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T-type calcium channels in the brain mediate the pathophysiology of epilepsy, pain, and sleep. Recently, we developed a novel therapeutic candidate, SAK3 (ethyl 8'-methyl-2',4-dioxo-2-(piperidin-1-yl)-2'H-spiro[cyclopentane-1,3'-imidazo[1,2-a] pyridine]-2-ene-3-carboxylate), for Alzheimer’s disease (AD). The cognitive improvement by SAK3 is closely associated with enhanced acetylcholine (ACh) release in the hippocampus. Since monoamines such as dopamine (DA), noradrenaline (NA), and serotonin (5-HT) are also involved in hippocampus-dependent learning and psychomotor behaviors in mice, we investigated the effects of SAK3 on these monoamine releases in the mouse brain. Oral administration of SAK3 (0.5 mg/kg, p.o.) significantly promoted DA and 5-HT releases in the naive mouse hippocampal CA1 region but not in the medial prefrontal cortex (mPFC), while SAK3 did not affect NA release in either brain region. The T-type calcium channel-specific inhibitor, NNC 55–0396 (1 μM) significantly antagonized SAK3-enhanced DA and 5-HT releases in the hippocampus. Interestingly, the α7 nicotinic ACh receptor (nAChR) antagonist, methyllycaconitine (1 nM) significantly inhibited DA release, and the α4 nAChR antagonist, dihydro-β-erythroidine (100 μM) significantly blocked both DA and 5-HT releases following SAK3 (0.5 mg/kg, p.o.) administration in the hippocampus. SAK3 did not alter basal monoamine contents both in the mPFC and hippocampus. SAK3 (0.5 mg/kg, p.o.) administration also significantly elevated DA and 5-HT releases in the hippocampal CA1 region of amyloid-precursor protein (APP)NL-GF knock-in (KI) mice. Moreover, hippocampal DA and 5-HT contents were significantly decreased in APPNL-GF KI mice. Taken together, our data suggest that SAK3 promotes monoamine DA and 5-HT releases by enhancing the T-type calcium channel and nAChR in the mouse hippocampus. [ABSTRACT FROM AUTHOR]

Mangrove endophytic fungi can produce impressive quantities of metabolites with promising antioxidant activities that may be useful to humans as novel physiological agents. In this study, we investigated the phylogenetic diversity and antioxidant potential of 46 fungal endophytes derived from the mangrove species Rhizophora stylosa and R. mucronata from the South China Sea. The fungal isolates were identified using a combination of morphological characteristics and phylogenetic analysis of the internal transcribed spacer (ITS) sequences. Seventeen genera belonging to 8 taxonomic orders of Ascomycota were discovered, specifically, Botryosphaeriales, Capnodiales, Diaporthales, Eurotiales, Glomerellales, Hypocreales, Pleosporales, and Xylariales. The most abundant fungal orders included Xylariales (35.49%) and Diaporthales (27.61%), which were predominantly represented by the culturable species Pestalotiopsis sp. (34.54%) and Diaporthe sp. (18.62%). The stems showed more frequent colonization and species diversity than the roots, leaves, hypocotyls, and flower tissues of the host plant. The antioxidant activities of all the isolated fungal extracts on four different culture media were assessed using improved 2,2′-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonicacid) (ABTS) methods. A relatively high proportion (84.8%) of the isolates displayed antioxidant capacity (%RSA > 50%). Further research also provided the first evidence that HQD-6 could produce flufuran as a significant radical scavenger with IC50 values of 34.85±1.56 and 9.75±0.58 μg/mL, respectively. Our findings suggest that the utilization of a biotope such as that of the endophytic fungal community thriving on the mangrove plants R. stylosa and R. mucronata may be suitable for use as a sustainable resource for natural antioxidants. [ABSTRACT FROM AUTHOR]

Histone H1 molecules play a key role in establishing and maintaining higher order chromatin structures. They can bind to linker DNA entering and exiting the nucleosome and regulate transcriptional activity. Tetrahymena thermophila has two histone H1, namely, macronuclear histone H1 and micronuclear histone H1 (Mlh1). Mlh1 is specifically localized at micronuclei during growth and starvation stages. Moreover, Mlh1 is localized around micronuclei and forms a specific structure during the conjugation stage. It co-localizes partially with spindle apparatus during micronuclear meiosis. Analysis of MLH1 knock-out revealed that Mlh1 was required for the micronuclear integrity and development during conjugation stage. Overexpression of Mlh1 led to abnormal conjugation progression. RT-PCR analysis indicated that the expression level of HMGB3 increased in ΔMLH1 strains, while the expression level of MLH1 increased in ΔHMGB3 cells during conjugation. These results indicate that micronuclear integrity and sexual development require normal expression level of Mlh1 and that HmgB3 and Mlh1 may functionally compensate each other in regulating micronuclear structure in T. thermophila. [ABSTRACT FROM AUTHOR]

