Vitamin D and prevention of colorectal cancer

BACKGROUND: Inadequate photosynthesis or oral intake of Vitamin D are associated with high incidence rates of colorectal cancer, but the dose-response relationship has not been adequately studied. METHODS: Dose-response gradients from observational studies of Vitamin D intake and serum 25-hydroxyvitamin D were plotted as trend lines. The point on each linear trend line corresponding to an odds ratio of 0.50 provided the prediagnostic Vitamin D intake or 25-hydroxyvitamin D concentration associated with 50% lower risk compared to <100IU/day Vitamin D or <13ng/ml serum 25-hydroxyvitamin D. Medians of these values were determined. RESULTS: Overall, individuals with >or=1000IU/day oral Vitamin D (p<0.0001) or >or=33ng/ml (82nmol/l) serum 25-hydroxyvitamin D (p<0.01) had 50% lower incidence of colorectal cancer compared to reference values. CONCLUSIONS: Intake of 1000IU/day of Vitamin D, half the safe upper intake established by the National Academy of Sciences, was associated with 50% lower risk. Serum 25-hydroxyvitamin D of 33ng/ml, which is known to be safe, also was associated with 50% lower risk. Prompt public health action is needed to increase intake of Vitamin D(3) to 1000IU/day, and to raise 25-hydroxyvitamin D by encouraging a modest duration of sunlight exposure.     

Obesity-associated mutations in the melanocortin 4 receptor provide novel insights into its function

Mutations in the Melanocortin 4 receptor are implicated in 1-6% of early onset or severe adult obesity cases. Most of the patients carry heterozygous missense mutations. Arguments for the pathogenicity of these mutations are based on the frequency of rare functionally relevant non-synonymous mutations in severely obese children and adults versus non-obese controls, the segregation of mutations with obesity in the family of the probands (although with incomplete penetrance) and the relevant functional defects described for these mutations. We have developed new assays to study the functional characteristics of these obesity-associated MC4R mutations. Systematic and comparative functional study of over 50 different obesity-associated mutations suggests that multiple functional alterations contribute to their pathogenicity. These studies also lead to new insights into the structure-function relationship of MC4R, provide novel hypotheses for the genetic predisposition to common obesity in humans and allow the development of new molecular tools for studying the physiological role of GPCRs.     

Coffee and Pancreatic Cancer in a Rural California County

In a study of the risk of fatal pancreatic cancer according to intake of regular and decaffeinated coffee, cases (N = 30) and controls (N = 47) were identified from death certificates and matched for age (± 5 years), sex, ethnicity, and date of death (± 5 years). Telephone interviews were completed with survivors of about 80% of both groups. In smokers, the relative risk for high (3 + cups) versus low (<3 cups) intake of regular coffee was 4.3 (P < .05), and high verus low decaffeinated coffee, 5.5 (P < .05). In nonsmokers, neither type of coffee influenced the risk. Mean daily intakes of alcohol and cigarettes were virtually identical in cases and controls, although cases had accumulated nonsignificantly more pack-years. Intakes of regular and decaffeinated coffee were uncorrelated, and the smoking-coffee interaction could not be readily explained by recall bias. If coffee intake increases the risk of pancreatic cancer, the mechanism could depend heavily on smoking.     

Analysis of taxol and related diterpenoids from cell cultures by liquid chromatography—electrospray mass spectrometry

Authentic taxanes (taxol, 10-deacetyltaxol, cephalomannine, 10-deacetylcephalomannine, baccatin III) and extracts from cell cultures derived from various yew tree species have been analyzed by microbore high-performance liquid chromatography (HPLC)—electrospray mass spectrometry (ESMS). All gave excellent positive-ion ES spectra with dominant protonated molecules at low nozzle-to-skimmer bias value (45 V). By increasing the voltage value to 85 V, fragmentation increased and structurally informative spectra were obtained. The fragments found were both of the C-13 side-chain and of the taxane ring, so their analysis gave important information about the taxane structure and any chemical modifications at different positions of the molecule. When tandem MS was used (argon gas, 25 eV collision energy), fragments similar to those obtained from collision-induced dissociation in the source were detected. The cell culture extracts were analyzed by microbore HPLC—ESMS and excellent spectra were obtained on 5–10 ng of separated compounds; even greater selectivity and sensitivity were obtained through use of selected-ion monitoring (SIM). With SIM, 100 pg of all taxanes could readily be detected. In the HPLC—ESMS mode, only 10% of the eluent was mass-analyzed, so 90% would be available for recovery through fraction collecting.     

