Effects of dynein on microtubule mechanics and centrosome positioning.

To determine forces on intracellular microtubules, we measured shape changes of individual microtubules following laser severing in bovine capillary endothelial cells. Surprisingly, regions near newly created minus ends increased in curvature following severing, whereas regions near new microtubule plus ends depolymerized without any observable change in shape. With dynein inhibited, regions near severed minus ends straightened rapidly following severing.

Economic analysis of nutrition interventions for chronic disease prevention: methods, research, and policy.

Increased interest in the potential societal benefit of incorporating health economics as a part of clinical translational science, particularly nutrition interventions, led the Office of Dietary Supplements at the National Institutes of Health to sponsor a conference to address key questions about the economic analysis of nutrition interventions to enhance communication among health economic methodologists, researchers, reimbursement policy makers, and regulators. Issues discussed included the state of the science, such as what health economic methods are currently used to judge the burden of illness, interventions, or healthcare policies, and what new research methodologies are available or needed to address knowledge and methodological gaps or barriers. Research applications included existing evidence-based health economic research activities in nutrition that are ongoing or planned at federal agencies.

Retinal disease course in Usher syndrome 1B due to MYO7A mutations.

PURPOSE. To determine the disease course in Usher syndrome type IB (USH1B) caused by myosin 7A (MYO7A) gene mutations. METHODS.

Anterior shoulder instability: a review of pathoanatomy, diagnosis and treatment.

The glenohumeral joint is inherently predisposed to instability by its bony architecture. The incidence of traumatic shoulder instability is 1.7% in the general population.

Content disputes in Wikipedia reflect geopolitical instability.

Indicators that rank countries according socioeconomic measurements are important tools for regional development and political reform. Those currently in widespread use are sometimes criticized for a lack of reproducibility or the inability to compare values over time, necessitating simple, fast and systematic measures. Here, we applied the 'guilt by association' principle often used in biological networks to the information network within the online encyclopedia Wikipedia to create an indicator quantifying the degree to which pages linked to a country are disputed by contributors.

Yellow maize with high β-carotene is an effective source of vitamin A in healthy Zimbabwean men.

Background: The bioconversion efficiency of yellow maize β-carotene to retinol in humans is unknown.

Objective: The objective of this study was to determine the vitamin A value of yellow maize β-carotene in humans.

Design: High β-carotene-containing yellow maize was grown in a hydroponic medium with 23 atom% (2)H(2)O during grain development.

Combined α-tocopherol and ascorbic acid protects against smoke-induced lung squamous metaplasia in ferrets.

Many epidemiological studies show the benefit of fruits and vegetables on reducing risk of lung cancer, the leading cause of cancer death in the United States. Previously, we demonstrated that cigarette smoke exposure (SM)-induced lung lesions in ferrets were prevented by a combination of low dose of β-carotene, α-tocopherol (AT), and ascorbic acid (AA). However, the role of a combination of AT and AA alone in the protective effect on lung carcinogenesis remains to be examined.

Combinations of protein-chemical complex structures reveal new targets for established drugs.

Biological networks are powerful tools for predicting undocumented relationships between molecules. The underlying principle is that existing interactions between molecules can be used to predict new interactions. Here we use this principle to suggest new protein-chemical interactions via the network derived from three-dimensional structures.

The three-dimensional molecular structure of the desmosomal plaque.

The cytoplasmic surface of intercellular junctions is a complex network of molecular interactions that link the extracellular region of the desmosomal cadherins with the cytoskeletal intermediate filaments. Although 3D structures of the major plaque components are known, the overall architecture remains unknown. We used cryoelectron tomography of vitreous sections from human epidermis to record 3D images of desmosomes in vivo and in situ at molecular resolution.

β-Cryptoxanthin supplementation prevents cigarette smoke-induced lung inflammation, oxidative damage, and squamous metaplasia in ferrets.

In epidemiologic studies, high intake of β-cryptoxanthin has been associated with a decreased risk of lung cancer, particularly among current smokers. However, data are not available from well-controlled animal studies to examine the effects of β-cryptoxanthin on cigarette smoke-induced lung lesions, and the biological mechanisms by which β-cryptoxanthin might affect lung carcinogenesis. We evaluated the effects of β-cryptoxanthin supplementation on cigarette smoke-induced squamous metaplasia, inflammation, and changes in protein levels of proinflammatory cytokine [tumor necrosis factor alpha (TNFα)] and transcription factors [nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1)], as well as on smoke-induced oxidative DNA damage [8-hydroxy-2'-deoxyguanosine (8-OHdG)] in the lung tissue of ferrets.

Sarcomere length fluctuations and flow in capillary endothelial cells.

Tensile force within non-muscle tissue cells is generated in actomyosin stress fibers, which are composed of contractile units called sarcomeres. The number of sarcomeres and sarcomere lengths dynamically change in the cell but the mechanisms by which these processes occur are not understood. Using live cell imaging of labeled sarcomeres, we show that sarcomere lengths continually fluctuate, with a fluctuation relaxation time of about 20 min.

