Morphological and biochemical changes in Phaeodactylum tricornutum triggered by culture media: Implications for industrial exploitation

Phaeodactylum tricornutum is a polymorphic marine diatom, displaying three main morphotypes: fusiform, triradiate and oval. It is of great interest for industrial biotechnology as a natural rich source of valuable eicosapentaenoic acid (EPA) and fucoxanthin. Changing culture conditions such as temperature and salinity has been shown to elicit morphological changes in P. tricornutum. However, limited information is available about the conditions that can be used for controlling cell morphology and growth of a particular cell morphotype with high biomass productivity. While the phenomenon of pleiomorphy is intrinsically interesting, there has not been a systematic study linking this behavior to the ability of P. tricornutum to perform as a platform for industrial biotechnology. In this study, the effects of culture medium and culture age on morphological and biochemical changes in P. tricornutum were investigated. Mann and Myers' medium was identified as eliciting significant morphotype conversion from fusiform to oval in P. tricornutum. Liquid cultures containing >90% oval cells were obtained and well-maintained in this medium under constant shaking condition, allowing high dry biomass concentration (0.73 g L−1) to be achieved. Biochemical composition analyses revealed that higher protein (% dry weight) was obtained from oval cell cultures compared to fusiform cell cultures maintained in f/2 medium over 21 days cultivation. Meanwhile, pigment was markedly accumulated in oval cell cultures whereas lipid and carbohydrate were highly accumulated in fusiform cell cultures. This work offered a novel way to regulate cell morphology of P. tricornutum and provided significant implications for upstream cultivation strategies to optimise manufacture of different classes of product in P. tricornutum

Evidence for Two Modes of Synergistic Induction of Apoptosis by Mapatumumab and Oxaliplatin in Combination with Hyperthermia in Human Colon Cancer Cells

Colorectal cancer is the third leading cause of cancer-related mortality in the world-- the main cause of death from colorectal cancer is hepatic metastases, which can be treated with isolated hepatic perfusion (IHP). Searching for the most clinically relevant approaches for treating colorectal metastatic disease by isolated hepatic perfusion (IHP), we developed the application of oxaliplatin concomitantly with hyperthermia and humanized death receptor 4 (DR4) antibody mapatumumab (Mapa), and investigated the molecular mechanisms of this multimodality treatment in human colon cancer cell lines CX-1 and HCT116 as well as human colon cancer stem cells Tu-12, Tu-21 and Tu-22. We showed here, in this study, that the synergistic effect of the multimodality treatment-induced apoptosis was caspase dependent and activated death signaling via both the extrinsic apoptotic pathway and the intrinsic pathway. Death signaling was activated by c-Jun N-terminal kinase (JNK) signaling which led to Bcl-xL phosphorylation at serine 62, decreasing the anti-apoptotic activity of Bcl-xL, which contributed to the intrinsic pathway. The downregulation of cellular FLICE inhibitory protein long isoform (c-FLIPL) in the extrinsic pathway was accomplished through ubiquitination at lysine residue (K) 195 and protein synthesis inhibition. Overexpression of c-FLIPL mutant (K195R) and Bcl-xL mutant (S62A) completely abrogated the synergistic effect. The successful outcome of this study supports the application of multimodality strategy to patients with colorectal hepatic metastases who fail to respond to standard chemoradiotherapy that predominantly targets the mitochondrial apoptotic pathway. © 2013 Song et al

Naturally occurring antiviral drug resistance in Avian H5N1 virus

Oral Presentations - Antivirals and ResistanceResistance to the neuraminidase inhibitor, oseltamivir, was found in H5N1 virus isolated from infected patients in Vietnam but no recent avian H5N1 isolates have been reported to possess known neuraminidase inhibitor resistance mutations. It is still not clear whether the NA1 gene neuraminidase mutation, His274Tyr, detected in H5N1 infected human cases originated during disease treatment or came from the avian virus source. A 2002 HK chicken H5N1 isolate was found to contain the His274Tyr mutation on NA1 and resistance to oseltamivir was confirmed using a cell-based assay. To investigate if His274Tyr might naturally occur at low levels mixed with wild type in H5N1 poultry infections we examined isolates from different hosts and geographical locations using a differential RT-PCR assay. The His274Ty quasi species was more frequently recognized in isolates from infected chickens than in isolates from ducks and geese, but no geographical difference was observed. Close surveillance of mutants in the virus population, combined with pursuit of alternative therapies, is essential to H5N1 pandemic containment strategies.postprin

Resistance exercise initiates mechanistic target of rapamycin (mTOR) translocation and protein complex co-localisation in human skeletal muscle

This is the final version. Available from the publisher via the DOI in this record.The mechanistic target of rapamycin (mTOR) is a central mediator of protein synthesis in skeletal muscle. We utilized immunofluorescence approaches to study mTOR cellular distribution and protein-protein co-localisation in human skeletal muscle in the basal state as well as immediately, 1 and 3 h after an acute bout of resistance exercise in a fed (FED; 20 g Protein/40 g carbohydrate/1 g fat) or energy-free control (CON) state. mTOR and the lysosomal protein LAMP2 were highly co-localised in basal samples. Resistance exercise resulted in rapid translocation of mTOR/LAMP2 towards the cell membrane. Concurrently, resistance exercise led to the dissociation of TSC2 from Rheb and increased in the co-localisation of mTOR and Rheb post exercise in both FED and CON. In addition, mTOR co-localised with Eukaryotic translation initiation factor 3 subunit F (eIF3F) at the cell membrane post-exercise in both groups, with the response significantly greater at 1 h of recovery in the FED compared to CON. Collectively our data demonstrate that cellular trafficking of mTOR occurs in human muscle in response to an anabolic stimulus, events that appear to be primarily influenced by muscle contraction. The translocation and association of mTOR with positive regulators (i.e. Rheb and eIF3F) is consistent with an enhanced mRNA translational capacity after resistance exercise.Biotechnology and Biological Science Research Council (BBSRC)Natural Sciences and Engineering Research Council (NSERC)China Scholarship CouncilNational Institute of Arthritis and Musculoskeletal and Skin DiseasesDepartment of Defens

Carbon Emission Flow in Networks

As the human population increases and production expands, energy demand and anthropogenic carbon emission rates have been growing rapidly, and the need to decrease carbon emission levels has drawn increasing attention. The link between energy production and consumption has required the large-scale transport of energy within energy transmission networks. Within this energy flow, there is a virtual circulation of carbon emissions. To understand this circulation and account for the relationship between energy consumption and carbon emissions, this paper introduces the concept of “carbon emission flow in networks” and establishes a method to calculate carbon emission flow in networks. Using an actual analysis of China's energy pattern, the authors discuss the significance of this new concept, not only as a feasible approach but also as an innovative theoretical perspective

Adalimumab in Patients with Active Noninfectious Uveitis

BACKGROUND: Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis. METHODS: This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported. RESULTS: The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years). CONCLUSIONS: In our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo