Single cell analysis reveals immune cell-adipocyte crosstalk regulating the transcription of thermogenic adipocytes.

Immune cells are vital constituents of the adipose microenvironment that influence both local and systemic lipid metabolism. Mice lacking IL10 have enhanced thermogenesis, but the roles of specific cell types in the metabolic response to IL10 remain to be defined. We demonstrate here that selective loss of IL10 receptor α in adipocytes recapitulates the beneficial effects of global IL10 deletion, and that local crosstalk between IL10-producing immune cells and adipocytes is a determinant of thermogenesis and systemic energy balance. Single Nuclei Adipocyte RNA-sequencing (SNAP-seq) of subcutaneous adipose tissue defined a metabolically-active mature adipocyte subtype characterized by robust expression of genes involved in thermogenesis whose transcriptome was selectively responsive to IL10Rα deletion. Furthermore, single-cell transcriptomic analysis of adipose stromal populations identified lymphocytes as a key source of IL10 production in response to thermogenic stimuli. These findings implicate adaptive immune cell-adipocyte communication in the maintenance of adipose subtype identity and function

Engineering mono- and multi-valent inhibitors on a modular scaffold.

Here we exploit the simple, ultra-stable, modular architecture of consensus-designed tetratricopeptide repeat proteins (CTPRs) to create a platform capable of displaying both single as well as multiple functions and with diverse programmable geometrical arrangements by grafting non-helical short linear binding motifs (SLiMs) onto the loops between adjacent repeats. As proof of concept, we built synthetic CTPRs to bind and inhibit the human tankyrase proteins (hTNKS), which play a key role in Wnt signaling and are upregulated in cancer. A series of mono-valent and multi-valent hTNKS binders was assembled. To fully exploit the modular scaffold and to further diversify the multi-valent geometry, we engineered the binding modules with two different formats, one monomeric and the other trimeric. We show that the designed proteins are stable, correctly folded and capable of binding to and inhibiting the cellular activity of hTNKS leading to downregulation of the Wnt pathway. Multivalency in both the CTPR protein arrays and the hTNKS target results in the formation of large macromolecular assemblies, which can be visualized both in vitro and in the cell. When delivered into the cell by nanoparticle encapsulation, the multivalent CTPR proteins displayed exceptional activity. They are able to inhibit Wnt signaling where small molecule inhibitors have failed to date. Our results point to the tremendous potential of the CTPR platform to exploit a range of SLiMs and assemble synthetic binding molecules with built-in multivalent capabilities and precise, pre-programmed geometries.BBSRC Doctoral Training Programme (DTP) scholarship Oliver Gatty Studentship AstraZeneca PhD studentship. UK Medical Research Foundation. CRUK Pioneer Award (C17838/A22676) CRUK BTERP Award (C17838/A27225) Leverhulme Trust (RPG-2014-089) Cambridge Newton Trust BBSRC project grant (BB/T002697/1)

Entrepreneurial growth and ownership under market socialism in China: a longitudinal case study of small business growth

How firms grow is still a mystery and a definitive explanation remains elusive. This is especially the case for emerging economies, where the development of research into business growth has been notably slow whilst emerging business ventures are developing at hyper speed. Since most empirical studies have focused on the quantitative differences in growth across firms, this paper adopts a longitudinal case study approach to explore the qualitative differences in terms of how various types of firm achieve their growth outcomes in the organisational development process over a prolonged period of time. Through a theoretical lens which focuses on growth process approaches, this study not only demonstrates that entrepreneurial processes take different forms and dimensions in different contexts, but it also provides insights into the interactions of various organisational factors underpinning the strategies and changes that lead to contrasting growth outcomes. Case study findings assert that the ownership factor is a key contingent factor that shapes management structure and resources which, in turn, affect particular entrepreneurial outcomes. Furthermore, a combination of leadership style and the approach to knowledge management also play critical roles in the learning process which, tends to determine the strategy choice of either high or low value added product strategy. The findings of this research are that small firms with a low value product strategy can improve their survival chances and growth through the vertical broadening of a product portfolio in synchrony with increasing production and technology advancement. The case study companies show a tendency to reinforce their industry position by adopting contrasting choices for growth. The paper addresses the challenges and managerial implications for Western company managers in different growth contexts

Characteristics of Different Systems for the Solar Drying of Crops

Solar dryers are used to enable the preservation of agricultural crops, food processing industries for dehydration of fruits and vegetables, fish and meat drying, dairy industries for production of milk powder, seasoning of wood and timber, textile industries for drying of textile materials. The fundamental concepts and contexts of their use to dry crops is discussed in the chapter. It is shown that solar drying is the outcome of complex interactions particular between the intensity and duration of solar energy, the prevailing ambient relative humidity and temperature, the characteristics of the particular crop and its pre-preparation and the design and operation of the solar dryer

A graphical approach for pinch-based source-sink matching and sensitivity analysis in carbon capture and storage systems

Carbon capture and storage (CCS) is regarded as an important interim technology for the reduction of carbon dioxide (CO2) emissions from large industrial facilities such as power plants and refineries. CCS involves capture of concentrated CO2 streams from point sources (industrial flue gases), followed by subsequent secure storage in an appropriate natural reservoir. Such reservoirs include various geological formations such as depleted oil or gas wells, inaccessible coal seams, and saline aquifers. In practice, such storage sites will have limitations on both CO2 storage capacity and injection rate, subject to geological characteristics. In this work, a graphical approach is proposed for matching multiple CO2 sources and storage sites (sinks) optimally within a predefined geographical region. The technique is developed on the basis of analogies with existing graphical pinch analysis approaches for the synthesis of industrial resource conservation networks (RCNs). Generalized principles for optimal CO2 source-sink matching based on pinch analysis insights are discussed in this work. In addition, sensitivity of the system to the uncertainties that occur in CCS planning (e.g., variation of actual injectivity and capacity as well as options for increase or decrease of source lifetime) is considered. Realistic case studies are shown to illustrate these various aspects of the methodology. © 2012 American Chemical Society. © 2013 American Chemical Society

Unified pinch approach for targeting of carbon capture and storage (CCS) systems with multiple time periods and regions

Carbon capture and storage (CCS) is a key technology for the mitigation of industrial carbon dioxide (CO2) emissions. It involves the reduction of emissions from large industrial facilities (i.e., sources) by capturing the CO2 from the exhaust gases and subsequently storing it in appropriate geological storage sites (i.e., sinks) such as depleted oil and/or gas reservoirs, saline aquifers, coal seams and other similar formations. In practice, these sites may not be readily available for storage at the same time or before the sources are operating, which gives rise to a temporal aspect in the planning problem. At the same time, sources and sinks may need to be clustered geographically to minimize the need to transport CO2 over long distances. This work presents an improved pinch analysis based methodology by simultaneously considering injectivity constraint of every sink as well as time of availability of various sources and sinks. Three illustrative case studies are used to demonstrate the applicability of the proposed methodology. The first two case studies illustrate graphical and algebraic variants, while the third case studies shows an extension that involves two distinct geographical regions. © 2014 Elsevier Ltd. All rights reserved