Background: The immunosuppression and immune dysregulation that follows severe injury includes type 2 immune responses manifested by elevations in interleukin (IL) 4, IL5, and IL13 early after injury. We hypothesized that IL33, an alarmin released early after tissue injury and a known regulator of type 2 immunity, contributes to the early type 2 immune responses after systemic injury.Methods and Findings: Blunt trauma patients admitted to the trauma intensive care unit of a level I trauma center were enrolled in an observational study that included frequent blood sampling. Dynamic changes in IL33 and soluble suppression of tumorigenicity 2 (sST2) levels were measured in the plasma and correlated with levels of the type 2 cytokines and nosocomial infection. Based on the observations in humans, mechanistic experiments were designed in a mouse model of resuscitated hemorrhagic shock and tissue trauma (HS/T). These experiments utilized wild-type C57BL/6 mice, IL33-/- mice, B6.C3(Cg)-Rorasg/sg mice deficient in group 2 innate lymphoid cells (ILC2), and C57BL/6 wild-type mice treated with anti-IL5 antibody. Severely injured human blunt trauma patients (n = 472, average injury severity score [ISS] = 20.2) exhibited elevations in plasma IL33 levels upon admission and over time that correlated positively with increases in IL4, IL5, and IL13 (P < 0.0001). sST2 levels also increased after injury but in a delayed manner compared with IL33. The increases in IL33 and sST2 were significantly greater in patients that developed nosocomial infection and organ dysfunction than similarly injured patients that did not (P < 0.05). Mechanistic studies were carried out in a mouse model of HS/T that recapitulated the early increase in IL33 and delayed increase in sST2 in the plasma (P < 0.005). These studies identified a pathway where IL33 induces ILC2 activation in the lung within hours of HS/T. ILC2 IL5 up-regulation induces further IL5 expression by CXCR2+ lung neutrophils, culminating in early lung injury. The major limitations of this study are the descriptive nature of the human study component and the impact of the potential differences between human and mouse immune responses to polytrauma. Also, the studies performed did not permit us to make conclusions about the impact of IL33 on pulmonary function.Conclusions: These results suggest that IL33 may initiate early detrimental type 2 immune responses after trauma through ILC2 regulation of neutrophil IL5 production. This IL33-ILC2-IL5-neutrophil axis defines a novel regulatory role for ILC2 in acute lung injury that could be targeted in trauma patients prone to early lung dysfunction. [ABSTRACT FROM AUTHOR]

Objective: Myosin light chain 9 (MYL9) is necessary for cytoskeletal dynamics and experimental metastasis, but its expression in esophageal squamous cell carcinoma (ESCC) has not been addressed. We investigated the expression pattern and clinical significance of MYL9 in patients with ESCC. Methods: We examined MYL9 expression using quantitative real-time PCR and western blotting in NE1 immortalized esophageal epithelial cells, ESCC cell lines, and paired ESCC tissues. MYL9 protein in 136 primary ESCC tissues and other types of solid tumor was detected using immunohistochemistry. The association between MYL9 expression and clinical parameters and survival was evaluated by statistical analysis. Results: MYL9 was significantly upregulated in the ESCC cell lines as compared with NE1 cells. In the paired ESCC samples, MYL9 mRNA and protein expression was not significantly different between lesion tissues and the matched adjacent noncancerous tissues. In ESCC tissue, both intratumoral and peritumoral stroma were positive for MYL9. In the 136 ESCC samples, high MYL9 expression in the tumor cells significantly correlated with histological differentiation (p = 0.028), recurrence (p = 0.01), and vital status (p < 0.01). Patients with high MYL9 expression in the tumor cells had poorer overall survival (OS) and recurrence-free survival. Multivariate analysis revealed that high MYL9 expression in tumor cells was an independent and significant risk factor affecting OS after curative treatment (hazard ratio = 2.254, 95% confidence interval = 1.347–3.771, p = 0.002). Conclusions: MYL9 expression might be a promising prognostic marker and therapeutic target in ESCC. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to examine changes in the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) scores within a one-year period after stroke/transient ischemic attack (TIA) in associating cognitive decline determined by a formal neuropsychological test battery. Methods: Patients with ischemic stroke/TIA received MoCA and MMSE at baseline within 14 days after stroke/TIA, at 3–6 months and 1-year follow-ups. The scores of MoCA and MMSE were considered to have declined if there were a reduction of ≥2 points in the respective scores measured across two time points. The decline in neuropsychological diagnosis transitional status was defined by a category transition from no cognitive impairment or any cognitive impairment to a more severe cognitive impairment or dementia. Results: 275 patients with a mean age of 59.8 ± 11.6 years, and education of 7.7 ± 4.3 years completed all the assessments at baseline, 3–6 months and 1-year follow-ups. A decline in MoCA scores from 3–6 months to 1 year was associated with higher risk of decline in diagnosis transitional status (odd ratio = 3.21, p = 0.004) in the same time period whereas there was no association with a decline in MMSE scores. Conclusions: The decline in MoCA scores from 3–6 months to 1 year after stroke/TIA has three times higher risk for decline in the diagnosis transitional status. The decline of MoCA scores (reduction ≥ 2points) is associated with the decline in neuropsychological diagnosis transitional status. [ABSTRACT FROM AUTHOR]

