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Background: Tea plants (Camellia sinensis) are used to produce one of the most important beverages worldwide. The nutritional value and healthful properties of tea are closely related to the large amounts of three major characteristic constituents including polyphenols (mainly catechins), theanine and caffeine. Although oil tea (Camellia oleifera) belongs to the genus Camellia, this plant lacks these three characteristic constituents. Comparative analysis of tea and oil tea via RNA-Seq would help uncover the genetic components underlying the biosynthesis of characteristic metabolites in tea. Results: We found that 3,787 and 3,359 bud genes, as well as 4,042 and 3,302 leaf genes, were up-regulated in tea and oil tea, respectively. High-performance liquid chromatography (HPLC) analysis revealed high levels of all types of catechins, theanine and caffeine in tea compared to those in oil tea. Activation of the genes involved in the biosynthesis of these characteristic compounds was detected by RNA-Seq analysis. In particular, genes encoding enzymes involved in flavonoid, theanine and caffeine pathways exhibited considerably different expression levels in tea compared to oil tea, which were also confirmed by quantitative RT-PCR (qRT-PCR). Conclusion: We assembled 81,826 and 78,863 unigenes for tea and oil tea, respectively, based on their differences at the transcriptomic level. A potential connection was observed between gene expression and content variation for catechins, theanine and caffeine in tea and oil tea. The results demonstrated that the metabolism was activated during the accumulation of characteristic metabolites in tea, which were present at low levels in oil tea. From the molecular biological perspective, our comparison of the transcriptomes and related metabolites revealed differential regulatory mechanisms underlying secondary metabolic pathways in tea versus oil tea. [ABSTRACT FROM AUTHOR]

Background: Radical hysterectomy and radiotherapy have long been mainstays of cervical cancer treatment. Early stage cervical cancer (FIGO stage IB1-IIA) is traditionally treated using radical surgery combined with radiotherapy, while locally advanced cervical cancer is treated using radiotherapy alone or chemoradiotherapy. In this retrospective study, we describe and analyse the presenting clinical features and outcomes in our cohort and evaluate possible risk factors for postoperative morbidity in women who underwent surgery for chronic radiation enteropathy (CRE). Methods: One hundred sixty-six eligible cervical cancer patients who underwent surgery for CRE were retrospectively identified between September 2003 and July 2014 in a prospectively maintained database. Among them, 46 patients received radical radiotherapy (RRT) and 120 received radical surgery plus radiotherapy (RS + RT). Clinical features, postoperative morbidity and mortality, and risk factors for postoperative morbidity were analysed. Results: RS + RT group patients were more likely to present with RTOG/EORTC grade III late morbidity (76.1 % vs 92.5 %; p = 0.004), while RRT group patients tended to show RTOG/EORTC grade IV late morbidity (23.9 % vs 7.5 %; p = 0.004). One hundred forty patients (84.3 %) were treated with aggressive resection (anastomosis 57.8 % and stoma 26.5 %). Overall and major morbidity, mortality and incidence of reoperation in the RRT and RS + RT groups did not differ significantly (63 % vs 64.2 % [p = 1.000], 21.7 % vs 11.7 % [p = 0.137], 6.5 % vs 0.8 % [p = 0.065] and 6.5 % vs 3.3 % [p = 0.360], respectively). However, incidence of permanent stoma and mortality during follow-up was higher in the RRT group than in the RS + RT group (44.2 % vs 12.6 % [p = 0.000] and 16.3 % vs 3.4 % [p = 0.004], respectively). In multivariate analysis, preoperative anaemia was significantly associated with overall morbidity (p = 0.015), while severe intra-abdominal adhesion (p = 0.017), ASA grades III-V (P = 0.022), and RTOG grade IV morbidity (P = 0.018) were predicators of major morbidity. Conclusions: Radiation-induced late morbidity tended to be severe in the RRT group with more patients suffering RTOG/EORTC grade IV morbidity, while there were no significant differences in postoperative morbidity, mortality and reoperation. Aggressive resection was feasible with acceptable postoperative outcomes. Severe intra-abdominal adhesion, ASA grades III-V and RTOG/EORTC grade IV late morbidity contributed significantly to major postoperative morbidity [ABSTRACT FROM AUTHOR]

Background: Percutaneous vertebroplasty (PVP) typically involves conventional lower-viscosity cement injection via bipedicular approach. Limited evidence is available comparing the clinical outcomes and complications in treating osteoporotic vertebral compression fractures (OVCFs) with PVP using high-viscosity cement through unipedicular or bipedicular approach. Methods and design: Fifty patients with OVCFs were randomly allocated into two groups adopting unipedicular or bipedicular PVP. The efficacy of unipedicular and bipedicular PVP was assessed by comparing operation time, X-ray exposure time, incidence of complications, vertebral height restoration, and improvement of the visual analogue scale (VAS), Oswestry disability index (ODI) and Short Form-36 (SF-36) General Health Survey scores. Results: The mean operative and exposure time to X-rays in the unipedicular PVP group was less than that of the bipedicular group (p < 0.05). No statistically significant differences were observed in the VAS score, ODI score, SF-36 score, cement leakage rate or vertebral height restoration between the two groups (p > 0.05). Conclusion: Unipedicular and bipedicular PVP are safe and effective treatments for OVCF. Compared with bipedicular PVP, unipedicular PVP entails a shorter surgical time and lower X-ray irradiation. [ABSTRACT FROM AUTHOR]

Interruption of the descending aorta is an extremely rare great vessel malformation. In this report, we describe a very unusual case of a 29-year-old female with a 13-year history of hypertension who was found to have an interruption of the descending aorta when she was hospitalized with a subarachnoid hemorrhage and symptoms of acute paraplegia. We successfully surgically corrected the defect using a Gore-Tex® graft to bypass the aortic interruption. The patient's blood pressure postoperatively returned to normal, and the patient recovered completely from her paraplegia by the time of her 5-month follow-up visit. [ABSTRACT FROM AUTHOR]

Background: The ability of 5α-reductase inhibitors (5ARIs) to decrease blood loss during transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH) remains controversial. We aimed to conduct a meta-analysis of all randomized controlled trials (RCTs) to establish the role of 5ARI use prior to TURP. Methods: We searched studies from the electronic databases PubMed, Embase, Scopus, and Cochrane Library from inception to March 25, 2014. Meta-analysis was performed using the statistical software Review Manager version 5.1. Results: Seventeen RCTs including 1489 patients were examined. We observed that preoperative treatment with finasteride can decrease total blood loss, blood loss per gram of resected prostate tissue, hemoglobin level alteration, microvessel density (MVD), and vascular endothelial growth factor level. Neither finasteride nor dutasteride reduced operative time, prostate volume, or the weight of gland resected. In contrast, pretreatment with dutasteride before TURP did not decrease the total blood loss or MVD. Conclusions: Pretreatment with finasteride does seem to reduce perioperative blood loss related to TURP for BPH patients. However, the effect of preoperative dutasteride was inconclusive. Further studies are required to strengthen future recommendations regarding the use of 5ARI as a standard pre-TURP treatment and its optimal regimen. [ABSTRACT FROM AUTHOR]

Background: The objective of this paper was to study antimicrobial activity and safety of Enterococcus faecium KQ 2.6 (E. faecium KQ 2.6) isolated from peacock feces. Methods: Agar well diffusion method was adopted in antimicrobial activity assay. Disk diffusion test was used to determine the antibiotic resistance. The identification and virulence potential of E. faecium KQ 2.6 were investigated using PCR amplification. Results: The results indicated that cell free supernatant (CFS) of the strain had the good antimicrobial activity against selected gram-positive and gram-negative bacteria. The biochemical characteristics of antimicrobial substances were investigated. The results indicated that the antimicrobial substances were still active after treatment with catalase and proteinase, respectively. Moreover, the stability of antimicrobial substances did not change after heat treatment at 40, 50, 60, 70 and 80°C for 30 min, respectively. The activity of antimicrobial substances remained stable at 4 and -20°C after long time storage. The antimicrobial activity of CFS was compared with that of the buffer with similar strength and pH. The inhibitory zone of the buffer was apparently smaller than that of CFS, which meant that the acid in CFS was not the only factor that was contributed to antibacterial activity of CFS. The antibiotic resistance and virulence potential were evaluated using disk diffusion test and PCR amplification. The results showed that E. faecium KQ 2.6 did not harbor any tested virulence genes such as gelE, esp, asa1, cylA, efaA and hyl. It was susceptible to most of tested antibiotics except for vancomycin and polymyxin B. Conclusion: E. faecium KQ 2.6 may be used as bio-preservative cultures for the production of fermented foods [ABSTRACT FROM AUTHOR]

Background: Jasmonic acid (JA) and methyl jasmonate (MeJA) regulate plant development, resistance to stress, and insect attack by inducing specific gene expression. However, little is known about the mechanism of plant defense against herbivore attack at a protein level. Using a high-resolution 2-D gel, we identified 62 MeJA-responsive proteins and measured protein expression level changes. Results: Among these 62 proteins, 43 proteins levels were increased while 11 proteins were decreased. We also found eight proteins uniquely expressed in response to MeJA treatment. Data are available via ProteomeXchange with identifier PXD001793. The proteins identified in this study have important biological functions including photosynthesis and energy related proteins (38.4%), protein folding, degradation and regulated proteins (15.0%), stress and defense regulated proteins (11.7%), and redox-responsive proteins (8.3%). The expression levels of four important genes were determined by qRT-PCR analysis. The expression levels of these proteins did not correlate well with their translation levels. To test the defense functions of the differentially expressed proteins, expression vectors of four protein coding genes were constructed to express in-fusion proteins in E. coli. The expressed proteins were used to feed Ostrinia furnacalis, the Asian corn borer (ACB). Our results demonstrated that the recombinant proteins of pathogenesis-related protein 1 (PR1) and thioredoxin M-type, chloroplastic precursor (TRXM) showed the significant inhibition on the development of larvae and pupae. Conclusions: We found MeJA could not only induce plant defense mechanisms to insects, it also enhanced toxic protein production that potentially can be used for bio-control of ACB. [ABSTRACT FROM AUTHOR]

Background: As a key link between innate and adaptive immune responses, the interferon (IFN) system is the first line of defense against viral infection. IFN, and in particular, IFN-α, has been used clinically as an effective therapeutic agent for viral infections. However, different subtypes of IFN-α demonstrate distinct antiviral activity. Therefore, it is important to identify IFN-α subtypes with high antiviral activity for the development of genetically engineered antiviral drugs. Results: In this study, we cloned the genes for 13 IFN-α subtypes from peripheral blood lymphocytes of the mink. The homologies of the 13 mink IFN-α genes were 93.6-99.3% and 88.8-98.4% at the nucleotide and amino acid sequence levels, respectively. In contrast to human and canine IFN-α subtypes, most mink IFN-α subtypes contained two N-glycosylation sites. We expressed and purified 13 mink IFN-α subtypes in Escherichia coli. The cytopathic effect inhibition assay showed that all the 13 recombinant mink IFN-α subtypes inhibited the propagation of vesicular stomatitis virus in WISH cells, with IFN-α2 and IFN-α12 demonstrating the highest activities. Furthermore, recombinant mink IFN-α2 and IFN-α12 significantly suppressed the propagation of canine distemper virus in Vero cells, with IFN-α2 demonstrating the highest activity. Conclusions: We identified the mink IFN-α2 subtype as a promising candidate for the development of effective antiviral drugs. [ABSTRACT FROM AUTHOR]

Background: High incidences of neck pain morbidity are challenging in various situations for populations based on their demographic, physiological and pathological characteristics. Chinese proprietary herbal medicines, as Complementary and Alternative Medicine (CAM) products, are usually developed from well-established and long-standing recipes formulated as tablets or capsules. However, good quantification and strict standardization are still needed for implementation of individualized therapies. The Qishe pill was developed and has been used clinically since 2009. The Qishe pill's personalized medicine should be documented and administered to various patients according to the ancient TCM system, a classification of personalized constitution types, established to determine predisposition and prognosis to diseases as well as therapy and life-style administration. Therefore, we describe the population pharmacokinetic profile of the Qishe pill and compare its metabolic rate in the three major constitution types (Qi-Deficiency, Yin-Deficiency and Blood-Stasis) to address major challenges to individualized standardized TCM. Methods/Design: Healthy subjects (N = 108) selected based on constitutional types will be assessed, and standardized pharmacokinetic protocol will be used for assessing demographic, physiological, and pathological data. Laboratory biomarkers will be evaluated and blood samples collected for pharmacokinetics(PK) analysis and second-generation gene sequencing. In single-dose administrations, subjects in each constitutional type cohort (N = 36) will be randomly divided into three groups to receive different Qishe pill doses (3.75, 7.5 and 15 grams). Multiomics, including next generation sequencing, metabolomics, and proteomics, will complement the Qishe pill's multilevel assessment, with cytochrome P450 genes as targets. In a comparison with the general population, a systematic population pharmacokinetic (PopPK) model for the Qishe pill will be established and verified. [ABSTRACT FROM AUTHOR]

Background: Human Borna disease virus (BDV) infections have recently been reported in China. BDV causes cognitive and behavioural disturbances in animals. The impact on human mental disorders is subject to debate, but previous studies worldwide have found neuropsychiatric patients more frequently infected than healthy controls. A few isolates were recovered from severely depressed patients, but contagiousness of BDV strain remains unknown. Method: We addressed the risk of infection in health care settings at the first affiliated hospital of Chongqing Medical University (CQMU), located in downtown Chongqing, a megacity in Southwest China. Between February 2012 and March 2013, we enrolled 1529 participants, of whom 534 were outpatients with major depressive disorder (MDD), 615 were hospital personnel, and 380 were healthy controls who underwent a health check. Infection was determined through BDV-specific circulating immune complexes (CIC), RNA, and selective antibodies (blood). Results: One-fifth of the hospital staff (21.8%) were found to be infected (CIC positive), with the highest prevalence among psychiatry and oncology personnel, which is twice as many as were detected in the healthy control group (11.1%), and exceeds the prevalence detected in MDD patients (18.2%). Conclusion: BDV circulates unnoticed in hospital settings in China, putting medical staff at risk and warranting clarification of infection modes and introduction of prevention measures. [ABSTRACT FROM AUTHOR]

Background: Over the last decade, emerging research methods, such as comparative genomic analysis and phylogenetic study, have yielded new insights into genotypes and phenotypes of closely related bacterial strains. Several findings have revealed that genomic structural variations (SVs), including gene gain/loss, gene duplication and genome rearrangement, can lead to different phenotypes among strains, and an investigation of genes affected by SVs may extend our knowledge of the relationships between SVs and phenotypes in microbes, especially in pathogenic bacteria. Results: In this work, we introduce a 'Genome Topology Network' (GTN) method based on gene homology and gene locations to analyze genomic SVs and perform phylogenetic analysis. Furthermore, the concept of 'unfixed ortholog' has been proposed, whose members are affected by SVs in genome topology among close species. To improve the precision of 'unfixed ortholog' recognition, a strategy to detect annotation differences and complete gene annotation was applied. To assess the GTN method, a set of thirteen complete M. tuberculosis genomes was analyzed as a case study. GTNs with two different gene homology-assigning methods were built, the Clusters of Orthologous Groups (COG) method and the orthoMCL clustering method, and two phylogenetic trees were constructed accordingly, which may provide additional insights into whole genome-based phylogenetic analysis. We obtained 24 unfixable COG groups, of which most members were related to immunogenicity and drug resistance, such as PPE-repeat proteins (COG5651) and transcriptional regulator TetR gene family members (COG1309). Conclusions: The GTN method has been implemented in PERL and released on our website. The tool can be downloaded from http://homepage.fudan.edu.cn/zhouyan/gtn/, and allows re-annotating the 'lost' genes among closely related genomes, analyzing genes affected by SVs, and performing phylogenetic analysis. With this tool, many immunogenic-related and drug resistance-related genes were found to be affected by SVs in M. tuberculosis genomes. We believe that the GTN method will be suitable for the exploration of genomic SVs in connection with biological features of bacterial strains, and that GTN-based phylogenetic analysis will provide additional insights into whole genome-based phylogenetic analysis. [ABSTRACT FROM AUTHOR]

Background: The literature pertaining to chiropractic students' opinions with respect to the desired future status of the chiropractic physician is limited and is an appropriate topic worthy of study. A previous pilot study was performed at a single chiropractic college. This current study is an expansion of this pilot project to collect data from chiropractic students enrolled in colleges throughout North America. Objective: The purpose of this study is to investigate North American chiropractic students' opinions concerning professional identity, role and future. Methods: A 23-item cross-sectional electronic questionnaire was developed. A total of 7,455 chiropractic students from 12 North American English-speaking chiropractic colleges were invited to complete the survey. Survey items encompassed demographics, evidence-based practice, chiropractic identity and setting, and scope of practice. Data were collected and descriptive statistical analysis was performed. Results: A total of 1,247 (16.7% response rate) questionnaires were electronically submitted. Most respondents agreed (34.8%) or strongly agreed (52.2%) that it is important for chiropractors to be educated in evidence-based practice. A majority agreed (35.6%) or strongly agreed (25.8%) the emphasis of chiropractic intervention is to eliminate vertebral subluxations/vertebral subluxation complexes. A large number of respondents (55.2%) were not in favor of expanding the scope of the chiropractic profession to include prescribing medications with appropriate advanced training. Most respondents estimated that chiropractors should be considered mainstream health care practitioners (69.1%). Several respondents (46.8%) think that chiropractic research should focus on the physiological mechanisms of chiropractic adjustments. Conclusion: The chiropractic students in this study showed a preference for participating in mainstream health care, report an exposure to evidence-based practice, and desire to hold to traditional chiropractic theories and practices. The majority of students would like to see an emphasis on correction of vertebral subluxation, while a larger percent found it is important to learn about evidence-based practice. These two key points may seem contradictory, suggesting cognitive dissonance. Or perhaps some students want to hold on to traditional theory (e.g., subluxation-centered practice) while recognizing the need for further research to fully explore these theories. Further research on this topic is needed. [ABSTRACT FROM AUTHOR]

Background The increased funding and reimbursement for the New Rural Cooperative Medical System (NRCMS) have provided residents in rural China with better access to inpatient services. This research aims to examine the level of inappropriate admissions to township hospitals under NRCMS, and the determinants that influence inappropriate admissions. Methods A total of 2,044 medical records in 10 township hospitals were collected from five counties in Midwestern China by stratified cluster sampling and evaluated using the Appropriateness Evaluation Protocol (AEP), which was developed by a Delphi expert consultation of 32 experts. A two-level logistic regression model by MLwiN 2.30 was used to examine the determinants of inappropriate admissions. Results Township hospitals had an average inappropriate admission rate of 26.5%. The highest rate of inappropriate admission was among patients aged more than 59 years old (35.71%). Inappropriate admissions mostly occurred for respiratory, cardiovascular, and circulatory diseases. Township hospital similarity and clustering were observed. Two-level logistic regression analysis showed that age, treating department, and disease were determinants of inappropriate admission. Conclusions Township hospitals have a high rate of inappropriate admissions. Explicit diagnostic criteria and a standardized supervision system should be developed to reduce this. [ABSTRACT FROM AUTHOR]

Introduction: In the field of skin tissue engineering, gelatin-chondroitin-6-sulfate-hyaluronic acid (Gel-C6S-HA) stents are a suitable bio skin substitute. The purpose was to investigate the effect of genetically-modified hair follicle stem cells (HFSCs), combined with Gel-C6S-HA scaffolds, on the vascularization of tissue-engineered skin. Methods: Three-dimensional (3D) Gel-C6S-HA scaffolds were prepared by freeze-drying. Vascular endothelial growth factor (VEGF) 165 gene-modified rat HFSCs (rHFSCs) were inoculated into the scaffolds and cultured for 7 days. Two bilateral full-thickness skin defects were created on the back of 18 Sprague–Dawley rats. Rats were randomly divided into four groups: Group A, HFSCs transduced with VEGF165 seeded onto Gel-C6S-HA scaffolds; Group B, HFSCs transduced with empty vector seeded onto Gel-C6S-HA scaffolds; Group C, Gel-C6S-HA scaffold only; Group D, Vaseline gauze dressing. These compositions were implanted onto the defects and harvested at 7, 14 and 21 days. Wound healing was assessed and compared among groups according to hematoxylin-eosin staining, CD31 expression, alpha smooth muscle actin (α-SMA) and major histocompatibility complex class I (MHC-I) immunohistochemistry, and microvessel density (MVD) count, to evaluate the new blood vessels. Results: SEM revealed the Gel-C6S-HA scaffold was spongy and 3D, with an average pore diameter of 133.23 ± 43.36 μm. Cells seeded on scaffolds showed good adherent growth after 7 days culture. No significant difference in rHFSC morphology, adherence and proliferative capacity was found before and after transfection (P >0.05). After 14 and 21 days, the highest rate of wound healing was observed in Group A (P <0.05). Histological and immunological examination showed that after 21 days, MVD also reached a maximum in Group A (P <0.05). Therefore, the number of new blood vessels formed within the skin substitutes was greatest in Group A, followed by Group B. In Group C, only trace amounts of mature subcutaneous blood vessels were observed, and few subcutaneous tissue cells migrated into the scaffolds. Conclusions: Tissue-engineered skin constructs, using 3D Gel-C6S-HA scaffolds seeded with VEGF165-modified rHFSCs, resulted in promotion of angiogenesis during wound healing and facilitation of vascularization in skin substitutes. This may be a novel approach for tissue-engineered skin substitutes [ABSTRACT FROM AUTHOR]

Background Refractory blood loss is a common problem in surgeries for acute type A aortic dissections. Significant evidence has supported the benefit of using recombinant activated factor VII (rFVIIa) to control of intractable bleeding in patients after cardiac surgery. In this prospective clinical study, we present a novel method to achieve intraoperative hemostasis by using a combination of platelets and rFVIIa during operations for acute type A aortic dissections. Methods Between May 2009 and August 2012, 71 patients with acute type A dissections who underwent emergency surgery were prospectively included and allocated to one of the following two intervention groups for hemostasis: 3 units platelets combined with 2.4 mg rFVIIa (n = 25), and conventional methods (n = 46). Results The patients who received the combination of platelets and rFVIIa required fewer transfusions of red blood cells (6.2 ± 3.1 units vs 9.8 ± 2.8 units; p < 0.05), fresh frozen plasma (736.9 ± 178.3 ml vs 1264.3 ± 245.2 ml, p < 0.05), platelet concentrates (3 units vs 5.0 ± 1.8 units, p < 0.001), and cryoprecipitate (2.8 ± 0.9 units vs 8.2 ± 2.3 units, p < 0.05). These patients also required less time for sternal closure (76.9 ± 17.2 min vs 102.3 ± 10.7 min, p < 0.05) compared with the conventional therapy patients. There was no statistically significant difference in the incidence of serious adverse events between these two groups. Conclusions Using a combination of platelets and rFVIIa is an effective strategy for achieving hemostasis during acute type A dissection surgery. This hemostatic strategy does not appear to be associated with an increase in postoperative adverse events. [ABSTRACT FROM AUTHOR]

Background: Post-fermented tea has been used for the prevention of metabolic syndrome in Western China. Present study reports the biochemical mechanism of lipid-lowering effects of Jing-wei fu tea (JWFT), a variety of post-fermented tea on high-fat diet-induced hyperglycemia and obesity in rats. Methods: Aqueous extract of JWFT was prepared by putting them in boiling water, and then concentrated under reduced pressure. The major compounds of JWFT were determined by high performance liquid chromatography (HPLC). High-fat diet fed rats were orally administered different doses of JWFT aqueous extract (0.5, 1.0 and 2.0 g/kg) for four weeks. At the end of this experiment, hepatic lipids, serum leptin and lipids levels were determined using enzyme-linked immunosorbent assay (ELISA). The hepatic fatty acid composition was analyzed using gas chromatography mass (GC-MS). The relative expression of lipids metabolism genes was analyzed using reverse transcriptase-polymerase chain reaction (RT-PCR). Results: The results showed that JWFT inhibited the increase in the body weight, abdominal adipose weight, serum lipids and hepatic lipids, and decreased serum leptin levels of high-fat diet fed rats. JWFT normalized hepatic fatty acid composition of hyperlipidemia rats by up-regulating hepatic acetyl-CoA carboxylase (ACC), stearoyl-CoA desaturase 1 (SCD1) and fatty acid synthase (FAS) gene expression, and down-regulating carnitine palmitoyl transferase-1 (CPT1). Furthermore, the results showed that JWFT inhibited the absorption of lipids. Conclusion: JWFT could mitigate the obesity-induced hepatic steatosis by regulating hepatic lipogenesis and lipolysis. [ABSTRACT FROM AUTHOR]

Background: WRAP53, including α, β and γ isoforms, plays an important role not only in the stability of p53 mRNA, but also in the assembly and trafficking of the telomerase holoenzyme. It has been considered an oncogene and is thought to promote the survival of cancer cells. The aim of this study was to detect the role of TCAB1 (except WRAP53α) in the occurrence and development of head and neck carcinomas. Methods: Immunohistochemistry was used to detect the TCAB1 expression in clinical specimen sections and performed western blotting to check the TCAB1 expression levels in cell lines. TCAB1 was depleted using shRNA lentivirus and the knockdown efficiency was assessed using q-PCR and Western blotting. We performed CCK-8 assays and flow cytometry to check the cell proliferation potential and used the trans-well assay to test the invasion ability in vitro. Xenografts were used to detect the tumor formation potential in vivo. Moreover, we performed cDNA microarray to investigate the candidate factors involved in this process. Results: We observed a notable overexpression of TCAB1 in head and neck carcinoma clinical specimens as well as in carcinoma cell lines. Knockdown of TCAB1 decreased the cellular proliferation potential and invasion ability in vitro. cDNA microarray analysis suggested the possible involvement of several pathways and factors associated with tumorigenesis and carcinoma development in the TCAB1-mediated regulation of cancers. Furthermore, the xenograft assay confirmed that the depletion of TCAB1 would inhibit tumor formation in nude mice. The immunohistochemistry results of the mice tumor tissue sections revealed that the cells in shTCAB1 xenografts showed decreased proliferation potential and increased apoptotic trend, meanwhile, the angiogenesis was inhibited in the smaller tumors form shTCAB1 cells. Conclusions: Our study demonstrated that depletion of TCAB1 decreased cellular proliferation and invasion potential both in vitro and in vivo. The data indicated that TCAB1 might facilitate the occurrence and development of head and neck carcinomas. In future, TCAB1 might be useful as a prognostic biomarker or a potential target for the diagnosis and therapy of head and neck carcinomas. [ABSTRACT FROM AUTHOR]

