Enhanced bioproduction of poly-3-hydroxybutyrate from wheat straw lignocellulosic hydrolysates

Project: EC/FP7/246449 - New tailor-made PNB-based nanocomposites for high performance applications produced from environmentally friendly production routesNOTICE: this is the author’s version of a work that was accepted for publication in New Biotechnology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in New Biotechnology, [Vol. 31, Issue 1, (January 2014)] DOI 10.1016/j.nbt.2013.10.004"Polyhydroxyalkanoates (PHAs) are bioplastics that can replace conventional petroleum derived products in various applications. One of the major barriers for their widespread introduction in the market is the higher production costs when compared with their petrochemical counterparts. In this work, a process was successfully implemented with high productivity based on wheat straw, a cheap and readily available agricultural residue, as raw material. The strain Burkholderia sacchari DSM 17165 which is able to metabolize glucose, xylose and arabinose, the main sugars present in wheat straw hydrolysates (WSH), was used. Results in shake flask showed that B. sacchari cells accumulated ca 70 % g P(3HB)/g cell-dry-weight with a yield of polymer on sugars (YP/S) of 0.18 g/g when grown on a mixture of commercial C6 and C5 sugars (control), while these values reached ca 60 % g P(3HB)/g cell-dry-weight and 0.19 g/g, respectively, when WSHs were used as carbon source. In fed-batch cultures carried out in 2L stirred tank reactors on WSH, a maximum polymer concentration of 105 g/L was reached after 61 h of cultivation corresponding to an accumulation of 72% of CDW. Polymer yield and productivity were 0.22 g P(3HB)/g total sugar consumed and 1.6 g/L. h, respectively. The selected feeding strategy successfully overcame the carbon catabolite repression phenomenon observed in sugar mixtures containing hexoses and pentoses. This is the first work describing fed-batch cultivations aiming at PHA production using real lignocellulosic hydrolysates. Additionally, the P(3HB) volumetric productivities attained are, by far, the highest achieved ever on agricultural wastes hydrolysates."U

Production of poly (3-hydroxybutyrate-co-4-hydroxybutyrate) by Burkholderia sacchari using wheat straw hydrolysates and gamma-butyrolactone

“NOTICE: this is the author’s version of a work that was accepted for publication in International Journal of Biological Macromolecules. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in International Journal of Biological Macromolecules, Vol. 71, Special issue, (November 2014). DOI 10.1016/j.ijbiomac.2014.04.054 ""Burkholderia sacchari DSM 17165 is able to grow and produce poly(3-hydroxybutyrate) both on hexoses and pentoses. In a previous study, wheat straw lignocellulosic hydrolysates (WSH) containing high C6 and C5 sugar concentrations were shown to be excellent carbon sources for P(3HB) production. Using a similar feeding strategy developed for P(3HB) production based on WSH, fedbatch cultures were developed aiming at the production of the copolymer P(3HB-co- 4HB) (poly(3-hydroxybutyrate-co-4-hydroxybutyrate)) by B. sacchari. The ability of this strain to synthesize P(3HB-co-4HB) was first shown in shake flasks using gammabutyrolactone (GBL) as precursor of the 4HB units. Fed-batch cultures using glucose as carbon source (control) and GBL were developed to achieve high copolymer productivities and 4HB incorporations. The attained P(3HBco- 4HB) productivity and 4HB molar % were 0.7 g/(L·h) and 4.7 molar %, respectively. The 4HB incorporation was improved to 6.3 and 11.8 molar % by addition of 2 g/L propionic and acetic acid, respectively. When WSH were used as carbon source under the same feeding conditions, the values achieved were 0.5 g/(L·h) and 5.0 molar %, respectively. Burkholderia sacchari, a strain able to produce biopolymers based on xylose-rich lignocellulosic hydrolysates, is for the first time reported to produce P(3HB-co-4HB) using gamma butyrolactone as precursor."This work has received funding from the European Union 7th Framework Programme (FP7/2007-2013) under Grant Agreement number 246449 / Project: Bugworkers - New tailor-made PHB-based nanocomposites for high performance applications produced from environmentally friendly production routes.Financial support: Fundação para a Ciência e Tecnologia, Portugal (fellowships SFRH/BPD/68587/2010 and SFRH/BPD/26678/2006)

Is the Combination of Sulfonylureas and Metformin Associated With an Increased Risk of Cardiovascular Disease or All-Cause Mortality?: A meta-analysis of observational studies

OBJECTIVE—Observational studies assessing the association of combination therapy of metformin and sulfonylurea on all-cause and/or cardiovascular mortality in type 2 diabetes have shown conflicting results. We therefore evaluated the effects of combination therapy of sulfonylureas and metformin on the risk of all-cause mortality and cardiovascular disease (CVD) among people with type 2 diabetes

Areas of natural occurrence of melipona scutellaris Latreille, 1811(Hymenoptera: Apidae) in the state of Bahia, Brazil.

The bee Melipona scutellaris is considered the reared meliponine species with the largest distribution in the North and Northeast regions of Brazil, with records from the state of Rio Grande do Norte down to the state of Bahia. Considering the importance of this species in the generation of income for family agriculture and in the preservation of areas with natural vegetation, this study aimed at providing knowledge on the distribution of natural colonies of M. scutellaris in the state of Bahia. Literature information, interviews with stinglessbee beekeepers, and expeditions were conducted to confirm the natural occurrence of the species. A total of 102 municipalities showed records for M. scutellaris, whose occurrence was observed in areas ranging from sea level up to 1,200-meter height. The occurrence of this species in the state of Bahia is considered to be restricted to municipalities on the coastal area and the Chapada Diamantina with its rainforests. Geographic coordinates, elevation, climate and vegetation data were obtained, which allowed a map to be prepared for the area of occurrence in order to support conservation and management policies for the species

The mTOR regulated RNA-binding protein LARP1 requires PABPC1 for guided mRNA interaction.

