Two novel mutations of Wiskott–Aldrich syndrome: the molecular prediction of interaction between the mutated WASP L101P with WASP-interacting protein by molecular modeling

AbstractWiskott–Aldrich syndrome (WAS) is an X-linked disorder characterized by eczema, thrombocytopenia and increased susceptibility of infections, with mutations of the WAS gene being responsible for WAS and X-linked thrombocytopenia. Herein, two novel mutations of WAS at T336C on exon 3, and at 1326–1329, a G deletion on exon 10, resulting in L101P missense mutation and frameshift mutation 444 stop, respectively, are reported. The affected patients with either mutation showed severe suppression of WAS protein (WASP) levels, T cell proliferation, and CFSE-labeled T cells division. Because WASP L101 have not shown direct nuclear Overhauser effect (NOE) contact with the WASP-interacting protein (WIP) in NMR spectroscopy, molecular modeling was performed to evaluate the molecular effect of WASP P101 to WIP peptide. It is presumed that P101 induced a conformational change in the Q99 residue of WASP and made the side chain of Q99 move away from the WIP peptide, resulting in disruption of the hydrogen bond between Q99 WASP and Y475 WIP. A possible model for the molecular pathogenesis of WAS has been proposed by analyzing the interactions of WASP and WIP using a molecular modeling study

Bucillamine prevents cisplatin-induced ototoxicity through induction of glutathione and antioxidant genes.

Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of γ-glutamylcysteine synthetase (γ-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine in vivo. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH

Association of Oncogenic Human Papillomaviruses(HPV 16, 18) with Cervical Intraepithelial Neoplasia and Cervical Cancer

The prevalence of oncogenic human papillomavirus (HPV) type 16 and 18 was investigated by polymerase chain reaction (PCR) method in cervical scrapes omitting prior DNA extraction. Samples were obtained from 70 gynecologic inpatients with normal cervix and 160 women with cervical neoplastic lesion ( N = 50 in cervical intraepithelial neoplasia (CIN) I, N = 50 in CIN II, N = 30 in CIN III, N = 30 in invasive cervical cancer). Eight members were excluded from the data due to failure of ,f3-g10bin amplification during the PCR procedure. The HPV 16 prevalence rate was 19.1 % (13/68) in the normal group, 38.8 % (19/49) in CIN 1,57.1 % (28/49) in CIN 11,75.9 % (22/29) in CIN III, 88.9% (24/27) in invasive cancer. For HPV type 18, DNA positivity was 4.4 % (3/68), 8.2 % (4/49), 12.2 % (6/49), 13.8 % (4/29), 18.5 % (5/27), respectively. In the whole series a consistent correlation was found between HPV positivity and severity of cervical lesion. HPV 16 was the more prevalent type and about five times more common than HPV 18. These results suggest that HPV 16 and 18 may be strongly associated with carcinogenesis of cervical cancer. The high risk HPV typing by direct PCR from cervical scrapes can be used as a useful marker for the presence of neoplastic cells and also served as a simple tool in identifying women who are at risk of developing dysplasia and cervical cancer

Quality Control-Driven Image Segmentation Towards Reliable Automatic Image Analysis in Large-Scale Cardiovascular Magnetic Resonance Aortic Cine Imaging

“The final authenticated version is available online at https://doi.org/10.1007/978-3-030-32245-8_83.”© 2019, Springer Nature Switzerland AG. Recent progress in fully-automated image segmentation has enabled efficient extraction of clinical parameters in large-scale clinical imaging studies, reducing laborious manual processing. However, the current state-of-the-art automatic image segmentation may still fail, especially when it comes to atypical cases. Visual inspection of segmentation quality is often required, thus diminishing the improvements in efficiency. This drives an increasing need to enhance the overall data processing pipeline with robust automatic quality scoring, especially for clinical applications. We present a novel quality control-driven (QCD) framework to provide reliable segmentation using a set of different neural networks. In contrast to the prior segmentation and quality scoring methods, the proposed framework automatically selects the optimal segmentation on-the-fly from the multiple candidate segmentations available, directly utilizing the inherent Dice similarity coefficient (DSC) predictions. We trained and evaluated the framework on a large-scale cardiovascular magnetic resonance aortic cine image sequences from the UK Biobank Study. The framework achieved segmentation accuracy of mean DSC at 0.966, mean prediction error of DSC within 0.015, and mean error in estimating lumen area ≤17.6 mm2 for both ascending aorta and proximal descending aorta. This novel QCD framework successfully integrates the automatic image segmentation along with detection of critical errors on a per-case basis, paving the way towards reliable fully-automatic extraction of clinical parameters for large-scale imaging studies

