Solute carriers involved in energy transfer of mitochondria form a homologous protein family

AbstractThe sequences of three mitochondrial carriers involved in energy transfer, the ADP/ATP carrier, phosphate carrier and uncoupling carrier, are analyzed. Similarly to what has been previously reported for the ADP/ATP carrier and the uncoupling protein, now also the phosphate carrier is found to have a tripartite structure comprising three similar repeats of approx. 100 residues each. The three sequences show a fair overall homology with each other. More significant homologies are found by comparing the repeats within and between the carriers in a scheme where the sequences are spliced into repeats, which are arranged for maximum homology by allowing possible insertions or deletions. A striking conservation of critical residues, glycine, proline, of charged and of aromatic residues is found throughout all nine repeats. This is indicative of a similar structural principle in the repeats. Hydropathy profiles of the three proteins and a search for amphipathic α-spans reveal six membrane-spanning segments for each carrier, providing further support for the basic structural identity of the repeats. The proposed folding pattern of the carriers in the membrane is exemplified with the phosphate carrier. A possible tertiary arrangement of the repeats and the membranespanning helices is shown. The emergence of a mitochondrial carrier family by triplication and by divergent evolution from a common gene of about 100 residues is discussed

Mitochondrial porin of Neurospora crassa

cDNA encoding porin of Neurospora crassa, the major protein component of the outer mitochondrial membrane, was isolated and the nucleotide sequence was determined. The deduced protein sequence consists of 283 amino acids (29,979 daltons) and shows sequence homology of around 43% to yeast porin; however, no significant homology to bacterial porins was apparent. According to secondary structure predictions, mitochondrial porin consists mainly of membrane-spanning sided beta-sheets. Porin was efficiently synthesized in vitro from the cDNA; this allowed us to study in detail its import into mitochondria. Thereby, three characteristics of import were defined: (i) import depended on the presence of nucleoside triphosphates; (ii) involvement of a proteinaceous receptor-like component on the surface of the mitochondria was demonstrated; (iii) insertion into the outer membrane was resolved into at least two distinct steps: specific binding to high-affinity sites and subsequent assembly to the mature form

Correlation of Patient Symptoms With Labral and Articular Cartilage Damage in Femoroacetabular Impingement.

BackgroundFemoroacetabular impingement (FAI) can lead to labral and articular cartilage injuries as well as early osteoarthritis of the hip. Currently, the association of patient symptoms with the progression of labral and articular cartilage injuries due to FAI is poorly understood.PurposeTo evaluate the correlation between patient-reported outcome (PRO) scores and cartilage compositional changes seen on quantitative magnetic resonance imaging (MRI) as well as cartilage and labral damage seen during arthroscopic surgery in patients with FAI.Study designCohort study; Level of evidence, 3.MethodsPatients were prospectively enrolled before hip arthroscopic surgery for symptomatic FAI. Patients were included if they had cam-type FAI without radiographic arthritis. All patients completed PRO scores, including the Hip disability and Osteoarthritis Outcome Score (HOOS) and a visual analog scale for pain. MRI with mapping sequences (T1ρ and T2) on both the acetabular and femoral regions was performed before surgery to quantitatively assess the cartilage composition. During arthroscopic surgery, cartilage and labral injury grades were recorded using the Beck classification. Pearson and Spearman correlation coefficients were then obtained to evaluate the association between chondrolabral changes and PRO scores.ResultsA total of 46 patients (46 hips) were included for analysis (mean age, 35.5 years; mean body mass index [BMI], 23.9 kg/m2; 59% male). Increasing BMI was correlated with a more severe acetabular cartilage grade (ρ = 0.37; 95% CI, 0.08-0.65). A greater alpha angle was correlated with an increased labral tear grade (ρ = 0.59; 95% CI, 0.37-0.82) and acetabular cartilage injuries (ρ = 0.61; 95% CI, 0.42-0.80). With respect to PRO scores, increasing femoral cartilage damage in the anterosuperior femoral head region, as measured on quantitative MRI using T1ρ and T2 mapping, correlated with lower (worse) scores on the HOOS Activities of Daily Living (r = 0.35; 95% CI, 0.06-0.64), Symptoms (r = 0.32; 95% CI, 0.06-0.57), and Pain (r = 0.31; 95% CI, 0.06-0.55) subscales. There was no correlation between PRO scores and acetabular cartilage damage or labral tearing found on quantitative MRI or during arthroscopic surgery.ConclusionFemoral cartilage damage, as measured on T1ρ and T2 mapping, appears to have a greater correlation with clinical symptoms than acetabular cartilage damage or labral tears in patients with symptomatic FAI