The mammalian target of rapamycin (mTOR) is a critical regulator of cell growth, integrating multiple signalling cues and pathways. Key among the downstream activities of mTOR is the control of the protein synthesis machinery. This is achieved, in part, via the co-ordinated regulation of mRNAs that contain a terminal oligopyrimidine tract (TOP) at their 5'ends, although the mechanisms by which this occurs downstream of mTOR signalling are still unclear. We used RNA-binding protein (RBP) capture to identify changes in the protein-RNA interaction landscape following mTOR inhibition. Upon mTOR inhibition, the binding of LARP1 to a number of mRNAs, including TOP-containing mRNAs, increased. Importantly, non-TOP-containing mRNAs bound by LARP1 are in a translationally-repressed state, even under control conditions. The mRNA interactome of the LARP1-associated protein PABPC1 was found to have a high degree of overlap with that of LARP1 and our data show that PABPC1 is required for the association of LARP1 with its specific mRNA targets. Finally, we demonstrate that mRNAs, including those encoding proteins critical for cell growth and survival, are translationally repressed when bound by both LARP1 and PABPC1

Science and Ideology in Economic, Political, and Social Thought

This paper has two sources: One is my own research in three broad areas: business cycles, economic measurement and social choice. In all of these fields I attempted to apply the basic precepts of the scientific method as it is understood in the natural sciences. I found that my effort at using natural science methods in economics was met with little understanding and often considerable hostility. I found economics to be driven less by common sense and empirical evidence, then by various ideologies that exhibited either a political or a methodological bias, or both. This brings me to the second source: Several books have appeared recently that describe in historical terms the ideological forces that have shaped either the direct areas in which I worked, or a broader background. These books taught me that the ideological forces in the social sciences are even stronger than I imagined on the basis of my own experiences. The scientific method is the antipode to ideology. I feel that the scientific work that I have done on specific, long standing and fundamental problems in economics and political science have given me additional insights into the destructive role of ideology beyond the history of thought orientation of the works I will be discussing

S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3

Cytosolic DNA-mediated activation of the transcription factor IRF3 is a key event in host antiviral responses. Here we found that infection with DNA viruses induced interaction of the metabolic checkpoint kinase mTOR downstream effector and kinase S6K1 and the signaling adaptor STING in a manner dependent on the DNA sensor cGAS. We further demonstrated that the kinase domain, but not the kinase function, of S6K1 was required for the S6K1-STING interaction and that the TBK1 critically promoted this process. The formation of a tripartite S6K1-STING-TBK1 complex was necessary for the activation of IRF3, and disruption of this signaling axis impaired the early-phase expression of IRF3 target genes and the induction of T cell responses and mucosal antiviral immunity. Thus, our results have uncovered a fundamental regulatory mechanism for the activation of IRF3 in the cytosolic DNA pathway

The Protozoan Parasite Toxoplasma gondii Selectively Reprograms the Host Cell Translatome

The intracellular parasite Toxoplasma gondii promotes infection by targeting multiple host cell processes; however, whether it modulates mRNA translation is currently unknown. Here, we show that infection of primary murine macrophages with type I or II T. gondii strains causes a profound perturbation of the host cell translatome. Notably, translation of transcripts encoding proteins involved in metabolic activity and components of the translation machinery was activated upon infection. In contrast, the translational efficiency of mRNAs related to immune cell activation and cytoskeleton/cytoplasm organization was largely suppressed. Mechanistically, T. gondii bolstered mechanistic target of rapamycin (mTOR) signaling to selectively activate the translation of mTOR-sensitive mRNAs, including those with a 5'-terminal oligopyrimidine (5' TOP) motif and those encoding mitochondrion-related proteins. Consistent with parasite modulation of host mTOR-sensitive translation to promote infection, inhibition of mTOR activity suppressed T. gondii replication. Thus, selective reprogramming of host mRNA translation represents an important subversion strategy during T. gondii infection

Is there an association between anxiety/depression and temporomandibular disorders in college students?

OBJECTIVE: Considering the high incidence of Temporomandibular Disorders (TMD) in the population aged 15-30 years and the fact that students are exposed to stressful psychosocial factors, the purposes of this study were: to verify clinical symptoms and jaw functionality in college students with TMD according to the anxiety/depression (A/D) level and to evaluate the correlation between A/D and functionality, maximum mouth opening (MMO) and pain and muscle activity. MATERIAL AND METHODS: Nineteen students with TMD diagnosed according to the Research Diagnostic Criteria for Temporomandibular Disorders underwent two assessments during an academic semester. The evaluations were based on questionnaires (MFIQ - Mandibular Function Impairment Questionnaire; HADS - Hospital Anxiety and Depression Scale), clinical measurements (MMO without pain, MMO and assisted MMO; palpation of joint and masticatory muscles), and electromyography. The HADS scores obtained in the two assessments were used to classify all data as either "high" or "low" A/D. Data normality, differences and correlations were tested with the Shapiro-Wilk test, Student's t-test (or the Wilcoxon test), and Spearman test, respectively. The alpha level was set at 0.05. RESULTS: None of the clinical variables were significantly different when comparing low and high A/D data. In low A/D there was a significant correlation between HADS score and: MFIQ (P=0.005, r=0.61), and MMO without pain (P=0.01, r=-0.55). CONCLUSIONS: Variation in A/D level did not change clinical symptoms or jaw functionality in college students with TMD. Apparently, there is a correlation between TMJ functionality and A/D level, which should be further investigated, taking into account the source of the TMD and including subjects with greater functional limitation

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets