Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass

Genetic and pharmacological studies have defined a role for the melanocortin-4 receptor (Mc4r) in the regulation of energy homeostasis. The physiological function of Mc3r, a melanocortin receptor expressed at high levels in the hypothalamus, has remained unknown. We evaluated the potential role of Mc3r in energy homeostasis by studying Mc3r-deficient (Mc3r(-/-)) mice and compared the functions of Mc3r and Mc4r in mice deficient for both genes. The 4-6-month Mc3r-/- mice have increased fat mass, reduced lean mass and higher feed efficiency than wild-type littermates, despite being hypophagic and maintaining normal metabolic rates. (Feed efficiency is the ratio of weight gain to food intake.) Consistent with increased fat mass, Mc3r(-/-) mice are hyperleptinaemic and male Mc3r(-/-) mice develop mild hyperinsulinaemia. Mc3r(-/-) mice did not have significantly altered corticosterone or total thyroxine (T4) levels. Mice lacking both Mc3r and Mc4r become significantly heavier than Mc4r(-/-) mice. We conclude that Mc3r and Mc4r serve non-redundant roles in the regulation of energy homeostasis.     

Solving the factorization problem with P systems

P systems have been used many times to face with computationally difficult problems, such as NP-complete decision problems and NP-hard optimization problems. In this paper we focus our attention on another computationally intractable problem: factorization. In particular, we first propose a simple method to encode binary numbers using multisets. Then, we describe three families of P systems: the first two allow to add and to multiply two binary encoded numbers, respectively, and the third solves the factorization problem.     

Soft System Dynamics Methodology (SSDM): Combining Soft Systems Methodology (SSM) and System Dynamics (SD)

Soft System Dynamics Methodology (SSDM), a systemic methodology product of the combination of two widely used systems-based methodologies from two different systems thinking paradigms, Systems Dynamics (SD) and Soft Systems Methodology (SSM), is presented. The paper argues that by combining some of SD and SSM stages, within the intellectual framework proposed by SSDM, a methodology developed by one of the authors¹ much can be gained in a systemic intervention to tackle complex social problematic situations. A framework for comparing the ontological, epistemological and methodological principles of SD, SSM and SSDM is proposed and the synthesizing and dialectical role of SSDM is advanced. The 10 stages of SSDM are outlined and illustrated by an application on a small Peruvian company; and a set of conclusions and points for further research are discussed.     

A Conceptual Framework Based on Maturana’s Ontology of the Observer to Explore the Checkland’s Soft Systems Methodology

This paper explores Checkland’s Soft Systems Methodology (SSM) through the lenses of a theoretical framework that incorporates key concepts from Maturana’s Ontology of the Observer (OoO) with the view of complementing Checkland’s SSM application process. We outline and examine paradigmatic compatibility between: Checkland’s ontological position (reality is problematic/chaotic) together with his interpretivist epistemology (multiple perceptions enrich the ever-changing reality); and Maturana’s OoO (we are immersed in the praxis of living in an ontological multi-universe). We argue that OoO resonates with key SSM theoretical underpinnings. After establishing compatibility between these two influential systems thinkers, we advance a conceptual framework in which Checkland’s SSM learning process is re-visited through a the framework grounded on Maturana’s OoO. The proposed framework illustrates how key ideas drawn from Maturana’s OoO can shed light into the way in which some of the main SSM devices (i.e.: Root definitions, Conceptual model) are used in the SSM process. By doing that, SSM is enriched and becomes more flexible as the stakeholders involved are placed within the domain of constitutive ontologies from which, a deeper dialogue can be promoted in a domain of coexistence in mutual acceptance. We argue that this is a suitable way to have more flexible and holistic views for a SSM intervention in particular to promote the learning process and debating proposed changes amongst the stakeholders involved. The proposed framework, when applied, may enhance the power of SSM learning process and when adopted can have substantial implications to complement the SSM process.

     

Alternative beneficiation of tantalite and removal of radioactive oxides from Ethiopian Kenticha pegmatite-spodumene ores

The beneficiation methods for Ethiopian Kenticha pegmatite-spodumene ores were assessed through mineralogical and quantitative analyses with X-ray diffraction (XRD) and energy-dispersive X-ray fluorescence (EDXRF). The tantalite in the upper zone of the Kenticha pegmatite-spodumene deposit is 58.7wt% higher than that in the inner zone. XRD analysis revealed that the upper zone is dominated by manganocolumbite, whereas the inner zone is predominantly tantalite-Mn. Repeated cleaning and beneficiation of the upper-zone ore resulted in concentrate compositions of 57.34wt% of Ta₂O₅ and 5.41wt% of Nb₂O₅. Washing the tantalite concentrates using 1vol% KOH and 1 M H₂SO₄ led to the removal of thorium and uranium radioactive oxides from the concentrate. The findings of this study suggest that the beneficiation and alkaline washing of Kenticha pegmatite-spodumene ores produce a high-grade export-quality tantalite concentrate with negligible radioactive oxides.     

Engineered reversal of the β-oxidation cycle for the synthesis of fuels and chemicals

Advanced (long-chain) fuels and chemicals are generated from short-chain metabolic intermediates through pathways that require carbon-chain elongation. The condensation reactions mediating this carbon-carbon bond formation can be catalysed by enzymes from the thiolase superfamily, including β-ketoacyl-acyl-carrier protein (ACP) synthases, polyketide synthases, 3-hydroxy-3-methylglutaryl-CoA synthases, and biosynthetic thiolases. Pathways involving these enzymes have been exploited for fuel and chemical production, with fatty-acid biosynthesis (β-ketoacyl-ACP synthases) attracting the most attention in recent years. Degradative thiolases, which are part of the thiolase superfamily and naturally function in the β-oxidation of fatty acids, can also operate in the synthetic direction and thus enable carbon-chain elongation. Here we demonstrate that a functional reversal of the β-oxidation cycle can be used as a metabolic platform for the synthesis of alcohols and carboxylic acids with various chain lengths and functionalities. This pathway operates with coenzyme A (CoA) thioester intermediates and directly uses acetyl-CoA for acyl-chain elongation (rather than first requiring ATP-dependent activation to malonyl-CoA), characteristics that enable product synthesis at maximum carbon and energy efficiency. The reversal of the β-oxidation cycle was engineered in Escherichia coli and used in combination with endogenous dehydrogenases and thioesterases to synthesize n-alcohols, fatty acids and 3-hydroxy-, 3-keto- and trans-Δ(2)-carboxylic acids. The superior nature of the engineered pathway was demonstrated by producing higher-chain linear n-alcohols (C?≥?4) and extracellular long-chain fatty acids (C?>?10) at higher efficiency than previously reported. The ubiquitous nature of β-oxidation, aldehyde/alcohol dehydrogenase and thioesterase enzymes has the potential to enable the efficient synthesis of these products in other industrial organisms.     

Management Sciences/Operational Research Units in Business and Management Courses in the UK

The paper reviews the development of management science/operational Research (MS/OR) in management education and explore how far the syllabuses of undergraduate business courses and MBA courses in the UK, are giving space to the teaching of management sciences methodologies (MSM). The academic phase of early MS/OR is outlined and a time-based framework to map the evolution of four MS/OR discourses informing a set of MSMs currently in use is advanced. At an undergraduate level the review is based on a sample taken from Universities and Colleges Admissions Services (UCAS) of business and management studies degrees and at a postgraduate level the review considers a sample of MBA programmes offered by six UK universities. Results indicate that most of the MBA courses include a core unit in quantitative methods in the first year and that universities are still at large teaching the ??hard?? end of the MSM spectrum, the type of problem solving methods developed in the 1950s and 1960s. Business courses incorporating units containing systemic thinking and management sciences methodologies developed from the 1970s to now (e.g.: soft systems methodology, viable systems model, cognitive mapping), are rarely taught at undergraduate (UG) level; and at post-graduate (PG) level they have been confined to a handful of institutions in the UK. The paper highlights the fact that MSMs associated with the soft and critical end of the spectrum are still lacking of credibility amongst the designers of management education at both undergraduate and graduate management education. Conclusions from the survey results are drawn and an agenda for further research is proposed.     

Palmitate-induced skeletal muscle insulin resistance does not require NF-κB activation

Palmitate activates the NF-κB pathway, and induces accumulation of lipid metabolites and insulin resistance in skeletal muscle cells. Little information is available whether and how these processes are causally related. Therefore, the objectives were to investigate whether intra-cellular lipid metabolites are involved in FA-induced NF-κB activation and/or insulin resistance in skeletal muscle and to investigate whether FA-induced insulin resistance and NF-κB activation are causally related. Inhibiting DGAT or CPT-1 by using, respectively, amidepsine or etomoxir increased DAG accumulation and sensitized myotubes to palmitate-induced insulin resistance. While co-incubation of palmitate with etomoxir increased NF-κB transactivation, co-incubation with amidepsine did not, indicating that DAG accumulation is associated with insulin resistance but not with NF-κB activation. Furthermore, pharmacological or genetic inhibition of the NF-κB pathway could not prevent palmitate-induced insulin resistance. In conclusion, we have demonstrated that activation of the NF-κB pathway is not required for palmitate-induced insulin resistance in skeletal muscle cells.     

Solving the factorization problem with P systems

P systems have been used many times to face with computationally difficult problems, such as NP-complete decision problems and NP-hard optimization problems. In this paper we focus our attention on another computationally intractable problem: factorization. In particular, we first propose a simple method to encode binary numbers using multisets. Then, we describe three families of P systems: the first two allow to add and to multiply two binary encoded numbers, respectively, and the third solves the factorization problem.