AI based video analysis of red blood cells in oscillating microchannels

The flow dynamics of red blood cells in vivo in blood capillaries and in vitro in microfluidic channels is rather complex. Cells can obtain differnet shapes such as discoid, parachute, slipper-like shapes and various intermediate states depending on flow conditions and their viscoelastic properties. We use artificial based analysis of shapes in an oscillating mircorchannel to categorize red blood cells (RBCs). Two population are prepared and tested for comparison. Healthy red blood cells and red blood cells treated with diamid to chemically modify their viscoelastic behavior. Based on image analysis and tensor flow decision making we group them into two categories and validate the algorithm on a separate samples achieving a 90% confidence. This methode is a first step to a non-invasive, lable free characterization of diseased red blood cells and will be useful for diagnostic purposes in haematology labs. The methode give quatitative data on the number of affected cells on a single cell level.Comment: 4 pages, 3 figure

Predicting the Effect of Moisture Content on the Flexural Properties of Southern Pine Dimension Lumber

Current procedures for adjusting lumber properties for changes in moisture content are based on trends observed with the mean properties. This study was initiated to develop analytical procedures for adjusting the flexural properties of 2-inch-thick southern pine dimension lumber applicable to all grades and sizes as well as all levels of the cumulative frequency distribution. Equations are derived for adjusting modulus of rupture (MOR), modulus of elasticity (MOE), moment capacity (RS), and flexural stiffness (EI) for changes in moisture content. The best of these equations are significantly more accurate than current procedures for adjusting strength properties (MOR and RS). Because MOE and EI are less affected by changes in moisture content, most of the equations, including the current American Society for Testing and Materials procedure, work well for these properties

Hypomethylation of CYP2E1 and DUSP22 Promoters Associated With Disease Activity and Erosive Disease Among Rheumatoid Arthritis Patients.

OBJECTIVE:Epigenetic modifications have previously been associated with rheumatoid arthritis (RA). In this study, we aimed to determine whether differential DNA methylation in peripheral blood cell subpopulations is associated with any of 4 clinical outcomes among RA patients. METHODS:Peripheral blood samples were obtained from 63 patients in the University of California, San Francisco RA cohort (all satisfied the American College of Rheumatology classification criteria; 57 were seropositive for rheumatoid factor and/or anti-cyclic citrullinated protein). Fluorescence-activated cell sorting was used to separate the cells into 4 immune cell subpopulations (CD14+ monocytes, CD19+ B cells, CD4+ naive T cells, and CD4+ memory T cells) per individual, and 229 epigenome-wide DNA methylation profiles were generated using Illumina HumanMethylation450 BeadChips. Differentially methylated positions and regions associated with the Clinical Disease Activity Index score, erosive disease, RA Articular Damage score, Sharp score, medication at time of blood draw, smoking status, and disease duration were identified using robust regression models and empirical Bayes variance estimators. RESULTS:Differential methylation of CpG sites associated with clinical outcomes was observed in all 4 cell types. Hypomethylated regions in the CYP2E1 and DUSP22 gene promoters were associated with active and erosive disease, respectively. Pathway analyses suggested that the biologic mechanisms underlying each clinical outcome are cell type-specific. Evidence of independent effects on DNA methylation from smoking, medication use, and disease duration were also identified. CONCLUSION:Methylation signatures specific to RA clinical outcomes may have utility as biomarkers or predictors of exposure, disease progression, and disease severity

Recommendations to reduce semi-tractor trailer incidents on Indiana's major roadways

The following analysis summarizes research and recommendations regarding the importance of safety associated with drivers utilizing Indiana’s major roadways, specifically, drivers operating semi-tractor trailers. This 34-page analysis including references, has been compiled over the course of one semester and details extensive themes related to the overall well-being of semi-tractor trailers. Based on extensive research, the following items are recommended to reduce semi-tractor trailer accidents on Indiana’s major roadways: • Install ignition interlocks on semi-tractor trailers • Implementing cable barriers is a cost-effective method to eliminate the risk of cars crossing the centerline while driving • Encourage the Indiana Department of Transportation (INDOT) and its partners to conduct research on where to place cable and steel barriers • Create speed restrictions in non-interstate highways for vehicles with a gross weight greater than 26,000 pounds (lbs.) to improve the safety of rural roadways • Increase the width of these roadways will decrease the possibility of vehicles departing the road • Create situational speed restrictions for the counties listed in the “Other Restrictions Regarding Semi-Tractor Trailers” section • Post speed limit and no passing zone signs in regular intervals with proper placement in rural areas where vehicles may attempt to pass local vehicles, including farm equipment, with limited knowledge of the architecture of the roadways • Consider advocating for rest areas to be implemented on U.S. state roads in addition to interstate roadways • Construct additional rest areas on I-69 near Petersburg, IN and on I-70 in either Vermillion or Gibson County • Expand upon the rest area in White County to resolve issues of capacity and safety The transportation infrastructure continues to be a vital instrument for the Crossroads of America. As a global center of transportation and logistics, the economy of Indiana relies heavily on freight movement (INDOT, n.d.). Freight movement will continue to aid the State of Indiana in competitive advantage compared to other states. By 2040, the expected increase of freight flow is 60 percent (INDOT, n.d.). The work behind this analysis directly supports the expansion of freight mobility while promoting Indiana as a leader in prioritizing driving safety

