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In the era of the Internet+, with the constant updating of new technologies and more and more software and hardware systems are being applied into public service of convention and exhibition industry, which obtains great leaping development. Every coin has two sides, along with the new technologies come lots of self-invited troubles to the advancement of convention and exhibition industry, and customization is just one of the cures to these problems. This article takes the example of the China International Travel Mart in Kunming in 2015 and puts forward a relatively simple customization plan to realize the efficient and ordered management of this CITM. Keywords—the Internet+; convention and exhibition industry; customization; CITM; public service

Porphyromonas gingivalis is present as a biofilm at the sites of periodontal infections. The detachment of gingival epithelial cells induced by P. gingivalis biofilms was examined using planktonic cultures as a comparison. Exponentially grown planktonic cultures or 40-h biofilms were co-incubated with epithelial cells in a 24-well plate for 4 h. Epithelial cell detachment was assessed using imaging. The activity of arginine-gingipain (Rgp) and gene expression profiles of P. gingivalis cultures were examined using a gingipain assay and quantitative PCR, respectively. P. gingivalis biofilms induced significantly higher cell detachment and displayed higher Rgp activity compared to the planktonic cultures. The genes involved in gingipain post-translational modification, but not rgp genes, were significantly up-regulated in P. gingivalis biofilms. The results underline the importance of including biofilms in the study of bacterial and host cell interactions.

Acrodysostosis is characterized by nasal hypoplasia, peripheral dysostosis, variable short stature, and intellectual impairment. Recently, mutations in PRKAR1A were reported in patients with acrodysostosis and hormone resistance. Subsequently, mutations in a phosphodiesterase gene (PDE4D) were identified in seven sporadic cases. We sequenced PDE4D in seven acrodysostosis patients from five families. Missense mutations were identified in all cases. Families showed de novo inheritance except one family with three affected children whose father was subsequently found to have subtle features of acrodysostosis. There were no recurrent mutations. Short stature and endocrine resistance are rare in this series; however, cognitive involvement and obesity were frequent. This last finding is relevant given PDE4D is insulin responsive and potentially involved in lipolysis. PDE4D encodes a cyclic AMP regulator and places PDE4D-related acrodysostosis within the same family of diseases as pseudohypoparathyroidism, pseudopseudohypoparathyroidism, PRKAR1A-related acrodysostosis and brachydactyly-mental retardation syndrome; all characterized by cognitive impairment and short distal extremities.

The signal processing of the medium-Earth-orbit synthetic aperture radar (SAR) is more challenging than that of the current low-Earth-orbit SAR because the imaging geometry is more complicated, and the range and azimuth variances are more severe. This paper deals with these imaging problems in three aspects. First, an advanced hyperbolic range equation (AHRE) is proposed for the first time, which is more precise for a spaceborne SAR than the conventional hyperbolic range equation (CHRE). Second, the point target spectrum based on the AHRE is analytically derived, which is useful for developing efficient SAR processing algorithms. Third, the well-known nonlinear chirp scaling (NLCS) algorithm is modified according to this new spectrum, and the so-called AHRE-based advanced NLCS (A-NLCS) algorithm is established. The simulation results validate the correctness of our method for L-band SAR systems at altitudes from 1000 to 10000 km with an azimuth resolution around 3 m. It is also shown that the A-NLCS algorithm has better performance than the CHRE-based algorithms in longer integration time cases. Therefore, we recommend the A-NLCS algorithm for a spaceborne SAR with a lower frequency, finer resolution, and higher satellite altitude.

In geosynchronous synthetic aperture radar (GEO SAR), the azimuth FM rate drastically falls and comes close to the variation rate of the Doppler centroid, due to the higher altitude. The effect of the variation of the Doppler parameters becomes significant and affects the azimuth resolution results. A concise azimuth resolution expression is deduced from the azimuth ambiguity function which involves the azimuth variance property and third-order range equation. It is more accurate for GEO SAR than the conventional expression. Meanwhile, the phenomenon where the traditional frequency algorithm becomes invalid is found. However, the time domain algorithm is still applicable when the azimuth FM rate approaches zero. Finally, the simulation results of the point targets at five typical areas verify the analysis.

