancer. Findings of the present study indicate that Hispanic women in the Phoenix metropolitan area are utilizing cervical cancer screening services with over 90 percent of women in all three acculturation groups ever having had a Pap exam and more than 50 percent having had the examination during the past year. However, results also indicate that of the Hispanic subgroups examined, lower acculturated Hispanic women have less knowledge about Pap smears and exhibit lower utilization rates for cervical cancer screening. These results suggest that lower-acculturated Hispanic women comprise the subgroup of Hispanics that is at greatest risk of presenting with advanced stages of cervical cancer. Results have implications for cancer screening and education programs for Hispanic women as well as implications for health care professionals who serve this population.

The construction and performance characteristics of polymeric membrane electrodes based on two neutral ionophores, 2,2'-(1Z,1'Z)-(1E,1'E)-(1,2-phenylenebis(methan-1-yl-1-ylidene))bis(azaan-1-yl-1-ylidene)bis(methylene)bis(azan-1-yl-1-ylidene)bis(methan-1-yl-ylidene)diphenol (L(1)) and 4,4'-(1E,1'E)-(butane-1,4-diylbis(azan-1-yl-1-ylidene))bis(methan-1-yl-1-ylidene)dinaphthalen-1-ol (L(2)) for quantification of cadmium ions, are described. The influences of membrane compositions on the potentiometric response of the electrodes have been found to substantially improve the performance characteristics. The best performance was obtained with the electrode having a membrane composition (w/w) of (L(1)) (2.6%):PVC (31.6%):DOP (63.2%):NaTPB (2.6%). The proposed electrode exhibits Nernstian response in the concentration range 5.0 x 10(-9) to 1.0 x 10(-1)M Cd(2+) with limit of detection 3.1 x 10(-9), performs satisfactorily over wide pH range (2.0-8.5) with a fast response time (11s). The electrode has been found to work satisfactorily in partially non-aqueous media up to 40% (v/v) content of methanol, ethanol and acetonitrile and could be used for a period of 2.5 months. The analytical usefulness of the proposed electrode has been evaluated by its application in the determination of cadmium in cigarette samples. The practical utility of the membrane electrode has also been observed in the presence of surfactants.

The incidence rates of cancers in men differ by countries of the world. We compared the incidence rates of three of the most common cancers (prostate, lung, and colon) in men residing in 164 different countries with the population-weighted light at night (LAN) exposure and with several developmental and environmental indicators, including per capita income, percent urban population, and electricity consumption. The estimate of per capita LAN exposure was a novel aspect of this study. Both ordinary least squares (OLS) and spatial error (SE) regression models were used in the analysis. We found a significant positive association between population exposure to LAN and incidence rates of prostate cancer, but no such association with lung cancer or colon cancer. The prostate cancer result is consistent with a biological theory and a limited number of previous studies of circadian disruption and risk. The LAN-prostate cancer connection is postulated to be due to suppression of melatonin and/or disruption of clock gene function. An analysis holding other variables at average values across the 164 countries yielded a risk of prostate cancer in the highest LAN-exposed countries 110% higher than in the lowest LAN exposed countries. This observed association is a necessary condition for a potentially large effect of LAN on risk of prostate cancer. However, it is not sufficient due to potential confounding by factors that increase the risk of prostate cancer and are also associated with LAN among the studied countries.