Background Beet necrotic yellow vein virus (BNYVV) is the infectious agent of sugar beet rhizomania, which consists of four or five plus-sense RNAs. RNA4 of BNYVV is not essential for virus propagation in Nicotiana benthamiana but has a major effect on symptom expression. Early reports showed that RNA4-encoded P31 was associated with severe symptoms, such as curling and dwarfing, in N. benthamiana. Results We discovered that the pathogenesis-related protein 10 (PR-10) gene can be up-regulated in BNYVV-infected N. benthamiana in the presence of RNA4 and that it had a close link with symptom development. Our frame-shift, deletion and substitution analysis showed that only the entire P31 could induce PR-10 up-regulation during BNYVV infection and that all the tryptophans and six cysteines (C174, C183, C186, C190, C197 and C199) in the cysteine-rich P31 had significant effects on PR-10 expression. However, P31 could not interact directly with PR-10 in yeast. Conclusions Our data demonstrated that only integrated P31 specifically induced PR-10 transcription, which coincided closely with the appearance of severe symptoms in BNYVV-infected N. benthamiana, although they could not interact directly with each other in yeast. [ABSTRACT FROM AUTHOR]

Background Epidermal growth factor receptor (EGFR) is amplified in 40% of human glioblastomas. However, most glioblastoma patients respond poorly to anti-EGFR therapy. MicroRNAs can function as either oncogenes or tumor suppressor genes, and have been shown to play an important role in cancer cell proliferation, invasion and apoptosis. Whether microRNAs can impact the therapeutic effects of EGFR inhibitors in glioblastoma is unknown. Methods miR-566 expression levels were detected in glioma cell lines, using real-time quantitative RT-PCR (qRT-PCR). Luciferase reporter assays and Western blots were used to validate VHL as a direct target gene of miR-566. Cell proliferation, invasion, cell cycle distribution and apoptosis were also examined to confirm whether miR-566 inhibition could sensitize anti-EGFR therapy. Results In this study, we demonstrated that miR-566 is up-regulated in human glioma cell lines and inhibition of miR-566 decreased the activity of the EGFR pathway. Lentiviral mediated inhibition of miR-566 in glioblastoma cell lines significantly inhibited cell proliferation and invasion and led to cell cycle arrest in the G0/G1 phase. In addition, we identified von Hippel-Lindau (VHL) as a novel functional target of miR-566. VHL regulates the formation of the ß-catenin/hypoxia-inducible factors-1a complex under miR-566 regulation. Conclusions miR-566 activated EGFR signaling and its inhibition sensitized glioblastoma cells to anti-EGFR therapy. [ABSTRACT FROM AUTHOR]

Background This single-arm study evaluated feasibility, safety, and initial efficacy of electroacupuncture for thalidomide/bortezomib-induced peripheral neuropathy (PN) in cancer patients with multiple myeloma. Methods Patients with neuropathy = grade 2 received 20 acupuncture treatments over 9 weeks. Results For the 19 evaluable patients, Functional Assessment of Cancer Therapy/Gynecological Oncology Group-Neurotoxicity (FACT/GOG/NTX) mean (SD) scores improved significantly between baseline and week 13 (20.8 [9.6] vs 13.2 [8.5], p = 0.0002). Moderate effect size differences began on week 4, with the largest effect size differences found at week 9 for FACT/GOG/NTX scores, worst pain in the last 24 hours, and pain severity (Cohen's d = 1.43, 1.19, and 1.08, respectively) and continuing through week 13 (Cohen's d = 0.86, 0.88, and 0.90, respectively). From baseline to week 13, additional significant improvements were seen as follows: postural stability (1.0 [0.6] vs 0.8 [0.4], p = 0.02); coin test (10.0 [7.4] vs 5.6 [1.9], p < 0.0001); button test (96.1 [144.4] vs 54.9 [47.3], p < 0.0001); and walking test (21.6 [10.0] vs 17.2 [7.7], p = 0.0003). No significant changes were seen with NCS. Conclusions Acupuncture may help patients experiencing thalidomide- or bortezomib-induced PN. Larger, randomized, clinical trials are needed. Trial registration ClinicalTrials.gov Identifier: NCT00891618. [ABSTRACT FROM AUTHOR]

Background Rats exhibit extremely limited motor function recovery after total transection of the spinal cord (SCT). We previously reported that SM-216289, a semaphorin3A inhibitor, enhanced axon regeneration and motor function recovery in SCT adult rats. However, these effects were limited because most regenerated axons likely do not connect to the right targets. Thus, rebuilding the appropriate connections for regenerated axons may enhance recovery. In this study, we combined semaphorin3A inhibitor treatment with extensive treadmill training to determine whether combined treatment would further enhance the "rewiring" of regenerated axons. In this study, which aimed for clinical applicability, we administered a newly developed, potent semaphorin3A inhibitor, SM-345431 (Vinaxanthone), using a novel drug delivery system that enables continuous drug delivery over the period of the experiment. Results Treatment with SM-345431 using this delivery system enhanced axon regeneration and produced significant, but limited, hindlimb motor function recovery. Although extensive treadmill training combined with SM-345431 administration did not further improve axon regeneration, hindlimb motor performance was restored, as evidenced by the significant improvement in the execution of plantar steps on a treadmill. In contrast, control SCT rats could not execute plantar steps at any point during the experimental period. Further analyses suggested that this strategy reinforced the wiring of central pattern generators in lumbar spinal circuits, which, in turn, led to enhanced motor function recovery (especially in extensor muscles). Conclusions This study highlights the importance of combining treatments that promote axon regeneration with specific and appropriate rehabilitations that promote rewiring for the treatment of spinal cord injury. [ABSTRACT FROM AUTHOR]

Background Quickly and accurately localizing small peripheral pulmonary lesions can avoid prolonged operative time and unplanned open thoracotomy. In this study, we aimed to introduce and evaluate a new technique combining virtual simulation and methylene blue staining for the localization of small peripheral pulmonary lesions. Methods Seventy four (74) patients with 80 peripheral pulmonary lesions<20 mm in size on computer tomography (CT) were virtually punctured using a radiotherapy planning simulator on the day before operation. Under general anaesthesia, methylene blue dye was injected to the virtually identified point according to the surface point, angle and depth previously determined by the simulator. The wedge resection of the marked lesion was performed under video-assisted thoracoscopic surgery (VATS) and the specimens were sent for immediate pathologic examination. According to pathology results, appropriate surgical procedures were decided and undertaken. Results The average lesion size was 10.4±3.5 mm (range: 4-17 mm) and the average distance to the pleural surface was 9.4±4.9 mm. Our preoperative localization procedure was successful in 75 of 80 (94%) lesions. Histological examination showed 28 benign lesions and 52 lung cancers. The shortest distance between the edges of the stain and lesion was 5.1±3.1 mm. Localization time was 17.4±2.3 min. All patients with malignant lesions subsequently underwent lobectomy and systematic lymph node dissection. No complications were observed in all participants. Conclusions The novel technique combining the preoperative virtual simulation and methylene blue staining techniques has a high success rate for localizing small peripheral pulmonary lesions, particularly for those tiny lesions which are difficult to visualise and palpate during VATS. [ABSTRACT FROM AUTHOR]

Background Melphalan resistance has been considered one of the major obstacles to improve outcomes in multiple myeloma (MM) therapy; unfortunately, the mechanistic details of this resistance remain unclear. Melphalan is a highly effective alkylating agent which causes many types of DNA lesions, including DNA base alkylation damage that is repaired by base excision repair (BER). We postulated that human apurinic/apyrimidinic endonuclease 1 (APE1), an essential BER enzyme, plays a vital role in acquired melphalan resistance. However, because APE1 is a multifunctional protein with redox activity and acetylation modification in addition to its major repair activity, the particular APE1 function that may play a more important role in melphalan resistance is unknown. Methods Two MM cell lines, RPMI-8226 and U266 were used to measure the difference in APE1 levels in melphalan-resistant and sensitive derivatives. APE1 functional mutants for DNA repair, redox and acetylation were employed to investigate the roles of individual APE1 activities in acquired melphalan resistance. Results Our results indicate that APE1 is overexpressed in both MM melphalan-resistant cells. Knocking down APE1 sensitizes the melphalan resistant MM cells to melphalan treatment. The exogenous expression of DNA repair mutant H309N and acetylation mutant K6R/K7R of APE1 failed to restore the melphalan resistance of the APE1 knockdown RPMI-8226 cells. The AP endonuclease activity and multidrug resistance protein 1 (MDR1) regulatory activity may play roles in the melphalan resistance of MM cells. Conclusions The present study has identified that the DNA repair functions and the acetylation modification of APE1 are involved in melphalan resistance of MM cells and has also shed light on future therapeutic strategies targeting specific APE1 functions by small molecule inhibitors. [ABSTRACT FROM AUTHOR]