Spotlight synthetic aperture radar (SAR) is a proven technique, which can provide high-resolution images as compared to those produced by traditional stripmap SAR. This paper addresses a high-resolution SAR focusing experiment based on Gaofen-3 satellite (GF-3) staring data with about 55 cm azimuth resolution and 240 MHz range bandwidth. In staring spotlight (ST) mode, the antenna always illuminates the same scene on the ground, which can extend the synthetic aperture. Based on a two-step processing algorithm, some special aspects such as curved-orbit model error correction, stop-and-go correction, and antenna pattern demodulation must be considered in image focusing. We provide detailed descriptions of all these aspects and put forward corresponding solutions. Using these suggested methods directly in an imaging module without any modification for other data processing software can make the most of the existing ground data processor. Finally, actual data acquired in GF-3 ST mode is used to validate these methodologies, and a well-focused, high-resolution image is obtained as a result of this focusing experiment.

Despite the increasing prevalence of clinical sequencing, the difficulty of identifying additional affected families is a key obstacle to solving many rare diseases. There may only be a handful of similar patients worldwide, and their data may be stored in diverse clinical and research databases. Computational methods are necessary to enable finding similar patients across the growing number of patient repositories and registries. We present the Matchmaker Exchange Application Programming Interface (MME API), a protocol and data format for exchanging phenotype and genotype profiles to enable matchmaking among patient databases, facilitate the identification of additional cohorts, and increase the rate with which rare diseases can be researched and diagnosed. We designed the API to be straightforward and flexible in order to simplify its adoption on a large number of data types and workflows. We also provide a public test data set, curated from the literature, to facilitate implementation of the API and development of new matching algorithms. The initial version of the API has been successfully implemented by three members of the Matchmaker Exchange and was immediately able to reproduce previously identified matches and generate several new leads currently being validated. The API is available at https://github.com/ga4gh/mme-apis.

Lateral meningocele syndrome (LMS), or Lehman syndrome, is a rare disorder characterized by multiple lateral spinal meningoceles, distinctive facial features, joint hypermobility and hypotonia, along with skeletal, cardiac, and urogenital anomalies. Heterozygous NOTCH3 mutations affecting the terminal exon 33 were recently reported as causative in six families with LMS. We report a boy with LMS, the fourteenth reported case, with a de novo 80 base pair deletion in exon 33 of NOTCH3. Our patient's prenatal findings, complex cardiac anomalies, and severe feeding difficulties further expand our understanding of this rare condition.

A novel approach combining the local frequency estimation with wavelet transform is presented to reduce interferometrie phase noise for InSAR. First, the maximum likelihood estimator is used to obtain the frequency range of the noisy interferogram. Then, the wavelet transform is employed to obtain the wavelet coefficients of the real and imaginary parts of the complex interferogram. For the wavelet coefficients within the estimated frequency range and that out of the range, the NeighShrink and VisuShrink methods are employed respectively to shrink them. As a result, the noise can be effectively filtered without the loss of detailed information of the interferogram based on the advantages of the two shrinkage methods. The performance of noise reduction and fringe preservation is verified by the experiments with real interferogram.

Charcot-Marie-Tooth disease is a group of genetically heterogeneous disorders characterized by a sensorimotor polyneuropathy with subsequent muscle atrophy, areflexia, and sensory loss. More than 60 genes have been linked to Charcot-Marie-Tooth phenotypes, including IGHMBP2. Until recently, mutations in IGHMBP2 were exclusively associated with spinal muscular atrophy with respiratory distress (SMARD1). We present a sibling pair with a novel homozygous truncating mutation in IGHMBP2. The patients presented with childhood-onset distal weakness, wasting in the upper and lower limbs, areflexia and decreased sensation, but no respiratory involvement. Exome sequencing was performed and a homozygous variant was identified (c.2601_2604del; p.Lys868Profs*109). Sanger sequencing confirmed the presence of this variant in a homozygous state in the two affected siblings, while both parents were heterozygous. Further analyses showed decreased mRNA and IGHMBP2 protein in a lymphoblast cell line derived from one of the siblings. We demonstrate the utility of next-generation sequencing in reaching a molecular diagnosis for a heterogeneous condition such as Charcot-Marie-Tooth. Taken together, our data and that from the literature suggest that the spectrum of clinical presentations associated with mutations in IGHMBP2 may be secondary, at least in part, to the amount of residual protein.

