Association of the mtDNA m.4171C>A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions

Background: An increasing number of mitochondrial DNA (mtDNA) mutations, mainly in complex I genes, have been associated with variably overlapping phenotypes of Leber’s hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and Leigh syndrome (LS). We here describe the first case in which the m.4171C>A/MT-ND1 mutation, previously reported only in association with LHON, leads also to a Leigh-like phenotype. Case presentation: A 16-year-old male suffered subacute visual loss and recurrent vomiting and vertigo associated with bilateral brainstem lesions affecting the vestibular nuclei. His mother and one sister also presented subacute visual loss compatible with LHON. Sequencing of the entire mtDNA revealed the homoplasmic m.4171C>A/MT-ND1 mutation, previously associated with pure LHON, on a haplogroup H background. Three additional non-synonymous homoplasmic transitions affecting ND2 (m.4705T>C/MT-ND2 and m.5263C>T/MT-ND2) and ND6 (m.14180T>C/MT-ND6) subunits, well recognized as polymorphisms in other mtDNA haplogroups but never found on the haplogroup H background, were also present. Conclusion: This case widens the phenotypic expression of the rare m.4171C>A/MT-ND1 LHON mutation, which may also lead to Leigh-like brainstem lesions, and indicates that the co-occurrence of other ND non-synonymous variants, found outside of their usual mtDNA backgrounds, may have increased the pathogenic potential of the primary LHON mutation

Superconducting tunable flux qubit with direct readout scheme

We describe a simple and efficient scheme for the readout of a tunable flux qubit, and present preliminary experimental tests for the preparation, manipulation and final readout of the qubit state, performed in incoherent regime at liquid Helium temperature. The tunable flux qubit is realized by a double SQUID with an extra Josephson junction inserted in the large superconducting loop, and the readout is performed by applying a current ramp to the junction and recording the value for which there is a voltage response, depending on the qubit state. This preliminary work indicates the feasibility and efficiency of the scheme.Comment: 10 pages, 5 figure

Swamp Works- Multiple Projects

My Surface Systems internship over the summer 2013 session covered a broad range of projects that utilized multiple fields of engineering and technology. This internship included a project to create a command center for a 120 ton regolith bin, for the design and assembly of a blast shield to add further protection for the Surface Systems engineers, for the design and assembly of a portable four monitor hyper wall strip that could extend as large as needed, research and programming a nano drill that could be utilized on a next generation robot or rover, and social media tasks including the making of videos, posting to social networking websites and creation of a new outreach program to help spread the word about the Swamp Works laboratory

Preliminary Inter-comparison of AIS Data and Optimal Ship Tracks

Optimal ship tracks computed via the VISIR model are compared to tracks recorded by the Automatic Identification System (AIS). The evaluation regards 43 tracks in the Southern Atlantic Ocean, sailed during 2016-2017 by different bulk carriers. In this exercise, VISIR is fed by wave analysis fields from the Copernicus Marine Environment Monitoring Service (CMEMS). In order to reproduce vessel speed loss in waves, a new methodology is developed, where kinematic information from AIS is fusioned with wave information from CMEMS. Resulting VISIR tracks are analyzed along with AIS tracks in terms of their topological features and duration. The tracks exhibit quite diverse topological shapes, including orthodromic, loxodromic, and other paths with complex and dynamic diversions. The distribution of AIS to VISIR track durations is analyzed in terms of several parameters, such as the AIS to VISIR track length and their Fréchet distance. Model features of VISIR affecting the results are discussed and future developments suggested by the results are outlined

Ternatin and improved synthetic variants kill cancer cells by targeting the elongation factor-1A ternary complex.

Cyclic peptide natural products have evolved to exploit diverse protein targets, many of which control essential cellular processes. Inspired by a series of cyclic peptides with partially elucidated structures, we designed synthetic variants of ternatin, a cytotoxic and anti-adipogenic natural product whose molecular mode of action was unknown. The new ternatin variants are cytotoxic toward cancer cells, with up to 500-fold greater potency than ternatin itself. Using a ternatin photo-affinity probe, we identify the translation elongation factor-1A ternary complex (eEF1A·GTP·aminoacyl-tRNA) as a specific target and demonstrate competitive binding by the unrelated natural products, didemnin and cytotrienin. Mutations in domain III of eEF1A prevent ternatin binding and confer resistance to its cytotoxic effects, implicating the adjacent hydrophobic surface as a functional hot spot for eEF1A modulation. We conclude that the eukaryotic elongation factor-1A and its ternary complex with GTP and aminoacyl-tRNA are common targets for the evolution of cytotoxic natural products

OPA1-related auditory neuropathy: site of lesion and outcome of cochlear implantation.