Background Breast milk contains complex nutrients and facilitates the maturation of various biological systems in infants. Exosomes, membranous vesicles of endocytic origin found in different body fluids such as milk, can mediate intercellular communication. We hypothesized that microRNAs (miRNAs), a class of non-coding small RNAs of 18-25 nt which are known to be packaged in exosomes of human, bovine and porcine milk, may play important roles in the development of piglets. Results In this study, exosomes of approximately 100 nm in diameter were isolated from porcine milk through serial centrifugation and ultracentrifugation procedures. Total RNA was extracted from exosomes, and 5S ribosomal RNA was found to be the major RNA component. Solexa sequencing showed a total of 491 miRNAs, including 176 known miRNAs and 315 novel mature miRNAs (representing 366 pre-miRNAs), which were distributed among 30 clusters and 35 families, and two predicted novel miRNAs were verified targeting 3'UTR of IGF-1R by luciferase assay. Interestingly, we observed that three miRNAs (ssc-let-7e, ssc-miR-27a, and ssc-miR-30a) could be generated from miRNA-offset RNAs (moRNAs). The top 10 miRNAs accounted for 74.5% (67,154 counts) of total counts, which were predicted to target 2,333 genes by RNAhybrid software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses using DAVID bioinformatics resources indicated that the identified miRNAs targeted genes enriched in transcription, immunity and metabolism processes, and 14 of the top 20 miRNAs possibly participate in regulation of the IgA immune network. Conclusions Our findings suggest that porcine milk exosomes contain a large number of miRNAs, which potentially play an important role in information transfer from sow milk to piglets. The predicted miRNAs of porcine milk exosomes in this study provide a basis for future biochemical and biophysical function studies. [ABSTRACT FROM AUTHOR]

Background Locoweeds cause significant livestock poisoning and economic loss all over the world. Animals can develop locoism, a chronic neurological disease, after grazing on locoweeds. Oxytropis kansuensis is a variety of locoweed that contains swainsonine as its main toxic ingredient. The purpose of this study was to investigate the apoptotic pathway induced in the cerebrum by swainsonine. Results Twenty-four Sprague-Dawley rats were randomly divided into four groups (experimental groups I, II, III and a control group) and 6 SD rats of each group were feed in 3 cages separately. Rats were penned as groups and fed with feeds containing 15% (SW content 0.03‰), 30% (SW content 0.06‰), or 45% (SW content 0.09‰) O. kansuensis for experimental groups I, II, and III, respectively, or complete feed in the case of the control group. One hundred and nineteen days after poisoning, and all rats showed neurological disorders at different degrees, which were considered to be successful established a chronic poisoning model of O. kansuensis. rats were sacrificed and the expression of Fas, FasL, Bcl- 2, Bax as well as cleaved caspase-3, -8 and -9 proteins in brain tissues were detected by Western blot. The results showed that SW treatment up-regulated Fas and Fas ligand (FasL) (P < 0.05), and that there was an increase in Bax and a decrease in Bcl-2 protein (P < 0.01). Moreover, SW treatment significantly increases the activation of caspase-3, 8 and -9, the key effectors in apoptosis pathway (P < 0.01).Conclusion Our data suggest that SW induces apoptosis in cells of the brain through death receptor and mitochondria-mediated, caspase-dependent apoptotic pathways in the brain tissue of SD rats. [ABSTRACT FROM AUTHOR]

Background: Infectious diseases emerge frequently in China, partly because of its large and highly mobile population. Therefore, a rapid and cost-effective pathogen screening method with broad coverage is required for prevention and control of infectious diseases. The availability of a large number of microbial genome sequences generated by conventional Sanger sequencing and next generation sequencing has enabled the development of a high-throughput high-density microarray platform for rapid large-scale screening of vertebrate pathogens. Methods: An easy operating pathogen microarray (EOPM) was designed to detect almost all known pathogens and related species based on their genomic sequences. For effective identification of pathogens from EOPM data, a statistical enrichment algorithm has been proposed, and further implemented in a user-friendly web-based interface. Results: Using multiple probes designed to specifically detect a microbial genus or species, EOPM can correctly identify known pathogens at the species or genus level in blinded testing. Despite a lower sensitivity than PCR, EOPM is sufficiently sensitive to detect the predominant pathogens causing clinical symptoms. During application in two recent clinical infectious disease outbreaks in China, EOPM successfully identified the responsible pathogens. Conclusions: EOPM is an effective surveillance platform for infectious diseases, and can play an important role in infectious disease control. [ABSTRACT FROM AUTHOR]

Background: Hantaviruses cause acute hemorrhagic fever with renal syndrome (HFRS). Currently, several types of inactivated HFRS vaccines are widely used, however the limited ability of these immunogen to elicit neutralizing antibodies restricts vaccine efficacy. Development of an effective vaccine to overcome this weakness is must. Methods: In the present study, a recombinant pseudotyped lentivirus bearing the hantaan virus (HTNV) envelope glycoproteins (GP), rLV-M, was constructed. C57BL/6 mice were immunized with the rLV-M and a series of immunological assays were conducted to determine the immunogenicity of the recombinant pseudotyped lentivirus. The humoral and cell-mediated immune responses induced by rLV-M were compared with those of the inactivated HFRS vaccine. Results: Indirect immunofluorescence assay (IFA) showed the rLV-M expressed target proteins in HEK-293cells. In mice, the rLV-M efficiently induced GP-specific humoral responses and protection against HTNV infection. Furthermore, the rLV-M induced higher neutralizing antibody titers than the inactivated HFRS vaccine control. Conclusions: The results indicated the potential of using a pseudotyped lentivirus as a delivery vector for a hantavirus vaccine immunogen. [ABSTRACT FROM AUTHOR]

Background: Electrical stimulation of brain structures has been widely used in rodent models for kindling or modeling deep brain stimulation used clinically. This requires surgical implantation of intracranial electrodes and subsequent chronic stimulation in individual animals for several weeks. Anchoring screws and dental acrylic have long been used to secure implanted intracranial electrodes in rats. However, such an approach is limited when carried out in mouse models as the thin mouse skull may not be strong enough to accommodate the anchoring screws. We describe here a screw-free, glue-based method for implanting bipolar stimulating electrodes in the mouse brain and validate this method in a mouse model of hippocampal electrical kindling. Methods: Male C57 black mice (initial ages of 6-8 months) were used in the present experiments. Bipolar electrodes were implanted bilaterally in the hippocampal CA3 area for electrical stimulation and electroencephalographic recordings. The electrodes were secured onto the skull via glue and dental acrylic but without anchoring screws. A daily stimulation protocol was used to induce electrographic discharges and motor seizures. The locations of implanted electrodes were verified by hippocampal electrographic activities and later histological assessments. Results: Using the glue-based implantation method, we implanted bilateral bipolar electrodes in 25 mice. Electrographic discharges and motor seizures were successfully induced via hippocampal electrical kindling. Importantly, no animal encountered infection in the implanted area or a loss of implanted electrodes after 4-6 months of repetitive stimulation/recording. Conclusion: We suggest that the glue-based, screw-free method is reliable for chronic brain stimulation and high-quality electroencephalographic recordings in mice. The technical aspects described this study may help future studies in mouse models. [ABSTRACT FROM AUTHOR]

Lenalidomide is an immunomodulatory agent which has been approved for multiple myeloma. Lenalidomide is also effective in and tolerated well by patients with follicular lymphoma, diffuse large B-cell lymphoma, and transformed large cell lymphoma. This review summarizes the results of current preclinical and clinical studies of lenalidomide, alone or in combination with the monoclonal antibody rituximab, as a therapeutic option for these three lymphoma types. This review will serve as a tool guiding future clinical investigations to improve survival rates for these three lymphomas. [ABSTRACT FROM AUTHOR]