Photothermal therapy (PTT), as a promising treatment for tumours, has rarely been reported for application in artery restenosis, which is a common complication of endovascular management due to enduring chronic inflammation and abnormal cell proliferation. In our study, biodegradable polypyrrole nanoparticles (PPy-NPs) were synthesized and characterized, including their size distribution, UV-vis-NIR absorbance, molar extinction coefficients, and photothermal properties. We then verified that PPy-NP incubation followed by 915 nm near-infrared (NIR) laser irradiation could effectively ablate inflammatory macrophages in vitro, leading to significant cell apoptosis and cell death. Further, it was found that a combination of local PPy-NP injection with 915 nm NIR laser irradiation could significantly alleviate arterial inflammation by eliminating infiltrating macrophages and further ameliorating artery stenosis in an ApoE(-/-) mouse model, without showing any obvious toxic side effects. Thus, we propose that PTT based on PPy-NPs as photothermal agents and a 915 nm NIR laser as a power source can serve as a new effective treatment for reducing inflammation and stenosis formation in inflamed arteries after endovascular management.

Limb girdle muscular dystrophy (LGMD) is a heterogeneous group of genetic disorders leading to progressive muscle degeneration and often associated with cardiac complications. We present two adult siblings with childhood-onset of weakness progressing to a severe quadriparesis with the additional features of triangular tongues and biventricular cardiac dysfunction. Whole exome sequencing identified compound heterozygous missense mutations that are predicted to be pathogenic in LIMS2. Biopsy of skeletal muscle demonstrated disrupted immunostaining of LIMS2. This is the first report of mutations in LIMS2 and resulting disruption of the integrin linked kinase (ILK)-LIMS-parvin complex associated with LGMD.

To achieve early diagnosis for inheritable hearing loss and determine carrier rate of deafness causing gene mutations in order to provide information for premarital, prenatal and postnatal genetic counseling.A total of 17 000 dried heel blood spots of normal newborns in Chengdu were collected with informed consent obtained from their parents. Genomic DNA was extracted from dried blood spots using Qiagen DNA extraction kits. Microarrays with 9 common mutation loci of 4 deafness-associated genes in Chinese population were used. Nine hot mutations including GJB2 (35delG, 176del16, 235delC and 299delAT), GJB3 (538CT), SLC26A4 (IVS 7-2AG, 2168AG), and mitochondrial DNA 12S rRNA (1555AG, 1494CT) were detected by PCR amplification and microarray hybridization. Mutations detected by microarray were verified by Sanger DNA sequencing.Of the 17 000 new-borns, 542 neonates had mutations of the 4 genes. Heterozygous mutations of GJB2, at 235delC, 299delAT, and 176del16 were identified in 254, 55, and 15 newborns, respectively. Two newborns had homozygous mutation of GJB2, 235delC. Heterozygous mutations at 538CT of GJB3, 2168AG and IVS 7-2AG of SLC26A4 were found in 23, 17 and 128 newborns, respectively. For mutation analysis of mitochondrial DNA 12S rRNA, 1494CT and 1555AG were homogeneous mutations in 4 and 42 neonates, respectively. In addition, 6 complexity mutations were detected, which demonstrated that one newborn had heterozygous mutations at GJB2 235delC and SLC26A4, IVS7-2AG, one had heterozygous mutation GJB2 235delC and 12S rRNA homogeneous mutation, 1555 AG, one heterozygous mutations at GJB2, 299delAT, and GJB3, 538CT, one at GJB2, 299delAT and 12S rRNA, 1555 AG, two at GJB2, 299delAT, and SLC26A4, IVS7-2AG. All mutations as above were confirmed by DNA sequencing.The total mutation carrier rate of the 4 deafness genes is 3.19% in healthy newborns at Chengdu. Mutations of GJB2 and SLAC26A4 are major ones (86.5% of total). The mutation rate of mitochondrial DNA 12S rRNA is 2.71‰, which may have deafness induced by aminoglycoside antibiotics. Newborn screening for mutation of genes related to hereditary deafness plays an important role in the early detection and proper management for neonatal deafness as well as genetic counseling for premarital, prenatal and postnatal diagnosis.

