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Background: Population-based estimates of the incidence and prognosis of brain metastases at diagnosis of hepatocellular carcinoma (HCC) are lacking. The aim of this study was to characterize the incidence proportion and survival of newly diagnosed hepatocellular carcinoma with brain metastases (HCCBM). Materials and methods: Data from Surveillance, Epidemiology, and End Results (SEER) program between 2010 and 2014 was evaluated. Patients with HCCBM were included. Multivariable logistic and Cox regression were performed to identify predictors of the presence of brain metastases at diagnosis and prognostic factors of overall survival (OS). We also built a nomogram based on Cox model to predict prognosis for HCCBM patients. Results: We identified 97 patients with brain metastases at the time of diagnosis of HCC, representing 0.33% of the entire cohort. Logistic regression showed patients with bone or lung metastases had greater odds of having brain metastases at diagnosis. Median OS for HCCBM was 2.40 months. Cox regression revealed unmarried and bone metastases patients suffered significantly shorter survival time. A nomogram was developed with internal validation concordance index of 0.639. Conclusions: This study provided population-based estimates of the incidence and prognosis for HCCBM patients. The nomogram could be a convenient individualized predictive tool for prognosis. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) is often comorbid with other psychiatric conditions in adults. Yet, less is known about its relationship with common metabolic disorders and how sex and ageing affect the overall comorbidity patterns of adult ADHD. We aimed to examine associations of adult ADHD with several common psychiatric and metabolic conditions. Through the linkage of multiple Swedish national registers, 5,551,807 adults aged 18 to 64 years and living in Sweden on December 31, 2013 were identified and assessed for clinical diagnoses of adult ADHD, substance use disorder (SUD), depression, bipolar disorder, anxiety, type 2 diabetes mellitus (T2DM), and hypertension. Logistic regression models and regression standardization method were employed to obtain estimates of prevalence, prevalence difference (PD), and prevalence ratio (PR). All comorbid conditions of interest were more prevalent in adults with ADHD (3.90% to 44.65%) than in those without (0.72% to 4.89%), with the estimated PRs being over nine for psychiatric conditions (p < 0.001) and around two for metabolic conditions (p < 0.001). Sex differences in the prevalence of comorbidities were observed among adults with ADHD. Effect modification by sex was detected on the additive scale and/or multiplicative scale for the associations of adult ADHD with all comorbidities. ADHD remained associated with all comorbidities in older adults aged 50 to 64 when all conditions were assessed from age 50 onwards. The comorbidity patterns of adult ADHD underscore the severity and clinical complexity of the disorder. Clinicians should remain vigilant for a wide range of psychiatric and metabolic problems in ADHD affected adults of all ages and both sexes. [ABSTRACT FROM AUTHOR]

Background: Perineural dexamethasone has been shown to prolong the duration of local anesthetic (LA) effect in regional anesthesia; however, the use of perineural dexamethasone as an adjuvant to to the transversus abdominis plane (TAP) block remains controversial. This meta-analysis sought to assess the efficacy of dexamethasone in prolonging the TAP block and enhancing recovery after abdominal surgery. Methods: We identified and analyzed 9 RCTs published on or before September 30, 2017, regardless of the original language, after searching the following 6 bibliographic databases: PubMed, EMBASE, Medline, Springer, Ovid, and the Cochrane Library. databases. These studies compared the effects of perineural dexamethasone mixed with local anesthetic versus local anesthetic alone in the TAP block. The Cochrane Collaboration’s Risk of Bias Tool was used to evaluate the methodological quality of each RCT. The primary outcomes were the time until the first request for postoperative analgesics and the analog pain scores at 2, 6, 12, and 24 h after surgery. The secondary outcomes were the analgesic consumption and the incidence of nausea and vomiting on the first day after surgery. We used Trial Sequential Analysis (TSA) to control for random errors. Results: Perineural dexamethasone prolonged the duration of LA effect in the TAP block [mean difference (MD): 2.98 h; 95% confidence interval (CI): 2.19 to 3.78] and reduced analog pain scores at 2 h [MD: -1.15; 95% CI: -2.14 to -0.16], 6 h [MD: -0.97; 95% CI: -1.51 to -0.44], and 12 h [MD: -0.93; 95% CI: -1.14 to -0.72] postoperatively. Furthermore, the use of perineural dexamethasone was associated with less analgesic consumption [standard mean difference: -1.29; 95% CI: -1.88 to -0.70] and a lower incidence of nausea and vomiting [odds ratio: 0.28; 95% CI: 0.16 to 0.49] on the first day after surgery. Conclusion: Dexamethasone prolongs the LA effect when used as an adjuvant in the TAP block and improves the analgesic effects of the block. [ABSTRACT FROM AUTHOR]

Parapoynx crisonalis (Walker, 1859) (Lepidoptera: Crambidae) is a major pest of aquatic vegetables and aquatic landscape plants. It has been responsible for causing considerable economic damage to water chestnut (Trapa natans) plants. In the Changsha vicinity of China, P. crisonalis has five generations a year. Populations of P. crisonalis were relatively low in April and began to rapidly rise at the beginning of May. At the end of July and early August, the population dropped dramatically. A rebound occurred at the end of August and early September, which was referred to as the second population peak. From then, until early November, the P. crisonalis population steadily diminished in preparation for overwintering. The primary factors influencing the seasonal dynamics of P. crisonalis were the climatic conditions, especially the temperature, and secondarily precipitation. Between May and October, the P. crisonalis adults were evenly distributed in the pond. In May and June, the eggs of P. crisonalis were present in an aggregate distribution, due to the effects of environmental heterogeneity. In July and August, however, they were found to be in a uniform distribution. [ABSTRACT FROM AUTHOR]

Dynamics of three MET antibody constructs (IgG1, IgG2, and IgG4) and the IgG4-MET antigen complex was investigated by creating their atomic models with an integrative experimental and computational approach. In particular, we used two-dimensional (2D) Electron Microscopy (EM) images, image class averaging, homology modeling, Rapidly exploring Random Tree (RRT) structure sampling, and fitting of models to images, to find the relative orientations of antibody domains that are consistent with the EM images. We revealed that the conformational preferences of the constructs depend on the extent of the hinge flexibility. We also quantified how the MET antigen impacts on the conformational dynamics of IgG4. These observations allow to create testable hypothesis to investigate MET biology. Our protocol may also help describe structural diversity of other antigen systems at approximately 5 Å precision, as quantified by Root-Mean-Square Deviation (RMSD) among good-scoring models. [ABSTRACT FROM AUTHOR]

Parapoynx crisonalis is an important pest of many aquatic vegetables including water chestnuts. Understanding the relationship between temperature variations and the population growth rates of P. crisonalis is essential to predicting its population dynamics in water chestnuts ponds. These relationships were examined in this study based on the age-stage, two-sex life table of P. crisonalis developed in the laboratory at 21, 24, 27, 30, 33 and 36°C. The results showed that the values of Sxj (age-stage–specific survival rate), fxj (age-stage-specific fecundity), lx (age specific survival rate) and mx (age-specific fecundity) increased as the temperature rose from 21 to 27°C, then decreased from 30 to 36°C. Temperature also had a significant effect on the net reproductive rate (R0), gross reproductive rate (GRR), intrinsic rate of increase (r) and finite rate of increase (λ). The value of these parameters were at low levels at 21, 33, and 36°C. Further, the r value decreased as the temperature rose from 24 to 30°C, while the GRR reached its highest level at 27°C. The results indicated that optimal growth and development of P. crisonalis occurred at temperatures between 24°C to 30°C when compared to the lowest temperature (21°C) and higher temperatures of 33°C and 36°C. [ABSTRACT FROM AUTHOR]

The leaf beetle Ambrostoma quadriimpressum (Coleoptera: Chrysomelidae) is a predominant forest pest that causes substantial damage to the lumber industry and city management. However, no effective and environmentally friendly chemical method has been discovered to control this pest. Until recently, the molecular basis of the olfactory system in A. quadriimpressum was completely unknown. In this study, antennae and leg transcriptomes were analyzed and compared using deep sequencing data to identify the olfactory genes in A. quadriimpressum. Moreover, the expression profiles of both male and female candidate olfactory genes were analyzed and validated by bioinformatics, motif analysis, homology analysis, semi-quantitative RT-PCR and RT-qPCR experiments in antennal and non-olfactory organs to explore the candidate olfactory genes that might play key roles in the life cycle of A. quadriimpressum. As a result, approximately 102.9 million and 97.3 million clean reads were obtained from the libraries created from the antennas and legs, respectively. Annotation led to 34344 Unigenes, which were matched to known proteins. Annotation data revealed that the number of genes in antenna with binding functions and receptor activity was greater than that of legs. Furthermore, many pathway genes were differentially expressed in the two organs. Sixteen candidate odorant binding proteins (OBPs), 10 chemosensory proteins (CSPs), 34 odorant receptors (ORs), 20 inotropic receptors [] and 2 sensory neuron membrane proteins (SNMPs) and their isoforms were identified. Additionally, 15 OBPs, 9 CSPs, 18 ORs, 6 IRs and 2 SNMPs were predicted to be complete ORFs. Using RT-PCR, RT-qPCR and homology analysis, AquaOBP1/2/4/7/C1/C6, AquaCSP3/9, AquaOR8/9/10/14/15/18/20/26/29/33, AquaIR8a/13/25a showed olfactory-specific expression, indicating that these genes might play a key role in olfaction-related behaviors in A. quadriimpressum such as foraging and seeking. AquaOBP4/C5, AquaOBP4/C5, AquaCSP7/9/10, AquaOR17/24/32 and AquaIR4 were highly expressed in the antenna of males, suggesting that these genes were related to sex-specific behaviors, and expression trends that were male specific were observed for most candidate olfactory genes, which supported the existence of a female-produced sex pheromone in A. quadriimpressum. All of these results could provide valuable information and guidance for future functional studies on these genes and provide better molecular knowledge regarding the olfactory system in A. quadriimpressum. [ABSTRACT FROM AUTHOR]