Platelet Releasate Proteome Profiling Reveals a Core Set of Proteins with Low Variance between Healthy Adults

Upon activation, platelets release a powerful cocktail of soluble and vesicular signals, collectively termed the "platelet releasate" (PR). Although several studies have used qualitative/quantitative proteomic approaches to characterize PR; with debated content and significant inter‐individual variability reported, confident, and reliable insights have been hindered. Using label‐free quantitative (LFQ)‐proteomics analysis, a reproducible, quantifiable investigation of the 1U mL^?1 thrombin‐induced PR from 32 healthy adults was conducted. MS proteomics data are available via ProteomeXchange, identifier PXD009310. Of the 894 proteins identified, 277 proteins were quantified across all donors and form a "core" PR. Bioinformatics and further LFQ‐proteomic analysis revealed that the majority (84%) of "core" PR proteins overlapped with the protein composition of human platelet‐derived exosomes. Vesicles in the exosomal‐size range were confirmed in healthy‐human PR and reduced numbers of similar‐sized vesicles were observed in the PR of a mouse model of gray platelet syndrome, known to be deficient in platelet alpha‐granules. Lastly, the variability of proteins in the PR was assessed, and reproducible secretion levels were found across all 32 healthy donors. Taken together, the PR contains valuable soluble and vesicular cargo and has low‐population variance among healthy adults, rendering it a potentially useful platform for diagnostic fingerprinting of platelet‐related disease.     

The role of the frontal ganglion in the control of protein metabolism inLocusta migratoria

Summary 1. After removal of the frontal ganglion, there is an immediate permanent decrease in the blood protein level.2. The cytoplasmic RNA concentration, the blood amino-acid level and the midgut protease level, also decrease after this operation.3. These effects cannot be reversed by feeding as is the case in starved animals.4. The above results provide clear evidence that the frontal ganglion plays a vital part in controlling protein synthesis in the growing locust.

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Die Bedeutung des Frontalganglions für die Kontrolle des Proteinstoffwechsels beiLocusta migratoria

Kurzfassung Am dritten Nymphenstadium vonLocusta migratoria konntenClarke &Langley (1963a) zeigen, daß die Entfernung des Frontalganglions eine völlige Einstellung des Körperwachstums zur Folge hat. Elektrophorese des Blutes operierter Tiere läßt eine starke permanente Abnahme des Proteingehaltes erkennen. Gleichzeitig kommt es zu einer allgemeinen Verringerung des RNS-Gehaltes der Gewebe. Diese ist besonders augenfällig in den aktivsten Geweben, wie etwa der Epidermis und dem Mitteldarmepithel. Weiterhin ergaben papierchromatographische Untersuchungen, daß — im Gegensatz zu der bei Hungertieren angetroffenen Situation — eine Abnahme der Aminosäurekonzentration des Blutes erfolgt, welche ihrerseits wiederum zu einem Zusammenbruch des Wasserhaushaltes führt. Noch nicht abgeschlossene Untersuchungen über die Mitteldarmproteasen deuten auf eine ungenügende Synthese dieser Enzyme in den Epithelzellen der operierten Tiere hin. Es wird eine allgemeine Kontrolle der Proteinsynthese durch das neurosekretorische System postuliert und angenommen, daß dieses System wiederum durch sensorische Impulse kontrolliert wird, welche von den pharyngealen Dehnungsrezeptoren über das Frontalganglion zum Gehirn gelangen.

