The transcription factor Gli3 promotes B cell development in fetal liver through repression of Shh

Before birth, B cells develop in the fetal liver (FL). In this study, we show that Gli3 activity in the FL stroma is required for B cell development. In the Gli3-deficient FL, B cell development was reduced at multiple stages, whereas the Sonic hedgehog (Hh [Shh])–deficient FL showed increased B cell development, and Gli3 functioned to repress Shh transcription. Use of a transgenic Hh-reporter mouse showed that Shh signals directly to developing B cells and that Hh pathway activation was increased in developing B cells from Gli3-deficient FLs. RNA sequencing confirmed that Hh-mediated transcription is increased in B-lineage cells from Gli3-deficient FL and showed that these cells expressed reduced levels of B-lineage transcription factors and B cell receptor (BCR)/pre-BCR–signaling genes. Expression of the master regulators of B cell development Ebf1 and Pax5 was reduced in developing B cells from Gli3-deficient FL but increased in Shh-deficient FL, and in vitro Shh treatment or neutralization reduced or increased their expression, respectively

Vacancies, twins, and the thermal stability of ultrafine-grained copper

Ultrafine-grained metals have impressive strength but lack the thermal stability necessary for most applications. Nano-scale, deformation twinned copper microstructures exhibit a rare combination of strength and stability. While storing less energy in their interfaces than other nanostructured metals, they also exhibit lower vacancy supersaturations, reducing the driving force and mobility for microstructure evolution. From a thermal stability perspective, the nano-twinned microstructure may thus be preferred over the more commonly produced nano-scale equiaxed microstructures

Organization of the Zone of Transition between the Pretectum and the Thalamus, with Emphasis on the Pretectothalamic Lamina

The zone of transition between the pretectum, derived from prosomere 1, and the thalamus, derived from prosomere 2, is structurally complex and its understanding has been hampered by cytoarchitectural and terminological confusion. Herein, using a battery of complementary morphological approaches, including cytoarchitecture, myeloarchitecture and the expression of molecular markers, we pinpoint the features or combination of features that best characterize each nucleus of the pretectothalamic transitional zone of the rat. Our results reveal useful morphological criteria to identify and delineate, with unprecedented precision, several [mostly auditory] nuclei of the posterior group of the thalamus, namely the pretectothalamic lamina (PTL; formerly known as the posterior limitans nucleus), the medial division of the medial geniculate body (MGBm), the suprageniculate nucleus (SG), and the ethmoid, posterior triangular and posterior nuclei of the thalamus. The PTL is a sparsely-celled and fiber rich flattened nucleus apposed to the lateral surface of the anterior pretectal nucleus (APT) that marks the border between the pretectum and the thalamus; this structure stains selectively with the Wisteria floribunda agglutinin (WFA), and is essentially immunonegative for the calcium binding protein parvalbumin (PV). The MGBm, located medial to the ventral division of the MGB (MGBv), can be unequivocally identified by the large size of many of its neurons, its dark immunostaining for PV, and its rather selective staining for WFA. The SG, which extends for a considerable caudorostral distance and deviates progressively from the MGB, is characterized by its peculiar cytoarchitecture, the paucity of myelinated fibers, and the conspicuous absence of staining for calretinin (CR); indeed, in many CR-stained sections, the SG stands out as a blank spot. Because most of these nuclei are small and show unique anatomical relationships, the information provided in this article will facilitate the interpretation of the results of experimental manipulations aimed at the auditory thalamus and improve the design of future investigations. Moreover, the previously neglected proximity between the MGBm and the caudal region of the scarcely known PTL raises the possibility that certain features or roles traditionally attributed to the MGBm may actually belong to the PTL

Patient safety in dentistry: development of a candidate 'never event' list for primary care

Introduction The 'never event' concept is often used in secondary care and refers to an agreed list of patient safety incidents that 'should not happen if the necessary preventative measures are in place'. Such an intervention may raise awareness of patient safety issues and inform team learning and system improvements in primary care dentistry. Objective To identify and develop a candidate never event list for primary care dentistry. Methods A literature review, eight workshops with dental practitioners and a modified Delphi with 'expert' groups were used to identify and agree candidate never events. Results Two-hundred and fifty dental practitioners suggested 507 never events, reduced to 27 distinct possibilities grouped across seven themes. Most frequently occurring themes were: 'checking medical history and prescribing' (119, 23.5%) and 'infection control and decontamination' (71, 14%). 'Experts' endorsed nine candidate never event statements with one graded as 'extreme risk' (failure to check past medical history) and four as 'high risk' (for example, extracting wrong tooth). Conclusion Consensus on a preliminary list of never events was developed. This is the first known attempt to develop this approach and an important step in determining its value to patient safety. Further work is necessary to develop the utility of this method

The potential of satellite data to study individual wildfire events

Geophysical Research Abstract of EGU General Assembly 2014, held 27 April - 2 May, 2014 in Vienna, Austria

