Search

In the Men's Lifestyle Validation Study (2011–2013), we examined the validity and relative validity of a physical activity questionnaire (PAQ), a Web-based 24-hour recall (Activities Completed Over Time in 24 Hours (ACT24)), and an accelerometer by multiple comparison methods. Over the course of 1 year, 609 men completed 2 PAQs, two 7-day accelerometer measurements, at least 1 doubly labeled water (DLW) physical activity level (PAL) measurement (n  = 100 with repeat measurements), and 4 ACT24s; they also measured their resting pulse rate. A subset (n  = 197) underwent dual-energy x-ray absorptiometry (n  = 99 with repeated measurements). The method of triads was used to estimate correlations with true activity using DLW PAL, accelerometry, and the PAQ or ACT24 as alternative comparison measures. Estimated correlations of the PAQ with true activity were 0.60 (95% confidence interval (95% CI): 0.52, 0.68) for total activity, 0.69 (95% CI: 0.61, 0.79) for moderate-to-vigorous physical activity (MVPA), and 0.76 (95% CI: 0.62, 0.93) for vigorous activity. Corresponding correlations for total activity were 0.53 (95% CI: 0.45, 0.63) for the average of 4 ACT24s and 0.68 (95% CI: 0.61, 0.75) for accelerometry. Total activity and MVPA measured by PAQ, ACT24, and accelerometry were all significantly correlated with body fat percentage and resting pulse rate, which are physiological indicators of physical activity. Using a combination of comparison methods, we found the PAQ and accelerometry to have moderate validity for assessing physical activity, especially MVPA, in epidemiologic studies. [ABSTRACT FROM AUTHOR]

Protein synthesis and semisynthesis offer immense promise for life sciences and have impacted pharmaceutical innovation. The absence of a generally applicable method for traceless peptide conjugation with a flexible choice of junction sites remains a bottleneck for accessing many important synthetic targets, however. Here we introduce the PALME (protein activation and ligation with multiple enzymes) platform designed for sequence-unconstrained synthesis and modification of biomacromolecules. The upstream activating modules accept and process easily accessible synthetic peptides and recombinant proteins, avoiding the challenges associated with preparation and manipulation of activated peptide substrates. Cooperatively, the downstream coupling module provides comprehensive solutions for sequential peptide condensation, cyclization and protein N/C-terminal or internal functionalization. The practical utility of this methodology is demonstrated by synthesizing a series of bioactive targets ranging from pharmaceutical ingredients to synthetically challenging proteins. The modular PALME platform exhibits unprecedentedly broad accessibility for traceless protein synthesis and functionalization, and holds enormous potential to extend the scope of protein chemistry and synthetic biology. [ABSTRACT FROM AUTHOR]

The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and dynamics remains poorly understood. Here by combining imaging and sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to detachment of lamina-associated domains (LADs) from the nuclear periphery accompanied with global chromatin redistribution and decompaction. Consequently, the inter-chromosomal as well as inter-compartment interactions are increased, but the structure of topologically associating domains (TADs) is not affected. Using live-cell genomic loci tracking, we further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nucleoplasm. Taken together, our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance, chromatin compaction, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting their crucial roles in chromatin higher-order structure and chromatin dynamics. [ABSTRACT FROM AUTHOR]

Diffusion-weighted imaging signal contrast can be quantified by apparent diffusion coefficient (ADC) maps, which reflect the diffusion properties of the examined tissue and are helpful for identifying pathology. To determine ADC values of cryptorchid testes in post-pubertal patients and assess performance for characterizing cryptorchid testes. The medical records from 35 patients with unilateral scrotal vacuity were retrospectively reviewed. Data were analyzed in three groups: Group A, normal testes (i.e. the contralateral testes of the patients with cryptorchidism or MTC); Group B, cryptorchid testes; and Group C, malignant transformation of cryptorchidism (MTC) (seminoma). DWI used b-values of 0 and 800 s/mm2. Mean ADC values were compared using the independent samples t-test. The ability of ADC values was assessed using receiver operating characteristic curve analysis. The sensitivity, specificity, and accuracy were calculated. Mean ADC values for normal testes, cryptorchid testes, and MTC were 1.18 ± 0.18×10−3 mm2/s, 1.82 ± 0.40×10−3 mm2/s, and 0.80 ± 0.06×10−3 mm2/s, respectively. There were statistically significant differences in mean ADC values between normal testes and cryptorchid testes or MTC (p < 0.001). The cut-off ADC value for differentiating normal testes from cryptorchid testes was 1.47 × 10−3 mm2/s. The sensitivity, specificity, and accuracy were 88%, 91%, and 90%, respectively. The cut-off ADC value for differentiating normal testes from MTC was 1.22 × 10−3 mm2/s. The sensitivity, specificity, and accuracy were 100%, 31%, and 43%, respectively. ADC values of cryptorchid testes may be used to inform clinical decision-making and also monitor testicular function in patients who retain undescended testicles or post-operatively. Mean ADC values of cryptorchidism and MTC (seminoma) were used to reflect their pathological features. [ABSTRACT FROM AUTHOR]