Enhancement of hole injection using ozone treated Ag nanodots dispersed on indium tin oxide anode for organic light emitting diodes

The authors report the enhancement of hole injection using an indium tin oxide (ITO) anode covered with ultraviolet (UV) ozone-treated Ag nanodots for fac tris (2-phenylpyridine) iridium Ir(ppy)3-doped phosphorescent organic light-emitting diodes (OLEDs). X-ray photoelectron spectroscopy and UV-visible spectrometer analysis exhibit that UV-ozone treatment of the Ag nanodots dispersed on the ITO anode leads to formation of Ag2O nanodots with high work function and high transparency. Phosphorescent OLEDs fabricated on the Ag2O nanodot-dispersed ITO anode showed a lower turn-on voltage and higher luminescence than those of OLEDs prepared with a commercial ITO anode. It was thought that, as Ag nanodots changed to Ag2O nanodots by UV-ozone treatment, the decrease of the energy barrier height led to the enhancement of hole injection in the phosphorescent OLEDs.This work was supported by Korea Research Foundation grant funded by Korean Government (MOEHRD: Basic Research Promotion Fund)(KRF-2006-003-D00243) and Ministry of Commerce, Industry, and Energy

Lead-free piezoceramics - Where to move on?

Lead-free piezoceramics aiming at replacing the market-dominant lead-based ones have been extensively searched for more than a decade worldwide. Some noteworthy outcomes such as the advent of commercial products for certain applications have been reported, but the goal, i.e., the invention of a lead-free piezocermic, the performance of which is equivalent or even superior to that of PZT-based piezoceramics, does not seem to be fulfilled yet. Nevertheless, the academic effort already seems to be culminated, waiting for a guideline to a future research direction. We believe that a driving force for a restoration of this research field needs to be found elsewhere, for example, intimate collaborations with related industries. For this to be effectively realized, it would be helpful for academic side to understand the interests and demands of the industry side as well as to provide the industry with new scientific insights that would eventually lead to new applications. Therefore, this review covers some of the issues that are to be studied further and deeper, so-to-speak, lessons from the history of piezoceramics, and some technical issues that could be useful in better understanding the industry demands. As well, the efforts made in the industry side will be briefly introduced for the academic people to catch up with the recent trends and to be guided for setting up their future research direction effectively.ope

Operative versus non-operative management of pediatric medial epicondyle fractures: a systematic review

There is ongoing debate about the management of medial epicondyle fractures in the pediatric population. This systematic review evaluated non-operative versus operative treatment of medial epicondyle fractures in pediatric and adolescent patients over the last six decades. A systematic review of the available literature was performed. Frequency-weighted mean union times were used to compare union rates for closed versus open treatments. Moreover, functional outcomes and range-of-motion variables were correlated with varying treatment modalities. Any complications, including ulnar nerve symptoms, pain, instability, infection, and residual deformity, were cataloged. Fourteen studies, encompassing 498 patients, met the inclusion/exclusion criteria. There were 261 males and 132 female patients; the frequency-weighted average age was 11.93 years. The follow-up range was 6–216 months. Under the cumulative random effects model, the odds of union with operative fixation was 9.33 times the odds of union with non-operative treatment (P < 0.0001). There was no significant difference between operative and non-operative treatments in terms of pain at final follow-up (P = 0.73) or ulnar nerve symptoms (P = 0.412). Operative treatment affords a significantly higher union rate over the non-operative management of medial epicondyle fractures. There was no difference in pain at final follow-up between operative and non-operative treatments. As surgical indications evolve, and the functional demands of pediatric patients increase, surgical fixation should be strongly considered to achieve stable fixation and bony union