Purpose: Liver metastasis is a common phenomenon in breast cancer patients. Hepatic lesions detected in breast cancer patients may be easily misdiagnosed as metastatic sites, rather than being treated as primary foci. This descriptive study aims to investigate the clinicopathological characteristics of second primary hepatocellular carcinoma in breast cancer patients and to infer in which circumstances liver biopsy is needed. Methods: Eighty-one consecutive breast cancer patients with hepatic lesions admitted to our department were retrospectively studied and analyzed from January 2009 to March 2014 according to Warren and Gates’ criteria for second primary cancers. Results: Second primary hepatocellular carcinoma was observed in sixteen of seventy eight patients with breast cancer. There was a significant difference in HBV status between the second HCC group and liver metastases group (P<0.0001). There was no significant difference in age (P = 0.2254) and family history (P = 0.1160) between second primary HCC and metastases group. Two of these patients had synchronous second primary hepatocellular carcinoma and the remaining fourteen patients had metachronous second primary HCC. All sixteen patients were infected with hepatitis, including hepatitis virus B and C, or resolved HBV infection. Conclusions: Breast cancer patients with either HBV infection or resolved HBV infection, regardless of an elevated AFP level, may receive liver biopsy to avoid unnecessary and inappropriate treatments for metastasis. Awareness of second primary HCC in breast cancer patients needs to be emphasized. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea virus (PEDV) was identified in the United States (U.S.) swine population for the first time in April 2013 and rapidly spread nationwide. However, no information has been published regarding the minimum infectious dose (MID) of PEDV in different pig models. The main objective of this study was to determine the oral minimum infectious dose of PEDV in naïve conventional neonatal piglets and weaned pigs. A U.S. virulent PEDV prototype isolate (USA/IN19338/2013) with known infectious titer was serially ten-fold diluted in virus-negative cell culture medium. Dilutions with theoretical infectious titers from 560 to 0.0056 TCID50/ml together with a medium control were orogastrically inoculated (10ml/pig) into 7 groups of 5-day-old neonatal pigs (n = 4 per group) and 7 groups of 21-day-old weaned pigs (n = 6 per group). In 5-day-old pigs, 10ml of inoculum having titers 560–0.056 TCID50/ml, corresponding to polymerase chain reaction (PCR) cycle threshold (Ct) values 24.2–37.6, resulted in 100% infection in each group; 10ml of inoculum with titer 0.0056 TCID50/ml (Ct>45) caused infection in 25% of the inoculated pigs. In 21-day-old pigs, 10ml of inoculum with titers 560–5.6 TCID50/ml (Ct 24.2–31.4) resulted in 100% infection in each group while 10ml of inoculum with titers 0.56–0.0056 TCID50/ml (Ct values 35.3 –>45) did not establish infection in any pigs under study conditions as determined by clinical signs, PCR, histopathology, immunohistochemistry, and antibody response. These data reveal that PEDV infectious dose is age-dependent with a significantly lower MID for neonatal pigs compared to weaned pigs. This information should be taken into consideration when interpreting clinical relevance of PEDV PCR results and when designing a PEDV bioassay model. The observation of such a low MID in neonates also emphasizes the importance of strict biosecurity and thorough cleaning/disinfection on sow farms. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy of midazolam for anxiety control in third molar extraction surgery. Methods: Electronic retrievals were conducted in Medline (via PubMed, 1950-2013.12), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 3), Embase (via OVID 1974-2013.12), and the System for Information on Grey Literature in Europe (SIGLE). The bibliographies of relevant clinical trials were also checked. Randomized controlled trials satisfying the inclusion criteria were evaluated, with data extraction done independently by two well-trained investigators. Disagreements were resolved by discussion or by consultation with a third member of the review team. Results: Ten studies were included, but meta-analysis could not be conducted because of the significant differences among articles. All but one article demonstrated that midazolam could relieve anxiety. One article demonstrated that propofol offered superior anxiolysis, with more rapid recovery than with midazolam. Compared with lorazepam and diazepam, midazolam did not distinctly dominate in its sedative effect, but was safer. Two articles used midazolam in multidrug intravenous sedation and proved it to be more effective than midazolam alone. Conclusion: It was found, by comparison and analysis, that midazolam might be effective for use for anxiety control during third molar extraction and can be safely administered by a dedicated staff member. It can also be used with other drugs to obtain better sedative effects, but the patient’s respiratory function must be monitored closely, because multidrug sedation is also more risky. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) can be diagnosed by noninvasive approaches with serum α-fetoprotein (AFP) levels >200 ng/ml and/or a radiological imaging study of tumor mass >2 cm in patients with chronic liver disease. Percutaneous fine needle aspiration (FNA) under ultrasound (US) guidance has a diagnostic specificity of 95% and is superior to radiological imaging studies. Aim: The aim of this study is to elucidate the effectiveness and complications of fine needle aspiration in a Chinese population with primary liver cancer and AFP levels ≤200 ng/ml. Materials and Methods: A retrospective study was conducted over a period of 28 years. This selection period included patients with a suspected diagnosis of primary liver cancer whose AFP levels were ≤200 ng/ml and who underwent US-FNA. This data was then analyzed with cytomorphological features correlating with medical history, radiological imaging, AFP, and follow-up information. Results: Of the 1,929 cases with AFP ≤200 mg/ml, 1,756 underwent FNA. Of these, 1,590 cases were determined malignant and the remaining 166 were determined benign. Further, 1,478 malignant cases were diagnosed by FNA alone, and of these, 1,138 were diagnosed as PLC. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the diagnoses were 92.96%, 100%, 100%, 59.71%, and 93.62% respectively. There was no significant difference in the sensitivity, specificity, PPV and NPV between the subgroups with tumor size<2 cm and ≥2 cm. Major complications included implantation metastasis and hemorrhage. Conclusion: Patients with PLC, especially those who present with an AFP ≤200 ng/ml, should undergo FNA. If negative results are obtained by FNA, it still could be HCC and repeated FNA procedure may be needed if highly suspicious of HCC on imaging study. The superiority of FNA in overall accuracy may outweigh its potential complications, such like hemorrhage and implantation metastasis. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic spleen-preserving Splenic hilar lymphadenectomy (LSPL) is required in laparoscopy-assisted total gastrectomy for advanced proximal gastric cancer. However, it is considerably difficult and risk in clinical practice. Thus, we explore the application of LSPL performed by following the perigastric fascias and the intrafascial space in D2 radical gastrectomy for advanced upper-third gastric cancer. Methods: From July 2010 to December 2012, 109 patients with T2–3 upper-third gastric cancer underwent LSPL. Of these patients, 55 underwent classic LSPL (classic group), and the remaining 54 patients underwent LSPL performed by following the fascias and intrafascial space (fascia group). Clinicopathologic characteristics and intraoperative and postoperative variables were compared between the two groups. Results: There were no significant differences in clinicopathological characteristics between the two groups (P>0.05). All of the operations were successful without conversion to laparotomy. The operation time, mean splenic hilar lymph node (LN) dissection time, mean total blood loss and mean blood loss from splenic hilar LN dissection were significantly lower in the fascia group than in the classic group (P<0.05), whereas the times to first flatus, fluid diet and soft diet and the duration of hospital stay were similar in both groups. The mean number of harvested LNs (No. 10 and No. 11d) was slightly higher in the fascia group, but the difference was not significant. No significant difference in morbidity was found between the fascia group and the classic group (9.3% vs.10.9%, P>0.05). At a median follow-up of 12 months(range 5 to 35 months), none of the patients had died or experienced recurrent or metastatic disease. Conclusion: LSPL performed by following the fascias and intrafascial space is an optimal and safe technique based on anatomical logic, and it reduces the difficulties associated with LSPL, making it easier to master and allowing its widespread adoption. [ABSTRACT FROM AUTHOR]