Preharvest sprouting reduces the maize quality and causes a significant yield loss in maize production. vp-wl2 is a Mutator (Mu)-induced viviparous mutant in maize, causing white or pale yellow kernels, dramatically reduced carotenoid and ABA content, and a high level of zeta-carotene accumulation. Here, we reported the cloning of the vp-wl2 gene using a modified digestion-ligation-amplification method (DLA). The results showed that an insertion of Mu9 in the first intron of the zeta-carotene desaturase (ZDS) gene results in the vp-wl2 mutation. Previous studies have suggested that ZDS is likely the structural gene of the viviparous9 (vp9) locus. Therefore, we performed an allelic test using vp-wl2 and three vp9 mutants. The results showed that vp-wl2 is a novel allele of the vp9 locus. In addition, the sequences of ZDS gene were identified in these three vp9 alleles. The vp-wl2 mutant gene was subsequently introgressed into four maize inbred lines, and a viviparous phenotype was observed with yield losses from 7.69% to 13.33%. [ABSTRACT FROM AUTHOR]

An emerging hallmark of cancer is reprogrammed cellular metabolism, and several cancers involve increased glucose intake and glutamine addiction. Hepatocellular carcinoma (HCC) is one of the most fatal cancers, and its molecular basis needs to be delineated to identify biomarkers for its potential treatment without resection. Therefore, this study aimed to determine the metabolism status of HCC by evaluating the expression of the glucose transporter GLUT1 and glutamine transporter ASCT2. We enrolled 192 patients with surgically resected HCC in this study. Their tissue samples were subjected to immunohistochemistry to detect GLUT1 and ASCT2 expression. The prognostic value of GLUT1 and ASCT2 expression and their combined metabolic index was determined by Kaplan–Meier analysis and the Cox proportional hazards model. We found that GLUT1 and ASCT2 expression was significantly upregulated in tumor tissues as compared to adjacent non-tumor tissues and was positively associated with tumor size. Survival analysis revealed that patients with high GLUT1 or ASCT2 expression had poor overall survival (OS) and recurrence-free survival (RFS). In HCC patients, ASCT2 expression was an independent negative prognostic factor for OS (hazard ratio [HR], 1.760; 95% confidence interval [CI] = 1.124−2.755; p = 0.013) and the metabolic index was an independent negative prognostic factor for OS (HR = 1.672, 95% CI = 1.275−2.193, p < 0.001) and RFS (HR = 1.362, 95% CI = 1.066−1.740, p = 0.013). In conclusion, the tumor metabolism status determined by expression of GLUT1 and ASCT2 and their metabolic index is a promising prognostic predictor for HCC patients. [ABSTRACT FROM AUTHOR]

Numerous α-galactosidase A (α-gal A) gene (GLA) mutations have been identified in Fabry disease (FD), but studies on genotype-phenotype correlation are limited. This study evaluated the features of GLA gene mutations and genotype-phenotype relationship in Chinese FD patients. Gene sequencing results, demographic information, clinical history, and laboratory findings were collected from 73 Chinese FD patients. Totally 47 mutations were identified, including 23 novel mutations which might be pathogenic. For male patients, those with frameshift and nonsense mutations presented the classical FD, whereas those with missense mutations presented both of classical and atypical phenotypes. Interestingly, two male patients with missense mutation p.R356G from two unrelated families, and two with p.R301Q from one family presented different phenotypes. A statistically significant association was found between the levels of α-gal A enzyme activity and ocular changes in males, though no significant association was found between residual enzyme activity level and genotype or clinical phenotypes. For female patients, six out of seven with frameshift mutations and one out of nine with missense mutation presented the classical FD, and α-gal A activity in those patients was found to be significantly lower than that of patients with atypical phenotypes (13.73 vs. 46.32 nmol/ml/h/mg). Our findings suggest that the α-gal A activity might be associated with the clinical severity in female patients with FD. But no obvious associations between activity level of α-gal A and genotype or clinical phenotypes were found for male patients. [ABSTRACT FROM AUTHOR]

