A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria.

To broadly explore mitochondrial structure and function as well as the communication of mitochondria with other cellular pathways, we constructed a quantitative, high-density genetic interaction map (the MITO-MAP) in Saccharomyces cerevisiae. The MITO-MAP provides a comprehensive view of mitochondrial function including insights into the activity of uncharacterized mitochondrial proteins and the functional connection between mitochondria and the ER. The MITO-MAP also reveals a large inner membrane-associated complex, which we term MitOS for mitochondrial organizing structure, comprised of Fcj1/Mitofilin, a conserved inner membrane protein, and five additional components. MitOS physically and functionally interacts with both outer and inner membrane components and localizes to extended structures that wrap around the inner membrane. We show that MitOS acts in concert with ATP synthase dimers to organize the inner membrane and promote normal mitochondrial morphology. We propose that MitOS acts as a conserved mitochondrial skeletal structure that differentiates regions of the inner membrane to establish the normal internal architecture of mitochondria

Effect of Strength on Velocity and Power During Back Squat Exercise in Resistance-Trained Men and Women

The purpose was to examine load-velocity and load-power relationships of back squat in resistance-trained men (n = 20, 21.3 ± 1.4 years, 183.0 ± 8.0 cm, 82.6 ± 8.0 kg, 11.5 ± 5.0% total body fat) and women (n = 18; 20.0 ± 1.0 years; 166.5 ± 6.9 cm; 63.9 ± 7.9 kg, 20.3 ± 5.0% body fat). Body composition testing was performed followed by determination of back squat 1 repetition maximum (1RM). After at least 72 hours of recovery, subjects returned to the laboratory and completed 2 repetitions at each of 7 separate loads (30, 40, 50, 60, 70, 80, and 90% 1RM) in a random order. During each repetition, peak and average velocity and power were quantified using a commercially available linear position transducer. Men produced higher absolute peak and average power and velocity at all loads. When power output was normalized for body mass, significant differences remained. However, when normalizing for strength, no significant differences were observed between sexes. Furthermore, when subjects were subdivided into strong and weak groups, those above the median 1RM produced higher peak power, but only at loads greater than 60% 1RM. It was concluded that differences between men and women may be a result of strength rather than biological sex. Furthermore, training for maximal strength may be an appropriate method to augment maximal power output in those athletes who exhibit low levels of strength

Heterogeneity of Plaque Structural Stress Is Increased in Plaques Leading to MACE: Insights From the PROSPECT Study.

OBJECTIVES: This study sought to determine if plaque structural stress (PSS) and other plaque stress parameters are increased in plaques that cause future major adverse cardiovascular event(s) (MACE) and if incorporating these parameters improves predictive capability of intravascular ultrasonography (IVUS). BACKGROUND: Less than 10% of coronary plaques identified as high-risk by intravascular imaging result in subsequent MACE. Thus, more specific measurements of plaque vulnerability are required for effective risk stratification. METHODS: Propensity score matching in the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study plaque cohort resulted in 35 nonculprit lesions (NCL) associated with future MACE and 66 matched NCL that remained clinically silent. PSS was calculated by finite element analysis as the mechanical loading within the plaque structure in the periluminal region. RESULTS: PSS was increased in the minimal luminal area (MLA) regions of NCL MACE versus no MACE plaques for all plaques (PSS: 112.1 ± 5.5 kPa vs. 90.4 ± 3.3 kPa, respectively; p = 0.001) and virtual histology thin-cap fibroatheromas (VH-TCFAs) (PSS: 119.2 ± 6.6 kPa vs. 95.8 ± 5.0 kPa, respectively; p = 0.005). However, PSS was heterogeneous over short segments, and PSS heterogeneity index (HI) was markedly greater in NCL MACE than in no-MACE VH-TCFAs (HI: 0.43 ± 0.05 vs. 0.29 ± 0.03, respectively; p = 0.01). Inclusion of PSS in plaque assessment improved the identification of NCLs that led to MACE, including in VH-TCFAs (p = 0.03) and plaques with MLA ≤4 mm2 (p = 0.03). Incorporation of an HI further improved the ability of PSS to identify MACE NCLs in a variety of plaque subtypes including VH-TCFA (p = 0.001) and plaques with MLA ≤4 mm2 (p = 0.002). CONCLUSIONS: PSS and variations in PSS are increased in the peri-MLA regions of plaques that lead to MACE. Moreover, longitudinal heterogeneity in PSS is markedly increased in MACE plaques, especially VH-TCFAs, potentially predisposing to plaque rupture. Incorporation of PSS and heterogeneity in PSS may improve the ability of IVUS to predict MACE.BH

On the combination of omics data for prediction of binary outcomes

Enrichment of predictive models with new biomolecular markers is an important task in high-dimensional omic applications. Increasingly, clinical studies include several sets of such omics markers available for each patient, measuring different levels of biological variation. As a result, one of the main challenges in predictive research is the integration of different sources of omic biomarkers for the prediction of health traits. We review several approaches for the combination of omic markers in the context of binary outcome prediction, all based on double cross-validation and regularized regression models. We evaluate their performance in terms of calibration and discrimination and we compare their performance with respect to single-omic source predictions. We illustrate the methods through the analysis of two real datasets. On the one hand, we consider the combination of two fractions of proteomic mass spectrometry for the calibration of a diagnostic rule for the detection of early-stage breast cancer. On the other hand, we consider transcriptomics and metabolomics as predictors of obesity using data from the Dietary, Lifestyle, and Genetic determinants of Obesity and Metabolic syndrome (DILGOM) study, a population-based cohort, from Finland

The Antarctic ozone hole during 2015 and 2016

We reviewed the 2015 and 2016 Antarctic ozone holes, making use of a variety of ground-based and spacebased measurements of ozone and ultraviolet radiation, supplemented by meteorological reanalyses. The ozone hole of 2015 was one of the most severe on record with respect to maximum area and integrated deficit and was notably longlasting, with many values above previous extremes in October, November and December. In contrast, all assessed metrics for the 2016 ozone hole were at or below their median values for the 37 ozone holes since 1979 for which adequate satellite observations exist. The 2015 ozone hole was influenced both by very cold conditions and enhanced ozone depletion caused by stratospheric aerosol resulting from the April 2015 volcanic eruption of Calbuco (Chile)

The Antarctic ozone hole during 2014

We review the 2014 Antarctic ozone hole, making use of a variety of ground-based and space-based measurements of ozone and ultra-violet radiation, supplemented by meteorological reanalyses. Although the polar vortex was relatively stable in 2014 and persisted some weeks longer into November than was the case in 2012 or 2013, the vortex temperature was close to the long-term mean in September and October with modest warming events occurring in both months, preventing severe depletion from taking place. Of the seven metrics reported here, all were close to their respective median values of the 1979–2014 record, being ranked between 16th and 21st of the 35 years for which adequate satellite observations exist

Meson Decay Constants from Isospin Mass Splittings in the Quark Model

Decay constants of $D$ and $B$ mesons are estimated within the framework of a heavy-quark approach using measured isospin mass splittings in the $D$, $D^*$, and $B$ states to isolate the electromagnetic hyperfine interaction between quarks. The values $f_D = (262 \pm 29)$ MeV and $f_B = (160 \pm 17)$ MeV are obtained. Only experimental errors are given; possible theoretical ambiguities, and suggestions for reducing them, are noted.Comment: 7 pages, LaTeX, EFI-92-3