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Shah McLean posted an update 6 months, 1 week ago
Neural progestin receptors (PR) function in reproduction, neural development, neuroprotection, learning, memory and the anxiety response. In the absence of progestins, PR can be activated by dopamine (DA) in the rodent hypothalamus to elicit female sexual behaviour. The present study investigated mechanisms of DA activation of PR by testing the hypothesis that proteins from DA-treated hypothalami interact with PR in the absence of progestins. Ovariectomised, oestradiol-primed mice were infused with a D1-receptor agonist, SKF38393 (SKF), into the third ventricle 30 minutes prior to death. Proteins from SKF-treated hypothalami were pulled-down with glutathione S-transferase-tagged mouse PR-A or PR-B and the interactomes were analysed by mass spectrometry. The largest functional group to interact with PR-A in a DA-dependent manner was synaptic proteins. To test the hypothesis that DA activation of PR regulates synaptic proteins, we developed oestradiol-induced PR-expressing hypothalamic-like neurones derived from human-induced pluripotent stem cells (hiPSCs). Similar to progesterone (P4), SKF treatment of hiPSCs increased synapsin1/2 expression. This SKF-dependent effect was blocked by the PR antagonist RU486, suggesting that PR are necessary for this DA-induced increase. The second largest DA-dependent PR-A protein interactome comprised metabolic regulators involved in glucose metabolism, lipid synthesis and mitochondrial energy production. Interestingly, hypothalamic proteins interacted with PR-A, but not PR-B, in an SKF-dependent manner, suggesting that DA promotes the interaction of multiple hypothalamic proteins with PR-A. These in vivo and in vitro results indicate novel mechanisms by which DA can differentially activate PR isoforms in the absence of P4 and provide a better understanding of ligand-independent PR activation in reproductive, metabolic and mental health disorders in women.Anatomic tunnel formation and remnant preservation are the recent trends in posterior cruciate ligament (PCL) reconstruction. However, it is difficult to observe the anatomical PCL footprint and perform the operation in the process of remnant-preserving PCL reconstruction. This study describes a single-bundle, transtibial PCL reconstruction technique with anatomic graft passage over the remnant PCL fibers. A femoral tunnel of PCL is created at 2 mm medial to the roof of the intercondylar notch and 3 mm proximal to the margin of the articular cartilage. The tibial insertion of PCL is observed using a figure-of-four position through a posterior trans-septal portal. A tibial bone tunnel is made below the distal center portion of the tibial insertion of residual PCL fibers. The graft is passed over the PCL through the tibial bone tunnel, the space between the anterior cruciate ligament (ACL) and the residual PCL fibers, to the femoral socket and is fixed by the EndoButton and screw. This technique is able to ensure a reasonable intra-articular length and optimal isometry. It has been applied in patients with PCL rupture and posterior instability of the knee joint, and no intraoperative or postoperative complications occurred. Our technology provides a valuable new treatment option for PCL rupture. Future comparative studies are needed to further clarify its beneficial effect.
To determine the medial metaphyseal beak (MMB) cut-off angle predicting Langenskiöld stage II of Blount’s disease and to study the intra-observer and inter-observer reliabilities of angle measurements and the influence of the experience level of observers.
A retrospective study was conducted on children aged 2-4 years from January 2000 to December 2017. Children were identified through a computer-based search. Children with Langenskiöld stage II of Blount’s disease who had been initially evaluated at our institution were categorized into Blount group and children who were diagnosed with physiologic bowing were categorized into control group. Data on the patients’ ages, genders, and affected sides were collected. The MMB angles were measured on standing anteroposterior radiographs of the knees. The angle was formed between one line drawn parallel to the medial cortex of the proximal tibia, and a second line running from the intersection of the first line with the proximal tibial metaphysis through to the m legs, with an MMB angle >122° predicting Langenskiöld stage II.
122° predicting Langenskiöld stage II.
Gastrointestinal (GI) motility is a complex physiological process that is critical for normal GI function. Disruption of GI motility frequently occurs in GI diseases or as side effects of therapeutics. Whole gut transit measurements, like carmine red leading-edge transit, in mice form the cornerstone of in vivo preclinical GI motility studies.
We have developed an easily achievable, labor-saving method to measure whole gut transit time in mice. selleck chemicals This approach uses inexpensive, commercially available materials to monitor pellet production over time via high definition cameras capturing time-lapse video for offline analysis.
We describe the assembly of our automated gut transit setup and validate this approach by comparing the results with loperamide to delay transit and conventional transit measurements. We demonstrate that compared to the control group, the loperamide group had slowed transit, evidenced by a decrease in total pellet production and prolonged whole gut transit time. The control group had an extended transit time compared with the results reported in the literature. Whole gut transit rates accelerated to times comparable to the literature by disrupting cages every 10-15min to imitate the conventional approach, suggesting that disruption affects the assay and supports the use of an automated approach.
A novel automated, inexpensive, and easily assembled whole gut transit setup is labor-saving and allows minimal disruption to animal behavior compared with the conventional approach.
A novel automated, inexpensive, and easily assembled whole gut transit setup is labor-saving and allows minimal disruption to animal behavior compared with the conventional approach.
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