Altered Lipid Accumulation in Nannochlropsis Salina CCAP849/3 Following EMS and UV Induced Mutagenesis

Microalgae have potential as a chemical feed stock in a range of industrial applications. Nannochloropsis salina was subject to EMS mutagenesis and the highest lipid containing cells selected using fluorescence-activated cell sorting. Assessment of growth, lipid content and fatty acid composition identified mutant strains displaying a range of altered traits including changes in the PUFA content and a total FAME increase of up to 156% that of the wild type strain. Combined with a reduction in growth this demonstrated a productivity increase of up to 76%. Following UV mutagenesis, lipid accumulation of the mutant cultures was elevated to more than 3 fold that of the wild type strain, however reduced growth rates resulted in a reduction in overall productivity. Changes observed are indicative of alterations to the regulation of the omega 6 Kennedy pathway. The importance of these variations in physiology for industrial applications such as biofuel production is discussed

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Critical weight loss is a major prognostic indicator for disease-specific survival in patients with head and neck cancer receiving radiotherapy

<p>Background: Pre-treatment weight loss (WL) is a prognostic indicator for overall survival (OS) in head and neck cancer (HNC) patients. This study investigates the association between WL before or during radiotherapy and disease-specific survival (DSS) in HNC patients.</p><p>Methods: In 1340 newly diagnosed HNC patients, weight change was collected before and during (adjuvant) radiotherapy with curative intent. Critical WL during radiotherapy was defined as >5% WL during radiotherapy or >7.5% WL until week 12. Differences in 5-year OS and DSS between WL groups were analysed by Cox's regression with adjustments for important socio-demographic and tumour-related confounders.</p><p>Results: Before radiotherapy, 70% of patients had no WL, 16% had 5-10% WL, and 5% had >10% WL. Five-year OS and DSS rates for these groups were 71%, 59%, 47%, and 42% (P10% WL before radiotherapy remained significantly associated with a worse OS (HR 1.7; 95% CI 1.2-2.5; P = 0.002) and DSS (HR 2.1; 95% CI 1.2-3.5; P = 0.007). The 5-year OS and DSS rates for patients with critical WL during radiotherapy were 62% and 82%, compared with 70% and 89% for patients without critical WL (P = 0.01; P = 0.001). After adjustment, critical WL during radiotherapy remained significantly associated with a worse DSS (HR 1.7; 95% CI 1.2-2.4; P = 0.004).</p><p>Conclusion: Weight loss both before and during radiotherapy are important prognostic indicators for 5-year DSS in HNC patients. Randomised studies into the prognostic effect of nutritional intervention are needed.</p>

Caveolin-1 Induces Formation of Membrane Tubules That Sense Actomyosin Tension and Are Inhibited by Polymerase I and Transcript Release Factor/Cavin-1

We found that PTRF/cavin-1 is lost coordinately with caveolin-1 in some cancer cells. When reexpressed in these cells, caveolin-1 formed membrane tubules that were under actomyosin-induced tension and recruited Rab8 and EHD proteins. PTRF/cavin-1 inhibited tubule formation by caveolin-1, showing a new function for the protein

Outcomes in Neurosurgical Patients Who Develop Venous Thromboembolism

International audienceOBJECTIVES: Registro Informatizado de Enfermedad TromboEmbólica (RIETE) database was used to investigate whether neurosurgical patients with venous thromboembolism (VTE) were more likely to die of bleeding or VTE and the influence of anticoagulation on these outcomes.METHODS:Clinical characteristics, treatment details, and 3-month outcomes were assessed in those who developed VTE after neurosurgery.RESULTS: Of 40 663 patients enrolled, 392 (0.96%) had VTE in less than 60 days after neurosurgery. Most patients in the cohort (89%) received initial therapy with low-molecular-weight heparin, (33% received subtherapeutic doses). In the first week, 10 (2.6%) patients died (8 with pulmonary embolism [PE], no bleeding deaths; P = .005). After the first week, 20 (5.1%) patients died (2 with fatal bleeding, none from PE). Overall, this cohort was more likely to develop a fatal PE than a fatal bleed (8 vs 2 deaths, P = .058).CONCLUSIONS: Neurosurgical patients developing VTE were more likely to die from PE than from bleeding in the first week, despite anticoagulation

