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Fraser syndrome (FS) is a rare autosomal recessive multiple congenital malformation syndrome characterized by cryptophthalmos, cutaneous syndactyly, renal agenesis, ambiguous genitalia, and laryngotracheal anomalies. It is caused by biallelic mutations of FRAS1, FREM2, and GRIP1 genes, encoding components of a protein complex that mediates embryonic epithelial-mesenchymal interactions. Anecdotal reports have described abnormal orodental findings in FS, but no study has as yet addressed the orodental findings of FS systematically. We reviewed dental radiographs of 10 unrelated patients with FS of different genetic etiologies. Dental anomalies were present in all patients with FS and included hypodontia, dental crowding, medial diastema, and retained teeth. A very consistent pattern of shortened dental roots of most permanent teeth as well as altered length/width ratio with shortened dental crowns of upper incisors was also identified. These findings suggest that the FRAS1-FREM complex mediates critical mesenchymal-epithelial interactions during dental crown and root development. The orodental findings of FS reported herein represent a previously underestimated manifestation of the disorder with significant impact on orodental health for affected individuals. Integration of dentists and orthodontists into the multidisciplinary team for management of FS is therefore recommended.Analytical techniques using ATP bioluminescence, which has a high quantum yield and substrate specificity, are widely used in various assays, such as luciferase reporter assays, in the biological sciences. Although most microplate luminometers can be used to measure ATP luminescence with 96-well or 384-well microplates, their ATP detection limits are typically several tens of amol, which is not sufficient for evaluating cell activities and variability within small samples, such as those containing only a few cells. To analyze cell activities at low ATP concentrations, a more sensitive microplate luminometer is required. Therefore, in this study, we developed an automated highly sensitive microplate luminometer that could perform reagent dispensing and bioluminescence measurement with a 96-well microplate within 10 min. ATP bioluminescence was detected by pressing a photomultiplier tube (PMT) against a microplate surface to seal the measured well with the light-receiving surface of the PMT. This enabled a high light collection efficiency and low luminescence crosstalk, defined as the intensity of stray light from an adjacent well. As a result, the ATP detection limit was 0.97 amol, and the luminescence crosstalk was 4.4 × 10-6 . Both values were one order of magnitude better than that of a typical microplate luminometer. In addition, the same gradient linearity of luminescence intensity against the ATP concentration was confirmed for both high and low ATP concentrations, and the dynamic range of our microplate luminometer was 106 . Selleckchem JNJ-64619178 Overall, our findings demonstrated that our novel microplate luminometer may have wide application in biological sciences research.Diabetes mellitus (DM) is now recognized as one of the risk factors for Alzheimer's disease (AD), and the disease-modifying effects of anti-diabetic drugs on AD have recently been attracting great attention. Sodium/glucose cotransporter 2 (SGLT2) inhibitors are a new class of anti-diabetic drugs targeting the SGLT2/solute carrier family 5 member 2 (SLC5A2) protein, which is known to localize exclusively in the brush border membrane of early proximal tubules in the kidney. However, recent data suggest that it is also expressed in other tissues. In the present study, we investigated the expression of SGLT2/SLC5A2 in human and mouse brains. Immunohistochemical staining of paraffin sections from autopsied human brains and C3H/He mouse brains revealed granular cytoplasmic immunoreactivity in choroid plexus epithelial cells and ependymal cells. Immunoblot analysis of the membrane fraction of mouse choroid plexus showed distinct immunoreactive bands at 70 and 26 kDa. Band patterns around 70 kDa in the membrane fraction of the choroid plexus were different from those in the kidney. Reverse transcription-polymerase chain reaction analysis confirmed the expression of Slc5a2 mRNA in the mouse choroid plexus. Our results provide in vivo evidence that SGLT2/SLC5A2 is expressed in cells facing the cerebrospinal fluid, in addition to early proximal tubular epithelial cells. These findings suggest that SGLT2 inhibitors may have another site of action in the brain. The effects of SGLT2 inhibitors on brain function and AD progression merit further investigation to develop better treatment options for DM patients.Background Differentiated thyroid cancer (DTC) reports a poorer health-related quality of life (HRQoL) than a norm population. Patients' illness perceptions are modifiable and known associates of HRQoL in other cancers. The aim was to examine the relationship between illness perceptions and HRQoL among DTC survivors. Methods DTC survivors registered in the Netherlands Cancer Registry diagnosed between 1990 and 2008, received a survey on illness perceptions (Brief-Illness Perception Questionnaire; B-IPQ) and HRQoL (European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30; EORTC QLQ-C30). Multiple regression analyses were conducted investigating the relation between illness perceptions and HRQoL, while controlling for sociodemographic and clinical characteristics. Results Two hundred and eighty-four DTC survivors were included. DTC survivors who believed their illness had many negative consequences; who perceived their illness as controllable by treatment; who had strong beliefs symptoms could be attributed to their illness; and who had strong beliefs their illness causes negative emotions, reported a poorer HRQoL. Conclusions Stronger negative illness perceptions are related to a poorer HRQoL among DTC survivors.Islet Amyloid Polypeptide (IAPP) is a hormone co-secreted with insulin and zinc from pancreatic β-cells. To overcome the low solubility of human IAPP, we characterized the zinc complexes species formed with i) a mutated form of rat-IAPP(1-37;R18H) able to mimic the human IAPP; ii) the r-IAPP(1-37) and the IAPP(1-8) fragment. Stoichiometry, speciation and coordination features of zinc(II) complexes were unveiled by ESI-MS, potentiometric and NMR-based measurements combined with DFT and free-energy simulations. Mononuclear species start to form around pH 6; Zn 2+ binds both His18 and N-amino terminus in rat-IAPP(1-37; R18H).The in silico study allows us to assess not only a structured turn compact domain in r-IAPP(1-37) and r-IAPP(1-37;R18H) featured by a different free energy barrier for the transition from the compact to elongated conformation upon the coordination of Zn 2+ but also to bring into light a coordination shell further stabilized by non-covalent interactions.