434 research outputs found

    Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development

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    Mitochondrial morphology is determined by a dynamic equilibrium between organelle fusion and fission, but the significance of these processes in vertebrates is unknown. The mitofusins, Mfn1 and Mfn2, have been shown to affect mitochondrial morphology when overexpressed. We find that mice deficient in either Mfn1 or Mfn2 die in midgestation. However, whereas Mfn2 mutant embryos have a specific and severe disruption of the placental trophoblast giant cell layer, Mfn1-deficient giant cells are normal. Embryonic fibroblasts lacking Mfn1 or Mfn2 display distinct types of fragmented mitochondria, a phenotype we determine to be due to a severe reduction in mitochondrial fusion. Moreover, we find that Mfn1 and Mfn2 form homotypic and heterotypic complexes and show, by rescue of mutant cells, that the homotypic complexes are functional for fusion. We conclude that Mfn1 and Mfn2 have both redundant and distinct functions and act in three separate molecular complexes to promote mitochondrial fusion. Strikingly, a subset of mitochondria in mutant cells lose membrane potential. Therefore, mitochondrial fusion is essential for embryonic development, and by enabling cooperation between mitochondria, has protective effects on the mitochondrial population

    Highlighting the learning in project-based undergraduate engineering education: pedagogical and methodological considerations

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    This paper presents a discussion of findings in relation to the pedagogy of Project Based Learning (PjBL) from a collaborative learning and teaching research project at UCL Engineering. It highlights the importance of adopting a) an understanding learning as a social practice in PjBL, and b) developing valid methodological approaches when capturing student learning experiences

    Fitness for purpose? project-based, collaborative learning in engineering undergraduate education

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    In response to evolving work practices in engineering (Royal Academy of Engineering 2010) and the ever-changing nature of vocational and professional knowledge (Broad, 2016), attention has rightly turned to the development of innovative pedagogies to facilitate the entry of graduates to the employment market. Project-based Learning (PjBL) is an example of such an innovative pedagogy and has been developed in some HE contexts to provide students with authentic learning experiences which are designed to embed team working and collaboration; problem solving and solution-finding alongside the development of technical knowledge and skills (Mills and Treagust, 2003). Yet despite the introduction of collaborative inquiry-based curricula in engineering, comprehensive understanding of the pedagogical practices that these innovative practices require has not yet emerged (Damşa & Nerland, 2016). At UCL Engineering, PjBL has been an integral feature of the Integrated Engineering Programme (IEP) undergraduate curriculum since 2014. Drawing upon an on-going collaborative Institute of Education/UCL ‘seed corn’ funded project, this paper will present data collected through observation of project-based learning scenarios and discussion with engineering undergraduates in situ. It will identify and discuss the nature of student learning and engagement in project-based learning activities, with particular attention to disciplinary issues and the development of student disciplinary knowledge. In so doing, it will assess whether PjBL is, indeed, ‘fit for purpose’

    Cytoskeleton-associated antigens from African trypanosomes are recognized by self-reactive antibodies of uninfected mice

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    Serum from uninfected mice of different strains, as well as from germ-free animals, contains antibodies which react specifically with at least two trypanosomal proteins, I/6 and MARP1. These antibody populations are highly specific for the respective proteins, are of similar affinity as hyperimmune antibodies, and consist of IgM as well as IgG isotypes. Hyperimmune antibody raised against the cross-reacting trypanosomal protein I/6 detects a 60 kDa protein in mouse 3T6 cells, which is a component of the fibroblast cytoskeleto

    Non-invasive neurosensory testing used to diagnose and confirm successful surgical management of lower extremity deep distal posterior compartment syndrome

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    <p>Abstract</p> <p>Background</p> <p>Chronic exertional compartment syndrome (CECS) is characterized by elevated pressures within a closed space of an extremity muscular compartment, causing pain and/or disability by impairing the neuromuscular function of the involved compartment. The diagnosis of CECS is primarily made on careful history and physical exam. The gold standard test to confirm the diagnosis of CECS is invasive intra-compartmental pressure measurements. Sensory nerve function is often diminished during symptomatic periods of CECS. Sensory nerve function can be documented with the use of non-painful, non-invasive neurosensory testing.</p> <p>Methods</p> <p>Non-painful neurosensory testing of the myelinated large sensory nerve fibers of the lower extremity were obtained with the Pressure Specified Sensory Device™ in a 25 year old male with history and invasive compartment pressures consistent with CECS both before and after running on a tread mill. After the patient's first operation to release the deep distal posterior compartment, the patient failed to improve. Repeat sensory testing revealed continued change in his function with exercise. He was returned to the operating room where a repeat procedure revealed that the deep posterior compartment was not completely released due to an unusual anatomic variant, and therefore complete release was accomplished.</p> <p>Results</p> <p>The patient's symptoms numbness in the plantar foot and pain in the distal calf improved after this procedure and his repeat sensory testing performed before and after running on the treadmill documented this improvement.</p> <p>Conclusion</p> <p>This case report illustrates the principal that non-invasive neurosensory testing can detect reversible changes in sensory nerve function after a provocative test and may be a helpful non-invasive technique to managing difficult cases of persistent lower extremity symptoms after failed decompressive fasciotomies for CECS. It can easily be performed before and after exercise and be repeated at multiple intervals without patient dissatisfaction. It is especially helpful when other traditional testing has failed.</p

    Hydrogen molecule in a magnetic field: The lowest states of the Pi manifold and the global ground state of the parallel configuration

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    The electronic structure of the hydrogen molecule in a magnetic field is investigated for parallel internuclear and magnetic field axes. The lowest states of the Π\Pi manifold are studied for spin singlet and triplet(Ms=1)(M_s = -1) as well as gerade and ungerade parity for a broad range of field strengths 0B100a.u.0 \leq B \leq 100 a.u. For both states with gerade parity we observe a monotonous decrease in the dissociation energy with increasing field strength up to B=0.1a.u.B = 0.1 a.u. and metastable states with respect to the dissociation into two H atoms occur for a certain range of field strengths. For both states with ungerade parity we observe a strong increase in the dissociation energy with increasing field strength above some critical field strength BcB_c. As a major result we determine the transition field strengths for the crossings among the lowest 1Σg^1\Sigma_g, 3Σu^3\Sigma_u and 3Πu^3\Pi_u states. The global ground state for B0.18a.u.B \lesssim 0.18 a.u. is the strongly bound 1Σg^1\Sigma_g state. The crossings of the 1Σg^1\Sigma_g with the 3Σu^3\Sigma_u and 3Πu^3\Pi_u state occur at B0.18B \approx 0.18 and B0.39a.u.B \approx0.39 a.u., respectively. The transition between the 3Σu^3\Sigma_u and 3Πu^3\Pi_u state occurs at B12.3a.u.B \approx 12.3 a.u. Therefore, the global ground state of the hydrogen molecule for the parallel configuration is the unbound 3Σu^3\Sigma_u state for 0.18B12.3a.u.0.18 \lesssim B \lesssim 12.3 a.u. The ground state for B12.3a.u.B \gtrsim 12.3 a.u. is the strongly bound 3Πu^3\Pi_u state. This result is of great relevance to the chemistry in the atmospheres of magnetic white dwarfs and neutron stars.Comment: submitted to Physical Review

    Beyond Trial Registration: A Global Trial Bank for Clinical Trial Reporting

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    The prose reporting of trial information could be powerfully augmented by a computable repository of trial information-a global "trial bank.
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