Fatal events in cancer patients receiving anticoagulant therapy for venous thromboembolism

none144siIn cancer patients treated for venous thromboembolism (VTE), including deep-vein thrombosis (DVT) and pulmonary embolism (PE), analyzing mortality associated with recurrent VTE or major bleeding is needed to determine the optimal duration of anticoagulation. This was a cohort study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) Registry database to compare rates of fatal recurrent PE and fatal bleeding in cancer patients receiving anticoagulation for VTE. As of January 2013, 44,794 patients were enrolled in RIETE, of whom 7911(18%) had active cancer. During the course of anticoagulant therapy (mean, 181 ±210 days), 178 cancer patients (4.3%) developed recurrent PE (5.5 per 100 patient-years; 95% CI: 4.8-6.4), 194 (4.7%) had recurrent DVT (6.2 per 100 patient-years; 95% confidence interval [CI]: 5.3-7.1), and 367 (8.9%) bled (11.3 per 100 patient-years; 95% CI: 10.2-12.5). Of 4125 patients initially presenting with PE, 43 (1.0%) died of recurrent PE and 45 (1.1%) of bleeding; of 3786 patients with DVT, 19 (0.5%) died of PE, and 55 (1.3%) of bleeding. During the first 3 months of anticoagulation, there were 59 (1.4%) fatal PE recurrences and 77 (1.9%) fatal bleeds. Beyond the third month, there were 3 fatal PE recurrences and 23 fatal bleeds. In RIETE cancer patients, the rate of fatal recurrent PE or fatal bleeding was much higher within the first 3 months of anticoagulation therapy.openFarge D.; Trujillo-Santos J.; Debourdeau P.; Bura-Riviere A.; Rodriguez-Beltran E.M.; Nieto J.A.; Peris M.L.; Zeltser D.; Mazzolai L.; Hij A.; Monreal M.; Durante A.; Alcalde M.; Arcelus J.I.; Ballaz A.; Barba R.; Barron M.; Barron-Andres B.; Bascunana J.; Bedate P.; Blanco-Molina A.; Bueso T.; Casado I.; Conget F.; Del Molino F.; Del Toro J.; Falga C.; Fernandez-Capitan C.; Fuentes M.I.; Gallego P.; Garcia J.; Garcia-Bragado F.; Gavin O.; Gomez V.; Gonzalez J.; Gonzalez-Bachs E.; Grau E.; Guil M.; Guijarro R.; Gutierrez J.; Hernandez L.; Jara-Palomares L.; Jaras M.J.; Jimenez D.; Jimenez S.; Lobo J.L.; Lopez-Jimenez L.; Lopez-Saez J.B.; Lorente M.A.; Lorenzo A.; Luque J.M.; Madridano O.; Macia M.; Maestre A.; Marchena P.J.; Martin M.; Monreal M.; Mora J.M.; Munoz F.J.; Nauffal M.D.; Nieto J.A.; Nunez M.J.; Ogea J.L.; Otero R.; Pedrajas J.M.; Peris M.L.; Riera-Mestre A.; Rivas A.; Rodriguez-Davila M.A.; Roman P.; Rosa V.; Ruiz J.; Ruiz-Ribo M.D.; Ruiz-Gamietea A.; Ruiz-Gimenez N.; Sahuquillo J.C.; Samperiz A.; Sanchez Munoz-Torrero J.F.; Soler S.; Tiberio G.; Tilvan R.M.; Tolosa C.; Trujillo J.; Uresandi F.; Valdes M.; Valero B.; Valle R.; Vela J.; Vidal G.; Villalobos A.; Villalta J.; Gadelha T.; Maly R.; Hirmerova J.; Tomko T.; Bertoletti L.; Bura-Riviere A.; Farge-Bancel D.; Grange C.; Hij A.; Mahe I.; Merah A.; Quere I.; Schellong S.; Babalis D.; Papadakis M.; Tzinieris I.; Faul J.; Braester A.; Brenner B.; Tzoran I.; Zeltser D.; Barillari G.; Ciammaichella M.; Dalla Valle F.; Di Micco P.; Duce R.; Maida R.; Pasca S.; Piovella C.; Poggio R.; Prandoni P.; Quintavalla R.; Rocci A.; Rota L.; Schenone A.; Tiraferri E.; Tonello D.; Tufano A.; Visona A.; Zalunardo B.; Brinquinho M.; Gomes D.; Goncalves F.; Santos M.; Saraiva M.; Bosevski M.; Kovacevic D.; Alatri A.; Aujeski D.; Bounameaux H.; Calanca L.; Mazzolai L.; Caprini J.Farge, D.; Trujillo-Santos, J.; Debourdeau, P.; Bura-Riviere, A.; Rodriguez-Beltran, E. M.; Nieto, J. A.; Peris, M. L.; Zeltser, D.; Mazzolai, L.; Hij, A.; Monreal, M.; Durante, A.; Alcalde, M.; Arcelus, J. I.; Ballaz, A.; Barba, R.; Barron, M.; Barron-Andres, B.; Bascunana, J.; Bedate, P.; Blanco-Molina, A.; Bueso, T.; Casado, I.; Conget, F.; Del Molino, F.; Del Toro, J.; Falga, C.; Fernandez-Capitan, C.; Fuentes, M. I.; Gallego, P.; Garcia, J.; Garcia-Bragado, F.; Gavin, O.; Gomez, V.; Gonzalez, J.; Gonzalez-Bachs, E.; Grau, E.; Guil, M.; Guijarro, R.; Gutierrez, J.; Hernandez, L.; Jara-Palomares, L.; Jaras, M. J.; Jimenez, D.; Jimenez, S.; Lobo, J. L.; Lopez-Jimenez, L.; Lopez-Saez, J. B.; Lorente, M. A.; Lorenzo, A.; Luque, J. M.; Madridano, O.; Macia, M.; Maestre, A.; Marchena, P. J.; Martin, M.; Monreal, M.; Mora, J. M.; Munoz, F. J.; Nauffal, M. D.; Nieto, J. A.; Nunez, M. J.; Ogea, J. L.; Otero, R.; Pedrajas, J. M.; Peris, M. L.; Riera-Mestre, A.; Rivas, A.; Rodriguez-Davila, M. A.; Roman, P.; Rosa, V.; Ruiz, J.; Ruiz-Ribo, M. D.; Ruiz-Gamietea, A.; Ruiz-Gimenez, N.; Sahuquillo, J. C.; Samperiz, A.; Sanchez Munoz-Torrero, J. F.; Soler, S.; Tiberio, G.; Tilvan, R. M.; Tolosa, C.; Trujillo, J.; Uresandi, F.; Valdes, M.; Valero, B.; Valle, R.; Vela, J.; Vidal, G.; Villalobos, A.; Villalta, J.; Gadelha, T.; Maly, R.; Hirmerova, J.; Tomko, T.; Bertoletti, L.; Bura-Riviere, A.; Farge-Bancel, D.; Grange, C.; Hij, A.; Mahe, I.; Merah, A.; Quere, I.; Schellong, S.; Babalis, D.; Papadakis, M.; Tzinieris, I.; Faul, J.; Braester, A.; Brenner, B.; Tzoran, I.; Zeltser, D.; Barillari, G.; Ciammaichella, M.; Dalla Valle, F.; Di Micco, P.; Duce, R.; Maida, R.; Pasca, S.; Piovella, C.; Poggio, R.; Prandoni, P.; Quintavalla, R.; Rocci, A.; Rota, L.; Schenone, A.; Tiraferri, E.; Tonello, D.; Tufano, A.; Visona, A.; Zalunardo, B.; Brinquinho, M.; Gomes, D.; Goncalves, F.; Santos, M.; Saraiva, M.; Bosevski, M.; Kovacevic, D.; Alatri, A.; Aujeski, D.; Bounameaux, H.; Calanca, L.; Mazzolai, L.; Caprini, J

