The carboxyl-terminal two-thirds of the ADP/ATP carrier polypeptide contains sufficient information to direct translocation into mitochondria

The precursor of the mitochondrial inner membrane protein ADP/ATP carrier is cytoplasmically synthesized without an amino-terminal peptide extension. We constructed a truncated precursor lacking the 103 amino acids from the amino terminus (about a third of the protein). Import of the truncated precursor into mitochondria showed the import characteristics of the authentic precursor, including nucleoside triphosphate dependence, requirement for a protease-sensitive component on the mitochondrial surface, two-step specific binding to the outer membrane, and membrane potential-dependent translocation into the inner membrane. We conclude that, in contrast to all other mitochondrial precursor proteins studied so far, domains of the ADP/ATP carrier distant from the amino terminus can carry specific targeting information for transport into mitochondria

Structural role of the tyrosine residues of cytochrome c

The tertiary structures of horse, tuna, Neurospora crassa, horse [Hse65,Leu67]- and horse [Hse65,Leu74]-cytochromes c were studied with high-resolution 1H n.m.r. spectroscopy. The amino acid sequences of these proteins differ at position 46, which is occupied by phenylalanine in the horse proteins but by tyrosine in the remaining two, and at positions 67, 74 and 97, which are all occupied by tyrosine residues in horse and tuna cytochrome c but in the other proteins are substituted by phenylalanine or leucine, though there is only one such substitution per protein. The various aromatic-amino-acid substitutions do not seriously affect the protein structure

Underflight calibration of SOHO/CDS and Hinode/EIS with EUNIS-07

Flights of Goddard Space Flight Center's Extreme-Ultraviolet Normal-Incidence Spectrograph (EUNIS) sounding rocket in 2006 and 2007 provided updated radiometric calibrations for SOHO/CDS and Hinode/EIS. EUNIS carried two independent imaging spectrographs covering wavebands of 300-370 A in first order and 170-205 A in second order. After each flight, end-to-end radiometric calibrations of the rocket payload were carried out in the same facility used for pre-launch calibrations of CDS and EIS. During the 2007 flight, EUNIS, SOHO CDS and Hinode EIS observed the same solar locations, allowing the EUNIS calibrations to be directly applied to both CDS and EIS. The measured CDS NIS 1 line intensities calibrated with the standard (version 4) responsivities with the standard long-term corrections are found to be too low by a factor of 1.5 due to the decrease in responsivity. The EIS calibration update is performed in two ways. One is using the direct calibration transfer of the calibrated EUNIS-07 short wavelength (SW) channel. The other is using the insensitive line pairs, in which one member was observed by EUNIS-07 long wavelength (LW) channel and the other by EIS in either LW or SW waveband. Measurements from both methods are in good agreement, and confirm (within the measurement uncertainties) the EIS responsivity measured directly before the instrument's launch. The measurements also suggest that the EIS responsivity decreased by a factor of about 1.2 after the first year of operation. The shape of the EIS SW response curve obtained by EUNIS-07 is consistent with the one measured in laboratory prior to launch. The absolute value of the quiet-Sun He II 304 A intensity measured by EUNIS-07 is consistent with the radiance measured by CDS NIS in quiet regions near the disk center and the solar minimum irradiance obtained by CDS NIS and SDO/EVE recently.Comment: 16 pages, 14 figures, 5 tables, accepted by ApJ Supplement (Sep. 2011

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY challenge

Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Extreme Ultra-Violet Spectroscopy of the Lower Solar Atmosphere During Solar Flares

The extreme ultraviolet portion of the solar spectrum contains a wealth of diagnostic tools for probing the lower solar atmosphere in response to an injection of energy, particularly during the impulsive phase of solar flares. These include temperature and density sensitive line ratios, Doppler shifted emission lines and nonthermal broadening, abundance measurements, differential emission measure profiles, and continuum temperatures and energetics, among others. In this paper I shall review some of the advances made in recent years using these techniques, focusing primarily on studies that have utilized data from Hinode/EIS and SDO/EVE, while also providing some historical background and a summary of future spectroscopic instrumentation.Comment: 34 pages, 8 figures. Submitted to Solar Physics as part of the Topical Issue on Solar and Stellar Flare

Tim50’s presequence receptor domain is essential for signal driven transport across the TIM23 complex

The Tim50 subunit of the mitochondrial TIM23 complex contains a presequence-binding domain that is essential for viability and precursor transport across the inner membrane

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Uniform nomenclature for the mitochondrial contact site and cristae organizing system

The mitochondrial inner membrane contains a large protein complex that functions in inner membrane organization and formation of membrane contact sites. The complex was variably named the mitochondrial contact site complex, mitochondrial inner membrane organizing system, mitochondrial organizing structure, or Mitofilin/Fcj1 complex. To facilitate future studies, we propose to unify the nomenclature and term the complex "mitochondrial contact site and cristae organizing system" and its subunits Mic10 to Mic60