Background: Abnormal hepatic gluconeogenesis is related to hyperglycemia in mammals with insulin resistance. Despite the strong evidences linking Krüppel-like factor 11 (KLF11) gene mutations to development of Type 2 diabetes, the precise physiological functions of KLF11 in vivo remain largely unknown. Results: In current investigation, we showed that KLF11 is involved in modulating hepatic glucose metabolism in mice. Overexpression of KLF11 in primary mouse hepatocytes could inhibit the expression of gluconeogenic genes, including phosphoenolpyruvate carboxykinase (cytosolic isoform, PEPCK-C) and peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α), subsequently decreasing the cellular glucose output. Diabetic mice with overexpression of KLF11 gene in livers significantly ameliorated hyperglycemia and glucose intolerance; in contrast, the knockdown of KLF11 expression in db/m and C57BL/6J mice livers impaired glucose tolerance. Conclusions: Our data strongly indicated the involvement of KLF11 in hepatic glucose homeostasis via modulating the expression of PEPCK-C. [ABSTRACT FROM AUTHOR]

Background: Recent evidence suggests that aberrant activation of Hedgehog (Hh) signaling by Gli transcription factors is characteristic of a variety of aggressive human carcinomas including ovarian cancer. Therefore, chemotherapeutic agents that inhibit activation of Gli transcription factors have emerged as promising novel therapeutic drugs for ovarian cancer. Results: In this study, we show that activation of Hh signaling promoted cellular migration and invasion, whereas blockade of Hh signaling with GANT61 suppressed cellular migration and invasion in ovarian cancer cells. After treatment with GANT61, cDNA microarray analyses revealed changes in many genes such as Integrin β4 subunit (ITGB4), focal adhesion kinase (FAK), etc. Furthermore, ITGB4 expression was up-regulated by Sonic Hedgehog (Shh) ligand and down-regulated by Hh signaling inhibitor. The Shh-mediated ovarian cell migration and invasion was blocked by neutralizing antibodies to ITGB4. In addition, phosphorylations of FAK were increased by Shh and decreased by Hh signaling inhibitor. Inhibition of Gli1 expression using siRNA mimicked the effects of GANT61 treatment, supporting the specificity of GANT61. Further investigations showed that activation of FAK was required for Shh-mediated cell migration and invasion. Finally, we found that down-regulation of Gli reduced the expression of ITGB4 and the phosphorylated FAK, resulting in the inhibition of tumor growth in vivo. Conclusions: The Hh signaling pathway induces cell migration and invasion through ITGB4-mediated activation of FAK in ovarian cancer. Our findings suggest that the diminishment of crosstalk between phosphorylated FAK and ITGB4 due to the down-regulation of Gli family transcription factors might play a pivotal role for inhibiting ovarian cancer progression. [ABSTRACT FROM AUTHOR]

Coral harbor diverse and specific bacteria play significant roles in coral holobiont function. Bacteria associated with three of the common and phylogenetically divergent reef-building corals in the South China Sea, Porites lutea, Galaxea fascicularis and Acropora millepora, were investigated using 454 barcoded-pyrosequencing. Three colonies of each species were sampled, and 16S rRNA gene libraries were constructed individually. Analysis of pyrosequencing libraries showed that bacterial communities associated with the three coral species were more diverse than previous estimates based on corals from the Caribbean Sea, Indo-Pacific reefs and the Red Sea. Three candidate phyla, including BRC1, OD1 and SR1, were found for the first time in corals. Bacterial communities were separated into three groups: P. lutea and G. fascicular, A. millepora and seawater. P. lutea and G. fascicular displayed more similar bacterial communities, and bacterial communities associated with A. millepora differed from the other two coral species. The three coral species shared only 22 OTUs, which were distributed in Alphaproteobacteria, Deltaproteobacteria, Gammaproteobacteria, Chloroflexi, Actinobacteria, Acidobacteria and an unclassified bacterial group. The composition of bacterial communities within each colony of each coral species also showed variation. The relatively small common and large specific bacterial communities in these corals implies that bacterial associations may be structured by multiple factors at different scales and that corals may associate with microbes in terms of similar function, rather than identical species. [ABSTRACT FROM AUTHOR]

Background: To evaluate the prevalence of the accessory left hepatic artery (ALHA; defined as a vessel arising from the left gastric artery, which, together with a typical left hepatic artery, supplies blood to the left lobe of the liver) and its short-term clinical implications in patients undergoing radical gastrectomy for gastric cancer. Methods: Clinical data of 1173 patients with gastric cancer who underwent laparoscopy-assisted radical gastrectomy were retrospectively analyzed. Groups of patients with and without ALHA were compared to identify differences in intraoperative and postoperative variables and changes in liver function. Results: Of the 1173 patients, 135 (11.5%) had an ALHA and 1038 (88.5%) did not. There were no significant between-group differences in clinicopathological and intraoperative characteristics, postoperative recovery, and morbidity and mortality rates (P>0.05 each). None of the patients had postoperative symptoms associated with impaired liver function. Glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and total bilirubin (TBIL) concentrations were similar preoperatively. TBIL concentrations on postoperative days 1, 3, and 7 were similar (P>0.05), while GOT and GPT activities were higher in the ALHA than in the non-ALHA group on days 1 and 7 (P<0.05), with all three markers similar in the two groups on day 14. In patients without chronic liver disease (CLD), GOT, GPT and TBIL concentrations were similar in patients with and without ALHA; whereas, in patients with CLD, GOT and GPT concentrations on days 1 and 3 and GOT on day 7 were higher in patients with than without ALHA. Conclusion: ALHA is a common anomaly that was found in 11.5% of patients. It can be safely severed during radical gastrectomy in patients without CLD, but should be left intact in patients with CLD to prevent liver dysfunction. If severed in the latter, the patient should be monitored and liver-protecting therapy may be necessary. [ABSTRACT FROM AUTHOR]

Although intracellular beta amyloid (Aβ) accumulation is known as an early upstream event in the degenerative course of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) myopathy, the process by which Aβdeposits initiate various degradative pathways, and their relationship have not been fully clarified. We studied the possible secondary responses after amyloid beta precursor protein (AβPP) deposition including unfolded protein response (UPR), ubiquitin proteasome system (UPS) activation and its correlation with autophagy system. Eight GNE myopathy patients and five individuals with normal muscle morphology were included in this study. We performed immunofluorescence and immunoblotting to investigate the expression of AβPP, phosphorylated tau (p-tau) and endoplasmic reticulum molecular chaperones. Proteasome activities were measured by cleavage of fluorogenic substrates. The expression of proteasome subunits and linkers between proteasomal and autophagy systems were also evaluated by immunoblotting and relative quantitative real-time RT-PCR. Four molecular chaperones, glucose-regulated protein 94 (GRP94), glucose-regulated protein 78 (GRP78), calreticulin and calnexin and valosin containing protein (VCP) were highly expressed in GNE myopathy. 20S proteasome subunits, three main proteasome proteolytic activities, and the factors linking UPS and autophagy system were also increased. Our study suggests that AβPP deposition results in endoplasmic reticulum stress (ERS) and highly expressed VCP deliver unfolded proteins from endoplasmic reticulum to proteosomal system which is activated in endoplasmic reticulum associated degradation (ERAD) in GNE myopathy. Excessive ubiquitinated unfolded proteins are exported by proteins that connect UPS and autophagy to autophagy system, which is activated as an alternative pathway for degradation. [ABSTRACT FROM AUTHOR]

Landscape change in and around protected areas is of concern worldwide given the potential impacts of such change on biodiversity. Given such impacts, we sought to understand the extent of changes in different land-cover types at two protected areas, Tarangire and Katavi National Parks in Tanzania, over the past 27 years. Using Maximum Likelihood classification procedures we derived eight land-cover classes from Landsat TM and ETM+ images, including: woody savannah, savannah, grassland, open and closed shrubland, swamp and water, and bare land. We determined the extent and direction of changes for all land-cover classes using a post-classification comparison technique. The results show declines in woody savannah and increases in barren land and swamps inside and outside Tarangire National Park and increases in woody savannah and savannah, and declines of shrubland and grassland inside and outside Katavi National Park. The decrease of woody savannah was partially due to its conversion into grassland and barren land, possibly caused by human encroachment by cultivation and livestock. Based upon these changes, we recommend management actions to prevent detrimental effects on wildlife populations. [ABSTRACT FROM AUTHOR]

Background:Previous observational studies have shown that insulin therapy may modify the risk of prostate cancer (PCa). However, these studies yielded controversial results. Thus, we performed this meta-analysis to determine whether insulin use was associated with PCa risk in patients with diabetes mellitus (DM). Method:A literature search was carried out in PubMed, EMBASE, and Cochrane Library Central database between January 1966 and January 2013. Fixed-effect and random-effect models were used to estimate pooled relative risks (RR) and corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity analyses were also performed. Result:A total of 11 (10 cohorts, and one case–control) studies published between 2007 and 2013 were included in the meta-analysis, representing data for 205,523 male subjects and 7,053 PCa cases. There were five studies investigating the influence of insulin and other glucose-lowering agents on the risk of PCa , and six studies investigating the influence of glargine and non-glargine insulin. Insulin use was not associated with PCa risk when compared with other glucose-lowering agents (RR=0.89, 95% CI, 0.72-1.09). Use of insulin glargine did not contribute to susceptibility to PCa as compared with use of non-glargine insulin (RR=1.26, 95% CI, 0.86-1.84). Sensitivity analysis confirmed the stability of present results, since no individual study affected the pooled result significantly. Conclusions:Our results suggest that, there may be no significant association between insulin use and risk of PCa as compared with other glucose-lowering agents in patients with DM, and there was no substantial evidence for increase risk of PCa among insulin glargine users as compared to non-glargine insulin users. Further studies are warranted to validate these conclusions. [ABSTRACT FROM AUTHOR]

