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141.
An experimental and computational study of screw pullout from cortical bone has been conducted. A novel modification of standard pullout tests providing real time image capture of damage mechanisms during screw pullout was developed. Pullout forces, measured using the novel test rig, have been validated against standard pullout tests. Pullout tests were conducted, considering osteon alignment, to investigate the effect of osteons aligned parallel to the axis of the orthopaedic screw (longitudinal pullout) as well as the effect of osteons aligned perpendicular to the axis of the screw (transverse pullout). Distinctive alternate failure mechanisms, for longitudinally and transversely orientated cortical bone during screw pullout, were uncovered. Vertical crack propagation, parallel to the axis of the screw, was observed for a longitudinal pullout. Horizontal crack propagation, perpendicular to the axis of the screw, was observed for a transverse pullout. Finite element simulation of screw pullout, incorporating material damage and crack propagation, was also performed. Simulations revealed that a homogenous material model for cortical bone predicts vertical crack propagation patterns for both longitudinal and transverse screw pullout. A bi-layered composite model representing cortical bone microstructure was developed. A unique set of material and damage properties was used for both transverse and longitudinal pullout simulations, with only layer orientations being changed. Simulations predicted: (i) higher pullout forces for transverse pullout; (ii) horizontal crack paths perpendicular to screw axis for transverse pullout, whereas vertical crack paths were computed for longitudinal pullout. Computed results agreed closely with experimental observations in terms of pullout force and crack propagation. 相似文献
142.
Greene BR Foran TG McGrath D Doheny EP Burns A Caulfield B 《Journal of applied biomechanics》2012,28(3):349-355
This study compares the performance of algorithms for body-worn sensors used with a spatiotemporal gait analysis platform to the GAITRite electronic walkway. The mean error in detection time (true error) for heel strike and toe-off was 33.9 ± 10.4 ms and 3.8 ± 28.7 ms, respectively. The ICC for temporal parameters step, stride, swing and stance time was found to be greater than 0.84, indicating good agreement. Similarly, for spatial gait parameters--stride length and velocity--the ICC was found to be greater than 0.88. Results show good to excellent concurrent validity in spatiotemporal gait parameters, at three different walking speeds (best agreement observed at normal walking speed). The reported algorithms for body-worn sensors are comparable to the GAITRite electronic walkway for measurement of spatiotemporal gait parameters in healthy subjects. 相似文献
143.
Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and risk for schizophrenia 总被引:1,自引:0,他引:1
Kim JY Liu CY Zhang F Duan X Wen Z Song J Feighery E Lu B Rujescu D St Clair D Christian K Callicott JH Weinberger DR Song H Ming GL 《Cell》2012,148(5):1051-1064
How extrinsic stimuli and intrinsic factors interact to regulate continuous neurogenesis in the postnatal mammalian brain is unknown. Here we show that regulation of dendritic development of newborn neurons by Disrupted-in-Schizophrenia 1 (DISC1) during adult hippocampal neurogenesis requires neurotransmitter GABA-induced, NKCC1-dependent depolarization through a convergence onto the AKT-mTOR pathway. In contrast, DISC1 fails to modulate early-postnatal hippocampal neurogenesis when conversion of GABA-induced depolarization to hyperpolarization is accelerated. Extending the period of GABA-induced depolarization or maternal deprivation stress restores DISC1-dependent dendritic regulation through mTOR pathway during early-postnatal hippocampal neurogenesis. Furthermore, DISC1 and NKCC1 interact epistatically to affect risk for schizophrenia in two independent case control studies. Our study uncovers an interplay between intrinsic DISC1 and extrinsic GABA signaling, two schizophrenia susceptibility pathways, in controlling neurogenesis and suggests critical roles of developmental tempo and experience in manifesting the impact of susceptibility genes on neuronal development and risk for mental disorders. 相似文献
144.
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146.