Time reclaimed: temporality and the experience of meaningful work

The importance of meaningful work has been identified in scholarly writings across a range of disciplines. However, empirical studies remain sparse and the potential relevance of the concept of temporality, hitherto somewhat neglected even in wider sociological studies of organizations, has not been considered in terms of the light that it can shed on the experience of work as meaningful. These two disparate bodies of thought are brought together to generate new accounts of work meaningfulness through the lens of temporality. Findings from a qualitative study of workers in three occupations with ostensibly distinct temporal landscapes are reported. All jobs had the potential to be both meaningful and meaningless; meaningfulness arose episodically through work experiences that were shared, autonomous and temporally complex. Schutz’s notion of the ‘vivid present’ emerged as relevant to understanding how work is rendered meaningful within an individual’s personal and social system of relevances

The relevance of spermatozoal RNA and quality in livestock production

Spermatozoal cells are known to contain a wide variety of both coding and non-coding transcripts, but the physiological role of these transcripts is not fully understood. Therefore, the overall aim of this study was to characterize both coding and non-coding transcripts contained in ovine spermatozoa, and identify differences in expression patterns between three different sheep breeds (Merino, Dohne and Poll Dorset), and ejaculates that vary in quality. A variety of coding (e.g. MVK, PAMR1, ATP2A3, KLK12, etc.) and noncoding transcripts (e.g. XLOC_025216, XLOC_048757, XLOC_001809, XLOC_025093, etc.) were found to be differentially expressed in different sheep breeds and ejaculates of contrasting quality. Some of these transcripts have been reported to be associated with spermatozoal function or physiology in the literature. Overall, these results provide novel insights into spermatozoal transcriptomes in sheep, and also potentially indicate their functional relevance

Dialectic tensions in the financial markets: a longitudinal study of pre- and post-crisis regulatory technology

This article presents the findings from a longitudinal research study on regulatory technology in the UK financial services industry. The financial crisis with serious corporate and mutual fund scandals raised the profile of compliance as governmental bodies, institutional and private investors introduced a ‘tsunami’ of financial regulations. Adopting a multi-level analysis, this study examines how regulatory technology was used by financial firms to meet their compliance obligations, pre- and post-crisis. Empirical data collected over 12 years examine the deployment of an investment management system in eight financial firms. Interviews with public regulatory bodies, financial institutions and technology providers reveal a culture of compliance with increased transparency, surveillance and accountability. Findings show that dialectic tensions arise as the pursuit of transparency, surveillance and accountability in compliance mandates is simultaneously rationalized, facilitated and obscured by regulatory technology. Responding to these challenges, regulatory bodies continue to impose revised compliance mandates on financial firms to force them to adapt their financial technologies in an ever-changing multi-jurisdictional regulatory landscape

The Self stepping into the shoes of the Other: Understanding and developing self-perceptions of empathy among prospective physical education teachers through a special school placement

Teachers who demonstrate a high degree of empathy are said to have more positive attitudes towards pupils with disabilities. Therefore, this article sought to explore the influence of a special school placement on prospective teachers’ self-perceptions of empathy. Thirty-two final year undergraduate students participated in focus group interviews and were selected because they aspired to be a physical education teacher and had attended a placement in a special school. Interview transcripts were analysed and the following themes constructed: Stepping into the shoes of the Other; Frustrated ‘for’ not ‘with’ pupils with disabilities; Empathy for planning inclusive lessons and ‘reading’ pupil body language; and Knowing when not to show empathy. All prospective teachers felt that: (a) they could empathise with pupils with disabilities; (b) situated learning experiences within the placement enabled them to reflect on the ways in which their empathy influences their teaching now and could continue to do so in the future; and (c) it was important that teachers demonstrated empathy. Thus, it is recommended that all prospective teachers gain some experience teaching in special schools. Our research also warns against teachers claiming the last, conclusive word about who children with disabilities are, what they think, how they feel and what they want, in myriad contexts and situations

Engineering the Controlled Assembly of Filamentous Injectisomes in E. coli K-12 for Protein Translocation into Mammalian Cells.

Bacterial pathogens containing type III protein secretion systems (T3SS) assemble large needle-like protein complexes in the bacterial envelope, called injectisomes, for translocation of protein effectors into host cells. The application of these molecular syringes for the injection of proteins into mammalian cells is hindered by their structural and genomic complexity, requiring multiple polypeptides encoded along with effectors in various transcriptional units (TUs) with intricate regulation. In this work, we have rationally designed the controlled expression of the filamentous injectisomes found in enteropathogenic Escherichia coli (EPEC) in the nonpathogenic strain E. coli K-12. All structural components of EPEC injectisomes, encoded in a genomic island called the locus of enterocyte effacement (LEE), were engineered in five TUs (eLEEs) excluding effectors, promoters and transcriptional regulators. These eLEEs were placed under the control of the IPTG-inducible promoter Ptac and integrated into specific chromosomal sites of E. coli K-12 using a marker-less strategy. The resulting strain, named synthetic injector E. coli (SIEC), assembles filamentous injectisomes similar to those in EPEC. SIEC injectisomes form pores in the host plasma membrane and are able to translocate T3-substrate proteins (e.g., translocated intimin receptor, Tir) into the cytoplasm of HeLa cells reproducing the phenotypes of intimate attachment and polymerization of actin-pedestals elicited by EPEC bacteria. Hence, SIEC strain allows the controlled expression of functional filamentous injectisomes for efficient translocation of proteins with T3S-signals into mammalian cells