Knowledge of protein function is important for biological, medical and therapeutic studies, but many proteins are still unknown in function. There is a need for more improved functional prediction methods. Our SVM-Prot web-server employed a machine learning method for predicting protein functional families from protein sequences irrespective of similarity, which complemented those similarity-based and other methods in predicting diverse classes of proteins including the distantly-related proteins and homologous proteins of different functions. Since its publication in 2003, we made major improvements to SVM-Prot with (1) expanded coverage from 54 to 192 functional families, (2) more diverse protein descriptors protein representation, (3) improved predictive performances due to the use of more enriched training datasets and more variety of protein descriptors, (4) newly integrated BLAST analysis option for assessing proteins in the SVM-Prot predicted functional families that were similar in sequence to a query protein, and (5) newly added batch submission option for supporting the classification of multiple proteins. Moreover, 2 more machine learning approaches, K nearest neighbor and probabilistic neural networks, were added for facilitating collective assessment of protein functions by multiple methods. SVM-Prot can be accessed at . [ABSTRACT FROM AUTHOR]

Background: Previously, we found an 11-gene signature could predict pelvic lymph node metastasis (PLNM), and WNT2 is one of the key genes in the signature. This study explored the expression and underlying mechanism of WNT2 in PLNM of cervical cancer. Methods: WNT2 expression level in cervical cancer was detected using western blotting, quantitative PCR, and immunohistochemistry. Two WNT2-specific small interfering RNAs (siRNAs) were used to explore the effects of WNT2 on invasive and metastatic ability of cancer cells, and to reveal the possible mechanism of WNT2 affecting epithelial—mesenchymal transition (EMT). The correlation between WNT2 expression and PLNM was further investigated in clinical cervical specimens. Results: Both WNT2 mRNA and protein expression was upregulated in cervical cancer. High WNT2 expression was significantly associated with tumor size, lymphovascular space involvement, positive parametrium, and most importantly, PLNM. PLNM and WNT2 expression were independent prognostic factors for overall survival and disease-free survival. WNT2 knockdown inhibited SiHa cell motility and invasion and reversed EMT by inhibiting the WNT2/β-catenin pathway. WNT2 overexpression in cervical cancer was associated with β-catenin activation and induction of EMT, which further contributed to metastasis in cervical cancer. Conclusion: WNT2 might be a novel predictor of PLNM and a promising prognostic indicator in cervical cancer. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to evaluate the diagnostic accuracy of Raman spectroscopy system in the detection of malignant breast lesions through a systemic review and meta-analysis of published studies. Methods: We conducted a comprehensive literature search of PubMed and Embase from 2000 to June 2015. Published studies that evaluated the diagnostic performance of Raman spectroscopy in distinguishing malignant breast lesions from benign lesions and normal tissues were included in our study. The pooled sensitivity, specificity, diagnostic odds ratio, and the area under the curve of summary receiver-operating characteristic curves was derived. A Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies guidelines was used to assess the quality of included studies. Results: The initial search produced a total of 157 articles after removing duplicates. Nine studies (8 in vitro and 1 in vivo) were eligible in this meta-analysis. We analyzed the eight in vitro studies with 1756 lesions, the pooled sensitivity and specificity of Raman spectroscopy system for the diagnosis of malignant breast lesions were 0.92 (95% CI 0.86–0.96) and 0.97 (97% CI 0.93–0.98), respectively. Diagnostic odds ratio was 266.70 (95% CI 89.38–795.79), and the area under the curve of summary receiver-operating characteristic curves was 0.98 (95% CI 0.97–0.99). Significant heterogeneity was found between studies. There was no evidence of considerable publication bias. Conclusions: Raman spectroscopy system is an optical diagnostic technology with great value for detecting malignant breast lesions. At the same time, it has advantages of being non-invasive, real-time, and easy to use. Thus it deserves to be further explored for intra-operatory breast tumor margin detection. [ABSTRACT FROM AUTHOR]