The mouse intracellular pathogen resistance 1 (Ipr1) gene plays important roles in mediating host immunity and previous work showed that it enhances macrophage apoptosis upon mycobacterium infection. However, to date, little is known about the regulation pattern of Ipr1 action. Recent studies have investigated the protein-coding genes and microRNAs regulated by Ipr1 in mouse macrophages, but the structure and the functional motif of the Ipr1 protein have yet to be explored. In this study, we analyzed the domains and functional motif of the Ipr1 protein. The resulting data reveal that Ipr1 protein forms a homodimer and that the Sp100-like domain mediates the targeting of Ipr1 protein to nuclear dots (NDs). Moreover, we found that an Ipr1 mutant lacking the classic nuclear localization signal (cNLS) also translocated into the nuclei, suggesting that the cNLS is not the only factor that directs Ipr1 nuclear localization. Additionally, mechanistic studies revealed that an arginine/lysine-rich element within the DNA-binding domain (SAND domain) is critical for Ipr1 binding to the importin protein receptor NPI-1, demonstrating that this element plays an essential role in mediating the nuclear localization of Ipr1 protein. Furthermore, our results show that this arginine/lysine-rich element contributes to the transcriptional regulation and apoptotic activity of Ipr1. These findings highlight the structural foundations of Ipr1 action and provide new insights into the mechanism of Ipr1-mediated resistance to mycobacterium. [ABSTRACT FROM AUTHOR]

Purpose: To determine the biometry of anterior segment dimensions of the human eye on both horizontal and vertical meridians with extended scan depth optical coherence tomography (OCT) during accommodation. Methods: Twenty pre-presbyopic volunteers, aged between 24 and 30, were recruited. The ocular anterior segment of each subject was imaged using an extended scan depth OCT under non- and 3.0 diopters (D) of accommodative demands on both horizontal and vertical meridians. All the images were analyzed to yield the following parameters: pupil diameter (PD), anterior chamber depth (ACD), anterior and posterior surface curvatures of the crystalline lens (ASC and PSC) and the lens thickness (LT). Two consecutive measurements were performed to assess the repeatability and reproducibility of this OCT. They were evaluated by calculating the within-subject standard deviation (SD), a paired t-test, intra-class correlation coefficients (ICC) and the coefficient of repeatability/reproducibility (CoR). Results: There were no significant differences between two consecutive measurements on either horizontal or vertical meridians under both two different accommodative statuses (P>0.05). The ICC for all parameters ranged from 0.775 to 0.998, except for the PSC (0.550) on the horizontal meridian under the non-accommodative status. In addition, the CoR for most of the parameters were excellent (0.004% to 4.89%). In all the parameters, only PD and PSC were found different between the horizontal and vertical meridians under both accommodative statuses (P<0.05). PD, ACD, ASC and PSC under accommodative status were significantly smaller than those under the non-accommodative status, except that the PSC at the vertical meridian did not change. In addition, LT was significantly increased when accommodation. Conclusion: The extended scan depth OCT successfully measured the dimensions of the anterior eye during accommodation with good repeatability and reproducibility on both horizontal and vertical meridians. The asymmetry of lens posterior surface and oval-shaped pupil were found during accommodation. [ABSTRACT FROM AUTHOR]

Tropical forests are major repositories of biodiversity, but are fast disappearing as land is converted to agriculture. Decision-makers need to know which of the remaining forests to prioritize for conservation, but the only spatial information on forest biodiversity has, until recently, come from a sparse network of ground-based plots. Here we explore whether airborne hyperspectral imagery can be used to predict the alpha diversity of upper canopy trees in a West African forest. The abundance of tree species were collected from 64 plots (each 1250 m2 in size) within a Sierra Leonean national park, and Shannon-Wiener biodiversity indices were calculated. An airborne spectrometer measured reflectances of 186 bands in the visible and near-infrared spectral range at 1 m2 resolution. The standard deviations of these reflectance values and their first-order derivatives were calculated for each plot from the c. 1250 pixels of hyperspectral information within them. Shannon-Wiener indices were then predicted from these plot-based reflectance statistics using a machine-learning algorithm (Random Forest). The regression model fitted the data well (pseudo-R2 = 84.9%), and we show that standard deviations of green-band reflectances and infra-red region derivatives had the strongest explanatory powers. Our work shows that airborne hyperspectral sensing can be very effective at mapping canopy tree diversity, because its high spatial resolution allows within-plot heterogeneity in reflectance to be characterized, making it an effective tool for monitoring forest biodiversity over large geographic scales. [ABSTRACT FROM AUTHOR]

DNA methylation has frequently been implicated in sex determination and differentiation in teleost species. In order to detect the DNA methylation patterns established during sexual differentiation in tiger pufferfish T. rubripes, we performed comprehensive whole genome methylation sequencing and analyses of the gonads of male, female, and pseudo male. We obtained a total of 33.12, 32.44, and 31.60 Gb clean data for male, female, and pseudo male, with a sequencing depth of 66.44×, 60.47× and 54.86×, respectively. The methylation level of cytosine (C) residues in the genomic DNA from gonads was 11.016%, 10.428%, and 11.083% in male, female, and pseudo male, respectively. More than 65% of C methylation was at CpG sites, and less than 1% was at CHG and CHH sites. In each regulatory element, there were low methylation levels on both sides of the transcription start site, and higher methylation levels in exons, introns, and downstream of genes. The highest mCpG was on chromosome 8 and the lowest mCpG was on chromosome 5. Comparisons of whole-genome DNA methylation between pairs of samples revealed that there were 3,173 differentially methylated regions (DMRs) between female and male, and 3,037 DMRs between male and pseudo male, corresponding to 0.232% and 0.223% of the length of the genome, respectively. There were only 1,635 DMRs between female and pseudo male, representing 0.127% of the length of the genome. A number of differentially methylated genes (DMGs) related to sex determination and differentiation were selected, such as amhr2 and pfcyp19a. After Bisulfite Sequencing PCR (BSP) verification, amhr2 was exhibited low methylation level in normal males and pseudo male, and high methylation level in normal females but pfcyp19a showed low methylation level in normal females and high methylation level in normal males and pseudo males. These results provide information about the molecular epigenetic mechanisms of DNA methylation during low-temperature induced masculinization of tiger pufferfish, and increase our understanding of the mechanisms of sex determination and differentiation in this important aquaculture fish species. [ABSTRACT FROM AUTHOR]

The brain uses its intrinsic dynamics to actively predict observed sensory inputs, especially under perceptual ambiguity. However, it remains unclear how this inference process is neurally implemented in biasing perception of ambiguous inputs towards the predicted percepts. The process of perceptual inference can be well illustrated by the phenomenon of bistable apparent motion in the Ternus display, in which subjective perception spontaneously alternates between element motion (EM) and group motion (GM) percepts depending on whether two consecutively presented frames are grouped over time or not. The frequency of alpha-band oscillations has long been hypothesized to gate the temporal window of perceptual grouping over time. Under this hypothesis, variation in the intrinsic alpha frequency should predict perceptual outcome of the bistable Ternus display. Moreover, we hypothesize that the perception system employs this prior knowledge on intrinsic alpha frequency to resolve perceptual ambiguity, by shifting perceptual inference towards the predicted percepts. Using electroencephalography and intracranial recordings, we showed that both between and within subjects, lower prestimulus alpha frequencies (PAFs) predicted the EM percepts since the two frames fell in the same alpha cycle and got temporally integrated, while higher PAFs predicted the GM percepts since the two frames fell in different alpha cycles. Multivariate decoding analysis between the EM percepts with lower PAFs and the GM percepts with higher PAFs further revealed a representation of the subsequently reported bistable percept in the neural signals shortly before the actual appearance of the second frame. Therefore, perceptual inference, based on variation in intrinsic PAFs, biases poststimulus neural representations by inducing preactivation of the predicted percepts. In addition, enhanced prestimulus blood-oxygen-level–dependent (BOLD) signals and network dynamics in the frontoparietal network, together with reduced prestimulus alpha power, upon perceiving the EM percepts suggest that temporal grouping is an attention-demanding process. [ABSTRACT FROM AUTHOR]

