FBXW7 targets mTOR for degradation and cooperates with PTEN in tumor suppression

The enzyme mTOR (mammalian target of rapamycin) is a major target for therapeutic intervention to treat many human diseases, including cancer, but very little is known about the processes that control levels of mTOR protein. Here, we show that mTOR is targeted for ubiquitination and consequent degradation by binding to the tumor suppressor protein FBXW7. Human breast cancer cell lines and primary tumors showed a reciprocal relation between loss of FBXW7 and deletion or mutation of PTEN (phosphatase and tensin homolog), which also activates mTOR. Tumor cell lines harboring deletions or mutations in FBXW7 are particularly sensitive to rapamycin treatment, which suggests that loss of FBXW7 may be a biomarker for human cancers susceptible to treatment with inhibitors of the mTOR pathway.     

Multipotent Drosophila intestinal stem cells specify daughter cell fates by differential notch signaling

The adult Drosophila midgut contains multipotent intestinal stem cells (ISCs) scattered along its basement membrane that have been shown by lineage analysis to generate both enterocytes and enteroendocrine cells. ISCs containing high levels of cytoplasmic Delta-rich vesicles activate the canonical Notch pathway and down-regulate Delta within their daughters, a process that programs these daughters to become enterocytes. ISCs that express little vesiculate Delta, or are genetically impaired in Notch signaling, specify their daughters to become enteroendocrine cells. Thus, ISCs control daughter cell fate by modulating Notch signaling over time. Our studies suggest that ISCs actively coordinate cell production with local tissue requirements by this mechanism.     

Major glycoprotein antigens that induce antibodies in AIDS patients are encoded by HTLV-III

Antibodies from the serum of patients with the acquired immune deficiency syndrome (AIDS) or with the AIDS-related complex and from the serum of seropositive healthy homosexuals, recognize two major glycoproteins in cells infected with human T-cell lymphotropic virus type III (HTLV III). These glycoproteins, gp160 and gp120, are encoded by the 2.5-kilobase open reading frame located in the 3' end of the HTLV-III genome, as determined by amino terminus sequence analysis of the radiolabeled forms of these proteins. It is hypothesized that gp160 and gp120 represent the major species of virus-encoded envelope gene products for HTLV-III.     

A new HTLV-III/LAV protein encoded by a gene found in cytopathic retroviruses

The DNA of the HTLV-III/LAV group of retroviruses contains certain additional open reading frames that are not found in typical avian or mammalian retroviruses. The role of these sequences in encoding for gene products that may be related to pathogenesis remains to be resolved. An open reading frame whose 5' end overlaps with the pol gene, but is unrelated to the env gene, has been observed in HTLV-III/LAV and visna virus, both cytopathic mammalian retroviruses. Evidence presented here shows that this open reading frame is a bona fide coding sequence of HTLV-III/LAV and that its product, a protein with a molecular weight of 23,000, induces antibody production in the natural course of infection.     

Reducing elasmobranch bycatch: Laboratory investigation of rare earth metal and magnetic deterrents with spiny dogfish and Pacific halibut

Spiny dogfish (Squalus acanthius) comprises a significant unwanted bycatch on demersal longlines set for halibut and cod in shelf waters of the east and west coasts of North America. In this laboratory study, attacks on baits were tested in the presence of two different rare earth materials (neodymium–iron–boride magnets and cerium mischmetal) believed to deter elasmobranch catch. Experiments were made with spiny dogfish and with Pacific halibut (Hippoglossus stenolepis) in pairwise tests of the rare earth materials and inert metal controls. Dogfish attacked and consumed baits tested with cerium mischmetal at a lower frequency than controls. Times to attack the baits were significantly higher in the presence of mischmetal, as were numbers of approaches before first attack. The time differential between mischmetal and control treatments and the number of baits consumed converged with increasing food deprivation (1 h, 2 d, and 4 d), but treatment differences were always significant. Cerium mischmetal appeared to be irritating to dogfish and may disrupt their bait detection and orientation abilities. Magnets also appeared to irritate dogfish but provided no protection for baits in feeding trials. Pacific halibut showed no reaction whatsoever to the rare earth magnets or cerium mischmetal. Mischmetal, therefore, may be useful in reducing spiny dogfish bycatch in the halibut fishery. Disadvantages in using mischmetal in commercial operations are expense, hazardous nature, and relatively rapid hydrolysis in seawater.     