The “robotic-assisted liver tumor coagulation therapy” (RALTCT) system is a promising candidate for large liver tumor treatment in terms of accuracy and speed. A prerequisite for effective therapy is accurate surgical planning. However, it is difficult for the surgeon to perform surgical planning manually due to the difficulties associated with robot-assisted large liver tumor therapy. These main difficulties include the following aspects: (1) multiple needles are needed to destroy the entire tumor, (2) the insertion trajectories of the needles should avoid the ribs, blood vessels, and other tissues and organs in the abdominal cavity, (3) the placement of multiple needles should avoid interference with each other, (4) an inserted needle will cause some deformation of liver, which will result in changes in subsequently inserted needles’ operating environment, and (5) the multiple needle-insertion trajectories should be consistent with the needle-driven robot’s movement characteristics. Thus, an effective multiple-needle surgical planning procedure is needed. To overcome these problems, we present an automatic multiple-needle surgical planning of optimal insertion trajectories to the targets, based on a mathematical description of all relevant structure surfaces. The method determines the analytical expression of boundaries of every needle “collision-free reachable workspace” (CFRW), which are the feasible insertion zones based on several constraints. Then, the optimal needle insertion trajectory within the optimization criteria will be chosen in the needle CFRW automatically. Also, the results can be visualized with our navigation system. In the simulation experiment, three needle-insertion trajectories were obtained successfully. In the in vitro experiment, the robot successfully achieved insertion of multiple needles. The proposed automatic multiple-needle surgical planning can improve the efficiency and safety of robot-assisted large liver tumor therapy, significantly reduce the surgeon’s workload, and is especially helpful for an inexperienced surgeon. The methodology should be easy to adapt in other body parts. [ABSTRACT FROM AUTHOR]

The results of clinical and experimental studies suggest that endotoxin/toll-like receptor 4 (TLR4)-mediated proinflammatory and profibrotic signaling activation is critical in the development of hepatic fibrosis. However, studies examining the role of specific TLR4 inhibitor are still lacking. The present study was aimed to prepare a human anti-TLR4 Fab fragment, named hTLR4-Fab01, and to explore its immune activity. We screened the positive clone of anti-human TLR4 phagemid from a human phage-display antibody library using recombinant TLR4 protein, which was used as template cDNA for the amplification of variable regions of the heavy (VH) chain and light chain (VL), then coupled with highly conserved regions of the heavy chain domain 1 (CH1) and the light chain (CL), respectively. Thus, the prokaryotic expression vector pETDuet-1 of hTLR4-Fab01 was constructed and transformed into Escherichia coli (E. coli) BL21. The characteristic of hTLR4-Fab01 was examined by SDS-PAGE, Western blotting, ELISA, affinity and kinetics assay. Further, our data demonstrate that hTLR4-Fab01 could specifically bind to TLR4, and its treatment obviously attenuated the proinflammatory effect, characterized by less LPS-induced TNF-α, IL-1, IL-6 and IL-8 production in human macrophages. In conclusion, we have successfully prepared the hTLR4-Fab01 with efficient activity for blocking LPS-induced proinflammatory cytokines production, suggesting that the hTLR4-Fab01 may be a potential candidate for the treatment of hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Objective: To search for biomarkers to differentiate primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). Methods: We isolated glomeruli from kidney biopsies of 6 patients with adult-onset steroid sensitiveFSGS and 5 patients with MCD, and compared the profiles of glomerular transcriptomes between the two groups of patients using microarray analysis. Results: Analysis of differential expressed genes (DEGs) revealed that up-regulated DEGs in FSGS patients compared with MCD patients were primarily involved in spermatogenesis, gamete generation, regulation of muscle contraction, response to unfolded protein, cell proliferation and skeletal system development. The down-regulated DEGs were primarily related to metabolic process, intracellular transport, oxidation/reduction andestablishment of intracellular localization. We validated the expression of the top 6 up-regulated and top 6 down-regulated DEGs using real-time PCR. Membrane metallo-endopeptidase (MME) is a down-regulated gene that was previously identified as a key gene for kidney development. Immunostaining confirmed that the protein expression of MME decreased significantly in FSGS kidneys compared with MCD kidneys. Conclusions: This report was the first study to examine transcriptomes in Chinese patients with various glomerular diseases. Expressions of MME both in RNA and protein level decreased significantly in glomeruli of FSGS kidneys compared with MCD kidneys. Our data suggested that MME might play a role in the normal physiological function of podocytes and a decrease in MME expression might be related to podocyte injury. We also identified genes and pathways specific for FSGS versus MCD, and our data could help identify potential new biomarkers for the differential diagnosis between these two diseases. [ABSTRACT FROM AUTHOR]

