Association of MRI T1 relaxation time with neuropsychological test performance in manganese- exposed welders.

This study examines the results of neuropsychological testing of 26 active welders and 17 similar controls and their relationship to welders' shortened MRI T1 relaxation time, indicative of increased brain manganese (Mn) accumulation. Welders were exposed to Mn for an average duration of 12.25 years to average levels of Mn in air of 0.11±0.05mg/m3. Welders scored significantly worse than controls on Fruit Naming and the Parallel Lines test of graphomotor tremor. Welders had shorter MRI T1 relaxation times than controls in the globus pallidus, substantia nigra, caudate nucleus, and the anterior prefrontal lobe. 63% of the variation in MRI T1 relaxation times was accounted for by exposure group. In welders, lower relaxation times in the caudate nucleus and substantia nigra were associated with lower neuropsychological test performance on tests of verbal fluency (Fruit Naming), verbal learning, memory, and perseveration (WHO-UCLA AVLT). Results indicate that verbal function may be one of the first cognitive domains affected by brain Mn deposition in welders as reflected by MRI T1 relaxation times.

The Influence of Religious Affiliation on Participant Responsiveness to the Complete Health Improvement Program (CHIP) Lifestyle Intervention.

Seventh-day Adventist (SDA) and non-SDA (21.3 and 78.7 %, respectively) individuals (n = 7172) participating in the Complete Health Improvement Program, a 30-day diet and lifestyle intervention, in North America (241 programs, 2006-2012) were assessed for changes in selected chronic disease risk factors: body mass index (BMI), blood pressure (BP), pulse, lipid profile and fasting plasma glucose (FPG). Reductions were greater among the non-SDA for BMI, pulse and blood lipids. Furthermore, the majority of non-SDA in the highest risk classifications for BP, lipids and FPG, but only some lipids among SDA, were able to show improvement by 20 % or more.

The efficacy and safety of probiotics in people with cancer: a systematic review.

BACKGROUND: Probiotics are living microorganisms that are generally thought of as being beneficial to the recipient. They have been shown to be effective in people with acute infectious diarrhoea, and cost-effective in antibiotic-associated diarrhoea. Probiotics may have a role in people with cancer, as various cancer treatments often lead to diarrhoea. However, as people with cancer are often immunocompromised, it is important to assess for adverse events (AEs) such as infection, which could potentially be a consequence of deliberate ingestion of living microorganisms. DESIGN: A systematic review was carried out to collect, analyse and synthesise all available data on the efficacy and safety of probiotics in people with cancer (PROSPERO registration: CRD42012003454). Randomised, controlled trials, identified through screening multiple databases and grey literature, were included for analysing efficacy, while all studies were included for the analysis of safety of probiotics. Primary outcomes were the reduction in duration, severity and incidence of antibiotic-associated diarrhoea and chemotherapy-associated diarrhoea, and AEs, especially probiotic-associated infection. Where possible, data were combined for meta-analysis by a random-effects model, assessing causes of heterogeneity, including differences in strains, dosage and patient characteristics. RESULTS: Eleven studies (N = 1557 participants) were included for assessing efficacy. Results show that probiotics may reduce the severity and frequency of diarrhoea in patients with cancer and may reduce the requirement for anti-diarrhoeal medication, but more studies are needed to assess the true effect. For example comparing probiotic use to control 25 groups on effect on Common Toxicity Criteria ≥2 grade diarrhoea, odds ratio (OR) = 0.32 [95% confidence interval (CI) of 0.13-0.79; P = 0.01]. Seventeen studies (N = 1530) were included in the safety analysis. Five case reports showed probiotic-related bacteraemia/fungaemia/positive blood cultures. CONCLUSIONS: Probiotics may be a rare cause of sepsis. Further evidence needs to be collated to determine whether probiotics provide a significant overall benefit for people with cancer.

The MicroRNA pathway plays a regulatory role in stem cell division.

