Nutritional and environmental regulation of the synthesis of highly unsaturated fatty acids and of fatty-acid oxidation in Atlantic salmon (Salmo salar L.) enterocytes and hepatocytes

The aim was to determine if highly unsaturated fatty acid (HUFA) synthesis and fatty acid oxidation in Atlantic salmon (Salmo salar L.) intestine was under environmental and/or seasonal regulation. Triplicate groups of salmon were grown through a full two-year cycle on two diets containing either fish oil (FO), or a diet with 75% of the FO replaced by a vegetable oil (VO) blend containing rapeseed, palm and linseed oils. At key points in the life cycle, fatty acyl desaturation/elongation (HUFA synthesis) and oxidation activities were determined in enterocytes and hepatocytes using [1-14C]18:3n-3 as substrate. As observed previously, HUFA synthesis in hepatocytes showed peak activity at seawater transfer and declined thereafter, with activity consistently greater in fish fed the VO diet. In fish fed FO, HUFA synthesis in enterocytes in the freshwater stage was at a similar level to that in hepatocytes. However, HUFA synthesis in enterocytes increased rapidly after seawater transfer and remained high for some months after transfer before decreasing to levels that were again similar to those observed in hepatocytes. Generally, enterocyte HUFA synthesis was higher in fish fed the VO diet compared to the FO diet. Oxidation of [1-14C]18:3n-3 in hepatocytes from fish fed FO tended to decrease during the freshwater phase but then increased steeply, peaking just after transfer before decreasing during the remaining seawater phase. At the peak in oxidation activity around seawater transfer, activity was significantly lower in fish fed VO compared to fish fed FO. In enterocytes, oxidation of [1-14C]18:3 in fish fed FO showed a peak in activity just prior to seawater transfer. In fish fed VO, other than high activity at 9 months, the pattern was similar to that obtained in enterocytes from fish fed FO with a high activity around seawater transfer and declining activity in seawater. In conclusion, fatty acid metabolism in intestinal cells appeared to be under dual nutritional and environmental or seasonal regulation. The temporal patterns for fatty acid oxidation were generally similar in the two cell types, but HUFA synthesis in enterocytes peaked over the summer seawater phase rather than at transfer, as with hepatocytes, suggesting possibly different regulatory cues

Gut evacuation rate and grazing impact of the krill Thysanoessa raschii and T. inermis

Gut evacuation rates and ingestion rates were measured for the krill Thysanoessa raschii and T. inermis in Godthåbsfjord, SW Greenland. Combined with biomass of the krill community, the grazing potential on phytoplankton along the fjord was estimated. Gut evacuation rates were 3.9 and 2.3 h−1 for T. raschii and T. inermis, respectively. Ingestion rates were 12.2 ± 7.5 µg C mg C−1 day−1 (n = 4) for T. inermis and 4.9 ± 3.2 µg C mg C−1 day−1 (n = 4) for T. raschii, corresponding to daily rations of 1.2 and 0.5 % body carbon day−1. Clearance experiments conducted in parallel to the gut evacuation experiment gave similar results for ingestion rates and daily rations. Krill biomass was highest in the central part of the fjord’s length, with T. raschii dominating. Community grazing rates from krill and copepods were comparable; however, their combined impact was low, estimated as <1 % of phytoplankton standing stock being removed per day during this late spring study

The development of a protoplanetary disk from its natal envelope

Class 0 protostars, the youngest type of young stellar objects, show many signs of rapid development from their initial, spheroidal configurations, and therefore are studied intensively for details of the formation of protoplanetary disks within protostellar envelopes. At millimetre wavelengths, kinematic signatures of collapse have been observed in several such protostars, through observations of molecular lines that probe their outer envelopes. It has been suggested that one or more components of the proto-multiple system NGC 1333-IRAS 4 (refs 1, 2) may display signs of an embedded region that is warmer and denser than the bulk of the envelope(3,4). Here we report observations that reveal details of the core on Solar System dimensions. We detect in NGC 1333-IRAS 4B a rich emission spectrum of H2O, at wavelengths 20-37 mu m, which indicates an origin in extremely dense, warm gas. We can model the emission as infall from a protostellar envelope onto the surface of a deeply embedded, dense disk, and therefore see the development of a protoplanetary disk. This is the only example of mid-infrared water emission from a sample of 30 class 0 objects, perhaps arising from a favourable orientation; alternatively, this may be an early and short-lived stage in the evolution of a protoplanetary disk.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62894/1/nature06087.pd