We report a new use of dendrimer-entrapped gold nanoparticles (Au DENPs) modified by polyethylene glycol (PEG) with good biocompatibility for in vitro and in vivo imaging of atherosclerotic mice by computed tomography (CT). In this study, Au DENPs were synthesized using poly(amidoamine) (PAMAM) dendrimers of generation 5 (G5.NH2) modified by PEG monomethyl ether (G5.NH2-m PEG20) as templates. In vitro cytotoxicity and flow cytometry assays show that the formed PEGylated Au DENPs have good biocompatibility and are non-cytotoxic at the Au concentration up to 300 μM. Silver staining and transmission electron microscopy (TEM) further confirm that the Au DENPs are able to be uptaken by macrophages and are located dominantly in the lysosomes of the cells. Importantly, the formed PEGylated Au DENPs are able to be used for CT imaging of murine macrophages in vitro and macrophages in atherosclerotic mice in vivo using apolipoprotein-E-gene-deficient mice as a model. These findings suggest that the formed PEGylated Au DENPs are a promising contrast agent for CT imaging of atherosclerosis.

To evaluate the clinical value of primary stenting for treating peripheral arterial diseases in below-the-knee arteries by comparing to percutaneous transluminal angioplasty (PTA).PubMed, ScienceDirect, Embase, and CBM databases were searched for relevant articles. Based on the different types of stents, we divided the primary stent group into the bare metal stent(BMS) group and drug-eluting stent(DES) group. The outcome measures were immediate technical success, freedom from target vessel revascularization (TVR-free) rate and limb salvage.Finally, 14 studies (published between 2001 and 2012) satisfying the inclusion criteria were identified. A total of 3 278 patients and 3 699 limbs constituted our final study population. The technical success rate of PTA was 90.95% (95% confidence interval (CI) 86.25%-94.15%). Only one study reported a technical failure of 4% (5/118) in the primary stent group. There were no significant differences in the 1-year primary patency and TVR-free rates between the PTA group and BMS groups (P0.05 and P0.05), respectively. The pooled estimates of 1-year primary patency and TVR-free rate in DES group were 85.05% (95%CI 79.95%-89.02%) and 90.52% (95%CI 83.68%-94.67%), respectively, which were better than those of the BMS (P0.001) and PTA groups (P0.001). The pooled estimate of 1-year limb salvage in the PTA, BMS, and DES groups was 88.41% (95%CI 84.53%-91.43%), 94.41% (95%CI 89.52%-97.1%), and 96.81% (95%CI 94.04%-98.32%), respectively. The BMS and DES groups had higher limb salvage rates than the PTA group (P0.001 for both comparisons). The rates of severe complications were low both in the PTA and primary stent groups. Although the influence analysis showed rather robust results, the heterogeneity was quite high and they were not adjusted for confounding variables.Primary BMS implantation had no advantage over PTA in reducing restenosis or revascularization for infrapopliteal disease. Primary DES implantation seems to be a promising treatment for focal infrapopliteal lesions.

We present an individual with a generalized and infantile onset lipodystrophy who later developed hypertriglyceridemia, pancreatitis, refractory diabetes, irregular menses and renal failure. She showed the hallmark features of a congenital, generalized lipodystrophy (CGL). Sequencing PPARG identified two pathogenic mutations; c.413_416delAATG; p.Glu138ValfsX168 and c.490C>T; p.R164W. The phenotype and presence of two mutations suggests that biallelic mutations at PPARG cause a CGL similar to that observed with biallelic AGPAT2 or BSCL2 mutations.

Free D-amino acids (D-AAs) are one of the most striking features of the peptidoglycan composition in bacteria and play a key role in regulating and disassembling bacterial biofilms. Previous studies have indicated that the antimicrobial peptide nisin can inhibit the growth of the cariogenic bacteria Streptococcus mutans. The present study investigated the effect of free amino acids either alone or in combination with nisin on biofilm and on planktonic S. mutans bacteria. The results of the MIC and MBC analyses showed that D-cysteine (Cys), D- or L-aspartic acid (Asp), and D- or L-glutamic acid (Glu) significantly improve the antibacterial activity of nisin against S. mutans and that the mixture of D-Cys, D-Asp, and D-Glu (3D-AAs) and the mixture of L-Cys, L-Asp, and L-Glu (3L-AAs) at a concentration of 40 mM can prevent S. mutans growth. Crystal violet staining showed that the D- or L-enantiomers of Cys, Asp, and Glu at a concentration of 40 mM can inhibit the formation of S. mutans biofilms, and their mixture generated a stronger inhibition than the components alone. Furthermore, the mixture of the three D-AAs or L-AAs may improve the antibacterial activity of nisin against S. mutans biofilms. This study underscores the potential of free amino acids for the enhancement of the antibacterial activity of nisin and the inhibition of the cariogenic bacteria S. mutans and biofilms.

