Transcriptional Interference Regulates the Evolutionary Development of Speech

The human capacity to speak is fundamental to our advanced intellectual, technological and social development. Yet so very little is known regarding the evolutionary genetics of speech or its relationship with the broader aspects of evolutionary development in primates. In this study, we describe a large family with evolutionary retrograde development of the larynx and wrist. The family presented with severe speech impairment and incremental retrograde elongations of the pisiform in the wrist that limited wrist rotation from 180◦ to 90◦ as in primitive primates. To our surprise, we found that a previously unknown primate-specific gene TOSPEAK had been disrupted in the family. TOSPEAK emerged de novo in an ancestor of extant primates across a 540 kb region of the genome with a pre-existing highly conserved long-range laryngeal enhancer for a neighbouring bone morphogenetic protein gene GDF6. We used transgenic mouse modelling to identify two additional GDF6 long-range enhancers within TOSPEAK that regulate GDF6 expression in the wrist. Disruption of TOSPEAK in the affected family blocked the transcription of TOSPEAK across the 3 GDF6 enhancers in association with a reduction in GDF6 expression and retrograde development of the larynx and wrist. Furthermore, we describe how TOSPEAK developed a human-specific promoter through the expansion of a penta-nucleotide direct repeat that first emerged de novo in the promoter of TOSPEAK in gibbon. This repeat subsequently expanded incrementally in higher hominids to form an overlapping series of Sp1/KLF transcription factor consensus binding sites in human that correlated with incremental increases in the promoter strength of TOSPEAK with human having the strongest promoter. Our research indicates a dual evolutionary role for the incremental increases in TOSPEAK transcriptional interference of GDF6 enhancers in the incremental evolutionary development of the wrist and larynx in hominids and the human capacity to speak and their retrogression with the reduction of TOSPEAK transcription in the affected family

A primer to common major gastrointestinal post-surgical anatomy on CT—a pictorial review

The post-operative abdomen can be challenging and knowledge of normal post-operative anatomy is important for diagnosing complications. The aim of this pictorial essay is to describe a few selected common, major gastrointestinal surgeries, their clinical indications and depict their normal post-operative computed tomography (CT) appearance. This essay provides some clues to identify the surgeries, which can be helpful especially when surgical history is lacking: recognition of the organ(s) involved, determination of what was resected and familiarity with the type of anastomoses used

Using remote sensing to assess peatland resilience by estimating oil surface moisture and drought recovery

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordPeatland areas provide a range of ecosystem services, including biodiversity, carbon storage, clean water, and flood mitigation, but many areas of peatland in the UK have been degraded through human land use including drainage. Here, we explore whether remote sensing can be used to monitor peatland resilience to drought. We take resilience to mean the rate at which a system recovers from perturbation; here measured literally as a recovery timescale of a soil surface moisture proxy from drought lowering. Our objectives were (1) to assess the reliability of Sentinel-1 Synthetic Aperture Radar (SAR) backscatter as a proxy for water table depth (WTD); (2) to develop a method using SAR to estimate below-ground (hydrological) resilience of peatlands; (3) to apply the developed method to different sites and consider the links between resilience and land management. Our inferences of WTD from Sentinel-1 SAR data gave results with an average Pearson’s correlation of 0.77 when compared to measured WTD values. The 2018 summer drought was used to assess resilience across three different UK peatland areas (Dartmoor, the Peak District, and the Flow Country) by considering the timescale of the soil moisture proxy recovery. Results show clear areas of lower resilience within all three study sites, which often correspond to areas of high drainage and may be particularly vulnerable to increasing drought severity/events under climate change. This method is applicable to monitoring peatland resilience elsewhere over larger scales, and could be used to target restoration work towards the most vulnerable areas.Leverhulme Trus

Vertical integration in production and services: development in transaction cost economics

In this paper, we first establish the core, fundamental concepts of Williamson's TCE, examining the different governance structures or the institutional alternatives that TCE theory proposes. We go on to describe some critical considerations and theoretical proposals that correspond fundamentally to Williamson's heuristic model, the integration of incentives in organizational forms, idiosyncratic demand, and how the concept of transaction is conceived in general.Peris-Ortiz, M.; Bonet, F.; Rueda Armengot, C. (2011). Vertical integration in production and services: development in transaction cost economics. Service Business. 5(1):87-97. doi:10.1007/s11628-011-0103-0S879751Alchian A (1965) The basic of some recent advances in the theory of management of the firm. J Ind Econ 14:30–41Alchian A (1969) Corporate management and property rights. In: Manne GH (ed) Economic Policy and Regulation of Corporate Securities. 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Mutation of Rubie, a Novel Long Non-Coding RNA Located Upstream of Bmp4, Causes Vestibular Malformation in Mice

