The history and development of the bassoon reed and embouchure

Thesis (M.M.)--Boston Universit

RAWUL: A new ubiquitin-like domain in PRC1 Ring finger proteins that unveils putative plant and worm PRC1 orthologs

<p>Abstract</p> <p>Background</p> <p>Polycomb group (PcG) proteins are a set of chromatin-modifying proteins that play a key role in epigenetic gene regulation. The PcG proteins form large multiprotein complexes with different activities. The two best-characterized PcG complexes are the PcG repressive complex 1 (PRC1) and 2 (PRC2) that respectively possess histone 2A lysine 119 E3 ubiquitin ligase and histone 3 lysine 27 methyltransferase activities. While PRC2-like complexes are conserved throughout the eukaryotic kingdoms, PRC1-like complexes have only been described in Drosophila and vertebrates. Since both complexes are required for the gene silencing mechanism in Drosophila and vertebrates, how PRC1 function is realized in organisms that apparently lack PRC1 such as plants, is so far unknown. In vertebrates, PRC1 includes three proteins, Ring1B, Ring1A, and Bmi-1 that form an E3 ubiquitin ligase complex. These PRC1 proteins have an N-terminally located Ring finger domain associated to a poorly characterized conserved C-terminal region.</p> <p>Results</p> <p>We obtained statistically significant evidences of sequence similarity between the C-terminal region of the PRC1 Ring finger proteins and the ubiquitin (Ubq)-like family proteins, thus defining a new Ubq-like domain, the RAWUL domain. In addition, our analysis revealed the existence of plant and worm proteins that display the conserved combination of a Ring finger domain at the N-terminus and a RAWUL domain at the C-terminus.</p> <p>Conclusion</p> <p>Analysis of the conserved domain architecture among PRC1 Ring finger proteins revealed the existence of long sought PRC1 protein orthologs in these organisms, suggesting the functional conservation of PRC1 throughout higher eukaryotes.</p

Reassessment of the evolution of wheat chromosomes 4A, 5A, and 7B.

Key messageComparison of genome sequences of wild emmer wheat and Aegilops tauschii suggests a novel scenario of the evolution of rearranged wheat chromosomes 4A, 5A, and 7B. Past research suggested that wheat chromosome 4A was subjected to a reciprocal translocation T(4AL;5AL)1 that occurred in the diploid progenitor of the wheat A subgenome and to three major rearrangements that occurred in polyploid wheat: pericentric inversion Inv(4AS;4AL)1, paracentric inversion Inv(4AL;4AL)1, and reciprocal translocation T(4AL;7BS)1. Gene collinearity along the pseudomolecules of tetraploid wild emmer wheat (Triticum turgidum ssp. dicoccoides, subgenomes AABB) and diploid Aegilops tauschii (genomes DD) was employed to confirm these rearrangements and to analyze the breakpoints. The exchange of distal regions of chromosome arms 4AS and 4AL due to pericentric inversion Inv(4AS;4AL)1 was detected, and breakpoints were validated with an optical Bionano genome map. Both breakpoints contained satellite DNA. The breakpoints of reciprocal translocation T(4AL;7BS)1 were also found. However, the breakpoints that generated paracentric inversion Inv(4AL;4AL)1 appeared to be collocated with the 4AL breakpoints that had produced Inv(4AS;4AL)1 and T(4AL;7BS)1. Inv(4AS;4AL)1, Inv(4AL;4AL)1, and T(4AL;7BS)1 either originated sequentially, and Inv(4AL;4AL)1 was produced by recurrent chromosome breaks at the same breakpoints that generated Inv(4AS;4AL)1 and T(4AL;7BS)1, or Inv(4AS;4AL)1, Inv(4AL;4AL)1, and T(4AL;7BS)1 originated simultaneously. We prefer the latter hypothesis since it makes fewer assumptions about the sequence of events that produced these chromosome rearrangements

Hansenula polymorpha Pex37 is a peroxisomal membrane protein required for organelle fission and segregation