In geosynchronous synthetic aperture radar (SAR), due to the complex relative motion between the satellite and the target, and the effect of the curvature on the earth surface, the conventional imaging geometry for ground resolution analysis should be innovated. In this paper, the imaging geometry is advanced by adding a pitch angle. Then, based on the new geometry, the range resolution and the Doppler gradient resolution in the ground plane are deduced using gradient method. Finally, the resolution analysis is verified by simulation results.

Background Congenital nonprogressive spinocerebellar ataxia is characterized by early gross motor delay, hypotonia, gait ataxia, mild dysarthria and dysmetria. The clinical presentation remains fairly stable and may be associated with cerebellar atrophy. To date, only a few families with autosomal dominant congenital nonprogressive spinocerebellar ataxia have been reported. Linkage to 3pter was demonstrated in one large Australian family and this locus was designated spinocerebellar ataxia type 29. The objective of this study is to describe an unreported Canadian family with autosomal dominant congenital nonprogressive spinocerebellar ataxia and to identify the underlying genetic causes in this family and the original Australian family. Methods and Results Exome sequencing was performed for the Australian family, resulting in the identification of a heterozygous mutation in the ITPR1 gene. For the Canadian family, genotyping with microsatellite markers and Sanger sequencing of ITPR1 gene were performed; a heterozygous missense mutation in ITPR1 was identified. Conclusions ITPR1 encodes inositol 1,4,5-trisphosphate receptor, type 1, a ligand-gated ion channel that mediates calcium release from the endoplasmic reticulum. Deletions of ITPR1 are known to cause spinocerebellar ataxia type 15, a distinct and very slowly progressive form of cerebellar ataxia with onset in adulthood. Our study demonstrates for the first time that, in addition to spinocerebellar ataxia type 15, alteration of ITPR1 function can cause a distinct congenital nonprogressive ataxia; highlighting important clinical heterogeneity associated with the ITPR1 gene and a significant role of the ITPR1-related pathway in the development and maintenance of the normal functions of the cerebellum.

Due to the significant azimuth variance property in medium-Earth-orbit (MEO) synthetic aperture radar (SAR) echo, it is difficult for the conventional SAR algorithms to achieve a good compromise between accuracy and efficiency. A novel algorithm based on Keystone transform (KT) and azimuth perturbation (AP) is introduced in this paper to handle this problem. The function of KT is to correct the range walk and thus to mitigate the azimuth variance effect on range processing. The function of AP is to equalize the Doppler histories in each range gate and thus to mitigate the azimuth variance effect on azimuth compressing. Simulation results of an L-band MEO SAR with 5 m resolution at 10,000 km altitude demonstrate the capability of our algorithm.

Acrodysostosis is characterized by nasal hypoplasia, peripheral dysostosis, variable short stature, and intellectual impairment. Recently, mutations in PRKAR1A were reported in patients with acrodysostosis and hormone resistance. Subsequently, mutations in a phosphodiesterase gene (PDE4D) were identified in seven sporadic cases. We sequenced PDE4D in seven acrodysostosis patients from five families. Missense mutations were identified in all cases. Families showed de novo inheritance except one family with three affected children whose father was subsequently found to have subtle features of acrodysostosis. There were no recurrent mutations. Short stature and endocrine resistance are rare in this series; however, cognitive involvement and obesity were frequent. This last finding is relevant given PDE4D is insulin responsive and potentially involved in lipolysis. PDE4D encodes a cyclic AMP regulator and places PDE4D-related acrodysostosis within the same family of diseases as pseudohypoparathyroidism, pseudopseudohypoparathyroidism, PRKAR1A-related acrodysostosis and brachydactyly-mental retardation syndrome; all characterized by cognitive impairment and short distal extremities.