The influence of micrometastases on prognosis and survival in stage I-II colon cancer patients: the Enroute⊕ Study

<p>Abstract</p> <p>Background</p> <p>The presence of lymph node metastases remains the most reliable prognostic predictor and the gold indicator for adjuvant treatment in colon cancer (CC). In spite of a potentially curative resection, 20 to 30% of CC patients testing negative for lymph node metastases (i.e. pN0) will subsequently develop locoregional and/or systemic metastases within 5 years. The presence of occult nodal isolated tumor cells (ITCs) and/or micrometastases (MMs) at the time of resection predisposes CC patients to high risk for disease recurrence. These pN0_micro+patients harbouring occult micrometastases may benefit from adjuvant treatment. The purpose of the present study is to delineate the subset of pN0 patients with micrometastases (pN0_micro+) and evaluate the benefits from adjuvant chemotherapy in pN0_micro+CC patients.</p> <p>Methods/design</p> <p>EnRoute+ is an open label, multicenter, randomized controlled clinical trial. All CC patients (age above 18 years) without synchronous locoregional lymph node and/or systemic metastases (clinical stage I-II disease) and operated upon with curative intent are eligible for inclusion. All resected specimens of patients are subject to an <it>ex vivo </it>sentinel lymph node mapping procedure (SLNM) following curative resection. The investigation for micrometastases in pN0 patients is done by extended serial sectioning and immunohistochemistry for pan-cytokeratin in sentinel lymph nodes which are tumour negative upon standard pathological examination. Patients with ITC/MM-positive sentinel lymph nodes (pN0_micro+) are randomized for adjuvant chemotherapy following the CAPOX treatment scheme or observation. The primary endpoint is 3-year disease free survival (DFS).</p> <p>Discussion</p> <p>The EnRoute+ study is designed to improve prognosis in high-risk stage I/II pN0 _micro+CC patients by reducing disease recurrence by adjuvant chemotherapy.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01097265">NCT01097265</a></p

Effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine on appetite, food intake and emotional processing in healthy volunteers

RATIONALE: The treatment of obesity is an increasing global health priority, yet few effective drug treatments are currently available. The discovery of novel anti-obesity therapies could be assisted by the validation of experimental (translational) medicine models in healthy volunteers that assess efficacy and safety at an early stage of drug development. OBJECTIVES: The aim of this study was to examine the effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) in an experimental medicine model assessing both appetite and mood. METHODS: Using a between-subjects, double-blind, placebo-controlled design, 24 male and 24 female participants were randomly assigned to either placebo, 15- or 30-mg mCPP treatment groups. Lunch was eaten from a Universal Eating Monitor (UEM) that measured eating rate, and the participants completed the P1vital® Oxford Emotional Test Battery (ETB) and a series of appetite and mood ratings. RESULTS: mCPP reduced appetite and, in women, enhanced measures of satiation. The drug also enhanced memory for emotional material in the word recall and recognition memory tasks of the ETB. CONCLUSIONS: The results provide new insight into the effects of mCPP on appetite, satiety and memory in humans. In addition, our data provide an illustration of the value of measuring changes in appetite and mood in healthy volunteers to determine the potential efficacy and safety of novel anti-obesity drugs

Convergence among Non-Sister Dendritic Branches: An Activity-Controlled Mean to Strengthen Network Connectivity