Although glutathione S-transferases (GST, EC 2.5.1.18) are involved in response to abiotic stress, limited information is available regarding gene function in tomato. In this study, a GST gene from tomato, designated LeGSTU2, was cloned and functionally characterized. Expression profile analysis results showed that it was expressed in roots and flowers, and the transcription was induced by salt, osmotic, and heat stress. The gene was then introduced to Arabidopsis by Agrobacterium tumefaciens-mediated transformation. Transgenic Arabidopsis plants were normal in terms of growth and maturity compared with wild-type plants. Transgenic plants also showed an enhanced resistance to salt and osmotic stress induced by NaCl and mannitol. The increased tolerance of transgenic plants was correlated with the changes in proline, malondialdehyde and antioxidative emzymes activities. Our results indicated that the gene from tomato plays a positive role in improving tolerance to salinity and drought stresses in Arabidopsis. [ABSTRACT FROM AUTHOR]

Radial peripapillary capillaries (RPCs) comprise a unique network of capillary beds within the retinal nerve fibre layer (RNFL) and play a critical role in satisfying the nutritional requirements of retinal ganglion cell (RGC) axons. Understanding the topographical and morphological characteristics of these networks through in vivo techniques may improve our understanding about the role of RPCs in RGC axonal health and disease. This study utilizes a novel, non-invasive and label-free optical imaging technique, speckle variance optical coherence tomography (svOCT), for quantitatively studying RPC networks in the human retina. Six different retinal eccentricities from 16 healthy eyes were imaged using svOCT. The same eccentricities were histologically imaged in 9 healthy donor eyes with a confocal scanning laser microscope. Donor eyes were subject to perfusion-based labeling techniques prior to retinal dissection, flat mounting and visualization with the microscope. Capillary density and diameter measurements from each eccentricity in svOCT and histological images were compared. Data from svOCT images were also analysed to determine if there was a correlation between RNFL thickness and RPC density. The results are as follows: (1) The morphological characteristics of RPC networks on svOCT images are comparable to histological images; (2) With the exception of the nasal peripapillary region, there were no significant differences in RPC density measurements between svOCT and histological images; (3) Capillary diameter measurements were significantly greater in svOCT images compared to histology; (4) There is a positive correlation between RPC density and RNFL thickness. The findings in this study suggest that svOCT is a reliable modality for analyzing RPC networks in the human retina. It may therefore be a valuable tool for aiding our understanding about vasculogenic mechanisms that are involved in RGC axonopathies. Further work is required to explore the reason for some of the quantitative differences between svOCT and histology. [ABSTRACT FROM AUTHOR]

Although there are considerable reports of magnetic field effects (MFE) on organisms, very little is known so far about the MFE-related signal transduction pathways. Here we establish a manipulative near-zero magnetic field (NZMF) to investigate the potential signal transduction pathways involved in MFE. We show that exposure of migratory white-backed planthopper, Sogatella furcifera, to the NZMF results in delayed egg and nymphal development, increased frequency of brachypterous females, and reduced longevity of macropterous female adults. To understand the changes in gene expression underlying these phenotypes, we examined the temporal patterns of gene expression of (i) CRY1 and CRY2 as putative magnetosensors, (ii) JHAMT, FAMeT and JHEH in the juvenile hormone pathway, (iii) CYP307A1 in the ecdysone pathway, and (iv) reproduction-related Vitellogenin (Vg). The significantly altered gene expression of CRY1 and CRY2 under the NZMF suggest their developmental stage-specific patterns and potential upstream location in magnetic response. Gene expression patterns of JHAMT, JHEH and CYP307A1 were consistent with the NZMF-triggered delay in nymphal development, higher proportion of brachypterous female adults, and the shortened longevity of macropterous female adults, which show feasible links between hormone signal transduction and phenotypic MFE. By conducting manipulative NZMF experiments, our study suggests an important role of the geomagnetic field (GMF) in modulating development and physiology of insects, provides new insights into the complexity of MFE-magnetosensitivity interactions, and represents an initial but crucial step forward in understanding the molecular basis of cryptochromes and hormone signal transduction involved in MFE. [ABSTRACT FROM AUTHOR]

MiR-200c has been shown to be related to cancer formation and progression. However, the prognostic and clinicopathologic significance of miR-200c expression in cancer remain inconclusive. We carried out this systematic review and meta-analysis to investigate the prognostic value of miR-200c expression in cancer. Pooled hazard ratios (HRs) of miR-200c for overall survival (OS) and progression-free survival (PFS) were calculated to measure the effective value of miR-200c expression on prognosis. The association between miR-200c expression and clinical significance was measured by odds ratios (ORs). Twenty-three studies were included in our meta-analysis. We found that miR-200c was not significantly correlated with OS (HR = 1.41, 95%Cl: 0.95-2.10; P = 0.09) and PFS (HR = 1.12, 95%Cl: 0.68-1.84; P = 0.67) in cancer. In our subgroup analysis, higher expression of miR-200c was significantly associated with poor OS in blood (HR = 2.10, 95%CI: 1.52-2.90, P<0.00001). Moreover, in clinicopathology analysis, miR-200c expression in blood was significantly associated with TNM stage, lymph node metastasis and distant metastasis. MiR-200c may have the potential to become a new blood biomarker to monitor cancer prognosis and progression. [ABSTRACT FROM AUTHOR]

