Cellular pyrin domain-only protein 2 is a candidate regulator of inflammasome activation

Pyrin domain (PYD) proteins have recently emerged as important signaling molecules involved in the development of innate immunity against intracellular pathogens through activation of inflammatory mediator pathways. ASC is the central adaptor protein, which links pathogen recognition by PYD-containing pathogen recognition receptors, known as PYD-Nod-like receptors (NLR), PAN, PYPAF, NALP, Nod, and Caterpiller proteins, to the activation of downstream effectors, including activation of caspase-1 and NF-kappaB. Activation of these effectors occurs when specific protein complexes, known as inflammasomes, are formed. PYD signal transduction leads to inflammasome assembly and activation of specific effector proteins. It is modulated by a cellular PYD-only protein (cPOP1), which binds to ASC and interferes with the recruitment of ASC to activated PYD-NLRs. Here we describe the identification and characterization of a second cellular POP (cPOP2), which shows highest homology to the PYD of PAN1. cPOP2 binds to ASC and PAN1, thereby blocking formation of cryopyrin and PAN1-containing inflammasomes, activation of caspase-1, and subsequent processing and secretion of bioactive interleukin-1beta. Existence of a second cPOP provides additional insights into inflammasome formation and suggests that POPs might be a common regulatory mechanism to "fine-tune" the activity of specific PYD-NLR family protein-containing inflammasomes.     

A Shope Fibroma virus PYRIN-only protein modulates the host immune response

PYRIN domain (PYD) proteins have recently emerged as important signaling molecules involved in the development of innate immunity to intracellular pathogens through activation of inflammatory mediator pathways. ASC is the central adaptor protein, which links pathogen recognition by PYD-containing pathogen recognition receptors to the activation of downstream effectors, including activation of Caspase-1 and NF-kappaB. The cellular PYD-only protein 1 (cPOP1) can block the recruitment of ASC to activated PAN receptors and thereby functions as an endogenous inhibitor of the PYD-mediated signal transduction pathway. Here we describe the identification and characterization of a Shope Fibroma homolog to cPOP1. Like cPOP1, a Shope Fibroma virus-encoded POP (vPOP), co-localizes and directly associates with ASC and inhibits PYD-mediated signal transduction. Poxviruses are known to encode immune evasive proteins to promote host cell infection and suppression of the host immune response. Poxvirus-encoded vPOPs represent a novel class of immune evasive proteins and impair the host response by blocking Cryopyrin and ASC inflammasome-mediated activation of pro-Caspase-1 and subsequent processing of pro-interleukin (IL)-1beta, and expression of vPOPs causes activation of NF-kappaB.     

Respiratory changes in human red cells

To investigate physiological respiratory changes in human red cells, we measured automated red cell parameters in samples from the pulmonary and radial arteries of 86 patients undergoing aorto-coronary bypass and from the pulmonary artery and the aorta in 23 patients. Our results showed higher mean corpuscular volume (88.53 +/- 5.06 fl vs. 88.12 +/- 4.94 fl, P < 0.000001), haematocrit (0.369 +/- 0.039 vs. 0.367 +/- 0.038, P < 0.0005), red cell distribution width (43.38 +/- 4.16 vs. 43.04 +/- 4.05 fl, P < 0.000001) and a lower mean corpuscular haemoglobin concentration (338.3 +/- 15.9 vs. 339.9 +/- 16.8 g/l, P < 0.005) in pulmonary arterial as compared to radial arterial blood. There were no differences with respect to haemoglobin concentration, red blood cell count, or mean corpuscular haemoglobin. Similar differences were observed between pulmonary arterial and aortic blood. Our results suggest cyclic respiratory modifications of red cell parameters attributable to the CO2 Jacobs-Stewart cycle.     

The lungs and platelet production

Several studies have suggested that thrombopoiesis may occur in the lungs. To investigate the role of the lungs in platelet production, we measured automated platelet parameters in blood from the pulmonary artery and the radial artery (n=125) or aorta (n=26) in patients undergoing aorto-coronary bypass. No significant differences were found between pulmonary and radial arterial blood with regard to platelet count (192.132 +/- 46.250 vs. 192.004 +/- 46.294 x 10(9)/l), mean platelet volume (11.03 +/- 1.04 vs. 11.03 +/- 1.03 fl), plateletcrit (0.212 +/- 0.051 vs. 0.212 +/- 0.051 x 10(-2)), platelet distribution width (14.48 +/- 2.16 vs. 14.47 +/- 2.08 fl) and platelet-large cell ratio (0.350 +/- 0.076 vs. 0.351 +/- 0.078). Similar results were obtained in comparisons between pulmonary arterial and aortic blood. A coefficient of linear correlation of 0.98 was found between the pulmonary and radial arterial and aortic platelet counts. These findings suggest that the platelet population entering the lungs was the same as the platelet population leaving them. Our results do not therefore support the theory of pulmonary platelet production.     