Background: S. erythraea is a Gram-positive filamentous bacterium used for the industrial-scale production of erythromycin A which is of high clinical importance. In this work, we sequenced the whole genome of a highproducing strain (E3) obtained by random mutagenesis and screening from the wild-type strain NRRL23338, and examined time-series expression profiles of both E3 and NRRL23338. Based on the genomic data and transcriptpmic data of these two strains, we carried out comparative analysis of high-producing strain and wild-type strain at both the genomic level and the transcriptomic level. Results: We observed a large number of genetic variants including 60 insertions, 46 deletions and 584 single nucleotide variations (SNV) in E3 in comparison with NRRL23338, and the analysis of time series transcriptomic data indicated that the genes involved in erythromycin biosynthesis and feeder pathways were significantly up-regulated during the 60 hours time-course. According to our data, BldD, a previously identified ery cluster regulator, did not show any positive correlations with the expression of ery cluster, suggesting the existence of alternative regulation mechanisms of erythromycin synthesis in S. erythraea. Several potential regulators were then proposed by integration analysis of genomic and transcriptomic data. Conclusion: This is a demonstration of the functional comparative genomics between an industrial S. erythraea strain and the wild-type strain. These findings help to understand the global regulation mechanisms of erythromycin biosynthesis in S. erythraea, providing useful clues for genetic and metabolic engineering in the future. [ABSTRACT FROM AUTHOR]

Background: Karyotyping is considered the gold standard for the genome-wide detection of genomic imbalances in prenatal diagnosis, but it has a number of inherent limitations, namely the time required to culture cell and the limited resolution(5 ~ 10 Mb). Although fluorescence in situ hybridization (FISH) can also be used as a rapid prenatal diagnosis for common aneuploidies, it is labor intensive, requires prior knowledge of the regions of interest, and can only be used to diagnose one or a few genomic regions simultaneously. Array comparative genomic hybridization (aCGH) can overcome the resolution, the locus-specific, and the time limitations of the karyotyping and FISH techniques and is currently the most powerful method for detecting chromosomal alterations in pre and postnatal clinical cases. Several investigations have suggested that the aCGH testing should be considered a firsttier test for the diagnosis of cytogenetic aberrations in the fetus. Results: This study used karyotyping, FISH, sequence-tagged site (STS) analysis and aCGH to diagnose a case of de novo duplication of chromosome 21q22.12-q22.3 with other concomitant deletion and duplication of small fragments in 21q associated with Down syndrome prenatally. Conclusions: FISH, aCGH and STS analysis are useful in prenatal investigation of the nature of de novo alterations of small fragments of the chromosome. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease (FMD) is one of most contagious animal diseases. It affects millions of cloven-hoofed animals and causes huge economic losses in many countries of the world. There are seven serotypes of which three (O, A and Asia 1) are endemic in China. Efficient control of FMD in China is crucial for the prevention and control of FMD in Asia and throughout the world. For the control of FMD, a powerful veterinary administration, a well-trained veterinary staff, a system of rapid and accurate diagnostic procedures and, in many countries, compulsory vaccination of susceptible animals are indispensable. This article strives to outline the Chinese animal disease control and prevention system, in particular for FMD, with the emphasis on diagnostic procedures applied in Chinese laboratories. In addition, new technologies for FMD diagnosis, which are currently in the phase of development or in the process of validation in Chinese laboratories, are described, such as lateral flow devices (LFD), Mab-based ELISAs, reverse transcription loop-mediated isothermal amplification (RT-LAMP) and gold nanopariticle immuno-PCR (GNP-IPCR). [ABSTRACT FROM AUTHOR]

Background: Critical illness polyneuropathy (CIP) and critical illness myopathy (CIM) are complications causing weakness of respiratory and limb muscles in critically ill patients. As an important differential diagnosis of Guillain- Barré syndrome (GBS), CIP and CIM should be diagnosed with caution, after a complete clinical and laboratory examination. Although not uncommon in ICU, CIP and CIM as severe complications of percutaneous nephrostolithotomy (PNL) have not been documented in literature. Case presentation: A 48-year-old Chinese woman was referred to our hospital, complaining of occasional pain in the right lower back for one month. Lithiasis was diagnosed by ultrasonographical and radiological examinations on the urinary system. PNL was indicated and performed. The patient developed CIP and CIM on the fourth day after PNL. Early recognition and treatment of the severe complications contributed to a satisfactory recovery of the patient. Conclusion: This case expands our understanding of the complications of PNL and underscores the importance of differentiating CIP/CIM from GBS in case of such patients developing weakness after the treatment. Clinical characteristics and examination results should be carefully evaluated to make the diagnosis of CIP or CIM. Both antiseptic prophylaxis and control of hyperglycemia might be effective for the prevention of CIP or CIM; aggressive treatment on sepsis and multiple organ failure is considered to be the most effective measure to reduce the incidence of CIP/CIM. [ABSTRACT FROM AUTHOR]

Background: To investigate the effects of treatment with Multi component Chinese Medicine Jinzhida (JZD) on behavioral deficits in diabetes-associated cognitive decline (DACD) rats and verify our hypothesis that JZD treatment improves cognitive function by suppressing the endoplasmic reticulum stress (ERS) and improving insulin signaling transduction in the rats' hippocampus. Methods: A rat model of type 2 diabetes mellitus (T2DM) was established using high fat diet and streptozotocin (30 mg/kg, ip). Insulin sensitivity was evaluated by the oral glucose tolerance test and the insulin tolerance test. After 7 weeks, the T2DM rats were treated with JZD. The step-down test and Morris water maze were used to evaluate behavior in T2DM rats after 5 weeks of treatment with JZD. Levels of phosphorylated proteins involved in the ERS and in insulin signaling transduction pathways were assessed by Western blot for T2DM rats' hippocampus. Results: Compared to healthy control rats, T2DM rats initially showed insulin resistance and had declines in acquisition and retrieval processes in the step-down test and in spatial memory in the Morris water maze after 12 weeks. Performance on both the step-down test and Morris water maze tasks improved after JZD treatment. In T2DM rats, the ERS was activated, and then inhibited the insulin signal transduction pathways through the Jun NH2-terminal kinases (JNK) mediated. JZD treatment suppressed the ERS, increased insulin signal transduction, and improved insulin resistance in the rats' hippocampus. Conclusions: Treatment with JZD improved cognitive function in the T2DM rat model. The possible mechanism for DACD was related with ERS inducing the insulin signal transduction dysfunction in T2DM rats' hippocampus. The JZD could reduce ERS and improve insulin signal transduction and insulin resistance in T2DM rats' hippocampus and as a result improved the cognitive function. [ABSTRACT FROM AUTHOR]

Background: With an increasing incidence of congenital heart defects (CHDs) in recent years, genotype-phenotype correlation and array-based methods have contributed to the genome-wide analysis and understanding of genetic variations in the CHD population. Here, we report a copy number deletion of chromosomal 14q23.1 in a female fetus with complex congenital heart defects. This is the first description of DAAM1 gene deletion associated with congenital heart anomalies.Case Presentation: Compared with the control population, one CHD fetus showed a unique copy number delation of 14q23.1, a region that harbored DAAM1 and KIAA0666 genes.Conclusions: Results suggest that the copy number deletion on chromosome 14q23.1 may be critical for cardiogenesis. However, the exact relationship and mechanism of how DAAM1 and KIAA0666 deletion contributes to the onset of CHD is yet to be determined. [ABSTRACT FROM AUTHOR]

Background: The fern genus Dryopteris (Dryopteridaceae) is among the most common and species rich fern genera in temperate forests in the northern hemisphere containing 225-300 species worldwide. The circumscription of Dryopteris has been controversial and various related genera have, over the time, been included in and excluded from Dryopteris. The infrageneric phylogeny has largely remained unclear, and the placement of the majority of the supraspecific taxa of Dryopteris has never been tested using molecular data. Results: In this study, DNA sequences of four plastid loci (rbcL gene, rps4-trnS spacer, trnL intron, trnL-F spacer) were used to reconstruct the phylogeny of Dryopteris. A total of 122 accessions are sampled in our analysis and they represent 100 species of the expanded Dryopteris including Acrophorus, Acrorumohra, Diacalpe, Dryopsis, Nothoperanema, and Peranema. All four subgenera and 19 sections currently recognized in Dryopteris s.s. are included. One species each of Arachniodes, Leptorumohra, and Lithostegia of Dryopteridaceae are used as outgroups. Our study confirms the paraphyly of Dryopteris and provides the first strong molecular evidence on the monophyly of Acrophorus, Diacalpe, Dryopsis, Nothoperanema, and Peranema. However, all these monophyletic groups together with the paraphyletic Acrorumohra are suggested to be merged into Dryopteris based on both molecular and morphological evidence. Our analysis identified 13 well-supported monophyletic groups. Each of the 13 clades is additionally supported by morphological synapomophies and is inferred to represent a major evolutionary lineagein Dryopteris. In contrast, monophyly of the four subgenera and 15 out of 19 sections currently recognized in Dryopteris s.s is not supported by plastid data. Conclusions: The genera, Acrophorus, Acrorumohra, Diacalpe, Dryopsis, Nothoperanema, and Peranema, should all be merged into Dryopteris. Most species of these genera share a short rhizome and catadromic arrangement of frond segments, unlike the sister genus of Dryopteris s.l., Arachniodes, which has anadromic arrangement of frond segments. The non-monophyly of the 19 out of the 21 supraspecific taxa (sections, subgenera) in Dryopteris strongly suggests that the current taxonomy of this genus is in need of revision. The disagreement between the previous taxonomy and molecular results in Dryopteris may be due partly to interspecific hybridization and polyplodization. More morphological studies and molecular data, especially from the nuclear genome, are needed to thoroughly elucidate the evolutionary history of Dryopteris. The 13 well-supported clades identified based on our data represent 13 major evolutionary lineages in Dryopteris that are also supported by morphological synapomophies. [ABSTRACT FROM AUTHOR]