National surveys reveal notable individual differences in U.S. citizens’ attitudes toward freedom of expression, including freedom of the press and speech. Recent theoretical developments and empirical findings suggest that ecological factors impact censorship attitudes in addition to individual difference variables (e.g., education, conservatism), but no research has compared the explanatory power of prominent ecological theories. This study tested climato-economic, parasite stress, and life history theories using four measures of attitudes toward censoring the press and offensive speech obtained from two national surveys in the U.S.A. Neither climate demands nor its interaction with state wealth—two key variables for climato-economic theory—predicted any of the four outcome measures. Interstate parasite stress significantly predicted two, with a marginally significant effect on the third, but the effects became non-significant when the analyses were stratified for race (as a control for extrinsic risks). Teenage birth rates (a proxy of human life history) significantly predicted attitudes toward press freedom during wartime, but the effect was the opposite of what life history theory predicted. While none of the three theories provided a fully successful explanation of individual differences in attitudes toward freedom of expression, parasite stress and life history theories do show potentials. Future research should continue examining the impact of these ecological factors on human psychology by further specifying the mechanisms and developing better measures for those theories. [ABSTRACT FROM AUTHOR]

This study aims to understand the level of contraceptive knowledge and attitudes towards contraception, and then to explore the association between the contraceptive behavior and unintended pregnancy in unmarried female university students in China. A cross-sectional study was conducted of university students in 49 universities across 7 cities in China from September 2007 to January 2008. We distributed 74,800 questionnaires, of which 69,842 were returned. In this paper, the data from 35,383 unmarried female university students were analyzed. The prevalence of sexual intercourse in unmarried female university students was 10.2%. The prevalence of unintended pregnancy in those sexually active female university students, was 31.8%. Among students with pregnancy, 53.5% experienced two or more pregnancies. 28.3% of the students with sexual intercourse reported that they always adopted contraceptive methods, and of those 82.9% chose to use male condoms. The majority (83.9%) of students with unintended pregnancy chose to terminate the latest pregnancy by surgical abortion or medical abortion. The contraceptive knowledge level of students who experienced unintended pregnancy was lower than those who did not. In China, about one third of unmarried female students with sexual intercourse experience unintended pregnancy. A variety of contraceptive methods are adopted, but the frequency of contraceptive use is low. Most of unmarried female students who experienced unintended pregnancy would choose to terminate the pregnancy with surgical or medical abortion. University students, especially the ones who have experienced unintended pregnancy, lack contraceptive and reproductive health knowledge. [ABSTRACT FROM AUTHOR]

Recent research in moral psychology have suggested that children make judgments about distributive justice early on in development, and in particular they appear to be able to use merit when distributing the benefits of a collective action. This prediction has recently been validated in various western cultures but it is unknown whether it also applies to more collectivistic cultures, in which the group might be favoured over the individual, and need over merit. Here, we investigate merit-based distributions among 81 children belonging to two Asian societies, China and Japan (mean age = 5.0 years). In line with the idea that children’s moral psychology develops early, we found that Chinese and Japanese children are able to use merit to distribute the benefits of a collective action. [ABSTRACT FROM AUTHOR]

Phytophthora capsici is a soil-borne plant pathogen with a wide range of hosts. The pathogen secretes a large array of effectors during infection of host plants, including Crinkler (CRN) effectors. However, it remains largely unknown on the roles of these effectors in virulence especially in P. capsici. In this study, we identified a cell death-inducing CRN effector PcCRN4 using agroinfiltration approach. Transient expression of PcCRN4 gene induced cell death in N. benthamiana, N. tabacum and Solanum lycopersicum. Overexpression of the gene in N. benthamiana enhanced susceptibility to P. capsici. Subcellular localization results showed that PcCRN4 localized to the plant nucleus, and the localization was required for both of its cell death-inducing activity and virulent function. Silencing PcCRN4 gene in P. capsici significantly reduced pathogen virulence. The expression of the pathogenesis-related gene PR1b in N. benthamiana was significantly induced when plants were inoculated with PcCRN4-silenced P. capsici transformant compared to the wilt-type. Callose deposits were also abundant at sites inoculated with PcCRN4-silenced transformant, indicating that silencing of PcCRN4 in P. capsici reduced the ability of the pathogen to suppress plant defenses. Transcriptions of cell death-related genes were affected when PcCRN4-silenced line were inoculated on Arabidopsis thaliana, suggesting that PcCRN4 may induce cell death by manipulating cell death-related genes. Overall, our results demonstrate that PcCRN4 is a virulence essential effector and it needs target to the plant nucleus to suppress plant immune responses. [ABSTRACT FROM AUTHOR]