Gupta A Décaillot FM Gomes I Tkalych O Heimann AS Ferro ES Devi LA 《The Journal of biological chemistry》2007,282(8):5116-5124
A growing body of evidence indicates that G-protein-coupled receptors undergo complex conformational changes upon agonist activation. It is likely that the extracellular region, including the N terminus, undergoes activation-dependent conformational changes. We examined this by generating antibodies to regions within the N terminus of micro-opioid receptors. We find that antibodies to the midportion of the N-terminal tail exhibit enhanced recognition of activated receptors, whereas those to the distal regions do not. The enhanced recognition is abolished upon treatment with agents that block G-protein coupling or deglycosylate the receptor. This suggests that the N-terminal region of mu receptors undergoes conformational changes following receptor activation that can be selectively detected by these region-specific antibodies. We used these antibodies to characterize micro receptor type-specific ligands and find that the antibodies accurately differentiate ligands with varying efficacies. Next, we examined if these antibodies can be used to investigate the extent and duration of activation of endogenous receptors. We find that peripheral morphine administration leads to a time-dependent increase in antibody binding in the striatum and prefrontal cortex with a peak at about 30 min, indicating that these antibodies can be used to probe the spatio-temporal dynamics of native mu receptors. Finally, we show that this strategy of targeting the N-terminal region to generate receptor conformation-specific antisera can be applied to other G(alpha)(i)-coupled (delta-opioid, CB1 cannabinoid, alpha(2A)-adrenergic) as well as G(alpha)(s)-(beta(2)-adrenergic) and G(alpha)(q)-coupled (AT1 angiotensin) receptors. Taken together, these studies describe antisera as tools that allow, for the first time, studies probing differential conformation states of G-protein-coupled receptors, which could be used to identify molecules of therapeutic interest. 相似文献
147.
Myles Balfe Ruairi Brugha Diarmuid O' Donovan Emer O' Connell Deirdre Vaughan 《BMC research notes》2010,3(1):229
Background
Self-conscious emotions (shame, guilt and embarrassment) are part of many individuals' experiences of seeking STI testing. These emotions can have negative impacts on individuals' interpretations of the STI testing process, their willingness to seek treatment and their willingness to inform sexual partners in light of positive STI diagnoses. Because of these impacts, researchers have called for more work to be completed on the connections between shame, guilt, embarrassment and STI testing. We examine the specific events in the STI testing process that trigger self-conscious emotions in young adults who seek STI testing; and to understand what it is about these events that triggers these emotions.Semi-structured interviews with 30 adults (21 women, 9 men) in the Republic of Ireland.Findings
Seven specific triggers of self-conscious emotions were identified. These were: having unprotected sex, associated with the initial reason for seeking STI testing; talking to partners and peers about the intention to seek STI testing; the experience of accessing STI testing facilities and sitting in clinic waiting rooms; negative interactions with healthcare professionals; receiving a positive diagnosis of an STI; having to notify sexual partners in light of a positive STI diagnosis; and accessing healthcare settings for treatment for an STI. Self-conscious emotions were triggered in each case by a perceived threat to respondents' social identities.Conclusion
There are multiple triggers of self-conscious emotions in the STI testing process, ranging from the initial decision to seek testing, right through to the experience of accessing treatment. The role of self-conscious emotions needs to be considered in each component of service design from health promotion approaches, through facility layout to the training of all professionals involved in the STI testing process.148.