Background: Hand, foot and mouth disease (HFMD) is spread widely across Asia, and the hospitalization burden is currently not well understood. Here, we estimated serotype-specific and age-specific hospitalization rates of HFMD in Southern China. Methods: We enrolled pediatric HFMD patients admitted to 3/3 county-level hospitals, and 3/23 township-level hospitals in Anhua county, Hunan (CN). Samples were collected to identify enterovirus serotypes by RT-PCRs between October 2013 and September 2016. Information on other eligible, but un-enrolled, patients were retrospectively collected from the same six hospitals. Monthly numbers of all-cause hospitalizations were collected from each of the 23 township-level hospitals to extrapolate hospitalizations associated with HFMD among these. Results: During the three years, an estimated 3,236 pediatric patients were hospitalized with lab-confirmed HFMD, and among these only one case was severe. The mean hospitalization rate was 660 (95% CI: 638–684) per 100,000 person-years for lab-confirmed HFMD, with higher rates among CV-A16 and CV-A6 associated HFMD (213 vs 209 per 100,000 person-years), and lower among EV-A71, CV-A10 and other enterovirus associated HFMD (134, 39 and 66 per 100,000 person-years respectively, p<0.001). Children aged 12–23 months had the highest hospitalization rates (3,594/100,000 person-years), followed by those aged 24–35 months (1,828/100,000 person-years) and 6–11 months (1,572/100,000 person-years). Compared with other serotypes, CV-A6-associated hospitalizations were evident at younger ages. Conclusions: Our study indicates a substantial hospitalization burden associated with non-severe HFMD in a rural county in southern China. Future mitigation policies should take into account the disease burden identified, and optimize interventions for HFMD. [ABSTRACT FROM AUTHOR]

The stand density of trees affects stand growth and is useful for estimating other forests structure parameters. We studied tree stand density in Jiufeng National Forest Park in Beijing. The number of spectral local maxima points (NSLMP) calculated within each sample plot was extracted by the spectral maximum filtering method using QuickBird imagery. Regression analysis of NSLMP and the true stand density collected by ground measurements using differential GPS and the total station were used to estimate stand density of the study area. We used NSLMP as an independent variable and the actual stand density as the dependent variable to develop separate statistical models for all stands in the coniferous forest and broadleaf forest. By testing the different combination of Normalized Difference Vegetation Index (NDVI) thresholds and window sizes, the optimal selection was identified. The combination of a 3 × 3 window size and NDVI ≥ 0.3 threshold in coniferous forest produced the best result using near-infrared band (coniferous forest R2 = 0.79, RMSE = 12.60). The best combination for broadleaf forest was a 3 × 3 window size and NDVI ≥ 0.1 with R2 = 0.44, RMSE = 9.02 using near-infrared band. The combination of window size and NDVI threshold for all unclassified forest was 3 × 3 window size and NDVI ≥ 0.3 with R2 = 0.70, RMSE = 11.20 using near-infrared band. A stand density planning map was constructed using the best models applied for different forest types. Different forest types require the use of different combination strategies to best extract the stand density by using the local maximum (LM). The proposed method uses a combination of high spatial resolution imagery and sampling plots strategy to estimate stand density. [ABSTRACT FROM AUTHOR]

New regulatory and consumer demands highlight the importance of animal feed as a part of our national food safety system. Porcine epidemic diarrhea virus (PEDV) is the first viral pathogen confirmed to be widely transmissible in animal food. Because the potential for viral contamination in animal food is not well characterized, the objectives of this study were to 1) observe the magnitude of virus contamination in an animal food manufacturing facility, and 2) investigate a proposed method, feed sequencing, to decrease virus decontamination on animal food-contact surfaces. A U.S. virulent PEDV isolate was used to inoculate 50 kg swine feed, which was mixed, conveyed, and discharged into bags using pilot-scale feed manufacturing equipment. Surfaces were swabbed and analyzed for the presence of PEDV RNA by quantitative real-time polymerase chain reaction (qPCR). Environmental swabs indicated complete contamination of animal food-contact surfaces (0/40 vs. 48/48, positive baseline samples/total baseline samples, positive subsequent samples/total subsequent samples, respectively; P < 0.05) and near complete contamination of non-animal food-contact surfaces (0/24 vs. 16/18, positive baseline samples/total baseline samples, positive subsequent samples/total subsequent samples, respectively; P < 0.05). Flushing animal food-contact surfaces with low-risk feed is commonly used to reduce cross-contamination in animal feed manufacturing. Thus, four subsequent 50 kg batches of virus-free swine feed were manufactured using the same system to test its impact on decontaminating animal food-contact surfaces. Even after 4 subsequent sequences, animal food-contact surfaces retained viral RNA (28/33 positive samples/total samples), with conveying system being more contaminated than the mixer. A bioassay to test infectivity of dust from animal food-contact surfaces failed to produce infectivity. This study demonstrates the potential widespread viral contamination of surfaces in an animal food manufacturing facility and the difficulty of removing contamination using conventional feed sequencing, which underscores the importance for preventing viruses from entering and contaminating such facilities. [ABSTRACT FROM AUTHOR]

In the auditory pathway, the inferior colliculus (IC) receives and integrates excitatory and inhibitory inputs from the lower auditory nuclei, contralateral IC, and auditory cortex (AC), and then uploads these inputs to the thalamus and cortex. Meanwhile, the AC modulates the sound signal processing of IC neurons, including their latency (i.e., first-spike latency). Excitatory and inhibitory corticofugal projections to the IC may shorten and prolong the latency of IC neurons, respectively. However, the synaptic mechanisms underlying the corticofugal latency modulation of IC neurons remain unclear. Thus, this study probed these mechanisms via in vivo intracellular recording and acoustic and focal electric stimulation. The AC latency modulation of IC neurons is possibly mediated by pre-spike depolarization duration, pre-spike hyperpolarization duration, and spike onset time. This study suggests an effective strategy for the timing sequence determination of auditory information uploaded to the thalamus and cortex. [ABSTRACT FROM AUTHOR]

Reprimo (RPRM) is a p53-induced tumor suppressor gene. Its aberrant DNA methylation is correlated with carcinogenesis and may be used as a surrogate marker for the early detection of gastric cancer. However, the detail information regarding its DNA methylation has not been revealed. Here, we investigated the RPRM gene methylation in gastric cancer tumor and plasma samples by methylation-sensitive melt curve analysis (MS-MCA) and bisulfite sequencing in depth. We developed a semi-quantitative method based on MS-MCA for detecting DNA methylation and unraveled the RPRM gene methylation pattern in gastric cancer. This study provides a solid foundation for the future application of detecting RPRM gene methylation in human plasma or serum samples to help diagnose gastric cancer or for prognosis evaluation. [ABSTRACT FROM AUTHOR]

Late embryogenesis abundant (LEA) proteins have been identified in a wide range of organisms and are believed to play a role in the adaptation of plants to stress conditions. In this study, we performed genome-wide identification of LEA proteins and their coding genes in Moso bamboo (Phyllostachys edulis) of Poaceae. A total of 23 genes encoding LEA proteins (PeLEAs) were found in P. edulis that could be classified to six groups based on Pfam protein family and homologous analysis. Further in silico analyses of the structures, gene amount, and biochemical characteristics were conducted and compared with those of O. sativa (OsLEAs), B. distachyon (BdLEAs), Z. mays (ZmLEAs), S. bicolor (SbLEAs), Arabidopsis, and Populus trichocarpa. The less number of PeLEAs was found. Evolutionary analysis revealed orthologous relationship and colinearity between P. edulis, O. sativa, B. distachyon, Z. mays, and S. bicolor. Analyses of the non-synonymous (Ka) and synonymous (Ks)substitution rates and their ratios indicated that the duplication of PeLEAs may have occurred around 18.8 million years ago (MYA), and divergence time of LEA family among the P. edulis-O. sativa and P. edulis–B. distachyon, P. edulis-S. bicolor, and P. edulis-Z. mays was approximately 30 MYA, 36 MYA, 48 MYA, and 53 MYA, respectively. Almost all PeLEAs contain ABA- and (or) stress-responsive regulatory elements. Further RNA-seq analysis revealed approximately 78% of PeLEAs could be up-regulated by dehydration and cold stresses. The present study makes insights into the LEA family in P. edulis and provides inventory of stress-responsive genes for further functional validation and transgenic research aiming to plant genetic improvement of abiotic stress tolerance. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer has an enrichment of stem-like cancer cells (CSCs) that contribute to chemoresistant tumors prone to metastasis and recurrence. Drug screening assays based on cytotoxicity cannot identify specific CSC inhibitors, because CSCs comprise only a small portion of cancer cell population, and it is difficult to propagate stable CSC populations in vitro for high-throughput screening (HTS) assays. Based on the important role of cancer cell epithelial-to-mesenchymal transition (EMT) in promoting CSCs, we hypothesized that inhibition of EMT can be a useful strategy for inhibiting CSCs, and therefore a feasible approach for HTS can be built for identification of CSC inhibitors, based on assays detecting EMT inhibition. Methods: An immunofluorescent assay was established and optimized for HTS to identify compounds that enhance E-cadherin expression, as a hallmark of inhibition of EMT. Four chemical libraries containing 41,472 compounds were screened in PANC-1 pancreatic cancer cell line. Positive hits were validated for EMT and CSC inhibition in vitro using sphere formation assay, western blotting, immune fluorescence, and scratch assay. Results: Initial hits were refined to 73 compounds with a secondary screening, among which 17 exhibited concentration dependent induction of E-cadherin expression. Six compounds were selected for further study which belonged to 2 different chemical structural clusters. A novel compound 1-(benzylsulfonyl) indoline (BSI, Compound #38) significantly inhibited pancreatic cancer cell migration and invasion. BSI inhibited histone deacetylase, increased histone 4 acetylation preferably, resulting in E-cadherin up-regulation. BSI effectively inhibited tumor spheres formation. Six more analogues of BSI were tested for anti-migration and anti-CSC activities. Conclusion: This study demonstrated a feasible approach for discovery of agents targeting EMT and CSCs using HTS, and identified a class of novel chemicals that could be developed as anti-EMT and anti-CSC drug leads. [ABSTRACT FROM AUTHOR]

