171 research outputs found

    Are there really shortcuts? estimating seat belt use with self-report measures

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    We examined the utility of estimating rates of automobile seat belt use with selfreport measures. Self-report measures overestimate belt use rates compared to observational surveys of the same population. Laws mandating seat belt use did not substantially affect the degree to which self-reports are upwardly biased. We found self-report measures overestimate observed belt use by 8.9 to 19.4 percentage points or by a factor of 1.2 to 2. Our best estimate is that self-reported seat belt use rates be discounted by 12 percentage points to estimate actual belt use rates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27668/1/0000050.pd

    Direct measurement of the mechanical work during translocation by the ribosome.

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    A detailed understanding of tRNA/mRNA translocation requires measurement of the forces generated by the ribosome during this movement. Such measurements have so far remained elusive and, thus, little is known about the relation between force and translocation and how this reflects on its mechanism and regulation. Here, we address these questions using optical tweezers to follow translation by individual ribosomes along single mRNA molecules, against an applied force. We find that translocation rates depend exponentially on the force, with a characteristic distance close to the one-codon step, ruling out the existence of sub-steps and showing that the ribosome likely functions as a Brownian ratchet. We show that the ribosome generates ∟13 pN of force, barely sufficient to unwind the most stable structures in mRNAs, thus providing a basis for their regulatory role. Our assay opens the way to characterizing the ribosomes full mechano-chemical cycle

    Molecular Adhesion between Cartilage Extracellular Matrix Macromolecules

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    In this study, we investigated the molecular adhesion between the major constituents of cartilage extracellular matrix, namely, the highly negatively charged proteoglycan aggrecan and the type II/IX/XI fibrillar collagen network, in simulated physiological conditions. Colloidal force spectroscopy was applied to measure the maximum adhesion force and total adhesion energy between aggrecan end-attached spherical tips (end radius R ≈ 2.5 μm) and trypsin-treated cartilage disks with undamaged collagen networks. Studies were carried out in various aqueous solutions to reveal the physical factors that govern aggrecan–collagen adhesion. Increasing both ionic strength and [Ca2+] significantly increased adhesion, highlighting the importance of electrostatic repulsion and Ca2+-mediated ion bridging effects. In addition, we probed how partial enzymatic degradation of the collagen network, which simulates osteoarthritic conditions, affects the aggrecan–collagen interactions. Interestingly, we found a significant increase in aggrecan–collagen adhesion even when there were no detectable changes at the macro- or microscales. It is hypothesized that the aggrecan–collagen adhesion, together with aggrecan–aggrecan self-adhesion, works synergistically to determine the local molecular deformability and energy dissipation of the cartilage matrix, in turn, affecting its macroscopic tissue properties.National Science Foundation (U.S.) (Grant CMMI-0758651)National Institutes of Health (U.S.) (Grant AR60331)United States. Dept. of Defense (National Defense Science and Engineering Graduate Fellowship (Grant N00244-09-1-0064))Shriners of North AmericaDrexel University (Faculty Start-up Grant

    Reductions in police-reported injuries associated with Michigan's safety belt law

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    This research measured the effects of Michigan's compulsory safety belt use law on traffic crashes and injuries of various severities. Using time-series methods, the authors analyzed monthly frequencies of crash-induced injuries and fatalities from January 1978 through December 1987. Exposure to risk of occupant injury was controlled statistically by including aggregate frequency of crashes as a covariate in time-series models. Effects of economic conditions on traffic crashes were controlled by including an index of unemployment as a covariate. The following statistically significant effects were associated with the safety belt law: (a) In crashes with minor vehicle damage, there was a 14.6% reduction in B-level injuries, an 11.0% reduction in C-level injuries, and a 13.0% reduction in aggregate (KABC) injuries; (b) in crashes with moderate vehicle damage, there was a 16.8% reduction in A-level injuries, an 11.6% reduction in B-level injuries, a 10.7% reduction in C-level injuries, and a 3.6% reduction in aggregate (KABC) injuries; (c) in crashes with severe vehicle damage, there was a 6.3% reduction in fatalities, an 11.8% reduction in B-level injuries, a 4.7% reduction in c-level injuries, and a 5.8% reduction in aggregate (KABC) injuries; (d) for all vehicle damage severities, there was a 14.0% reduction in B-level injuries, an 8.3% reduction in C-level injuries, and a 6.4% reduction in injuries to front-seat occupants. Based on these results, Michigan's adult safety belt law has prevented 31,710 injuries from July 1985 through December 1988.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28625/1/0000439.pd

    Lrp4 Mediates Bone Homeostasis and Mechanotransduction through Interaction with Sclerostin In Vivo