Fayal Abderemane-Ali Nathan D. Rossen Megan E. Kobiela Robert A. Craig II Catherine E. Garrison Zhou Chen Claire M. Colleran Lauren A. OConnell J. Du Bois John P. Dumbacher Daniel L. Minor Jr. 《The Journal of general physiology》2021,153(9)
Many poisonous organisms carry small-molecule toxins that alter voltage-gated sodium channel (NaV) function. Among these, batrachotoxin (BTX) from Pitohui poison birds and Phyllobates poison frogs stands out because of its lethality and unusual effects on NaV function. How these toxin-bearing organisms avoid autointoxication remains poorly understood. In poison frogs, a NaV DIVS6 pore-forming helix N-to-T mutation has been proposed as the BTX resistance mechanism. Here, we show that this variant is absent from Pitohui and poison frog NaVs, incurs a strong cost compromising channel function, and fails to produce BTX-resistant channels in poison frog NaVs. We also show that captivity-raised poison frogs are resistant to two NaV-directed toxins, BTX and saxitoxin (STX), even though they bear NaVs sensitive to both. Moreover, we demonstrate that the amphibian STX “toxin sponge” protein saxiphilin is able to protect and rescue NaVs from block by STX. Taken together, our data contradict the hypothesis that BTX autoresistance is rooted in the DIVS6 N→T mutation, challenge the idea that ion channel mutations are a primary driver of toxin resistance, and suggest the possibility that toxin sequestration mechanisms may be key for protecting poisonous species from the action of small-molecule toxins. 相似文献
149.
A soluble cytochrome was isolated and purified from the slime mould Physarum polycephalum and identified as cytochrome c by room-temperature and low-temperature (77 degrees K) difference spectroscopy. A close similarity between P. polycephalum and mammalian cytochromes c was suggested by a comparison of the initial rates of oxidation of both proteins by mammalian mitochondria. This similarity was further emphasized by redox titrations and gel-electrophoretic studies which indicated that P. polycephalum cytochrome c has an oxidation-reduction midpoint potential of +257mV at pH7.0 and a molecular weight of 12500+/-1500 (mean+/-maximum deviation for a set of six measurements). P. polycephalum exhibits an absolute requirement for protohaemin for growth. The (59)Fe-labelled haemin was prepared by chemical synthesis from protoporphyrin. The purified product had a specific radioactivity of 0.8+/-0.02muCi/mol. Growth of P. polycephalum in the presence of [(59)Fe]haemin resulted in the incorporation of (59)Fe into the plasmodial cytochrome c. The specific radioactivity of the cytochrome c haem was 0.36+/-0.02muCi/mol. The high specific radioactivity of the cytochrome haem indicates that synthesis of the holoenzyme must proceed by direct attachment of haem to the apoprotein rather than by the intermediate formation of a protoporphyrinogen-apoprotein complex. The observed decrease in the specific radioactivity of the haem group is attributed to exchange of the (59)Fe with unlabelled iron in the plasmodia either before or during attachment of the haem group to the apoprotein. 相似文献
150.
Alterations in skeletal perfusion with simulated microgravity: a possible mechanism for bone remodeling. 总被引:4,自引:0,他引:4
P N Colleran M K Wilkerson S A Bloomfield L J Suva R T Turner M D Delp 《Journal of applied physiology》2000,89(3):1046-1054
Bone loss occurs as a consequence of exposure to microgravity. Using the hindlimb-unloaded rat to model spaceflight, this study had as its purpose to determine whether skeletal unloading and cephalic fluid shifts alter bone blood flow. We hypothesized that perfusion would be diminished in the hindlimb bones and increased in skeletal structures of the forelimbs and head. Using radiolabeled microspheres, we measured skeletal perfusion during control standing and after 10 min, 7 days, and 28 days of hindlimb unloading (HU). Femoral and tibial perfusion were reduced with 10 min of HU, and blood flow to the femoral shaft and marrow were further diminished with 28 days of HU. Correspondingly, the mass of femora (-11%, P < 0. 05) and tibiae (-6%, P < 0.1) was lowered with 28 days of HU. In contrast, blood flow to the skull, mandible, clavicle, and humerus was increased with 10 min HU but returned to control levels with 7 days HU. Mandibular (+10%, P < 0.05), clavicular (+18%, P < 0.05), and humeral (+8%, P < 0.1) mass was increased with chronic HU. The data demonstrate that simulated microgravity alters bone perfusion and that such alterations correspond to unloading-induced changes in bone mass. These results support the hypothesis that alterations in bone blood flow provide a stimulus for bone remodeling during periods of microgravity. 相似文献