Here, we describe a novel peroxin, Pex37, in the yeast Hansenula polymorpha. H. polymorpha Pex37 is a peroxisomal membrane protein, which belongs to a protein family that includes, among others, the Neurospora crassa Woronin body protein Wsc, the human peroxisomal membrane protein PXMP2, the Saccharomyces cerevisiae mitochondrial inner membrane protein Sym1, and its mammalian homologue MPV17. We show that deletion of H. polymorpha PEX37 does not appear to have a significant effect on peroxisome biogenesis or proliferation in cells grown at peroxisome‐inducing growth conditions (methanol). However, the absence of Pex37 results in a reduction in peroxisome numbers and a defect in peroxisome segregation in cells grown at peroxisome‐repressing conditions (glucose). Conversely, overproduction of Pex37 in glucose‐grown cells results in an increase in peroxisome numbers in conjunction with a decrease in their size. The increase in numbers in PEX37‐overexpressing cells depends on the dynamin‐related protein Dnm1. Together our data suggest that Pex37 is involved in peroxisome fission in glucose‐grown cells. Introduction of human PXMP2 in H. polymorpha pex37 cells partially restored the peroxisomal phenotype, indicating that PXMP2 represents a functional homologue of Pex37. H.polymorpha pex37 cells did not show aberrant growth on any of the tested carbon and nitrogen sources that are metabolized by peroxisomal enzymes, suggesting that Pex37 may not fulfill an essential function in transport of these substrates or compounds required for their metabolism across the peroxisomal membrane

Rationale for Advocacy Training in Undergraduate Medical Education

Advocacy is the outspoken support of a cause or group of people. Within the context of medicine, it includes any individual or organized effort that strives to improve health outcomes, expand the inclusivity of the field or promote awareness of a systemic problem that can be ameliorated through legislative efforts. Examples of advocacy in medicine range from fighting for a patient’s costly prescription drug to be covered by insurance, to ensuring that historically underrepresented groups are given the opportunity to achieve a presence in a certain specialty, to contacting legislators to fund efforts to decrease the overcrowding of emergency rooms in public hospitals.  Thus, advocacy is crucial across all specialties in the medical field. We believe increasing the exposure of medical students to advocacy training is imperative and will provide them with the necessary tools to beneficially influence the field during their careers. The American Medical Association (AMA) states that physicians must “advocate for the social, economic, educational and political changes that ameliorate suffering and contribute to human well-being” in its Declaration of Professional Responsibility, and other physician and specialty organizations urge such important professional activity as well.1-7 Undergraduate Medical Education (UGME) refers to the instruction received during medical school by students when pursuing an M.D. or D.O. degree. Graduate Medical Education (GME), on the other hand, refers to any type of education after completing an M.D. or D.O. degree, which usually includes residency or fellowship training. Both the United States and Canada recognize the importance of training physicians in advocacy at the GME level, however, advocacy training at the UGME level is less cohesive.8,9 In addition, even at the GME level, though some specialties such as pediatrics do have a requirement for advocacy training, there are no standardized curricula or standards across specialties.10,11 UGME currently lacks compulsory advocacy training integration into the medical school curriculum, although The American Council for Graduate Medical Education (ACGME) in the USA and the Royal College of Physicians and Surgeons (RCPS) in Canada recognize training in advocacy as an objective of GME.12 This could explain the gap between the AMA’s vision of professional responsibility and medical students’ perception of their duties as future physicians. In a 2014 survey, McCrea and Murdoch-Eaton found that medical students “expressed limited appreciation of the concept of social accountability and acknowledged little explicit teaching around underpinning core concepts such as awareness of local health needs, advocacy and nurturing of altruism.”13 They did, however, recognize “the importance of qualities such as advocacy in their future professional careers.” In order to close this gap, UGME should ensure curricular components that foster the nurturing of advocacy are included from an early stage in the instruction of medicine. This will help prevent negative ramifications such as the decline in interest for social issues during medical training, which Bhate et al. describe.14 Bhate also notes that training in advocacy has been shown to change physician’s attitudes towards its practice. Additionally, Press et al. argues that “exposing all medical students to advocacy within medicine may help shape and define their perceived professional role.”15 As advocacy in healthcare can contribute to the enactment of regulations and standards that ultimately improve the public’s health, students should be exposed to formal training that equips them with the necessary tools to engage in effective advocacy and understand their responsibility for engagement. UGME should, therefore, have a requisite to offer advocacy training that is evidence-based, influenced by clinical expertise and contextualized to account for social, economic and political realities. Lastly, these advocacy-driven initiatives are likely to lead to an improvement in patient-centered measures such as patient satisfaction. Feuerwerker et al. argue that the creation of a position called "Patient Advocate" by a medical student in pre-clinical years would make patients feel more satisfied with their care in the ED and teach students to actively solve patient's frustrations.16 In a similar project, Ward et al. show through their “Patient Advocate Project” that outpatient satisfaction survey data from pre-, peri-, and post-provider (patient advocate) periods demonstrate the implementation of a Patient Advocate Project improved overall satisfaction scores in the ED during the peri-intervention period.17 Knowing that advocacy training can positively impact the quality of care as judged from a patient’s perspective should stand out as a driving force to implement these changes at a formative time in the careers of medical professionals: during UGME training