Hearing impairment is the second most prevalent clinical feature after optic atrophy in Dominant Optic Atrophy associated with mutations in the OPA1 gene. In this study we characterized the hearing dysfunction in OPA1-linked disorders and provided effective rehabilitative options to improve speech perception. We studied two groups of OPA1 subjects, one comprising 11 patients (7 males; age range 13-79 years) carrying OPA1 mutations inducing haploinsufficiency, the other, 10 subjects (3 males; age range 5-58 years) carrying OPA1 missense mutations. Both groups underwent audiometric assessment with pure tone and speech perception evaluation, and otoacoustic emissions and auditory brainstem response recording. Cochlear potentials were recorded through transtympanic electrocochleography from the group of patients harboring OPA1 missense mutations and were compared to recordings obtained from 20 normally-hearing controls and from 19 subjects with cochlear hearing loss. Eight patients carrying OPA1 missense mutations underwent cochlear implantation. Speech perception measures and electrically-evoked auditory nerve and brainstem responses were obtained after one year of cochlear implant use. Nine out of 11 patients carrying OPA1 mutations inducing haploinsufficiency had normal hearing function. In contrast, all but one subject harboring OPA1 missense mutations displayed impaired speech perception, abnormal brainstem responses and presence of otoacoustic emissions consistent with auditory neuropathy. In electrocochleography recordings, cochlear microphonic had enhanced amplitudes while summating potential showed normal latency and peak amplitude consistent with preservation of both outer and inner hair cell activities. After cancelling the cochlear microphonic, the synchronized neural response seen in both normally-hearing controls and subjects with cochlear hearing loss was replaced by a prolonged, low-amplitude negative potential that decreased in both amplitude and duration during rapid stimulation consistent with neural generation. The use of cochlear implant improved speech perception in all but one patient. Brainstem potentials were recorded in response to electrical stimulation in five subjects out of six, whereas no compound action potential was evoked from the auditory nerve through the cochlear implant. These findings indicate that underlying the hearing impairment in patients carrying OPA1 missense mutations is a disordered synchrony in auditory nerve fiber activity resulting from neural degeneration affecting the terminal dendrites. Cochlear implantation improves speech perception and synchronous activation of auditory pathways by by-passing the site of lesion

Inhibitory loop robustly induces anticipated synchronization in neuronal microcircuits

We investigate the synchronization properties between two excitatory coupled neurons in the presence of an inhibitory loop mediated by an interneuron. Dynamic inhibition together with noise independently applied to each neuron provide phase diversity in the dynamics of the neuronal motif. We show that the interplay between the coupling strengths and the external noise controls the phase relations between the neurons in a counterintuitive way. For a master-slave configuration (unidirectional coupling) we find that the slave can anticipate the master, on average, if the slave is subject to the inhibitory feedback. In this nonusual regime, called anticipated synchronization (AS), the phase of the postsynaptic neuron is advanced with respect to that of the presynaptic neuron. We also show that the AS regime survives even in the presence of unbalanced bidirectional excitatory coupling. Moreover, for the symmetric mutually coupled situation, the neuron that is subject to the inhibitory loop leads in phase.We gratefully acknowledge CNPq Grants No. 480053/2013-8 and No. 310712/2014-9, FACEPE Grant No. APQ-0826-1.05/15, and CAPES Grant No. PVE 88881.068077/2014-01 for financial support. This article was produced as part of the activities of FAPESP Research, Innovation and Dissemination Center for Neuromathematics (Grant No. 2013/07699-0, S.Paulo Research Foundation) and it was partially funded by the Ministerio de Economía y Competitividad, España, through Project No. TEC2016-80063.Peer reviewe