Background: Evidence indicates that CYP1A1 MspI polymorphism might be a possible risk factor for several malignancies. A growing body of literature has been devoted to the association of CYP1A1 MspI polymorphism with acute myeloid leukemia (AML). However, the results remain conflicting. The aim of the present study was to derive a more precise estimation of the relationship. Methods: Meta-analyses assessing the association of CYP1A1 MspI variation with AML were conducted and subgroup analyses on ethnicity and age groups were further performed. Eligible studies were identified for the period up to May 2012. Results: A total of ten case-control studies including 1330 cases and 3688 controls were selected for analysis. The overall data failed to indicate a significant association of CYP1A1 MspI polymorphism with AML risk (C vs T: OR = 1.13; 95%CI = 0.87-1.48; CC vs TT: OR = 1.72; 95%CI = 0.99-3.01; CC + TC vs TT: OR = 1.16; 95%CI = 0.86-1.55). In subgroup analysis stratified by ethnicity, significant AML risk was shown among Asians (CC + TC vs TT: OR = 1.33; 95%CI = 1.09-1.62) but not Caucasians or mixed races. In subgroup analysis regarding age groups, no associations were observed in either the childhood AML or the adult AML subgroups. Conclusion: The results of the present study suggested that CYP1A1 MspI polymorphism might be a risk factor for AML among Asians. Further investigations are needed to confirm the conclusions. [ABSTRACT FROM AUTHOR]

Background: Array-based comparative genomic hybridization (aCGH) is a new technique for detectingsubmicroscopic deletions and duplications, and can overcome many of the limitations associated with classic cytogenetic analysis. However, its clinical use in spontaneous abortion needs comprehensive evaluation. We used aCGH to investigate chromosomal imbalances in 100 spontaneous abortions and compared the results with Gbanding karyotyping and fluorescence in situ hybridization (FISH). Inconsistent results were verified by quantitative fluorescence PCR. Results: Abnormalities were detected in 61 cases. aCGH achieved the highest detection rate (93.4%, 57/61) compared with traditional karyotyping (77%, 47/61) and FISH analysis (68.9%, 42/61). aCGH identified all chromosome abnormalities reported by traditional karyotyping and interphase FISH analysis, with the exception of four triploids. It also detected three additional aneuploidy cases in 37 specimens with 'normal' karyotypes, one mosaicism and 10 abnormalities in 14 specimens that failed to grow in vitro. Conclusions: aCGH analysis circumvents many limitations in traditional karyotyping or FISH. The accuracy and efficiency of aCGH in spontaneous abortions highlights its clinical usefulness for the future. As aborted tissues have the potential to be contaminated with maternal cells, the threshold value of detection in aCGH should be lowered to avoid false negatives. [ABSTRACT FROM AUTHOR]

Background: The fungus Marssonina brunnea is a causal pathogen of Marssonina leaf spot that devastates poplar plantations by defoliating susceptible trees before normal fall leaf drop. Results: We sequence the genome of M. brunnea with a size of 52 Mb assembled into 89 scaffolds, representing the first sequenced Dermateaceae genome. By inoculating this fungus onto a poplar hybrid clone, we investigate how M. brunnea interacts and co-evolves with its host to colonize poplar leaves. While a handful of virulence genes in M. brunnea, mostly from the LysM family, are detected to up-regulate during infection, the poplar down-regulates its resistance genes, such as nucleotide binding site domains and leucine rich repeats, in response to infection. From 10,027 predicted proteins of M. brunnea in a comparison with those from poplar, we identify four poplar transferases that stimulate the host to resist M. brunnea. These transferas-encoding genes may have driven the co-evolution of M. brunnea and Populus during the process of infection and anti-infection. Conclusions: Our results from the draft sequence of the M. brunnea genome provide evidence for genome-genome interactions that play an important role in poplar-pathogen co-evolution. This knowledge could help to design effective strategies for controlling Marssonina leaf spot in poplar. [ABSTRACT FROM AUTHOR]

Foot-and-Mouth Disease (FMD), as a major global animal disease, affects millions of animals worldwide and remains the main sanitary barrier to the international and national trade of animals and animal products. Inactivated vaccination is the most effective measure for prevention of FMD at present, but fail to induce long-term protection and content new requires for production of FMD vaccines. As a number of Researchers hope to obtain satisfactory novel vaccines by new bio-technology, novel vaccines have been studied for more than thirty years. Here reviews the latest research progress of new vaccines, summarizes some importance and raises several suggestions for the future of FMD vaccine. [ABSTRACT FROM AUTHOR]

Background: Mitogen-activated protein kinase (MAPK) cascades play pivotal roles in mediating biotic and abiotic stress responses. In plants, MAPKs are classified into four major groups (A-D) according to their sequence homology and conserved phosphorylation motifs. Members of group A and B have been extensively characterized, but little information on the group D MAPKs has been reported. Results: In this study, we isolated and characterised GhMPK16, the first group D MAPK gene found in cotton. Southern blot analysis suggests GhMPK16 is single copy in the cotton genome, and RNA blot analysis indicates that GhMPK16 transcripts accumulate following pathogen infection and treatment with multiple defense-related signal molecules. The analysis of the promoter region of GhMPK16 revealed a group of putative cis-acting elements related to stress responses. Subcellular localization analysis suggests that GhMPK16 acts in the nucleus. Transgenic Arabidopsis overexpressing GhMPK16 displayed significant resistance to fungi (Colletotrichum nicotianae and Alternaria alternata) and bacteria (Pseudomonas solanacearum) pathogen, and the transcripts of pathogen-related (PR) genes were more rapidly and strongly induced in the transgenic plants. Furthermore, transgenic Arabidopsis showed reduced drought tolerance and rapid H2O2 accumulation. Conclusion: These results suggest that GhMPK16 might be involved in multiple signal transduction pathways, including biotic and abiotic stress signaling pathways. [ABSTRACT FROM AUTHOR]

Background: After several years in the juvenile phase, trees undergo flowering transition to become mature (florally competent) trees. This transition depends on the balanced expression of a complex network of genes that is regulated by both endogenous and environmental factors. However, relatively little is known about the molecular processes regulating flowering transition in woody plants compared with herbaceous plants. Results: Comparative transcript profiling of spring shoots after self-pruning was performed on a spontaneously early flowering trifoliate orange mutant (precocious trifoliate orange, Poncirus trifoliata) with a short juvenile phase and the wild-type (WT) tree by using massively parallel signature sequencing (MPSS). A total of 16,564,500 and 16,235,952 high quality reads were obtained for the WT and the mutant (MT), respectively. Interpretation of the MPSS signatures revealed that the total number of transcribed genes in the MT (31,468) was larger than in the WT (29,864), suggesting that newly initiated transcription occurs in the MT. Further comparison of the transcripts revealed that 2735 genes had more than twofold expression difference in the MT compared with the WT. In addition, we identified 110 citrus flowering-time genes homologous with known elements of flowering-time pathways through sequencing and bioinformatics analysis. These genes are highly conserved in citrus and other species, suggesting that the functions of the related proteins in controlling reproductive development may be conserved as well. Conclusion: Our results provide a foundation for comparative gene expression studies between WT and precocious trifoliate orange. Additionally, a number of candidate genes required for the early flowering process of precocious trifoliate orange were identified. These results provide new insight into the molecular processes regulating flowering time in citrus. [ABSTRACT FROM AUTHOR]

Background: Insect cuticle plays essential roles in many physiological functions. During molting and metamorphosis tremendous changes occur in silkworm cuticle where multiple proteins exist and genes encoding them constitute about 1.5% of all Bombyx mori genes. Results: In an effort to determine their expression profiles, a microarray-based investigation was carried out using mRNA collected from larvae to pupae. The results showed that a total of 6676 genes involved in various functions and physiological pathways were activated. The vast majority (93%) of cuticular protein genes were expressed in selected stages with varying expression patterns. There was no correlation between expression patterns and the presence of conserved motifs. Twenty-six RR genes distributed in chromosome 22 were co-expressed at the larval and wandering stages. The 2 kb upstream regions of these genes were further analyzed and three putative elements were identified. Conclusions: Data from the present study provide, for the first time, a comprehensive expression profile of genes in silkworm epidermal tissues and evidence that putative elements exist to allow massive production of mRNAs from specific cuticular protein genes. [ABSTRACT FROM AUTHOR]

