The processing peptidase of yeast mitochondria

Two proteins co-operate in the proteolytic cleavage of mitochondrial precursor proteins: the mitochondrial processing peptidase (MPP) and the processing enhancing protein (PEP). In order to understand the structure and function of this novel peptidase, we have isolated mutants of Saccharomyces cerevisiae which were temperature sensitive in the processing of mitochondrial precursor proteins. Here we report on the mif2 mutation which is deficient in MPP. Mitochondria from the mif2 mutant were able to import precursor proteins, but not to cleave the presequences. The MPP gene was isolated. MPP is a hydrophilic protein consisting of 482 amino acids. Notably, MPP exhibits remarkable sequence similarity to PEP. We speculate that PEP and MPP have a common origin and have evolved into two components with different but mutually complementing functions in processing of precursor proteins

The structural and stratigraphic development of the Casco Bay Group at Harpswell Neck, Maine

Guidebook for field trips in southwestern Maine: New England Intercollegiate Geological Conference, 78th annual meeting, Bates College, Lewiston, Maine, October 17, 18, and 19, 1986: Trip C-

Mining and Manipulation of Antibiotic Biosynthesis in Streptomyces

New small-molecule drugs are needed, both to address existing disease and to combat the rise of antibiotic resistance in pathogenic microbes. A major source of antibiotics and other valuable therapeutic agents remains the natural products produced by Streptomyces and allied bacteria. The advent of genome-level sequencing has changed how such bioactive products are identified in two ways: first, by enabling new approaches to engineering of known clusters to obtain new analogues; and secondly by enabling mining of their large (8-12 Mbp) genomes to make rapid links between valuable compounds and the gene clusters responsible for their biosynthesis; as well as a complete inventory of orphan clusters for decryption. In this work, both of these aspects were explored. Accelerated Evolution (AE) is a new method of induced recombination in Streptomyces that produces libraries of analogues of a parent compound in a single experiment. It has been previously applied to a typical assembly-line biosynthetic pathway involving a multimodular polyketide synthase, that for the immunosuppressant rapamycin. Here, the utility of AE was initially explored with several polyketide antibiotics, before focussing on the polyene filipin. Unfortunately, this system proved refractory to the AE method, since only recombinants which had either lost filipin production, or which maintained some level of filipin production, were recovered. These results suggested that deeper understanding of the fundamental processes of recombination in Streptomyces are now needed to allow the AE approach to flourish. A genome mining approach was taken to identify and analyse the gene cluster in Streptomyces albus DMS40763 for pseudouridimycin (PUM), a rare C-nucleoside antibiotic and a newly-recognised selective inhibitor of bacterial RNA polymerase. The fully-sequenced genome (8.01 Mbp) of S. albus was analysed and 27 biosynthetic gene clusters were found, including those for 11 novel assembly-line systems. A strong candidate for the PUM gene cluster was identified through BLAST searches with a gene probe (truD) found in the gene cluster for a different C-nucleoside in other Streptomyces spp., hinting at a common mechanism for formation of the C-nucleoside moiety. Identification of the enzymes predicted to be encoded by the gene cluster allowed a detailed biosynthetic pathway to be proposed. Several genes from the PUM cluster were expressed and purified as recombinant proteins in Escherichia coli, and the proposed enzymatic roles of two of them were verified. One of these, a pseudouridine oxidase, also showed activity against uridine. Consistent with this finding, feeding of uracil to a mutant S. albus lacking the pseudouridine synthase-like gene truD gave production of the novel N-linked analogue of PUM, suggesting that the biosynthetic enzymes may be sufficiently flexible to incorporate other, non-natural nucleosides into PUM analogues for testing

Mitochondrial heat-shock protein hsp60 is essential for assembly of proteins imported into yeast mitochondria

A nuclear encoded mitochondrial heat-shock protein hsp60 is required for the assembly into oligomeric complexes of proteins imported into the mitochondrial matrix. hsp60 is a member of the 'chaperonin' class of protein factors, which include the Escherichia coli groEL protein and the Rubisco subunit-binding protein of chloroplast

Patient and researcher perspectives on facilitating patient and public involvement in rheumatology research

No abstract available

Electrically pumped continuous wave quantum dot lasers epitaxially grown on patterned, on-axis (001) Si

High performance III-V lasers at datacom and telecom wavelengths on on-axis (001) Si are needed for scalable datacenter interconnect technologies. We demonstrate electrically injected quantum dot lasers grown on on-axis (001) Si patterned with {111} v-grooves lying in the [110] direction. No additional Ge buffers or substrate miscut was used. The active region consists of five InAs/InGaAs dot-in-a-well layers. We achieve continuous wave lasing with thresholds as low as 36 mA and operation up to 80°C

Convocation

Program listing performers and works performe

Historical Perspective

In Re: Amundsen P. Cerebral angiography via the femoral artery with particular reference to cerebrovascular disease

To promote or not to promote fundamental British values? Teachers' standards, diversity and teacher education

In this article we seek to problematize the presence of the requirement within the teachers’ standards (DfE, 2012), that they ‘should not undermine fundamental British values’ in the context of initial teacher education in England. The inclusion of this statement within the teachers’ code of conduct has made its way from the counter-terrorism strategy, Prevent and raises questions about Britishness, values and the relationship between the state and the profession more generally. We argue that the inclusion of the phrase within a statutory document that regulates the profession is de facto a politicization of the profession by the state thereby instilling the expectation that teachers are state instruments of surveillance. The absence of any wider debate around the inclusion of the statement is also problematic as is the lack of training for pre-service and inservice teachers since it means this concept of fundamental British values is unchallenged and its insidious racialising implications are unrecognised by most teachers