Background: The vestibular apparatus of the vertebrate inner ear uses three fluid-filled semicircular canals to sense angular acceleration of the head. Malformation of these canals disrupts the sense of balance and frequently causes circling behavior in mice. The Epistatic circler (Ecl) is a complex mutant derived from wildtype SWR/J and C57L/J mice. Ecl circling has been shown to result from the epistatic interaction of an SWR-derived locus on chromosome 14 and a C57L-derived locus on chromosome 4, but the causative genes have not been previously identified. Methodology/Principal Findings: We developed a mouse chromosome substitution strain (CSS-14) that carries an SWR/J chromosome 14 on a C57BL/10J genetic background and, like Ecl, exhibits circling behavior due to lateral semicircular canal malformation. We utilized CSS-14 to identify the chromosome 14 Ecl gene by positional cloning. Our candidate interval is located upstream of bone morphogenetic protein 4 (Bmp4) and contains an inner ear-specific, long non-coding RNA that we have designated Rubie (RNA upstream of Bmp4 expressed in inner ear). Rubie is spliced and polyadenylated, and is expressed in developing semicircular canals. However, we discovered that the SWR/J allele of Rubie is disrupted by an intronic endogenous retrovirus that causes aberrant splicing and premature polyadenylation of the transcript. Rubie lies in the conserved gene desert upstream of Bmp4, within a region previously shown to be important for inner ear expression of Bmp4. We found that the expression patterns of Bmp4 and Rubie are nearly identical in developing inner ears

What we talk about when we talk about "global mindset": managerial cognition in multinational corporations

Recent developments in the global economy and in multinational corporations have placed significant emphasis on the cognitive orientations of managers, giving rise to a number of concepts such as “global mindset” that are presumed to be associated with the effective management of multinational corporations (MNCs). This paper reviews the literature on global mindset and clarifies some of the conceptual confusion surrounding the construct. We identify common themes across writers, suggesting that the majority of studies fall into one of three research perspectives: cultural, strategic, and multidimensional. We also identify two constructs from the social sciences that underlie the perspectives found in the literature: cosmopolitanism and cognitive complexity and use these two constructs to develop an integrative theoretical framework of global mindset. We then provide a critical assessment of the field of global mindset and suggest directions for future theoretical and empirical research

Conducting interactive experiments online

Online labor markets provide new opportunities for behavioral research, but conducting economic experiments online raises important methodological challenges. This particularly holds for interactive designs. In this paper, we provide a methodological discussion of the similarities and differences between interactive experiments conducted in the laboratory and online. To this end, we conduct a repeated public goods experiment with and without punishment using samples from the laboratory and the online platform Amazon Mechanical Turk. We chose to replicate this experiment because it is long and logistically complex. It therefore provides a good case study for discussing the methodological and practical challenges of online interactive experimentation. We find that basic behavioral patterns of cooperation and punishment in the laboratory are replicable online. The most important challenge of online interactive experiments is participant dropout. We discuss measures for reducing dropout and show that, for our case study, dropouts are exogenous to the experiment. We conclude that data quality for interactive experiments via the Internet is adequate and reliable, making online interactive experimentation a potentially valuable complement to laboratory studies

Addressing fluorogenic real-time qPCR inhibition using the novel custom Excel file system 'FocusField2-6GallupqPCRSet-upTool-001' to attain consistently high fidelity qPCR reactions

The purpose of this manuscript is to discuss fluorogenic real-time quantitative polymerase chain reaction (qPCR) inhibition and to introduce/define a novel Microsoft Excel-based file system which provides a way to detect and avoid inhibition, and enables investigators to consistently design dynamically-sound, truly LOG-linear qPCR reactions very quickly. The qPCR problems this invention solves are universal to all qPCR reactions, and it performs all necessary qPCR set-up calculations in about 52 seconds (using a pentium 4 processor) for up to seven qPCR targets and seventy-two samples at a time – calculations that commonly take capable investigators days to finish. We have named this custom Excel-based file system "FocusField2-6GallupqPCRSet-upTool-001" (FF2-6-001 qPCR set-up tool), and are in the process of transforming it into professional qPCR set-up software to be made available in 2007. The current prototype is already fully functional