Molecular Dynamics Simulation of Macromolecules Using Graphics Processing Unit

Molecular dynamics (MD) simulation is a powerful computational tool to study the behavior of macromolecular systems. But many simulations of this field are limited in spatial or temporal scale by the available computational resource. In recent years, graphics processing unit (GPU) provides unprecedented computational power for scientific applications. Many MD algorithms suit with the multithread nature of GPU. In this paper, MD algorithms for macromolecular systems that run entirely on GPU are presented. Compared to the MD simulation with free software GROMACS on a single CPU core, our codes achieve about 10 times speed-up on a single GPU. For validation, we have performed MD simulations of polymer crystallization on GPU, and the results observed perfectly agree with computations on CPU. Therefore, our single GPU codes have already provided an inexpensive alternative for macromolecular simulations on traditional CPU clusters and they can also be used as a basis to develop parallel GPU programs to further speedup the computations.Comment: 21 pages, 16 figure

Roles of bacterial extracellular vesicles in systemic diseases

Accumulating evidence suggests that in various systems, not all bidirectional microbiota–host interactions involve direct cell contact. Bacterial extracellular vesicles (BEVs) may be key participants in this interkingdom crosstalk. BEVs mediate microbiota functions by delivering effector molecules that modulate host signaling pathways, thereby facilitating host–microbe interactions. BEV production during infections by both pathogens and probiotics has been observed in various host tissues. Therefore, these vesicles released by microbiota may have the ability to drive or inhibit disease pathogenesis in different systems within the host. Here, we review the current knowledge of BEVs and particularly emphasize their interactions with the host and the pathogenesis of systemic diseases

Phytohormone Abscisic Acid Improves Spatial Memory and Synaptogenesis Involving NDR1/2 Kinase in Rats

The abscisic acid (ABA) is a phytohormone involved in plant growth, development and environmental stress response. Recent study showed ABA can also be detected in other organisms, including mammals. And it has been reported that ABA can improve learning and memory in rats. In this study, we attempted to investigate the effects of ABA on the alternation of dendritic spine morphology of pyramidal neurons in developmental rats, which may underlie the learning and memory function. Behavior tests showed that ABA significantly improved spatial memory performance. Meanwhile, Golgi-Cox staining assay showed that ABA significantly increased the spine density and the percentage of mushroom-like spines in pyramidal neurons of hippocampus, indicating that ABA increased dendritic spine formation and maturation, which may contribute to the improvement of spatial memory. Furthermore, ABA administration increased the protein expression of NDR1/2 kinase, as well as mRNA levels of NDR2 and its substrate Rabin8. In addition, NDR1/2 shRNA prohibited the ABA-induced increases in the expression of NDR1/2 and spine density. Together, our study indicated that ABA could improve learning and memory in rats and the effect are possibly through the regulation of synaptogenesis, which is mediated via NDR1/2 kinase pathway

Design and implementation of LPWA-based air quality monitoring system

Increasing attention has been paid to air quality monitoring with a rapid development in industry and transportation applications in the modern society. However, the existing air quality monitoring systems cannot provide satisfactory spatial and temporal resolutions of the air quality information with low costs in real time. In this paper, we propose a new method to implement the air quality monitoring system based on state-of-the-art Internet-of-Things (IoT) techniques. In this system, portable sensors collect the air quality information timely, which is transmitted through a low power wide area network. All air quality data are processed and analyzed in the IoT cloud. The completed air quality monitoring system, including both hardware and software, is developed and deployed successfully in urban environments. Experimental results show that the proposed system is reliable in sensing the air quality, which helps reveal the change patterns of air quality to some extent

An IoT-cloud based wearable ECG monitoring system for smart healthcare

Public healthcare has been paid an increasing attention given the exponential growth human population and medical expenses. It is well known that an effective health monitoring system can detect abnormalities of health conditions in time and make diagnoses according to the gleaned data. As a vital approach to diagnose heart diseases, ECG monitoring is widely studied and applied. However, nearly all existing portable ECG monitoring systems cannot work without a mobile application, which is responsible for data collection and display. In this paper, we propose a new method for ECG monitoring based on Internet-of-Things (IoT) techniques. ECG data are gathered using a wearable monitoring node and are transmitted directly to the IoT cloud using Wi-Fi. Both the HTTP and MQTT protocols are employed in the IoT cloud in order to provide visual and timely ECG data to users. Nearly all smart terminals with a web browser can acquire ECG data conveniently, which has greatly alleviated the cross-platform issue. Experiments are carried out on healthy volunteers in order to verify the reliability of the entire system. Experimental results reveal that the proposed system is reliable in collecting and displaying real-time ECG data, which can aid in the primary diagnosis of certain heart diseases

DataSheet1_Analysis of RPGR gene mutations in 41 Chinese families affected by X-linked inherited retinal dystrophy.PDF