Purpose Mutations in the homeobox transcription factor paired-like homeodomain transcription factor 2 (PITX2) cause Axenfeld–Reiger syndrome (ARS), which is associated with anterior segment dysgenesis (ASD) and glaucoma. To understand ARS pathogenesis, it is essential to know the normal functions of PITX2 and the proteins with which PITX2 interacts in the eye. Therefore, we used a unique cDNA library that we created from human trabecular meshwork (TM) primary cells to discover PITX2-interacting proteins (PIPs). Methods A human TM cDNA library was created from primary cells in the ProQuest Two-Hybrid prey vector: pEXP-AD502. Human PITX2A and PITX2C isoforms were used independently as “bait” to identify novel PIPs. A total of 1.25×106 clones were screened by yeast two-hybrid (Y2H) analyses. PIPs obtained from each Y2H experiment were confirmed by yeast retransformation and mammalian co-immunoprecipitation assays. Results EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2) was identified by both PITX2A and PITX2C isoforms as a novel PIP from Y2H analyses. EFEMP2 is 443 amino acids long with six epidermal growth factor (EGF)-like modules and one fibulin-like module. The PITX2-interaction domain in EFEMP2 lies between the second EGF-like module and the COOH-terminal fibulin-like module. Co-immunoprecipitation assays in COS-7 cells confirmed the interaction between PITX2 and EFEMP2. Conclusions We discovered EFEMP2 as a novel PITX2-interacting protein. Further, our cDNA library made from human TM primary cells is a unique and effective resource to identify novel interacting proteins for glaucoma and ASD candidates. This resource could be used both for discovery and validation of interactomes identified from in silico analysis.

Joubert syndrome related disorders (JSRDs) have broad but variable phenotypic overlap with other ciliopathies. The molecular etiology of this overlap is unclear but probably arises from disrupting common functional module components within primary cilia. To identify additional module elements associated with JSRDs, we performed homozygosity mapping followed by next-generation sequencing (NGS) and uncovered mutations in TMEM237 (previously known as ALS2CR4). We show that loss of the mammalian TMEM237, which localizes to the ciliary transition zone (TZ), results in defective ciliogenesis and deregulation of Wnt signaling. Furthermore, disruption of Danio rerio (zebrafish) tmem237 expression produces gastrulation defects consistent with ciliary dysfunction, and Caenorhabditis elegans jbts-14 genetically interacts with nphp-4, encoding another TZ protein, to control basal body-TZ anchoring to the membrane and ciliogenesis. Both mammalian and C. elegans TMEM237/JBTS-14 require RPGRIP1L/MKS5 for proper TZ localization, and we demonstrate additional functional interactions between C. elegans JBTS-14 and MKS-2/TMEM216, MKSR-1/B9D1, and MKSR-2/B9D2. Collectively, our findings integrate TMEM237/JBTS-14 in a complex interaction network of TZ-associated proteins and reveal a growing contribution of a TZ functional module to the spectrum of ciliopathy phenotypes.

The kth-order polynomial range model (PRM) for Medium-Earth-Orbit (MEO) Synthetic Aperture Radar (SAR) signal processing is proposed, analyzed, and verified in this paper. The coefficients of the PRM are calculated according to the relative state vectors between the satellite and the given target on earth, which implies power series expansion around the beam center crossing time. In addition, the relevant two-dimensional spectrum is deduced out as well by using the principle of stationary phase (POSP) and the series reversion approximation. The accuracy of this spectrum is flexible and limited both by the order of the PRM and the order of the spectrum in an expanded form. Therefore, the PRM-based spectrum is general for MEO SAR with any azimuth resolution at any orbit height.

The conjugate Lorenz chaotic system is a newly coined chaotic system. In this paper, the Takagi-Sugeno (T-S) fuzzy model for the chaotic system is presented; then based on Lyapunov stability theory and using the linear matrix inequalities (LMIs) technique, the robust sliding mode controller for the T-S fuzzy conjugate Lorenz system with uncertainties was designed. The obtained sliding mode controller guarantees the global fuzzy conjugate Lorenz system confined on the sliding surface is asymptotically stable. Finally, numerical simulations are given to illuminate the effectiveness of the theoretical results.