One of the key characteristics of stem cells is their capacity for self-renewal for long periods of time. In this respect, stem cells are similar to cancer cells, which also have the ability to escape cell cycle stop signals. Therefore, a critical question in stem cell and cancer biology is how cell division is regulated in these cell types. In this review, we summarize recent progress and describe future challenges to understanding the role the microRNA pathway plays in regulating mechanisms controlling stem cell division.

Characterization of a novel subset of cardiac cells and their progenitors in the Drosophila embryo.

The Drosophila heart is a simple organ composed of two major cell types: cardioblasts, which form the simple contractile tube of the heart, and pericardial cells, which flank the cardioblasts. A complete understanding of Drosophila heart development requires the identification of all cell types that comprise the heart and the elucidation of the cellular and genetic mechanisms that regulate the development of these cells. Here, we report the identification of a new population of heart cells: the Odd skipped-positive pericardial cells (Odd-pericardial cells). We have used descriptive, lineage tracing and genetic assays to clarify the cellular and genetic mechanisms that control the development of Odd-pericardial cells. Odd skipped marks a population of four pericardial cells per hemisegment that are distinct from previously identified heart cells. We demonstrate that within a hemisegment, Odd-pericardial cells develop from three heart progenitors and that these heart progenitors arise in multiple anteroposterior locations within the dorsal mesoderm. Two of these progenitors divide asymmetrically such that each produces a two-cell mixed-lineage clone of one Odd-pericardial cell and one cardioblast. The third progenitor divides symmetrically to produce two Odd-pericardial cells. All remaining cardioblasts in a hemisegment arise from two cardioblast progenitors each of which produces two cardioblasts. Furthermore, we demonstrate that numb and sanpodo mediate the asymmetric divisions of the two mixed-lineage heart progenitors noted above.

odd-skipped is expressed in multiple tissues during Drosophila embryogenesis.

The odd-skipped (odd) gene encodes a zinc finger protein that represses other segmentation genes in the early Drosophila embryo. Though odd is initially expressed in a striped pattern that reflects its function within the segmentation hierarchy, it is also expressed in a variety of patterns during later stages of embryogenesis. To identify the cells and tissues that correspond to these latter patterns, we examined the distribution of the Odd protein at all embryonic stages. Our results indicate that Odd is a specific and persistent marker for subsets of cells in developing mesoderm, ectoderm, and neural tissue. We conclude that Odd is a useful tool for studying cell specification, cell migrations and morphogenetic movements during organogenesis of the heart, gut and central nervous system.

Persistent and heritable structural damage induced in heterochromatic DNA from rat liver by N-nitrosodimethylamine.

Analysis, by benzoylated DEAE-cellulose chromatography, has been made of structural change in eu- and heterochromatic DNA from rat liver following administration of the carcinogen N-nitrosodimethylamine (10 mg/kg body weight). Either hepatic DNA was prelabeled with [3H]thymidine administered 2-3 weeks before injection of the carcinogen or the labeled precursor was given during regenerative hyperplasia in rats treated earlier with N-nitrosodimethylamine. Following phenol extraction of either whole liver homogenate or nuclease-fractionated eu- and heterochromatin, carcinogen-modified DNA was examined by stepwise or caffeine gradient elution from benzoylated DEAE-cellulose. In whole DNA, nitrosamine-induced single-stranded character was maximal 4-24 h after treatment, declining rapidly thereafter; gradient elution of these DNA preparations also provided short-term evidence of structural change. Following incubation of purified nuclei with micrococcal nuclease, 10-12% of labeled DNA was solubilized (eu-chromatin) by 1.0 unit of micrococcal nuclease (5 mg of DNA)-1 mL-1 after 9 min. In prelabeled animals, administration of N-nitrosodimethylamine caused a marked fall in the specific radioactivity of solubilized DNA, while that of sedimenting DNA was not affected. Caffeine gradient chromatography suggested short-term nitrosamine-induced structural change in euchromatic DNA, while increased binding of heterochromatic DNA was evident for up to 3 months after carcinogen treatment. Preparations of newly synthesized heterochromatic DNA from animals subjected to hepatectomy up to 2 months after carcinogen treatment provided evidence of heritable structural damage. Carcinogen-induced binding of heterochromatic DNA to benzoylated DEAE-cellulose was indicative of specific structural lesions whose affinity equalled that of single-stranded DNA up to 1.0 kilobase in length.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term persistence of nitrosamine-induced structural damage to heterochromatic DNA.