A systematic screen for protein-lipid interactions in Saccharomyces cerevisiae.

Protein-metabolite networks are central to biological systems, but are incompletely understood. Here, we report a screen to catalog protein-lipid interactions in yeast. We used arrays of 56 metabolites to measure lipid-binding fingerprints of 172 proteins, including 91 with predicted lipid-binding domains.

Enzymatic formation of apo-carotenoids from the xanthophyll carotenoids lutein, zeaxanthin and β-cryptoxanthin by ferret carotene-9',10'-monooxygenase.

Xanthophyll carotenoids, such as lutein, zeaxanthin and β-cryptoxanthin, may provide potential health benefits against chronic and degenerative diseases. Investigating pathways of xanthophyll metabolism are important to understanding their biological functions. Carotene-15,15'-monooxygenase (CMO1) has been shown to be involved in vitamin A formation, while recent studies suggest that carotene-9',10'-monooxygenase (CMO2) may have a broader substrate specificity than previously recognized.

The triple PCL sign: bucket handle tears of both medial and lateral menisci in a chronically ACL-deficient knee.

Bucket handle tears of both menisci in the setting of acute or chronic anterior cruciate ligament (ACL) tears of the same knee have rarely been reported in the literature. This article presents a case of a bucket handle tear affecting both the medial and lateral menisci in a patient with chronic ACL rupture. Both bucket handle tears were displaced and locked in the intercondylar notch.

Domain recombination: a workhorse for evolutionary innovation.

Although the combination of modular domains within proteins has been proposed as a determining feature of evolutionary innovation and flexibility, direct evidence for this mechanism of evolution has been sketchy. Two papers, one creating new domain combinations in the yeast mating pathway and another involving a comprehensive analysis of protein function and domain architecture across major organisms, have provided firm evidence that the recombining of domains can lead to evolutionary innovation. The results will guide future studies in synthetic and evolutionary biology.

Does an enhanced surface finish improve acetabular fixation in revision total hip arthroplasty?

High-porosity "cancellous metal" coatings have been introduced to increase the fixation and biologic incorporation of acetabular cups. The strength of initial fixation provided by a cancellous metal cups vs conventional alternatives in the deficient revision acetabulum was investigated. Cancellous, plasma-sprayed, and beaded cups (n = 9) were implanted under controlled conditions into a validated model of the revision acetabulum.

An automated stochastic approach to the identification of the protein specificity determinants and functional subfamilies.

Background: Recent progress in sequencing and 3 D structure determination techniques stimulated development of approaches aimed at more precise annotation of proteins, that is, prediction of exact specificity to a ligand or, more broadly, to a binding partner of any kind.

Results: We present a method, SDPclust, for identification of protein functional subfamilies coupled with prediction of specificity-determining positions (SDPs). SDPclust predicts specificity in a phylogeny-independent stochastic manner, which allows for the correct identification of the specificity for proteins that are separated on a phylogenetic tree, but still bind the same ligand.

WD40 proteins propel cellular networks.

Recent findings indicate that WD40 domains play central roles in biological processes by acting as hubs in cellular networks; however, they have been studied less intensely than other common domains, such as the kinase, PDZ or SH3 domains. As suggested by various interactome studies, they are among the most promiscuous interactors. Structural studies suggest that this property stems from their ability, as scaffolds, to interact with diverse proteins, peptides or nucleic acids using multiple surfaces or modes of interaction.

Modular architecture of nucleotide-binding pockets.

Recently, modularity has emerged as a general attribute of complex biological systems. This is probably because modular systems lend themselves readily to optimization via random mutation followed by natural selection. Although they are not traditionally considered to evolve by this process, biological ligands are also modular, being composed of recurring chemical fragments, and moreover they exhibit similarities reminiscent of mutations (e.

Acute inhibition of fatty acid import inhibits GLUT4 transcription in adipose tissue, but not skeletal or cardiac muscle tissue, partly through liver X receptor (LXR) signaling.

Objective: Insulin-mediated glucose uptake is highly sensitive to the levels of the facilitative GLUT protein GLUT4. Transcription of the GLUT4 gene is repressed in states of insulin deficiency and insulin resistance and can be induced by states of enhanced energy output, such as exercise. The cellular signals that regulate GLUT4 transcription are not well understood.

Arsenic microdistribution and speciation in toenail clippings of children living in a historic gold mining area.

Arsenic is naturally associated with gold mineralisation and elevated in some soils and mine waste around historical gold mining activity in Victoria, Australia. To explore uptake, arsenic concentrations in children's toenail clippings and household soils were measured, and the microdistribution and speciation of arsenic in situ in toenail clipping thin sections investigated using synchrotron-based X-ray microprobe techniques. The ability to differentiate exogenous arsenic was explored by investigating surface contamination on cleaned clippings using depth profiling, and direct diffusion of arsenic into incubated clippings.