Background: The natural product Emodin demonstrates a wide range of pharmacological properties including anticancer, anti-inflammatory, antiproliferation, vasorelaxant and anti-H. pylori activities. Although its H. pylori inhibition was discovered, no acting target information against Emodin has been revealed to date. Results: Here we reported that Emodin functioned as a competitive inhibitor against the recombinant β-hydroxyacyl-ACP dehydratase from Helicobacter pylori (HpFabZ), and strongly inhibited the growth of H. pylori strains SS1 and ATCC 43504. Surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) based assays have suggested the kinetic and thermodynamic features of Emodin/HpFabZ interaction. Additionally, to inspect the binding characters of Emodin against HpFabZ at atomic level, the crystal structure of HpFabZ-Emodin complex was also examined. The results showed that Emodin inhibition against HpFabZ could be implemented either through its occupying the entrance of the tunnel or embedding into the tunnel to prevent the substrate from accessing the active site. Conclusion: Our work is expected to provide useful information for illumination of Emodin inhibition mechanism against HpFabZ, while Emodin itself could be used as a potential lead compound for further anti-bacterial drug discovery. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are expressed by a wide range of eukaryotic organisms, and function in diverse biological processes. Numerous miRNAs have been identified in Bombyx mori, but the temporal expression profiles of miRNAs corresponding to each stage transition over the entire life cycle of the silkworm remain to be established. To obtain a comprehensive overview of the correlation between miRNA expression and stage transitions, we performed a whole-life test and subsequent stage-by-stage examinations on nearly one hundred miRNAs in the silkworm. Results: Our results show that miRNAs display a wide variety of expression profiles over the whole life of the silkworm, including continuous expression from embryo to adult (miR-184), up-regulation over the entire life cycle (let-7 and miR-100), down-regulation over the entire life cycle (miR-124), expression associated with embryogenesis (miR-29 and miR-92), up-regulation from early 3rd instar to pupa (miR-275), and complementary pulses in expression between miR-34b and miR-275. Stage-by-stage examinations revealed further expression patterns, such as emergence at specific time-points during embryogenesis and up-regulation of miRNA groups in late embryos (miR-1 and bantam), expression associated with stage transition between instar and molt larval stages (miR-34b), expression associated with silk gland growth and spinning activity (miR-274), continuous high expression from the spinning larval to pupal and adult stages (miR-252 and miR-31a), a coordinate expression trough in day 3 pupae of both sexes (miR-10b and miR-281), up-regulation in pupal metamorphosis of both sexes (miR-29b), and down-regulation in pupal metamorphosis of both sexes (miR-275). Conclusion: We present the full-scale expression profiles of miRNAs throughout the life cycle of Bombyx mori. The whole-life expression profile was further investigated via stage-by-stage analysis. Our data provide an important resource for more detailed functional analysis of miRNAs in this animal. [ABSTRACT FROM AUTHOR]

Inhibitory, interneuronal networks are known to underlie high-frequency (gamma, 40-80 Hz) population oscillations, and they are also known to underlie low-frequency rhythms. For example, spontaneous, slow (0.5-4 Hz) rhythms occur in rodent hippocampus. However, it is unclear whether an inhibitory network can generate population oscillations much slower than the intrinsic firing frequencies of its constituent neurons. Here we show that an inhibitory network model in the absence of any slow processes is able to produce low-frequency rhythms. To obtain this, we bridge our network model simulations with a dynamical mean-field (DMA) model to approximate the location of relevant parameter regimes. The individual interneuron model is a two-dimensional conductance-based model and the network is formed with fast, inhibitory GABAA type synapses. The DMA model representing a large all-to-all coupled system consists of 30 equations that include equations describing synaptic noises. Bifurcation analysis is used to explore the DMA model, in particular, to identify parameter regimes for which bursting activities occur. These parameters are used in network simulations. The network model consists of an all-to-all coupled network of 20 interneurons. Each interneuron is described by: CdV/dt = Iapp + bη-gL(V-EL)- gNam(V-ENa)-gKn(V-EK)-gsyn(V-Esyn) ∑isi; m(V) = 1/(1+exp(- 4/3-V/15)); dn/dt = 1/(1+exp(-5-V/5))-n; dsi/dt=a(1-si)/ (1+exp(-Vi/2))-si/τ, where ∑isi sums the (inhibitory) synaptic gating variables from other interneurons in the network, η represents white noise of unit strength and b represents the strength of the noise. Figure 1 shows a raster plot from a 30 second network simulation (left) with the corresponding average summated synaptic activities (right). The parameters used are taken from identified bursting regimes in the DMA model analysis. Parameters values: Iapp= 4.8 µA/cm²; b= 0.08 ms1/2mA/cm²; gL= 8 mS/ cm²; gK= 10 mS/cm²; gNa= 20 mS/cm²; gsyn= 0.0263 mS/ cm²; EL= -80 mV; EK= -90 mV; ENa= 60 mV; Esyn= -85 mV; τ = 10 ms; C = 1 µF/cm². The intrinsic firing frequency at Iapp = 4.8 µA/cm² for these neurons (with zero noise) is 52 Hz. Slow population rhythms (approx 0.5 Hz), or bursts of synaptic activities, can be seen to emerge due to a "switching" between sparsely firing and coherently firing network states. A DMA model analysis has been used to find parameter regimes that allow slow rhythms to be expressed by inhibitory network models. These regimes are identified by bursting activities in a simpler mean-field model. Given the bridging used between the DMA model and the network simulations, we expect that this slow pattern should also occur in much larger network models. We have previously obtained values for synaptic "noise" parameters underlying slow hippocampal rhythms. It will be interesting to determine whether bursting in the DMA models, and thus slow population rhythms in large network simulations, occur using these experimentally-based synaptic noise parameter values. If so, this would suggest a novel way in which slow rhythms could emerge in biological, inhibitory networks. [ABSTRACT FROM AUTHOR]

The article summarizes the results of a study on the role of neural inhibition in shaping the in vitro spontaneous hippocampal network rhythms of rodents. It has found a link between the transition from the quiescent to the rhythmic state of spontaneous rhythmic field potentials (SRFPs) and inhibitory conductance dominance with inhibitory fluctuations of over 10%. It concludes that SRFPs are inhibitory-based rhythms. The quiescent state is also inihibitory dominant.

A correction to the article "MicroRNA Expression Profiling During the Life Cycle of the Silkworm (Bombyx mori)" published in a previous issue of the journal is presented.

Background: α-galactosidase has been widely used in animal husbandry to reduce anti-nutritional factors (such as α-galactoside) in feed. Intestine-specific and substrate inducible expression of α-galactosidase would be highly beneficial for transgenic animal production., Methods: To achieve the intestine-specific and substrate inducible expression of α-galactosidase, we first identified intestine-specific promoters by comparing the transcriptional activity and tissue specificity of four intestine-specific promoters from human intestinal fatty acid binding protein, rat intestinal fatty acid binding protein, human mucin-2 and human lysozyme. We made two chimeric constructs combining the promoter and enhancer of human mucin-2, rat intestinal trefoil factor and human sucrase-isomaltase. Then a modified lac operon system was constructed to investigate the induction of α-galactosidase expression and enzyme activity by isopropyl β-D-1-thiogalactopyranoside (IPTG) and an α-galactosidase substrate, α-lactose.We declared that the research carried out on human (Zhai Yafeng) was in compliance with the Helsinki Declaration, and experimental research on animals also followed internationally recognized guidelines., Results: The activity of the human mucin-2 promoter was about 2 to 3 times higher than that of other intestine-specific promoters. In the lac operon system, the repressor significantly decreased (P < 0.05) luciferase activity by approximately 6.5-fold and reduced the percentage of cells expressing green fluorescent protein (GFP) by approximately 2-fold. In addition, the expression level of α-galactosidase mRNA was decreased by 6-fold and α-galactosidase activity was reduced by 8-fold. In line with our expectations, IPTG and α-lactose supplementation reversed (P < 0.05) the inhibition and produced a 5-fold increase of luciferase activity, an 11-fold enhancement in the percentage of cells with GFP expression and an increase in α-galactosidase mRNA abundance (by about 5-fold) and α-galactosidase activity (by about 7-fold)., Conclusions: We have successfully constructed a high specificity inducible lac operon system in an intestine-derived cell line, which could be of great value for gene therapy applications and transgenic animal production.