The manner by which axons distribute synaptic connections along dendrites remains a fundamental unresolved issue in neuronal development and physiology. We found in vitro and in vivo indications that dendrites determine the density, location and strength of their synaptic inputs by controlling the distance of their branches from those of their neighbors. Such control occurs through collective branch convergence, a behavior promoted by AMPA and NMDA glutamate receptor activity. At hubs of convergence sites, the incidence of axo-dendritic contacts as well as clustering levels, pre- and post-synaptic protein content and secretion capacity of synaptic connections are higher than found elsewhere. This coupling between synaptic distribution and the pattern of dendritic overlapping results in ‘Economical Small World Network’, a network configuration that enables single axons to innervate multiple and remote dendrites using short wiring lengths. Thus, activity-mediated regulation of the proximity among dendritic branches serves to pattern and strengthen neuronal connectivity

A high-density transcript linkage map with 1,845 expressed genes positioned by microarray-based Single Feature Polymorphisms (SFP) in Eucalyptus

<p>Abstract</p> <p>Background</p> <p>Technological advances are progressively increasing the application of genomics to a wider array of economically and ecologically important species. High-density maps enriched for transcribed genes facilitate the discovery of connections between genes and phenotypes. We report the construction of a high-density linkage map of expressed genes for the heterozygous genome of <it>Eucalyptus </it>using Single Feature Polymorphism (SFP) markers.</p> <p>Results</p> <p>SFP discovery and mapping was achieved using pseudo-testcross screening and selective mapping to simultaneously optimize linkage mapping and microarray costs. SFP genotyping was carried out by hybridizing complementary RNA prepared from 4.5 year-old trees xylem to an SFP array containing 103,000 25-mer oligonucleotide probes representing 20,726 unigenes derived from a modest size expressed sequence tags collection. An SFP-mapping microarray with 43,777 selected candidate SFP probes representing 15,698 genes was subsequently designed and used to genotype SFPs in a larger subset of the segregating population drawn by selective mapping. A total of 1,845 genes were mapped, with 884 of them ordered with high likelihood support on a framework map anchored to 180 microsatellites with average density of 1.2 cM. Using more probes per unigene increased by two-fold the likelihood of detecting segregating SFPs eventually resulting in more genes mapped. <it>In silico </it>validation showed that 87% of the SFPs map to the expected location on the 4.5X draft sequence of the <it>Eucalyptus grandis </it>genome.</p> <p>Conclusions</p> <p>The <it>Eucalyptus </it>1,845 gene map is the most highly enriched map for transcriptional information for any forest tree species to date. It represents a major improvement on the number of genes previously positioned on <it>Eucalyptus </it>maps and provides an initial glimpse at the gene space for this global tree genome. A general protocol is proposed to build high-density transcript linkage maps in less characterized plant species by SFP genotyping with a concurrent objective of reducing microarray costs. HIgh-density gene-rich maps represent a powerful resource to assist gene discovery endeavors when used in combination with QTL and association mapping and should be especially valuable to assist the assembly of reference genome sequences soon to come for several plant and animal species.</p

Genome-wide linkage and association study implicates the 10q26 region as a major genetic contributor to primary nonsyndromic vesicoureteric reflux

Abstract Vesicoureteric reflux (VUR) is the commonest urological anomaly in children. Despite treatment improvements, associated renal lesions – congenital dysplasia, acquired scarring or both – are a common cause of childhood hypertension and renal failure. Primary VUR is familial, with transmission rate and sibling risk both approaching 50%, and appears highly genetically heterogeneous. It is often associated with other developmental anomalies of the urinary tract, emphasising its etiology as a disorder of urogenital tract development. We conducted a genome-wide linkage and association study in three European populations to search for loci predisposing to VUR. Family-based association analysis of 1098 parent-affected-child trios and case/control association analysis of 1147 cases and 3789 controls did not reveal any compelling associations, but parametric linkage analysis of 460 families (1062 affected individuals) under a dominant model identified a single region, on 10q26, that showed strong linkage (HLOD = 4.90; ZLRLOD = 4.39) to VUR. The ~9Mb region contains 69 genes, including some good biological candidates. Resequencing this region in selected individuals did not clearly implicate any gene but FOXI2, FANK1 and GLRX3 remain candidates for further investigation. This, the largest genetic study of VUR to date, highlights the 10q26 region as a major genetic contributor to VUR in European populations