Travelling and splitting of a wave of hedgehog expression involved in spider-head segmentation

During development segmentation is a process that generates a spatial periodic pattern. Peak splitting of waves of gene expression is a mathematically predicted, simple strategy accounting for this type of process, but it has not been well characterized biologically. Here we show temporally repeated splitting of gene expression into stripes that is associated with head axis growth in the spider Achaearanea embryo. Preceding segmentation, a wave of hedgehog homologue gene expression is observed to travel posteriorly during development stage 6. This stripe, co-expressing an orthodenticle homologue, undergoes two cycles of splitting and shifting accompanied by convergent extension, serving as a generative zone for the head segments. The two orthodenticle and odd-paired homologues are identified as targets of Hedgehog signalling, and evidence suggests that their activities mediate feedback to maintain the head generative zone and to promote stripe splitting in this zone. We propose that the 'stripe-splitting' strategy employs genetic components shared with Drosophila blastoderm subdivision, which are required for participation in an autoregulatory signalling network

Identification of Novel Functional Inhibitors of Acid Sphingomyelinase

We describe a hitherto unknown feature for 27 small drug-like molecules, namely functional inhibition of acid sphingomyelinase (ASM). These entities named FIASMAs (Functional Inhibitors of Acid SphingoMyelinAse), therefore, can be potentially used to treat diseases associated with enhanced activity of ASM, such as Alzheimer's disease, major depression, radiation- and chemotherapy-induced apoptosis and endotoxic shock syndrome. Residual activity of ASM measured in the presence of 10 µM drug concentration shows a bimodal distribution; thus the tested drugs can be classified into two groups with lower and higher inhibitory activity. All FIASMAs share distinct physicochemical properties in showing lipophilic and weakly basic properties. Hierarchical clustering of Tanimoto coefficients revealed that FIASMAs occur among drugs of various chemical scaffolds. Moreover, FIASMAs more frequently violate Lipinski's Rule-of-Five than compounds without effect on ASM. Inhibition of ASM appears to be associated with good permeability across the blood-brain barrier. In the present investigation, we developed a novel structure-property-activity relationship by using a random forest-based binary classification learner. Virtual screening revealed that only six out of 768 (0.78%) compounds of natural products functionally inhibit ASM, whereas this inhibitory activity occurs in 135 out of 2028 (6.66%) drugs licensed for medical use in humans

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Mineralogy and geochronology of U(-Au) deposits from the Pine Creek geosyncline, Northern Territory, Australia, and from the Athabasca Basin, Saskatchewan and Alberta, Canada

With 321 figs., 33 tabs.SIGLEAvailable from TIB Hannover: RO 5514(59) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Safety of Combined Abdominal Sacral Colpopexy and Sigmoid Resection With Suture Rectopexy: A Retrospective Cohort Study

Objectives This study aimed to determine if abdominal sacral colpopexy (ASC) using mesh can be safely combined with sigmoid resection and anastomosis. Methods This is a single institution, retrospective chart review of patients who underwent combined ASC and suture rectopexy with sigmoid resection between January 1, 2007, and December 31, 2011. Charts were screened for outcome data and complications related to the placement of synthetic mesh at the time of bowel resection to include readmission and reoperation rates, infection, bowel obstruction, fistula, and mesh erosion. Outcome data for patients receiving combined procedures were compared to 2 separate cohorts of patients as follows: a group that underwent only ASC with polypropylene mesh and a group that underwent only sigmoid resection plus or minus suture rectopexy. The DINDO surgical classification system was used for each cohort to further analyze complications. Results There were 133 patients in the ASC only group (ASC only), 34 in the combined ASC and sigmoid resection group (Combined), and 27 in the sigmoidectomy plus rectopexy group (Colorectal only). The Colorectal only cohort had a higher rate of postoperative ileus; ASC only 3.8%, Combined 5.9%, Colorectal 22.2% (P = 0.004). There were otherwise no differences in intraoperative and postoperative complications or in the DINDO classification scores. Conclusions Abdominal sacral colpopexy with placement of synthetic mesh at the time of sigmoid resection and anastomosis does not seem to increase the rate of intraoperative or postoperative complications

Safety of Combined Abdominal Sacral Colpopexy and Sigmoid Resection With Suture Rectopexy: A Retrospective Cohort Study

Objectives This study aimed to determine if abdominal sacral colpopexy (ASC) using mesh can be safely combined with sigmoid resection and anastomosis. Methods This is a single institution, retrospective chart review of patients who underwent combined ASC and suture rectopexy with sigmoid resection between January 1, 2007, and December 31, 2011. Charts were screened for outcome data and complications related to the placement of synthetic mesh at the time of bowel resection to include readmission and reoperation rates, infection, bowel obstruction, fistula, and mesh erosion. Outcome data for patients receiving combined procedures were compared to 2 separate cohorts of patients as follows: a group that underwent only ASC with polypropylene mesh and a group that underwent only sigmoid resection plus or minus suture rectopexy. The DINDO surgical classification system was used for each cohort to further analyze complications. Results There were 133 patients in the ASC only group (ASC only), 34 in the combined ASC and sigmoid resection group (Combined), and 27 in the sigmoidectomy plus rectopexy group (Colorectal only). The Colorectal only cohort had a higher rate of postoperative ileus; ASC only 3.8%, Combined 5.9%, Colorectal 22.2% (P = 0.004). There were otherwise no differences in intraoperative and postoperative complications or in the DINDO classification scores. Conclusions Abdominal sacral colpopexy with placement of synthetic mesh at the time of sigmoid resection and anastomosis does not seem to increase the rate of intraoperative or postoperative complications