     

Biodiversity and trophic structure of invertebrate assemblages associated with understorey red algae in a Laminaria digitata bed

Although the composition of invertebrate assemblages associated with kelps has motivated several studies in the recent past, little is known about assemblages associated with smaller, understorey macroalgae in these ecosystems. Here, the composition of invertebrate assemblages living within understorey macroalgae of a kelp (Laminaria digitata) forest has been studied over two sampling dates, and the structure of the food web investigated using stable isotopes. A total of 145 species of mobile fauna, mainly amphipods and gastropods, were identified. Although differences were date-dependent, we showed that the three species considered (Palmaria palmata, Mastocarpus stellatus, Ellisolandia elongata) sheltered different associated assemblages, including high host-specificity, which suggests that the animal diversity associated with rocky shores is enhanced by a high algal diversity. Overall, a dominance of gastropods was observed for the two-dimensional, leaf-like P. palmata, while the three-dimensionally structured species (M. stellatus, E. elongata) were characterized by a dominance of amphipods. Stable isotopes highlighted different trophic structures; E. elongata-associated assemblages were most likely relying on a dominant food source, sediment organic matter, while other assemblages were based on a wider diversity of food sources (algae, sediment, suspended organic matter). Our results illustrate the need to consider the microhabitats formed by understorey macroalgae in order to thoroughly assess the diversity and understand the functioning of coastal rocky ecosystems.     

Twenty-four-hour pattern of operations-related injury occurrence and severity of off-site/on-call volunteer French firefighters

We assessed the 24-h pattern of operations-related injuries (ORI) experienced by scheduled off-site/on-call French volunteer firefighters (VFF) through analysis of an archival database. Occurrence and severity – evaluated by number of lost work days (LWD) and total medical costs (TMC) – of ORI were explored in terms of risk ratios, respectively, number of ORI/number of service operations (RR_ORI), number of LWD/number of ORI (RS_LWD,) and TMC/number of ORI (RS_TMC). Additionally, the collective work performance of all involved VFF was measured in terms of the lag time (LT) between emergency call-center firefighter-answered communication for service of observer-presumed out-of-hospital cardiac arrest (OHCA) and departure of vehicle from fire station to render aid, designated LT_OHCA. Cosinor and cross-correlation statistical methods were applied. A total of 252 ORI occurred while performing 146,479 service operations. High-amplitude 24 h variation was detected in RR_ORI (p < .003), SR_LWD (p < .001), SR_TMC (p < .012), and LT_OHCA (p < .001), all with nocturnal peak time. Coherence was found between the day/night variation of LT_OHCA and RR_ORI (r = 0.7, p < .0002), SR_LWD (r = 0.5, p < .02), and SR_TMC (r = 0.4, p < .05). This investigation verifies the occurrence and severity of ORI of scheduled off-site/on-call VFF exhibit high-amplitude 24 h patterning with nocturnal excess that closely coincides with their day/night work performance measured by LT_OHCA. These findings, which are essentially identical to ones of a previous study entailing on-site/on-call career firefighters, indicate the need for fatigue management and ORI prevention programs not yet available to VFF, who compose the majority of the field service workforce of French fire departments.

Abbreviations:FF: firefighters; CFF: career firefighters; VFF: volunteer firefighters; FD: fire department; LT_OHCA: lag time (LT) response in min:sec between fire department call-center-answered communication for service of presumed out-of-hospital cardiac arrest (OHCA) and departure from fire station of vehicle to render aid; LWD: lost work days; ORI: operations-related injuries; SR_LWD: severity ratio of operations-related injuries in terms of number of lost work days, calculated as number of lost work days/number of operations-related injuries; RR_ORI: risk ratio of operations-related injuries calculated as number of operations-related injuries/number of operations; SR_TMC: severity ratio of operations-related injuries in terms of total medical costs, calculated as total medical costs/number of operations-related injuries; TMC: total medical costs     

Seven principles to rule them all

Coen offers a unified explanation of natural selection, development, learning and cultural change, based on seven fundamental principles: population variation, persistence, reinforcement, competition, cooperation, combinatorial richness and recurrence. I discuss whether all seven principles are justified, successfully fit the four processes, encompass life processes only, and have any strong explanatory import. I find each of these claims doubtful.