Exposure to antibiotics is considered to be the major driver in the selection of antibiotic-resistant bacteria and may induce diverse biological responses in bacteria. MTAD is a common intracanal irrigant, but its bactericidal activity remains to be improved. Previous studies have indicated that the antimicrobial peptide nisin can significantly improve the bactericidal activity of MTAD against Enterococcus faecalis. However, the effects of MTAD and its modification at sub-minimum inhibitory concentration (sub-MIC) levels on Enterococcus faecalis growth and the expression of pathogenic genes still need to be explored. In this study, the results of post-antibiotic effects (PAE) and post-antibiotic sub-MIC effects (PASME) showed that MTADN (nisin in combination with MTAD) had the best post-antibiotic effect. E. faecalis after challenge with MTAD was less sensitive to alkaline solutions compared with MTAN (nisin in place of doxycycline in MTAD) and MTADN. E. faecalis induced with sub-MIC of MTAD generated resistance to the higher concentration, but induction of E. faecalis with MTAN did not cause resistance to higher concentrations. Furthermore, real-time polymerase chain reaction (RT-PCR) showed that the stress caused by sub-MIC exposure to MTAD, MTAN, or MTADN resulted in up- or down-regulation of nine stress genes and four virulence-associated genes in E. faecalis and resulted in different stress states. These findings suggested that nisin improved the post-antibacterial effect of MTAD at sub-MIC levels and has considerable potential for use as a modification of MTAD.

Enterococcus faecalis rank among the leading causes of nosocomial infections worldwide and possesses both intrinsic and acquired resistance to a variety of antibiotics. Development of new antibiotics is limited, and pathogens continually generate new antibiotic resistance. Many researchers aim to identify strategies to effectively kill this drug-resistant pathogen. Here, we evaluated the effect of the antimicrobial peptide nisin on the antibacterial activities of 18 antibiotics against E. faecalis. The MIC and MBC results showed that the antibacterial activities of 18 antibiotics against E. faecalis OG1RF, ATCC 29212, and strain E were significantly improved in the presence of 200 U/ml nisin. Statistically significant differences were observed between the results with and without 200 U/ml nisin at the same concentrations of penicillin or chloramphenicol (p

Background We recently described a novel autosomal recessive neurodevelopmental disorder with intellectual disability in four patients from two related Hutterite families. Identity-by-descent mapping localized the gene to a 5.1 Mb region at chromosome 16p13.3 containing more than 170 known or predicted genes. The objective of this study was to identify the causative gene for this rare disorder. Methods and results Candidate gene sequencing followed by exome sequencing identified a homozygous missense mutation p.Gly46Arg, in THOC6. No other potentially causative coding variants were present within the critical region on chromosome 16. THOC6 is a member of the THO/TREX complex which is involved in coordinating mRNA processing with mRNA export from the nucleus. In situ hybridization showed that thoc6 is highly expressed in the midbrain and eyes. Cellular localization studies demonstrated that wild-type THOC6 is present within the nucleus as is the case for other THO complex proteins. However, mutant THOC6 was predominantly localized to the cytoplasm, suggesting that the mutant protein is unable to carry out its normal function. siRNA knockdown of THOC6 revealed increased apoptosis in cultured cells. Conclusion Our findings associate a missense mutation in THOC6 with intellectual disability, suggesting the THO/TREX complex plays an important role in neurodevelopment.

Mandibulofacial dysostosis with microcephaly (MFDM) is a rare sporadic syndrome comprising craniofacial malformations, microcephaly, developmental delay, and a recognizable dysmorphic appearance. Major sequelae, including choanal atresia, sensorineural hearing loss, and cleft palate, each occur in a significant proportion of affected individuals. We present detailed clinical findings in 12 unrelated individuals with MFDM; these 12 individuals compose the largest reported cohort to date. To define the etiology of MFDM, we employed whole-exome sequencing of four unrelated affected individuals and identified heterozygous mutations or deletions of EFTUD2 in all four. Validation studies of eight additional individuals with MFDM demonstrated causative EFTUD2 mutations in all affected individuals tested. A range of EFTUD2-mutation types, including null alleles and frameshifts, is seen in MFDM, consistent with haploinsufficiency; segregation is de novo in all cases assessed to date. U5-116kD, the protein encoded by EFTUD2, is a highly conserved spliceosomal GTPase with a central regulatory role in catalytic splicing and post-splicing-complex disassembly. MFDM is the first multiple-malformation syndrome attributed to a defect of the major spliceosome. Our findings significantly extend the range of reported spliceosomal phenotypes in humans and pave the way for further investigation in related conditions such as Treacher Collins syndrome. © 2012 The American Society of Human Genetics.