Background and Purpose: It has been accepted that AMPK (Adenosine monophosphate–activated protein kinase) activation exhibits many beneficial effects on glucolipid metabolism. Lysophosphatidylcholine (LPC) is an important lysophospholipid which can improve blood glucose levels in diabetic mice and attenuate inflammation by activating AMPK signal pathway in macrophages. Synthetic alkylphospholipids (ALPs), such as miltefosine, is used as an alternate of LPC for the clinical application. Here, we investigated whether miltefosine could have an impact on hepatic steatosis and related metabolic disorders. Experimental Approach: Mice were fed with high fat diet (HFD) for 16 weeks to generate an obese model. Next, the obese mice were randomly divided into three groups: saline-treated and miltefosine-treated (2.5 or 5 mg/kg/d) groups. Miltefosine was intraperitoneally administrated into mice for additional 4 weeks plus HFD treatment. Key Results: It was shown that miltefosine treatment could substantially improve glucose metabolism, prevented hepatic lipid accumulation, and inhibited liver inflammation in HFD-fed mice by activating AMPK signal pathway. In vitro, miltefosine stimulated AMPKα phosphorylation both in time and dose dependent manner and decreased lipid accumulation in liver cells. When a specific AMPK inhibitor compound C was used to treat mice, the antagonistic effects of miltefosine on HFD-induced mouse hyperlipidaemia and liver steatosis were abolished. Treatment with miltefosine also dramatically inhibited the HFD-induced liver inflammation in mice. Conclusions and Implications: Here we demonstrated that miltefosine might be a new activator of AMPK signal pathway in vivo and in vitro and be useful for treatment of hepatic steatosis and related metabolic disorders. [ABSTRACT FROM AUTHOR]

The contribution of circulating antibody to the protection of naïve piglets against porcine epidemic diarrhea virus (PEDV) was evaluated using a passive antibody transfer model. Piglets (n = 62) derived from 6 sows were assigned to one of 6 different treatments using a randomized block design which provided for allocation of all treatments to all sows' litters. Each treatment was designed to achieve a different level of circulating anti-PEDV antibody via intraperitoneally administration of concentrated serum antibody. Piglets were orally inoculated with PEDV (USA/IN/2013/19338E, 1 x 103 TCID50 per piglet) 24 hours later and then monitored for 14 days. Piglets remained with their dam throughout the experiment. Sow milk samples, piglet fecal samples, and data on piglet clinical signs, body weight, and body temperature were collected daily. Fecal samples were tested by PEDV real-time reverse transcriptase PCR. Serum, colostrum, and milk were tested for PEDV IgG, IgA, and virus-neutralizing antibody. The data were evaluated for the effects of systemic PEDV antibody levels on growth, body temperature, fecal shedding, survival, and antibody response. The analysis showed that circulating antibody partially ameliorated the effect of PEDV infection. Specifically, antibody-positive groups returned to normal body temperature faster and demonstrated a higher rate of survivability than piglets without PEDV antibody. When combined with previous literature on PEDV, it can be concluded that both systemic antibodies and maternal secretory IgA in milk contribute to the protection of the neonatal pig against PEDV infections. Overall, the results of this experiment suggested that passively administered circulating antibodies contributed to the protection of neonatal piglets against PEDV infection. [ABSTRACT FROM AUTHOR]

A type 2 vaccine-derived poliovirus (VDPV), differing from the Sabin 2 strain at 8.6% (78/903) of VP1 nucleotide positions, was isolated from seawater collected from a seaport in São Paulo State, Brazil. The P1/capsid region is related to the Sabin 2 strain, but sequences within the 5'-untranslated region and downstream of the P1 region were derived from recombination with other members of Human Enterovirus Species C (HEV-C). The two known attenuating mutations had reverted to wild-type (A481G in the 5'-UTR and Ile143Thr in VP1). The VDPV isolate had lost the temperature sensitive phenotype and had accumulated amino acid substitutions in neutralizing antigenic (NAg) sites 3a and 3b. The date of the initiating OPV dose, estimated from the number of synonymous substitutions in the capsid region, was approximately 8.5 years before seawater sampling, a finding consistent with a long time of virus replication and possible transmission among several individuals. Although no closely related type 2 VDPVs were detected in Brazil or elsewhere, this VDPV was found in an area with a mobile population, where conditions may favor both viral infection and spread. Environmental surveillance serves as an important tool for sensitive and early detection of circulating poliovirus in the final stages of global polio eradication. [ABSTRACT FROM AUTHOR]

Neuropsychological and functional MRI data suggest that two functionally and anatomically dissociable streams of visual processing exist: a ventral perception-related stream and a dorsal action-related stream. However, relatively little is known about how the two streams interact in the intact brain during the production of adaptive behavior. Using functional MRI and a virtual three-dimensional paradigm, we aimed at examining whether the parieto-occipital junction (POJ) acts as an interface for the integration and processing of information between the dorsal and ventral streams in the near and far space processing. Virtual reality three-dimensional near and far space was defined by manipulating binocular disparity, with -68.76 arcmin crossed disparity for near space and +68.76 arcmin uncrossed disparity for near space. Our results showed that the POJ and bilateral superior occipital gyrus (SOG) showed relative increased activity when responded to targets presented in the near space than in the far space, which was independent of the retinotopic and perceived sizes of target. Furthermore, the POJ showed the enhanced functional connectivity with both the dorsal and ventral streams during the far space processing irrespective of target sizes, supporting that the POJ acts as an interface between the dorsal and ventral streams in disparity-defined near and far space processing. In contrast, the bilateral SOG showed the enhanced functional connectivity only with the ventral stream if retinotopic sizes of targets in the near and far spaces were matched, which suggested there was a functional dissociation between the POJ and bilateral SOG. [ABSTRACT FROM AUTHOR]

Nitrogen (N) is an essential nutrient for plants, and it directly affects grain yield and protein content in cereal crops. Plant root systems are not only critical for anchorage in the soil, but also for N acquisition. Therefore, genes controlling root development might also affect N uptake by plants. In this study, the responses of nitrogen on root architecture of mutant rtcs and wild-type of maize were investigated by morphological and physiological analysis. Subsequently, we performed a comparative RNA-Seq analysis to compare gene expression profiles between mutant rtcs roots and wild-type roots under different N conditions. We identified 786 co-modulated differentially expressed genes (DEGs) related to root development. These genes participated in various metabolic processes. A co-expression cluster analysis and a cis-regulatory motifs analysis revealed the importance of the AP2-EREBP transcription factor family in the rtcs-dependent regulatory network. Some genotype-specific DEGs contained at least one LBD motif in their promoter region. Further analyses of the differences in gene transcript levels between rtcs and wild-type under different N conditions revealed 403 co-modulated DEGs with distinct functions. A comparative analysis revealed that the regulatory network controlling root development also controlled gene expression in response to N-deficiency. Several AP2-EREBP family members involved in multiple hormone signaling pathways were among the DEGs. These transcription factors might play important roles in the rtcs-dependent regulatory network related to root development and the N-deficiency response. Genes encoding the nitrate transporters NRT2-1, NAR2.1, NAR2.2, and NAR2.3 showed much higher transcript levels in rtcs than in wild-type under normal-N conditions. This result indicated that the LBD gene family mainly functions as transcriptional repressors, as noted in other studies. In summary, using a comparative RNA-Seq-based approach, we identified DEGs related to root development that also participated in the N-deficiency response in maize. These findings will increase our understanding of the molecular regulatory networks controlling root development and N-stress responses. [ABSTRACT FROM AUTHOR]

