Patterning of the vertebrate skeleton requires the coordinated activity of Hox genes. In particular, Hox10 proteins are essential to set the transition from thoracic to lumbar vertebrae because of their rib-repressing activity. In snakes, however, the thoracic region extends well into Hox10-expressing areas of the embryo, suggesting that these proteins are unable to block rib formation. Here, we show that this is not a result of the loss of rib-repressing properties by the snake proteins, but rather to a single base pair change in a Hox/Paired box (Pax)-responsive enhancer, which prevents the binding of Hox proteins. This polymorphism is also found in Paenungulata, such as elephants and manatees, which have extended rib cages. In vivo, this modified enhancer failed to respond to Hox10 activity, supporting its role in the extension of rib cages. In contrast, the enhancer could still interact with Hoxb6 and Pax3 to promote rib formation. These results suggest that a polymorphism in the Hox/Pax-responsive enhancer may have played a role in the evolution of the vertebrate spine by differently modulating its response to rib-suppressing and rib-promoting Hox proteins. 相似文献
Hypersensitivity pneumonitis (HP) represents a group of immunologically mediated lung disorders provoked by recurrent exposure to various environmental agents. HP is multifaceted and may mimic almost any interstitial lung disease, some infectious diseases,and even bronchiolar disorders. In the absence of a diagnostic gold standard,diagnosis of HP requires a combination of clinical, environmental, radiologic, physiologic,and pathologic findings that represent a diagnostic challenge for clinicians and-in the chronic form-even for experienced pathologists. Therapeutic approach includes avoiding further exposure and, depending on the clinical form, the administration of a course of prednisone. New anti-inflammatory, immunoregulatory, and antifibrotic drugs are urgently needed for this and other interstitial lung diseases. 相似文献
To explore the association between loneliness and efficacy to engage in health behaviors that are known to reduce the risk of early mortality in people with serious mental illness (SMI). This secondary data analysis was based on a cross-sectional study of 113 participants with SMI residing in New Hampshire. Ordinary Least Squares regressions were used to examine bivariate relationships between variables of interest. Participants had a primary mental health diagnosis of major depressive disorder (37.2%), schizophrenia spectrum disorder (28.3%), bipolar disorder (29.2%), or posttraumatic stress disorder (5.3%). High levels of loneliness were associated with low levels of self-efficacy to manage chronic diseases (p =?0.0001), as well as low levels of self-efficacy to manage psychological well-being (R2 =?.31; F =?9.49, p =?0.0001; RMSE =?1.66). Loneliness may serve as a barrier to healthy behaviors, and thus, contribute to early mortality among people with SMI. The growing body of literature that demonstrates the importance of addressing loneliness in people with SMI should stimulate policymakers and researchers to target loneliness as a mechanism to address early mortality in people with SMI.
AbstractObjective: The aim of the present study was to evaluate the therapeutic potential of autologous DCs loaded with whole tumor cell lysate of CTVT generated under a simplified and rapid procedure in vitro production process, in a vulvar submucosal model of CTVT in dogs.Materials and methods: We generated a model of intravulvar CTVT in dogs. A CTVT lysate antigen was prepared according to the method of 1-butanol and after administered with complete Freund's adjuvant via subcutaneous in female healthy dogs and challenge with CTVT cells to corroborate the immunogenicity. Short-time generated dendritic cell pulsed with CTVT whole-lysate was performed, and analyzed by FITC-dextran uptake assay and characterized using anti-canine monoclonal antibodies CD14, CD80, CD83, and DLAII by flow cytometry. Dendritic cell therapy was administered in a frequency of three times every 2 weeks when the CTVT had 4 months of growth and 89?±?5 cm diameter. The CD3+, CD4+ and CD8+ lymphocytes were determined by flow cytometry, and IFN-γ by ELISA assay.Results and discussion: The administration of CTVT whole-lysate resulted in tumor prevention. The short-time generated dendritic cell pulsed with CTVT whole-lysate administration resulted in an efficient reduction and elimination of CTVT, probably due to the increase in lymphocyte populations (CD3+, CD4+, and CD8+), IFN-γ production and tumor infiltrating lymphocytes.Conclusion: In conclusion, this study demonstrates the efficacy of immunotherapy based in short-time generated dendritic cell pulsed with CTVT whole-lysate for the treatment of CTVT, and offer veterinary oncologists new alternative therapies to treat this and another malignancy. 相似文献
Journal of Clinical Immunology - Patients with inborn errors of immunity (IEI) have a compromised or inappropriate immune response. Although they might be considered a high-risk group for severe... 相似文献
The purpose of this study was to investigate the effects of a 6-week aerobic training period on the time to fatigue (tlim) during exercise performed at the maximal lactate steady state (MLSS). Thirteen untrained male subjects (TG; age 22.5 ± 2.4 years, body mass 72.9 ± 6.7 kg and VO2max 44.9 ± 4.8 mL kg?1 min?1) performed a cycle ergometer test until fatigue at the MLSS power output before and after 6 weeks of aerobic training. A group of eight control subjects (CG; age 25.1 ± 2.4 years, body mass 70.1 ± 9.8 kg and VO2max 45.2 ± 4.1 mL kg?1 min?1) also performed the two tests but did not train during the 6-week period. There were no differences between the groups with respect to the VO2max or MLSS power output (MLSSw) before the treatment period. The VO2max and the MLSSw of the TG increased by 11.2 ± 7.2 % (pre-treatment = 44.9 ± 4.8 vs. post-treatment = 49.8 ± 4.5 mL kg?1 min?1) and 14.7 ± 8.9 % (pre-treatment = 150 ± 27 vs. post-treatment = 171 ± 26 W), respectively, after 6 weeks of training. The results of the CG were unchanged. There were no differences in tlim between the groups or within groups before and after training. Six weeks of aerobic training increases MLSSw and VO2max, but it does not alter the tlim at the MLSS. 相似文献
The progesterone receptor (PR) gene plays an important role in reproduction-related events. Data on polymorphisms in the PR gene have revealed associations with cancer, particularly for the Alu insertion polymorphism, which has been suggested to affect progesterone receptor function and contribute to tumor promotion in the mammary gland.
Material and methods
We examined the role of the Alu insertion polymorphism in the PR gene by comparing the genotypes of 209 healthy Mexican women with those of 481 Mexican women with breast cancer (BC).
Results
The genotype frequencies observed in the controls and BC patients were 0% and 4% for T2/T2 (Alu insertion), 16% and 21% for T1/T2, and 84% and 75% for T1/T1 (Alu deletion), respectively. The obtained odds ratio (OR) was 1.7, with a 95% confidence interval (95% CI) of 1.1–2.6, p = 0.009, for the T1/T2–T2/T2 genotypes. The association was also evident when the distributions of the T1/T2–T2/T2 genotypes in patients in the following categories were compared: obesity grade II (OR = 1.81, 95% CI: 1.03–3.18, p = 0.039) and the chemotherapy response (OR = 1.91, 95% CI: 1.27–3.067, p = 0.002).
Conclusions
The T1/T2–T2/T2 genotypes of the Alu insertion polymorphism in the PR gene are associated with BC susceptibility in the analyzed Mexican population. 相似文献