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    Wnt signaling plays a key role in regulating bone remodeling. In vitro studies suggest that sclerostin's inhibitory action on Lrp5 is facilitated by the membrane-associated receptor Lrp4. We generated an Lrp4 R1170W knockin mouse model (Lrp4KI), based on a published mutation in patients with high bone mass (HBM). Lrp4KI mice have an HBM phenotype (assessed radiographically), including increased bone strength and formation. Overexpression of a Sost transgene had osteopenic effects in Lrp4-WT but not Lrp4KI mice. Conversely, sclerostin inhibition had blunted osteoanabolic effects in Lrp4KI mice. In a disuse-induced bone wasting model, Lrp4KI mice exhibit significantly less bone loss than wild-type (WT) mice. In summary, mice harboring the Lrp4-R1170W missense mutation recapitulate the human HBM phenotype, are less sensitive to altered sclerostin levels, and are protected from disuse-induced bone loss. Lrp4 is an attractive target for pharmacological targeting aimed at increasing bone mass and preventing bone loss due to disuse

    Predictors of fetal anemia and cord blood malaria parasitemia among newborns of HIV-positive mothers

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    Background: Malaria and HIV infections during pregnancy can individually or jointly unleash or confound pregnancy outcomes. Two of the probable outcomes are fetal anemia and cord blood malaria parasitemia. We determined clinical and demographic factors associated with fetal anemia and cord blood malaria parasitemia in newborns of HIV-positive women from two districts in Ghana. Results: We enrolled 1,154 antenatal attendees (443 HIV-positive and 711 HIV-negative) of which 66% were prospectively followed up at delivery. Maternal malaria parasitemia, and anemia rates among HIV+ participants at enrolment were 20.3% and 78.7% respectively, and 12.8% and 51.6% among HIV- participants. Multivariate linear and logistic regression models were used to study associations. Prevalence of fetal anemia (cord hemoglobin level < 12.5 g/dL) and cord parasitemia (presence of P. falciparum in cord blood at delivery) were 57.3% and 24.4% respectively. Factors found to be associated with fetal anemia were maternal malaria parasitemia and maternal anemia. Infant cord hemoglobin status at delivery was positively and significantly associated with maternal hemoglobin and gestational age whilst female gender of infant was negatively associated with cord hemoglobin status. Maternal malaria parasitemia status at recruitment and female gender of infant were positively associated with infant cord malaria parasitemia status. Conclusions: Our data show that newborns of women infected with HIV and/or malaria are at increased risk of anemia and also cord blood malaria parasitemia. Prevention of malaria infection during pregnancy may reduce the incidence of both adverse perinatal outcomes. Š 2013 Laar et al.; licensee BioMed Central Ltd

    Expression of a Degradation‐Resistant β‐Catenin Mutant in Osteocytes Protects the Skeleton From Mechanodeprivation‐Induced Bone Wasting

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    Mechanical stimulation is a key regulator of bone mass, maintenance, and turnover. Wnt signaling is a key regulator of mechanotransduction in bone, but the role of β‐catenin—an intracellular signaling node in the canonical Wnt pathway—in disuse mechanotransduction is not defined. Using the β‐catenin exon 3 flox (constitutively active [CA]) mouse model, in conjunction with a tamoxifen‐inducible, osteocyte‐selective Cre driver, we evaluated the effects of degradation‐resistant β‐catenin on bone properties during disuse. We hypothesized that if β‐catenin plays an important role in Wnt‐mediated osteoprotection, then artificial stabilization of β‐catenin in osteocytes would protect the limbs from disuse‐induced bone wasting. Two disuse models were tested: tail suspension, which models fluid shift, and botulinum‐toxin (botox)‐induced muscle paralysis, which models loss of muscle force. Tail suspension was associated with a significant loss of tibial bone mass and density, reduced architectural properties, and decreased bone formation indices in uninduced (control) mice, as assessed by dual‐energy X‐ray absorptiometry (DXA), micro‐computed tomography (µCT), and histomorphometry. Activation of the βcatCA allele in tail‐suspended mice resulted in little to no change in those properties; ie, these mice were protected from bone loss. Similar protective effects were observed among botox‐treated mice when the βcatCA was activated. RNAseq analysis of altered gene regulation in tail‐suspended mice yielded 35 genes, including Wnt11, Gli1, Nell1, Gdf5, and Pgf, which were significantly differentially regulated between tail‐suspended β‐catenin stabilized mice and tail‐suspended nonstabilized mice. Our findings indicate that selectively targeting/blocking of β‐catenin degradation in bone cells could have therapeutic implications in mechanically induced bone disease
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