BDNF heterozygous mice demonstrate age-related changes in striatal and nigral gene expression

TrkB receptors mediate the effects of BDNF on striatal medium spiny neurons and mesencephalic dopamine neurons. The effect of partial BDNF gene deletion on locomotor activity and the gene expression of these neurons was evaluated at 3, 12, and 24 months of age in BDNF heterozygous (BDNF(LacZ/neo+)) and wildtype mice. BDNF(LacZ/neo+) mice displayed less spontaneous horizontal activity than wildtypes at 3 and 24 months of age. Whereas striatal preproenkephalin and preprodynorphin mRNA and mesencephalic tyrosine hydroxylase mRNA levels were significantly lower at all ages in BDNF(LacZ/neo+) mice, GAD67 mRNA was only lower at 24 months. In contrast, BDNF(LacZ/neo+) mice expressed more trkB mRNA in the striatum at 3 months and less at 24 months of age than wildtypes. Total striatal cell number in the two genotypes was not different at 12 months of age, whereas Golgi staining revealed that the spine density on distal dendrites of medium spiny neurons was less in BDNF(LacZ/neo+) mice than in wildtypes at 24 months of age. These data indicate that endogenous BDNF is required to maintain the normal phenotype and functioning of striatal projection neurons and mesencephalic dopamine neurons and that exaggerated dysfunction of these neurons and a concomitant decline in locomotor behavior occurs during aging.     

Tension patterns of the anteromedial and posterolateral grafts in a double‐bundle anterior cruciate ligament reconstruction

The two functional bundles of the anterior cruciate ligament (ACL), namely, the anteromedial (AM) and posterolateral (PL) bundles, must work in concert to control displacement of the tibia relative to the femur for complex motions. Thus, the replacement graft(s) for a torn ACL should possess similar tension patterns. The objective of the study was to examine whether a double‐bundle ACL reconstruction with the semitendinosus‐gracilis autografts could replicate the tension patterns of those for the intact ACL under controlled in vitro loading conditions. By means of a robotic/universal force moment sensor (UFS) testing system, the in situ force vectors (both magnitude and direction) for the AM and PL bundles of the ACL, as well as their respective replacement grafts, were determined and compared on nine human cadaveric knees. It was found that double‐bundle ACL reconstruction could closely replicate the in situ force vectors. Under a 134‐N anterior tibial load, the resultant force vectors for the intact ACL and the reconstructed ACL had a difference of 5 to 11 N (p > 0.05) in magnitude and 1 to 13° (p > 0.05) in direction. Whereas, under combined rotatory loads of 10‐N‐m valgus and 5‐N‐m internal tibial torques, the corresponding differences were 10 to 16 N and 4° to 11°, respectively. Again, there were no statistically significant differences except at 30° of flexion where the force vector for the AM graft had a 15° (p < 0.05) lower elevation angle than did the AM bundle. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 879–884, 2009     

Women’s household decision-making autonomy and safer sex negotiation in Nigeria: An analysis of the Nigeria Demographic and Health Survey

Although married women’s safer sex negotiation with their husbands is critical in reducing new HIV infections in Nigeria, its linkage to women’s household decision-making autonomy is less explored in Nigeria. Drawing data from the 2013 Nigeria Demographic and Health Survey and using the logistic regression technique, we examined the associations between women’s household decision-making autonomy and two indicators of the ability to engage in safer sex including whether married women 1) can refuse sex and 2) ask for condom use during sexual intercourse with husbands. Findings indicate that 64% and 41% of married women can refuse sex and ask for condom use, respectively. While the impact of women’s household decision-making autonomy on the ability to refuse sex remained statistically significant after controlling for theoretically relevant variables (OR?=?1.15; p?p?相似文献   

Biomechanics and anterior cruciate ligament reconstruction

For years, bioengineers and orthopaedic surgeons have applied the principles of mechanics to gain valuable information about the complex function of the anterior cruciate ligament (ACL). The results of these investigations have provided scientific data for surgeons to improve methods of ACL reconstruction and postoperative rehabilitation. This review paper will present specific examples of how the field of biomechanics has impacted the evolution of ACL research. The anatomy and biomechanics of the ACL as well as the discovery of new tools in ACL-related biomechanical study are first introduced. Some important factors affecting the surgical outcome of ACL reconstruction, including graft selection, tunnel placement, initial graft tension, graft fixation, graft tunnel motion and healing, are then discussed. The scientific basis for the new surgical procedure, i.e., anatomic double bundle ACL reconstruction, designed to regain rotatory stability of the knee, is presented. To conclude, the future role of biomechanics in gaining valuable in-vivo data that can further advance the understanding of the ACL and ACL graft function in order to improve the patient outcome following ACL reconstruction is suggested.