Temperature and storage period over spermatic parameters of jundiá, Rhamdia quelen (Quoy & Gaimard, 1824)

The aim of this work was to evaluate the spermatic parameters of jundia, Rhamdia quelen, semen stored for short periods under different temperatures. Fifteen males were used in a time factorial experimental design (13 × 3 × 3 × 3). The sperm was stored at: 15; 25 and 35°C and activated in water at: 15; 25 and 35°C each, respectively, within storage periods of: 0; 2; 4; 6; 8; 10; 12; 16; 20; 24; 32; 40 and 48 h after collection. The treatments were performed in triplicates and in sequential protocols every 50 h. The motility parameters were evaluated using Pearson's correlation analysis and the significant parameters (P < 0.05) were summarized using principal component analysis forming two predicted groups. Group 01 composed the following parameters: curvilinear velocity, wobble and linearity; group 02 comprised average path velocity, straight line velocity, beating cross frequency and motility rate. Effects (P < 0.05) of treatments were observed only in group 02, with interaction between time and temperature of exposure and between exposure time and water temperature. Superior results of spermatic parameters of group 02 were observed right after collection. However, the exposure and spermatic activation at 15°C assured significant results 48 h after collection when compared with 25 and 35°C.     

Dual functions of ferrous sulfate as a pore-size controller and a carbon-yield enhancer in fabricating cellulose based porous carbons

This study reports the dual-functions of ferrous sulfate, i.e. as a carbon-yield-enhancer and as a pore-size-controller, in the preparation of porous carbons from rice straws. Through the impregnation of rice straws with 0.5 M aq. FeSO₄, the carbon yield of the resultant porous carbons increased by ca. 10% and the size of the newly created pores was precisely controlled at the diameter of 0.53 nm during carbonization process. The observed results were discussed from the view points of the thermal degradation mechanism of cellulose and the pillar effects by the in-situ formed crystallites of Fe₃O₄. The inherent magnetic property due to the presence of magnetite, Fe₃O₄, was an additional merit of the obtained porous carbons.     

Forecasting the Genetic Impacts of Net Pen Failures on Gulf of Mexico Cobia Populations Using Individual‐based Model Simulations

Offshore net pen fish farming provides a cost‐efficient means for production of marine finfish, and there is great interest in development of net pen operations in domestic waters. However, there are concerns over the possible genetic and ecological impacts that escaped fish may have on wild populations. We used individual‐based simulations, with parameter values informed by life history and genetic data, to investigate the short‐term (50 yr) impacts of net pen failures on the genetic composition of cobia, Rachycentron canadum, stocks in the Gulf of Mexico. Higher net pen failure rates resulted in greater genetic impacts on the wild population. Additionally, the use of more genetically differentiated source populations led to larger influxes of non‐native alleles and greater temporal genetic change in the population as a result of net pen failure. Our results highlight the importance of considering the appropriate source population for broodstock collection in net pen aquaculture systems and help to provide a general set of best management practices for broodstock selection and maintenance in net pen aquaculture operations. A thorough understanding of the genetic diversity, stock structure, and population demography of target species is important to determine the impact escapees can have on wild populations.     