Background: This study analyzed the phenotypes and genotypes of 41 Chinese families with inherited retinal dystrophy (IRD) and RPGR gene mutations.Methods: This retrospective analysis evaluated a cohort of 41 patients who were subjected to a specific Hereditary Eye Disease Enrichment Panel (HEDEP) analysis. All (likely) pathogenic variants were determined by Sanger sequencing, and co-segregation analyses were performed on the available family members. All cases were subjected to Sanger sequencing for RPGR open reading frame 15 (ORF15) mutations.Results: A total of 41 probands from different families with a clinical diagnosis of retinitis pigmentosa (RP; 34 cases) and cone-rod dystrophy (CORD; 7 cases) were included in this cohort. According to clinical information, 2, 18, and 21 cases were first assigned as autosomal dominant (AD), sporadic, and X-linked (XL) inheritance, respectively. Several cases of affected females who presented with a male phenotype have been described, posing challenges at diagnosis related to the apparent family history of AD. Mutations were located in RPGR exons or introns 1–14 and in ORF15 of 12 of 41 (29.3%) and 29 of 41 (70.7%) subjects, respectively. Thirty-four (likely) pathogenic mutations were identified. Frameshifts were the most frequently observed variants, followed by nonsense, splice, and missense mutations. Herein, a detailed description of four RP patients carrying RPGR intronic mutations is reported, and in vitro splice assays were performed to confirm the pathogenicity of these intronic mutations.Conclusion: Our findings provide useful insights for the genetic and clinical counseling of patients with XL IRD, which will be useful for ongoing and future gene therapy trials.</p

Androgen receptor and heat shock protein 27 co-regulate the malignant potential of molecular apocrine breast cancer

Abstract Background The most striking feature of molecular apocrine breast cancer (MABC) is the expression of androgen receptor (AR). We report here the mechanism of the AR in regulating the behavior of MABC. Methods The MABC cell line, MDA-MB-453, and the nonMABC cell line, MCF7, were used in this study. The effect of dihydrotestosterone (DHT) and heat shock protein 27 (HSP27) on cell proliferation was quantified using the cell counter kit-8 (CCK8) and clonogenic assays in vitro and by a xenograft tumor model in vivo. The expression of the AR and HSP27 was analyzed using western blot, qPCR, and immunofluorescence assays. Complexes of the AR and HSP27 were detected by co-immunoprecipitation (Co-IP). Results In MDA-MB-453 cells, DHT promoted cell proliferation and stimulated AR and HSP27 translocation from the cytoplasm to the nucleus, whereas, it inhibited MCF7 cell growth, and only the AR translocated into the nucleus. HSP27 knock-down decreased the proliferative ability of MDA-MB-453 cells, which could be rescued by DHT, while HSP27 and DHT had synergistic effects on MCF7 cells. HSP27 phosphorylation was a prerequisite for AR translocation into the nucleus, especially phosphorylation on serine 82. In addition, DHT stimulated the tumorigenic and metastatic capacities of MDA-MB-453 cells, while HSP27 knock-down decreased the rate of tumor formation and induced apoptosis in cells. Conclusions The results suggest that HSP27 assists the AR in regulating the malignant behavior of MABC, and these findings might be helpful in the treatment of MABC

AR–PDEF pathway promotes tumour proliferation and upregulates MYC-mediated gene transcription by promoting MAD1 degradation in ER-negative breast cancer

Abstract Background Androgen receptor (AR) is expressed in 60%~ 70% oestrogen receptor (ER)-negative breast cancer (BC) cases and promotes the growth of this cancer subtype. Expression of prostate-derived Ets factor (PDEF), a transcription factor, is highly restricted to epithelial cells in hormone-regulated tissues. MYC and its negative regulator MAD1 play an important role in BC progression. Previously, we found that PDEF expression is strongly correlated with AR expression. However, the relationship between AR and PDEF and the function of PDEF in ER-negative BC proliferation are unclear. Methods AR and PDEF expression in ER-negative BC tissues and cell lines was determined by performing immunohistochemistry or western blotting. Protein expression levels and location were analysed by performing western blotting, RT-qPCR and immunofluorescence staining. Co-immunoprecipitation and chromatin immunoprecipitation assays were performed to validate the regulation of AR–PDEF–MAD1–MYC axis. Moreover, the effect of AR and PDEF on BC progression was investigated both in vitro and in vivo. Results We found that PDEF was overexpressed in ER-negative BC tissues and cell lines and appeared to function as an oncogene. PDEF expression levels were strongly correlated with AR expression in ER-negative BC, and PDEF transcription was positively regulated by AR. PDEF upregulated MYC-mediated gene transcription by promoting MAD1 degradation in ER-negative BC. Finally, we found that compared with the inhibition of AR expression alone, simultaneous inhibition of AR and PDEF expression further suppressed tumour proliferation both in vitro and in vivo. Conclusions Our data highlight the role of the AR–PDEF–MAD1–MYC axis in BC progression and suggest that PDEF can be used as a new clinical therapeutic target for treating ER-negative BC

Concise and efficient synthesis of eliglustat

<p>Eliglustat, a ceramide glucosyltransferase inhibitor, was synthesized in six steps with 28.4% overall yield. The key features include the use of a diastereoselective aldol reaction to construct two contiguous stereocenters and a selective sulfonylation of a 1,3-diol catalyzed by dibutyltin oxide.</p