Evolution of NCoR-1 and NCoR-2 corepressor alternative mRNA splicing in placental mammals.

ObjectiveThe NCoR-1 and NCoR-2 corepressors are products of an early gene duplication near the beginning of vertebrate evolution and play both overlapping and divergent roles in development and physiology. Alternative-splicing of NCoR-1 and NCoR-2 further customizes their functions. To better understand the evolutionary basis of this phenomenon we extended our prior study of NCoR-1 and NCoR-2 alternative-splicing to an expanded series of species.ResultsAlternative-splicing of NCoR-2 was observed in all vertebrates examined whereas alternative-splicing of NCoR-1 was largely limited to placental mammals. Notably the most prominent of the NCoR-1 alternative-splicing events specific to the placental lineage, in exon 37 that plays a key role in murine metabolism, mimics in many features an analogous alternative-splicing event that appeared in NCoR-2 much earlier at the beginning of the vertebrate radiation. Detection of additional alternative-splicing events, at exons 28 in NCoR-1 or NCoR-2, was limited to the Rodentia or Primates examined, indicating both corepressor paralogs continued to acquire additional splice variations more recently and independently of one another. Our results suggest that the NCoR-1/NCoR-2 paralogs have been subject to a mix of shared and distinct selective pressures, resulting in the pattern of divergent and convergent alternative-splicing observed in extant species

Corepressor diversification by alternative mRNA splicing is species specific.

BackgroundSMRT and NCoR are corepressor paralogs that help mediate transcriptional repression by a variety of transcription factors, including the nuclear hormone receptors. The functions of both corepressors are extensively diversified in mice by alternative mRNA splicing, generating a series of protein variants that differ in different tissues and that exert different, even diametrically opposite, biochemical and biological effects from one another.ResultsWe report here that the alternative splicing previously reported for SMRT appears to be a relatively recent evolutionary phenomenon, with only one of these previously identified sites utilized in a teleost fish and a limited additional number of the additional known sites utilized in a bird, reptile, and marsupial. In contrast, extensive SMRT alternative splicing at these sites was detected among the placental mammals. The alternative splicing of NCoR previously identified in mice (and shown to regulate lipid and carbohydrate metabolism) is likely to have arisen separately and after that of SMRT, and includes an example of convergent evolution.ConclusionsWe propose that the functions of both SMRT and NCoR have been diversified by alternative splicing during evolution to allow customization for different purposes in different tissues and different species

What makes a good induction supporter?

The Teacher Induction Scheme, introduced in 2002, marked the first major change to new teacher induction in Scotland in 37 years. This paper gives an outline of these changes set against developments in mentoring theory in the wider context. It argues that the personal qualities of the induction supporter are crucial to developing an effective mentoring relationship. The views of student teachers are used to describe preferred characteristics of effective mentors and effective induction provision. A person specification is created by the comments of the "Class of 2002" — the first probationer teachers to have taken part in the Scheme

An improved high throughput protein-protein interaction assay for nuclear hormone receptors

The Glutathione-S-Transferase (GST) “pulldown” assay has been used extensively to assay protein interactions in vitro. This methodology has been especially useful for investigating the interactions of nuclear hormone receptors with a wide variety of their interacting partners and coregulatory proteins. Unfortunately, the original GST-pulldown technique relies on multiple binding, washing and elution steps performed in individual microfuge tubes, and requires repeated centrifugation, aspiration, and suspension steps. This type of batch processing creates a significant liquid handling bottleneck, limiting the number of sample points that can be incorporated into one experiment and producing inherently less efficient washing and elution than would a flow-through methodology. In this manuscript, we describe the adaptation of this GST-pulldown assay to a 96-well filter plate format. The use of a multi-well filter plate makes it possible to assay more samples in significantly less time using less reagents and more efficient sample processing than does the traditional single tube assay

Furthering alternative cultures of valuation in higher education research

The value of higher education is often implicit or assumed in educational research. The underlying and antecedent premises that shape and influence debates about value remain unchallenged which perpetuates the dominant, but limiting, terms of the debate and fosters reductionism. I proceed on the premise that analyses of value are not self–supporting or self-referential but are embedded within prevailing cultures of valuation. I contend that challenging, and providing alternatives to, dominant narratives of higher education requires an appreciation of those cultures. I therefore highlight some of the existing cultures of valuation and their influence. I then propose Sayer’s concept of lay normativity as a culture of valuation and discuss how it translates into the practices of research into higher education, specifically the practice of analysis. I animate the discussion by detecting the presence of lay normativity in the evaluative space of the capability approach

Cascading training down into the classroom: The need for parallel planning

Cascade models of in-service training are widely considered to be a cost effective means of introducing educational change to large numbers of teachers. Data from 511 teachers completing a cascade training programme that introduced current ideas about and procedures for teaching English to young learners, suggests that provision of training alone is no guarantee that cascade training aims will actually be applied in classrooms. The paper considers implications for cascade projects, suggesting that planning needs to be a parallel process if an adequate return on outlay, in the sense of teachers applying skills introduced in training in their classrooms, is to be achieved

Stiff person syndrome presenting with sudden onset of shortness of breath and difficulty moving the right arm: a case report

<p>Abstract</p> <p>Introduction</p> <p>First described in 1956, stiff person syndrome is characterized by episodes of slowly progressive stiffness and rigidity in both the paraspinal and limb muscles. Although considered a rare disorder, stiff person syndrome is likely to be under-diagnosed due to a general lack of awareness of the disease in the medical community.</p> <p>Case presentation</p> <p>A 27-year-old Hispanic woman presented to our emergency department with a sudden onset of shortness of breath and difficulty moving her right arm. Her physical examination was remarkable in that her abdomen was firm to palpation and her right upper extremity was rigid on passive and active ranges of motion. Her right fingers were clenched in a fist. Her electromyography findings were consistent with stiff person syndrome in the right clinical setting. Stiff person syndrome is confirmed by testing for the anti-glutamic acid decarboxylase antibody. Her test for this was positive.</p> <p>Conclusion</p> <p>Stiff person syndrome may not be a common condition. However, if disregarded in the differential diagnosis, it can lead to several unnecessary tests being carried out causing a delay in treatment. This case report reveals some of the characteristic features of stiff person syndrome with an atypical presentation.</p

Corepressors: custom tailoring and alterations while you wait

A diverse cadre of metazoan transcription factors mediate repression by recruiting protein complexes containing the SMRT (silencing mediator of retinoid and thyroid hormone receptor) or N-CoR (nuclear receptor corepressor) corepressors. SMRT and N-CoR nucleate the assembly of still larger corepressor complexes that perform the specific molecular incantations necessary to confer transcriptional repression. Although SMRT and N-CoR are paralogs and possess similar molecular architectures and mechanistic strategies, they nonetheless exhibit distinct molecular and biological properties. It is now clear that the functions of both SMRT and N-CoR are further diversified through alternative mRNA splicing, yielding a series of corepressor protein variants that participate in distinctive transcription factor partnerships and display distinguishable repression properties. This review will discuss what is known about the structure and actions of SMRT, N-CoR, and their splicing variants, and how alternative splicing may allow the functions of these corepressors to be adapted and tailored to different cells and to different developmental stages