Eccentric exercise slows in vivo microvascular reactivity during brief contractions in human skeletal muscle

Unaccustomed exercise involving eccentric contractions results in muscle soreness and an overall decline in muscle function, however, little is known about the effects of eccentric exercise on microvascular reactivity in human skeletal muscle. Fourteen healthy men and women performed eccentric contractions of the dorsiflexor muscles in one leg, while the contralateral leg served as a control. At baseline, and 24 and 48 h after eccentric exercise, the following were acquired bilaterally in the tibialis anterior muscle: 1) transverse relaxation time (T2)-weighted magnetic resonance images to determine muscle cross-sectional area (mCSA) and T2; 2) blood oxygen level-dependent (BOLD) images during and following brief, maximal voluntary contractions (MVC) to monitor the hyperemic responses with participants positioned supine in a 3T magnet; 3) muscle strength; and 4) pain pressure threshold. Compared with the control leg, eccentric exercise resulted in soreness, decline in strength (∼20%), increased mCSA (∼7%), and prolonged T2 (∼7%) at 24 and 48 h ( P &lt; 0.05). The BOLD response to a brief MVC was altered 24 and 48 h after eccentric exercise, such that time-to-peak (∼35%, P &lt; 0.05) and time-to-half-recovery (∼23%, P &lt; 0.05) were prolonged. The altered contraction-induced hyperemic response suggests slowed microvascular reactivity and altered matching of O2 delivery to O2 utilization within muscle tissue showing signs of muscle damage. These changes in microvascular regulation after eccentric exercise may impede rapid adjustments in muscle blood flow at exercise onset and during activities involving brief bursts of muscle activation, which may impair O2 delivery and contribute to reduced muscle function after eccentric exercise. </jats:p

Ultra-low-dose non-contrast CT and CT angiography can be used interchangeably for assessing maximal abdominal aortic diameter

BACKGROUND: Routine CT scans may increasingly be used to document normal aortic size and to detect incidental abdominal aortic aneurysms. PURPOSE: To determine whether ultra-low-dose non-contrast CT (ULDNC-CT) can be used instead of the gold standard CT angiography (CTA) for assessment of maximal abdominal aortic diameter. MATERIALS AND METHODS: This retrospective study included 50 patients who underwent CTA and a normal-dose non–contrast CT for suspected renal artery stenosis. ULDNC-CT datasets were generated from the normal-dose non–contrast CT datasets using a simulation technique. Using the centerline technique, radiology consultants (n = 4) and residents (n = 3) determined maximal abdominal aortic diameter. The limits of agreement with the mean (LOAM) was used to access observer agreement. LOAM represents how much a measurement by a single observer may plausibly deviate from the mean of all observers on the specific subject. RESULTS: Observers completed 1400 measurements encompassing repeated CTA and ULDNC-CT measurements. The mean diameter was 24.0 and 25.0 mm for CTA and ULDNC-CT, respectively, yielding a significant but minor mean difference of 1.0 mm. The 95% LOAM reproducibility was similar for CTA and ULDNC-CT (2.3 vs 2.3 mm). In addition, the 95% LOAM and mean diameters were similar for CTA and ULDNC-CT when observers were grouped as consultants and residents. CONCLUSIONS: Ultra-low-dose non–contrast CT exhibited similar accuracy and reproducibility of measurements compared with CTA for assessing maximal abdominal aortic diameter supporting that ULDNC-CT can be used interchangeably with CTA in the lower range of aortic sizes

Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly

The molecular motor dynein concentrates at the kinetochore region of mitotic chromosomes in animals to accelerate spindle microtubule capture and to control spindle checkpoint signaling. In this study, we describe the molecular mechanism used by the Rod-Zw10-Zwilch complex and the adaptor Spindly to recruit dynein to kinetochores in Caenorhabditis elegans embryos and human cells. We show that Rod's N-terminal beta-propeller and the associated Zwilch subunit bind Spindly's C-terminal domain, and we identify a specific Zwilch mutant that abrogates Spindly and dynein recruitment in vivo and Spindly binding to a Rod beta-propeller-Zwilch complex in vitro. Spindly's N-terminal coiled-coil uses distinct motifs to bind dynein light intermediate chain and the pointed-end complex of dynactin. Mutations in these motifs inhibit assembly of a dynein-dynactin-Spindly complex, and a null mutant of the dynactin pointed-end subunit p27 prevents kinetochore recruitment of dynein-dynactin without affecting other mitotic functions of the motor. Conservation of Spindly-like motifs in adaptors involved in intracellular transport suggests a common mechanism for linking dynein to cargo.This work was supported by a European Research Council Starting Grant (Dyneinome 338410) and a European Molecular Biology Organization Installation Grant to R. Gassmann. This work was also supported by funding from the Fundacao para a Ciencia e a Tecnologia to R. Gassmann (IF/01015/2013/CP1157/CT0006), C. Pereira (SFRH_BPD_95648_2013), and D.J. Barbosa (SFRH_BPD_101898_2014). Some C. elegans strains were provided by the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health Office of Research Infrastructure Programs (P40 OD010440)