Background and Aim: Autophagy is a cellular process to regulate the turnover of misfolded/aggregated proteins or dysfunctional organelles such as damaged mitochondria. Microtubule-associated protein MAP1S (originally named C19ORF5) is a widely-distributed homologue of neuronal-specific MAP1A and MAP1B with which autophagy marker light chain 3 (LC3) was originally co-purified. MAP1S bridges autophagic components with microtubules and mitochondria through LC3 and positively regulates autophagy flux from autophagosomal biogenesis to degradation. The MAP1S-mediated autophagy suppresses tumorigenesis as suggested in a mouse liver cancer model and in prostate cancer patients. The TGFβ signaling pathway plays a central role in pancreatic tumorigenesis, and high levels of TGFβ suggest a tumor suppressive function and predict a better survival for some patients with resectable pancreatic ductal adenocarcinoma. In this study, we try to understand the relationship between TGFβ and MAP1S-mediated autophagy in pancreatic ductal adenocarcinoma. Methods: We collected the tumor and its adjacent normal tissues from 33 randomly selected patients of pancreatic ductal adenocarcinomas to test the association between TGFβ and autophagy markers MAP1S and LC3. Then we tested the cause and effect relation between TGFβ and autophagy markers in cultured pancreatic cancer cell lines. Results: Here we show that levels of TGFβ and autophagy markers MAP1S and LC3 are dramatically elevated in tumor tissues from patients with pancreatic ductal adenocarcinomas. TGFβ increases levels of MAP1S protein and enhances autophagy flux. Conclusion: TGFβ may suppress the development of pancreatic ductal adenocarcinomas by enhancing MAP1S-mediated autophagy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the dynamic change of CD34 level during the survival process of narrow pedicle flaps. Methods: Twenty-five white pigs were randomly and equally divided into 5 experimental groups. Five different type of narrow pedicle with different length-to-width ratio were employed, and each type of narrow pedicle was covered with 5 different size random flaps and which was classified into A, B, C, D and E for 5 groups. Group A was control group. Each type narrow pedicle with 5 different skin flaps were implanted onto the back of the pigs along the midline of back with a reverse direction. A 0.3 cm×0.3 cm full thickness skin flap in the middle of distal segment was collected and on 3rd, 5th, 7th and 14th days of post-operation. The expression of CD34 was measured by immunohistochemistry and enzyme-linked immunosorbent (ELISA). Results: Histological examination showed that with the increasing of length-to-width ratio of the narrow pedicle skin flaps, the expression of CD34 increased in the skin flaps. Increased level of CD34 was found on 3rd day post-operation, and the peak expression was found on 7th day. Persistent high level of CD34 was found until 14th day. Conclusion: Increased CD34 level in the distal skin flap, there is the association between CD34 level and ischemia injury. Moreover, CD34 expression plays an important role during the repair processes of pedicle flaps. [ABSTRACT FROM AUTHOR]

Background: Chemical stimulation of white adipose tissue (WAT) induces adipose afferent reflex (AAR), and thereby causes a general sympathetic activation. Paraventricular nucleus (PVN) is important in control of sympathetic outflow. This study was designed to investigate the role of γ-aminobutyric acid (GABA) in PVN in regulating the AAR. Methodology/Principal Findings: Experiments were carried out in anesthetized rats. Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were continuously recorded. AAR was evaluated by the RSNA and MAP responses to electrical stimulation of the right epididymal WAT (eWAT) afferent nerve. Electrical stimulation of eWAT afferent nerve increase RSNA. Bilateral microinjection of the GABAA receptor agonist isoguvacine or the GABAB receptor agonist baclofen attenuated the AAR. The effect of isoguvacine on the AAR was greater than that of baclofen. The GABAA receptor antagonist gabazine enhanced the AAR, while the GABAB receptor antagonist CGP-35348 had no significant effect on the AAR. Bilateral PVN microinjection of vigabatrin, a selective GABA-transaminase inhibitor, to increase endogenous GABA levels in the PVN abolished the AAR. The inhibitory effect of vigabatrin on the AAR was attenuated by the pretreatment with gabazine or CGP-35348. Pretreatment with combined gabazine and CGP-35348 abolished the effects of vigabatrin. Conclusions: Activation of GABAA or GABAB receptors in the PVN inhibits the AAR. Blockade of GABAA receptors in the PVN enhances the AAR. Endogenous GABA in the PVN plays an important role in regulating the AAR. [ABSTRACT FROM AUTHOR]

Background: The effect of rebamipide on repairing intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs and its mechanism remain unclear. In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage. Methods: BALB/c mice were administered aspirin (200 mg/kg/d) for 5 days to induce acute small intestinal injury (SII). Subsequently, SII mice were treated with rebamipide (320 mg/kg/d) for 5 days. The structure of intestinal barrier was observed with transmission electron microscope, and Zo-1 and occludin expressions were detected. The proliferative index was indicated by the percentage of proliferating cell nuclear antigen positive cells. The prostaglandin E2 (PGE2) levels in the small intestine tissues were measured by an enzyme immunoassay. The mRNA and protein expression levels of cyclooxygenase (COX) and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively. Results: COX expression was significantly down-regulated in aspirin induced SII (P < 0.05). In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly. The proliferative index increased after rebamipide treatment when compared with that in the control mice. The expressions of COX-2, β-catenin, and c-myc and the PGE2 concentrations in small intestinal tissues were significantly increased in mice with rebamipide treatments (P < 0.05). Conclusion: Rebamipide administration in aspirin-induced SII mice could improve the intestinal barrier structure and promote the regeneration of small intestinal epithelial injury through up-regulating COX-2 expression and the accumulation of β-catenin. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic gastrectomy (LG) for gastric cancer has increased in popularity due to advances in surgical techniques. The aim of this study is to validate the efficacy and safety of laparoscopic gastrectomy for gastric cancer compared with open gastrectomy (OG). Methods: The study comprised 3,580 patients who were treated with curative intent either by laparoscopic gastrectomy (2,041 patients) or open gastrectomy (1,539 patents) between January 2005 and October 2013. The surgical outcomes were compared between the two groups. Results: Laparoscopic gastrectomy was associated with significantly less blood loss, transfused patient number, time to ground activities, and post-operative hospital stay, but with similar operation time, time to first flatus, and time to resumption of diet, compared with the open gastrectomy. No significant difference in the number of lymph nodes dissected was observed between these two groups. The morbidity and mortality rates of the LG group were comparable to those of the OG group (13.6% vs. 14.4%, P = 0.526, and 0.3% vs. 0.2%, P = 0.740). The 3-year disease-free and overall survival rates between the two groups were statistically significant (P<0.05). According to the UICC TNM classification of gastric cancer, the 3-year disease-free and overall survival rates were not statistically different at each stage. Conclusions: Our single-center study of a large patient series revealed that LG for gastric cancer yields comparable surgical outcomes. This result was also true of local advanced gastric cancer (AGC). A well-designed randomized controlled trial comparing surgical outcomes between LG and OG in a larger number of patients for AGC can be carried out. [ABSTRACT FROM AUTHOR]

Background: The 7th UICC N stage may be unsuitable for remnant gastric cancer (RGC) because the original disease and previous operation usually cause abnormal lymphatic drainage. However, the prognostic significance of the current TNM staging system in RGC has not been studied. Methods: Prospective data from 153 RGC patients who underwent curative gastrectomy from Jan 1995 to Aug 2009 were reviewed. All patients were classified according to tumor size (<3 cm as N0;>3&≤5 cm as N1;>5&≤7 cm as N2; and>7 cm as N3). The overall survival was estimated using the Kaplan-Meier method, and hazard ratios (HRs) were calculated using the Cox proportional hazard model. Results: Tumor sizes ranged from 1.0 to 15.0 cm (median 5.0 cm). Tumor size, depth of invasion and lymph node (LN) metastasis were significant prognostic factors based on both the univariate and multivariate analyses (P<0.05). In the survival analysis, the seventh edition UICC-TNM classification provided a detailed classification; however, some subgroups of the UICC-TNM classification did not have significantly different survival rates. The combination of the seventh edition T classification and the suggested N classification, with ideal relative risk (RR) results and P value, was distinctive for subgrouping the survival rates except for the IA versus IB and II A versus IIB. A modified staging system based on tumor size, predicted survival more accurately than the conventional TNM staging system. Conclusions: In RGCs, tumor size is an independent prognostic factor and a modified TNM system based on tumor size accurately predicts survival. [ABSTRACT FROM AUTHOR]

Purpose: This study was designed to formulate a model that efficiently predicts splenic hilar lymph node metastasis (SHLNM) in patients with proximal gastric cancer and to assess indications for laparoscopic spleen-preserving no.10 lymph node dissection (LSPNo.10LND) based on this model. Methods: Patients (N = 346) with proximal gastric cancer who underwent LSPNo.10LND from January 2010 to October 2013 were prospectively enrolled and retrospectively evaluated. Groups of patients with and without SHLNM were compared, and independent risk factors for SHLNM determined. An optimal predictive model of SHLNM in patients with proximal gastric cancer was well established. Results: Of the 346 patients with proximal gastric cancer, only 35 (10.1%) were diagnosed with SHLNM. Depth of invasion, tumor location and metastases to No.7 and No.11 lymph nodes (LNs) were independent risk factors for SHLNM (p<0.0001 each). A model involving depth of invasion, tumor location and metastasis to No.7 and 11 LNs yielded a lowest Akaike’s information criterion (AIC) of −913.535 and a highest area under the ROC curve (AUC) of 0.897(95%CI:0.851–0.944). Stratification analysis showed no SHLNMs in the absence of serosal invasion of the lesser curvature and metastases at No.7 and No.11 LNs (T2-3∶0/87, 95% CI: 0.00–4.15). Conclusions: A model including depth of invasion, tumor location and metastases at No.7 and No.11 LNs was found optimal for predicting SHLNM for proximal gastric cancers. LSPNo.10LND may be avoided when tumors on the lesser curvature did not show serosal invasion or metastases at No.7 and No.11 LNs. [ABSTRACT FROM AUTHOR]