Different levels of damage and repair to eu- and heterochromatic DNA from the livers of rats receiving a dose of 10 mg/kg N-nitrosodimethylamine (NDMA) were apparent. Preincorporated 3H-thymidine was lost rapidly from euchromatic DNA but persisted in the heterochromatic fraction. Persistent damage, determined as single-stranded regions binding to benzoylated DEAE-cellulose (BD-cellulose), was evident in heterochromatic DNA for up to three months. By subjecting rats treated with NDMA to partial hepatectomy, generation of single-stranded regions in the newly synthesized heterochromatic DNA could be demonstrated. Such structural defects were evident when hepatectomy was performed two months after administration of the carcinogen. These findings indicate that structural damage to nontranscribed DNA is one of the most persistent molecular lesions following exposure to nitrosamines.

Digestion of repair sites in rat liver DNA by endogenous nucleases.

The proportion of sheared rat liver DNA recovered from benzoylated DEAE-cellulose in the final stage following stepwise elution with NaCl and caffeine solutions was dependent upon the DNA isolation procedure. An increase in the proportion of DNA containing single stranded regions, consequent upon delay or addition of Mg2+ prior to phenol extraction, suggested nuclease mediated degradation. Administration of methyl methanesulphonate to rats resulted in a consistent proportional increase in the caffeine-eluted fraction. The results of caffeine gradient elution of control and alkylated DNA from benzoylated DEAE-cellulose were consistent with repair-associated single stranded regions being substrates for endogenous single strand-specific exonucleases.

Single-strand-specific degradation of DNA during isolation of rat liver nuclei.

We have investigated structural change in rat liver DNA produced by different isolation procedures and specifically compared the integrity of DNA derived by phenol extraction from isolated and purified nuclei with preparations extracted immediately from a crude liver homogenate containing intact nuclei. As indicated by stepwise elution from benzoylated DEAE-cellulose, most structural change in DNA was evident following nuclei isolation. Damage principally involved generation of single-stranded regions in otherwise double-stranded DNA fragments; totally single-stranded DNA was not detected by hydroxylapatite chromatography. Caffeine gradient elution suggested formation of single-stranded regions extending for up to several kilobases. In neutral sucrose gradients, differences in sedimentation rates of respective DNA samples consequent upon S1 nuclease digestion could be detected after isolation of nuclei, though not in other circumstances. The observed single-strand-specific nuclease digestion of DNA could apparently be reduced if steps were taken to reduce autodigestion during nuclei isolation by reduction of temperature and covalent cation concentration. The results are discussed in terms of the use of exogenous and endogenous nucleases in chromatin fractionation studies involving isolated nuclei and possible artifactual findings that may be generated by single-strand-specific autodigestion.

Chiasma frequency and distribution in a maize family segregating for k10 and trisomy 10.

Chiasma frequency was determined from total chiasma counts, and the distribution of these exchanges was determined by the ratio of proximal to distal chiasmata. No effect of trisomy 10 could be demonstrated. Confirmation was obtained of earlier work showing more proximal and fewer distal chiasmata in K10 plants than in controls. However, diakinesis data failed to confirm the ability of K10 to increase total chiasmata as suggested from metaphase I results.

The effect of accessory chromatin on chiasma distribution in maize.

From an analysis of metaphase I bivalent configurations in Zea mays L. it was possible to determine the effects of two supernumerary elements on chiasma formation. Both the B chromosome and abnormal chromosome 10 increased chiasma frequency. In addition to enhancing total exchanges, both elements caused a redistribution of chiasmata from distal to more proximal locations.

Nondisjunction: localization of the controlling site in the maize B chromosome.

Nondisjunction of the B chromosome in maize has been considered to be controlled by heterochromatin in its long arm. Experiments reported here indicate that the control site actually lies in a short, relatively euchromatic segment distal to the major heterochromatin of the long arm.