Effects of extrusion processing on digestibility of peas, lupins, canola meal and soybean meal in silver perch Bidyanus bidyanus (Mitchell) diets

Two experiments were conducted to investigate effects of processing on apparent digestibility coefficients (ADCs) of legumes and oilseeds for juvenile silver perch, Bidyanus bidyanus (～49 g). The first experiment evaluated interactive effects of ingredients (lupins or field peas), processing (whole seed; hulls on or hulls off) and extrusion cooking (raw or extruded) on ADCs for juvenile silver perch (～4 g fish^?1). The second experiment was a three‐fixed‐factor anova designed to evaluate interactive effects of ingredients (soybean meal or canola meal), extrusion cooking (raw or extruded) and inclusion content (30% or 50% of the diet) on ADCs for juvenile silver perch (～4 g fish^?1). Lupin protein was more digestible than that of peas (ADC for crude protein 91% vs. 85% for peas) but the organic matter was less digestible (ADC for organic matter 50% vs. 67% for peas). Dehulling lupins significantly improved ADCs for all indices (dry matter, organic matter, energy and crude protein), but extrusion had no effect because lupins do not contain starch or heat‐labile anti‐nutrients. Conversely, for starch‐rich peas that contain heat‐labile trypsin inhibitors, both dehulling and extrusion significantly improved ADCs. Digestibility of soybean meal was much higher than that of canola meal. For soybean meal, neither processing, content nor their interaction affected digestibility but extrusion improved ADCs for dry matter, organic matter and energy but there was an interaction with content. Although higher overall, digestibility for these indices declined with increasing content for extruded product while there were only minor effects of inclusion for raw product. Benefits of extrusion were attributed to reductions in anti‐nutrients, including phytic acid. For canola, there were no interactions between extrusion and content for any ADC. Increasing content reduced ADCs for crude protein, dry matter and organic matter but did not effect energy. Surprisingly, extrusion of canola also reduced digestibility for all ADCs. Dehulling improved both lupins and peas. Crude protein for all ingredients was well digested with ingredients ranked: lupins>soybean meal>peas>canola meal. Energy digestibility was best for soybean meal and worst for lupins. Extrusion greatly improved digestibility of peas and to a lesser extent soybean meal, gave no benefits to lupins and was detrimental for canola.     

Protein and energy utilization and the requirements for maintenance in juvenile mulloway (<Emphasis Type="Italic">Argyrosomus japonicus</Emphasis>)

This study describes the digestible protein (DP) and digestible energy (DE) utilization in juvenile mulloway, and determined the requirements for maintenance. This was achieved by feeding triplicate groups of fish weighing 40 or 129 g held at two temperatures (20 or 26°C), on a commercial diet (21.4 g DP mJ DE⁻¹) at four different ration levels ranging from 0.25% of its initial body weight to apparent satiation over 8 weeks. Weight gain and protein and energy retention increased linearly with increasing feed intake. However, energy retention efficiency (ERE) and protein retention efficiency (PRE) responses were curvilinear with optimal values, depending on fish size, approaching or occurring at satiated feeding levels. Maximum predicted PRE was affected by body size, but not temperature; PRE values were 0.50 and 0.50 for small mulloway, and 0.41 and 0.43 for large mulloway, at 20 and 26°C respectively. ERE demonstrated a similar response, with values of 0.42 and 0.43 for small, and 0.32 and 0.34 for large mulloway at 20 and 26°C respectively. Utilization efficiencies for growth based on linear regression for DP (0.58) and DE (0.60) were independent of fish size and temperature. The partial utilization efficiencies of DE for protein (k _p) and lipid (k _l) deposition estimated using a factorial multiple regression approach were 0.49 and 0.75 respectively. Maintenance requirements estimated using linear regression were independent of temperature for DP (0.47 g DP kg^−0.7 day⁻¹) while maintenance requirements for DE increased with increasing temperature (44.2–49.6 kJ DE kg^−0.8 day⁻¹). Relative feed intake was greatest for small mulloway fed to satiation at 26°C and this corresponded to a greater increase in growth. Large mulloway fed to satiation ate significantly more at 26°C, but did not perform better than the corresponding satiated group held at 20°C. Mulloway should be fed to satiation to maximize growth potential if diets contain 21.4 g DP mJ DE⁻¹.