Natural history of patients with venous thromboembolism and hereditary hemorrhagic telangiectasia. Findings from the RIETE registry

Background: Limited data exist about the clinical presentation, ideal therapy and outcomes of patients with hereditary hemorrhagic telangiectasia (HHT) who develop venous thromboembolism (VTE). Methods: We used the data in the RIETE Registry to assess the clinical characteristics, therapeutic approaches and clinical outcomes during the course of anticoagulant therapy in patients with HHT according to initial presentation as pulmonary embolism (PE) or deep venous thrombosis (DVT). Results: Of 51,375 patients with acute VTE enrolled in RIETE from February 2009 to January 2019, 23 (0.04%) had HHT: 14 (61%) initially presented with PE and 9 (39%) with DVT alone. Almost half (47.8%) of the patients with VTE had a risk factor for VTE. Most PE and DVT patients received low-molecular-weight heparin for initial (71 and 100%, respectively) and long-term therapy (54 and 67%, respectively). During anticoagulation for VTE, the rate of bleeding events (major 2, non-major 6) far outweighed the rate of VTE recurrences (recurrent DVT 1): 50.1 bleeds per 100 patient-years (95%CI: 21.6-98.7) vs. 6.26 recurrences (95%CI: 0.31-30.9; p = 0.020). One major and three non-major bleeding were epistaxis. No patient died of bleeding. One patient died shortly after being diagnosed with acute PE. Conclusions: During anticoagulation for VTE in HHT patients, there were more bleeding events than VTE recurrences. Most bleeding episodes were non-major epistaxis

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

International audienceIn 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field