Jinbao Qin,1,* Chen Peng,2,* Binghui Zhao,2,* Kaichuang Ye,1 Fukang Yuan,1 Zhiyou Peng,1 Xinrui Yang,1 Lijia Huang,1 Mier Jiang,1 Qinghua Zhao,3 Guangyu Tang,2 Xinwu Lu1,4 1Department of Vascular Surgery, Shanghai Ninth People’s Hospital Affiliated to Shanghai JiaoTong University, School of Medicine; 2Department of Radiology, Shanghai Tenth People’s Hospital Affiliated toTongji University, School of Medicine; 3Department of Orthopaedics, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong University; 4Vascular Center ofShanghai JiaoTong University, Shanghai, People’s Republic of China *These authors contributed equally tothis work Abstract: Macrophages are becoming increasingly significant in the progression of atherosclerosis (AS). Molecular imaging of macrophages may improve the detection and characterization of AS. In this study, dendrimer-entrapped gold nanoparticles (Au DENPs) with polyethylene glycol (PEG) and fluorescein isothiocyanate (FI) coatings were designed, tested, and applied as contrast agents for the enhanced computed tomography (CT) imaging of macrophages in atherosclerotic lesions. Cell counting kit-8 assay, fluorescence microscopy, silver staining, and transmission electron microscopy revealed that the FI-functionalized Au DENPs are noncytotoxic at high concentrations (3.0µM) and can be efficiently taken up by murine macrophages in vitro. These nanoparticles were administered to apolipoprotein E knockout mice as AS models, which demonstrated that the macrophage burden in atherosclerotic areas can be tracked noninvasively and dynamically three-dimensionally in live animals using micro-CT. Our findings suggest that the designed PEGylated gold nanoparticles are promising biocompatible nanoprobes for the CT imaging of macrophages in atherosclerotic lesions and will provide new insights into the pathophysiology of AS and other concerned inflammatory diseases. Keywords: atherosclerosis, CT, in vivo imaging

IntroductionTherapeutic angiogenesis by transplantation of autologous/allogeneic adipose-derived stem cells (ADSCs) is a potential approach for severe ischemic diseases. However, poor viability, adhesion, migration and differentiation limit the therapeutic efficiency after the cells were transplanted into the targeted area. Periostin, an extracellular matrix protein, exhibits a critical role in wound repair as well as promotes cell adhesion, survival, and angiogenesis.MethodADSCs were obtained and genetically engineered with periostin gene (P-ADSCs). The viability, proliferation, migration, and apoptosis of P-ADSCs under hypoxia were analyzed. Moreover, P-ADSCs were implanted into Apo E deficient mice with hind limb ischemia. The Laser Doppler perfusion index, immunofluorescence, and histological pathology assay were tested to evaluate the therapeutic effects. The associated molecular mechanism of periostin on the proliferation, adhesion, migration, and differentiation of ADSCs was also analyzed.ResultsThe in vitro studies have shown that periostin-transfected ADSCs (P-ADSCs) promoted viability, proliferation, and migration of ADSCs. Apoptosis of ADSCs was inhibited under hypoxic conditions. The Laser Doppler perfusion index was significantly higher in the P-ADSCs group compared with that in the ADSC and control groups after 4 weeks. Immunofluorescence and histological pathology assay showed that the P-ADSCs were in and around the ischemic sites, and some cells differentiated into capillaries and endothelium. Microvessel densities were significantly improved in P-ADSCs group compared with those in the control group. The molecular mechanisms that provide the beneficial effects of periostin were connected with the upregulated expression of integrinβ1/FAK/PI3K/Akt/eNOS signal pathway and the increased secretion of growth factors.ConclusionOverexpression of periostin by gene transfection on ADSCs promotes survival, migration, and therapeutic efficiency, which will bring new insights into the treatment of critical limb ischemia.

This article proposes an imaging algorithm based on Keystone Transform for bistatic SAR with a stationary receiver. It can efficiently be applied to high-resolution spotlight mode, and can directly be process the bistatic SAR data which have been ranged compressed by the synchronization reference pulses. Both simulation and experimental results validate the good performance of this algorithm.