Rheumatoid Arthritis Naive T Cells Share Hypermethylation Sites With Synoviocytes.

ObjectiveTo determine whether differentially methylated CpGs in synovium-derived fibroblast-like synoviocytes (FLS) of patients with rheumatoid arthritis (RA) were also differentially methylated in RA peripheral blood (PB) samples.MethodsFor this study, 371 genome-wide DNA methylation profiles were measured using Illumina HumanMethylation450 BeadChips in PB samples from 63 patients with RA and 31 unaffected control subjects, specifically in the cell subsets of CD14+ monocytes, CD19+ B cells, CD4+ memory T cells, and CD4+ naive T cells.ResultsOf 5,532 hypermethylated FLS candidate CpGs, 1,056 were hypermethylated in CD4+ naive T cells from RA PB compared to control PB. In analyses of a second set of CpG candidates based on single-nucleotide polymorphisms from a genome-wide association study of RA, 1 significantly hypermethylated CpG in CD4+ memory T cells and 18 significant CpGs (6 hypomethylated, 12 hypermethylated) in CD4+ naive T cells were found. A prediction score based on the hypermethylated FLS candidates had an area under the curve of 0.73 for association with RA case status, which compared favorably to the association of RA with the HLA-DRB1 shared epitope risk allele and with a validated RA genetic risk score.ConclusionFLS-representative DNA methylation signatures derived from the PB may prove to be valuable biomarkers for the risk of RA or for disease status

Heavy-Quark Symmetry and the Electromagnetic Decays of Excited Charmed Strange Mesons

Heavy-hadron chiral perturbation theory (HH$\chi$PT) is applied to the decays of the even-parity charmed strange mesons, D_{s0}(2317) and D_{s1}(2460). Heavy-quark spin symmetry predicts the branching fractions for the three electromagnetic decays of these states to the ground states D_s and D_s^* in terms of a single parameter. The resulting predictions for two of the branching fractions are significantly higher than current upper limits from the CLEO experiment. Leading corrections to the branching ratios from chiral loop diagrams and spin-symmetry violating operators in the HH$\chi$PT Lagrangian can naturally account for this discrepancy. Finally the proposal that the D_{s0}(2317) (D_{s1}(2460)) is a hadronic bound state of a D (D^*) meson and a kaon is considered. Leading order predictions for electromagnetic branching ratios in this molecular scenario are in very poor agreement with existing data.Comment: 25 pages, 3 figure

Characterization of an electron conduit between bacteria and the extracellular environment

A number of species of Gram-negative bacteria can use insoluble minerals of Fe(III) and Mn(IV) as extracellular respiratory electron acceptors. In some species of Shewanella, deca-heme electron transfer proteins lie at the extracellular face of the outer membrane (OM), where they can interact with insoluble substrates. To reduce extracellular substrates, these redox proteins must be charged by the inner membrane/periplasmic electron transfer system. Here, we present a spectro-potentiometric characterization of a trans-OM icosa-heme complex, MtrCAB, and demonstrate its capacity to move electrons across a lipid bilayer after incorporation into proteoliposomes. We also show that a stable MtrAB subcomplex can assemble in the absence of MtrC; an MtrBC subcomplex is not assembled in the absence of MtrA; and MtrA is only associated to the membrane in cells when MtrB is present. We propose a model for the modular organization of the MtrCAB complex in which MtrC is an extracellular element that mediates electron transfer to extracellular substrates and MtrB is a trans-OM spanning ß-barrel protein that serves as a sheath, within which MtrA and MtrC exchange electrons. We have identified the MtrAB module in a range of bacterial phyla, suggesting that it is widely used in electron exchange with the extracellular environment