Background and Purpose: Little is known about the interactions between the default mode network (DMN) subregions in relapsing-remitting multiple sclerosis (RRMS). This study used diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) to examine alterations of long white matter tracts in paired DMN subregions and their functional connectivity in RRMS patients. Methods: Twenty-four RRMS patients and 24 healthy subjects participated in this study. The fiber connections derived from DTI tractography and the temporal correlation coefficient derived from rs-fMRI were combined to examine the inter-subregion structural-functional connectivity (SC-FC) within the DMN and its correlations with clinical markers. Results: Compared with healthy subjects, the RRMS patients showed the following: 1) significantly decreased SC and increased FC in the pair-wise subregions; 2) two significant correlations in SC-FC coupling patterns, including the positive correlation between slightly increased FC value and long white matter tract damage in the PCC/PCUN-MPFC connection, and the negative correlations between significantly increased FC values and long white matter tract damage in the PCC/PCUN-bilateral mTL connections; 3) SC alterations [log(N track) of the PCC/PCUN-left IPL, RD value of the MPFC-left IPL, FA value of the PCC/PCUN-left mTL connections] correlated with EDSS, increases in the RD value of MPFC-left IPL connection was positively correlated to the MFIS; and decreases in the FA value of PCC/PCUN-right IPL connection was negatively correlated with the PASAT; 4) decreased SC (FA value of the MPFC-left IPL, track volume of the PCC/PCUN-MPFC, and log(N track) of PCC/PCUN-left mTL connections) was positively correlated with brain atrophy. Conclusions: In the connections of paired DMN subregions, we observed decreased SC and increased FC in RRMS patients. The relationship between MS-related structural abnormalities and clinical markers suggests that the disruption of this long-distance “inter-subregion” connectivity (white matter) may significantly impact the integrity of the network's function. [ABSTRACT FROM AUTHOR]

Background: Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis. Methods: Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observational studies (case-control and cohort) about the effect of 5-aminosalicylates on the risk of colorectal neoplasia among patients with ulcerative colitis. The Newcastle-Ottawa Scale was used to assess the quality of studies. Adjusted odds ratios (ORs) were extracted from each study. A random-effects model was used to generate pooled ORs and 95% confidence intervals (95%CI). Publication bias and heterogeneity were assessed. Results: Seventeen studies containing 1,508 cases of colorectal neoplasia and a total of 20,193 subjects published from 1994 to 2012 were analyzed. 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis (OR 0.63; 95%CI 0.48–0.84). Pooled OR of a higher average daily dose of 5-aminosalicylates (sulfasalazine ≥ 2.0 g/d, mesalamine ≥ 1.2 g/d) was 0.51 [0.35–0.75]. Pooled OR of 5-aminosalicylates use in patients with extensive ulcerative colitis was 1.00 [0.53–1.89]. Conclusion: Our pooled results indicated that 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis, especially in the cases with a higher average daily dose of 5-aminosalicylates use. However, the chemopreventive benefit of 5-aminosalicylates use in patients with extensive ulcerative colitis was limited. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that there are many common cell biological features shared by neurons and podocytes; however, the mechanism of podocyte foot process formation remains unclear. Comparing the mechanisms of process formation between two cell types should provide useful guidance from the progress of neuron research. Studies have shown that some mature proteins of podocytes, such as podocin, nephrin, and synaptopodin, were also expressed in neurons. In this study, using cell biological experiments and immunohistochemical techniques, we showed that some neuronal iconic molecules, such as Neuron-specific enolase, nestin and Neuron-specific nuclear protein, were also expressed in podocytes. We further inhibited the expression of Neuron-specific enolase, nestin, synaptopodin and Ubiquitin carboxy terminal hydrolase-1 by Small interfering RNA in cultured mouse podocytes and observed the significant morphological changes in treated podocytes. When podocytes were treated with Adriamycin, the protein expression of Neuron-specific enolase, nestin, synaptopodin and Ubiquitin carboxy terminal hydrolase-1 decreased over time. Meanwhile, the morphological changes in the podocytes were consistent with results of the Small interfering RNA treatment of these proteins. The data demonstrated that neuronal iconic proteins play important roles in maintaining and regulating the formation and function of podocyte processes. [ABSTRACT FROM AUTHOR]

Background: The aim of this meta-analysis was to compare the long-term survival, mortality, morbidity and the operation-related events in patients with periampullary and pancreatic carcinoma undergoing pylorus-preserving pancreaticoduodenectomy (PPPD) and pylorus-resecting pancreaticoduodenectomy (PRPD). Method: A systematic search of literature databases (Cochrane Library, PubMed, EMBASE and Web of Science) was performed to identify studies. Outcome measures comparing PPPD versus PRPD for periampullary and pancreatic carcinoma were long-term survival, mortality, morbidity (overall morbidity, delayed gastric emptying [DGE], pancreatic fistula, wound infection, postoperative bleeding, biliary leakage, ascites and gastroenterostomy leakage) and operation related events (hospital stays, operating time, intraoperative blood loss and red blood cell transfusions). Results: Eight randomized controlled trials (RCTs) including 622 patients were identified and included in the analysis. Among these patients, it revealed no difference in long-term survival between the PPPD and PRPD groups (HR = 0.23, p = 0.11). There was a lower rate of DGE (RR = 2.35, p = 0.04, 95% CI, 1.06–5.21) with PRPD. Mortality, overall morbidity, pancreatic fistula, wound infection, postoperative bleeding, biliary leakage, ascites and gastroenterostomy leakage were not significantly different between the groups. PPPDs were performed more quickly than PRPDs (WMD = 53.25 minutes, p = 0.01, 95% CI, 12.53–93.97); and there was less estimated intraoperative blood loss (WMD = 365.21 ml, p = 0.006, 95% CI, 102.71–627.71) and fewer red blood cell transfusions (WMD = 0.29 U, p = 0.003, 95% CI, 0.10–0.48) in patients undergoing PPPD. The hospital stays showed no significant difference. Conclusions: PPPD had advantages over PRPD in operating time, intraoperative blood loss and red blood cell transfusions, but had a significantly higher rate of DGE for periampullary and pancreatic carcinoma. PPPD and PRPD had comparable mortality and morbidity including pancreatic fistulas, wound infections, postoperative bleeding, biliary leakage, ascites and gastroenterostomy leakage. Our conclusions were limited by the available data. Further evaluations of high-quality RCTs are needed. [ABSTRACT FROM AUTHOR]

Wheat (Triticum aestivum L.) is one of the most important crops cultivated worldwide. Identifying the complete transcriptome of wheat grain could serve as foundation for further study of wheat seed development. However, the relatively large size and the polyploid complexity of the genome have been substantial barriers to molecular genetics and transcriptome analysis of wheat. Alternatively, RNA sequencing has provided some useful information about wheat genes. However, because of the large number of short reads generated by RNA sequencing, factors that are crucial to transcriptome assembly, including software, candidate parameters and assembly strategies, need to be optimized and evaluated for wheat data. In the present study, four cDNA libraries associated with wheat grain development were constructed and sequenced. A total of 14.17 Gb of high-quality reads were obtained and used to assess different assembly strategies. The most successful approach was to filter the reads with Q30 prior to de novo assembly using Trinity, merge the assembled contigs with genes available in wheat cDNA reference data sets, and combine the resulting assembly with an assembly from a reference-based strategy. Using this approach, a relatively accurate and nearly complete transcriptome associated with wheat grain development was obtained, suggesting that this is an effective strategy for generation of a high-quality transcriptome from RNA sequencing data. [ABSTRACT FROM AUTHOR]

: Mora and colleagues show that ongoing greenhouse gas emissions are likely to have a considerable effect on several biogeochemical properties of the world's oceans, with potentially serious consequences for biodiversity and human welfare. [ABSTRACT FROM AUTHOR]

Background: Enteral nutrition is increasingly advocated in the treatment of acute pancreatitis, but its timing is still controversial. The aim of this meta-analysis was to find out the feasibility of early enteral nutrition within 48 hours of admission and its possible advantages. Methods and Findings: We searched PubMed, EMBASE Databases, Web of Science, the Cochrane library, and scholar.google.com for all the relevant articles about the effect of enteral nutrition initiated within 48 hours of admission on the clinical outcomes of acute pancreatitis from inception to December 2012. Eleven studies containing 775 patients with acute pancreatitis were analyzed. Results from a pooled analysis of all the studies demonstrated that early enteral nutrition was associated with significant reductions in all the infections as a whole (OR 0.38; 95%CI 0.21–0.68, P<0.05), in catheter-related septic complications (OR 0.26; 95%CI 0.11–0.58, P<0.05), in pancreatic infection (OR 0.49; 95%CI 0.31–0.78, P<0.05), in hyperglycemia (OR 0.24; 95%CI 0.11–0.52, P<0.05), in the length of hospitalization (mean difference −2.18; 95%CI −3.48−(−0.87); P<0.05), and in mortality (OR 0.31; 95%CI 0.14–0.71, P<0.05), but no difference was found in pulmonary complications (P>0.05). The stratified analysis based on the severity of disease revealed that, even in predicted severe or severe acute pancreatitis patients, early enteral nutrition still showed a protective power against all the infection complications as a whole, catheter-related septic complications, pancreatic infection complications, and organ failure that was only reported in the severe attack of the disease (all P<0.05). Conclusion: Enteral nutrition within 48 hours of admission is feasible and improves the clinical outcomes in acute pancreatitis as well as in predicted severe or severe acute pancreatitis by reducing complications. [ABSTRACT FROM AUTHOR]