Mosquito-borne diseases continue to remain major threats to human and animal health and impediments to socioeconomic development. Increasing mosquito resistance to chemical insecticides is a great public health concern, and new strategies/technologies are necessary to develop the next-generation of vector control tools. We propose to develop a novel method for mosquito control that employs nanoparticles (NPs) as a platform for delivery of mosquitocidal dsRNA molecules to silence mosquito genes and cause vector lethality. Identifying optimal NP chemistry and morphology is imperative for efficient mosquitocide delivery. Toward this end, fluorescently labeled polyethylene glycol NPs of specific sizes, shapes (80 nm x 320 nm, 80 nm x 5000 nm, 200 nm x 200 nm, and 1000 nm x 1000 nm) and charges (negative and positive) were fabricated by Particle Replication in Non-Wetting Templates (PRINT) technology. Biodistribution, persistence, and toxicity of PRINT NPs were evaluated in vitro in mosquito cell culture and in vivo in Anopheles gambiae larvae following parenteral and oral challenge. Following parenteral challenge, the biodistribution of the positively and negatively charged NPs of each size and shape was similar; intense fluorescence was observed in thoracic and abdominal regions of the larval body. Positively charged NPs were more associated with the gastric caeca in the gastrointestinal tract. Negatively charged NPs persisted through metamorphosis and were observed in head, body and ovaries of adults. Following oral challenge, NPs were detected in the larval mid- and hindgut. Positively charged NPs were more efficiently internalized in vitro than negatively charged NPs. Positively charged NPs trafficked to the cytosol, but negatively charged NPs co-localized with lysosomes. Following in vitro and in vivo challenge, none of the NPs tested induced any cytotoxic effects. [ABSTRACT FROM AUTHOR]

Background: Nanotechnology offers great potential for molecular genetic investigations and potential control of medically important arthropods. Major advances have been made in mammalian systems to define nanoparticle (NP) characteristics that condition trafficking and biodistribution of NPs in the host. Such information is critical for effective delivery of therapeutics and molecules to cells and organs, but little is known about biodistribution of NPs in mosquitoes. Methodology/Principal Findings: PRINT technology was used to construct a library of fluorescently labeled hydrogel NPs of defined size, shape, and surface charge. The biodistribution (organ, tissue, and cell tropisms and trafficking kinetics) of positively and negatively charged 200 nm x 200 nm, 80 nm x 320 nm, and 80 nm x 5000 nm NPs was determined in adult Anopheles gambiae mosquitoes as a function of the route of challenge (ingestion, injection or contact) using whole body imaging and fluorescence microscopy. Mosquitoes readily ingested NPs in sugar solution. Whole body fluorescence imaging revealed substantial NP accumulation (load) in the alimentary tracts of the adult mosquitoes, with the greatest loads in the diverticula, cardia and foregut. Positively and negatively charged NPs differed in their biodistribution and trafficking. Following oral challenge, negatively charged NPs transited the alimentary tract more rapidly than positively charged NPs. Following contact challenge, negatively charged NPs trafficked more efficiently in alimentary tract tissues. Following parenteral challenge, positively and negatively charged NPs differed in tissue tropisms and trafficking in the hemocoel. Injected NPs were also detected in cardia/foregut, suggesting trafficking of NPs from the hemocoel into the alimentary tract. Conclusions/Significance: Herein we have developed a tool box of NPs with the biodistribution and tissue tropism characteristics for gene structure/function studies and for delivery of vector lethal cargoes for mosquito control. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis has decreased significantly in prevalence and intensity of infection in China, thus more accurate and sensitive methods are desperately needed for the further control of schistosomiasis. The present work aimed to assess the utility of the loop-mediated isothermal amplification (LAMP) for detection of light intensity infection or false-negative patients and patients post-treatment, targeting the highly repetitive retrotransposon SjR2 of Schistosoma japonicum. Methodology/ Principal Findings: LAMP was first assessed in rabbits with low intensity infection (EPG<10). Then 110 patient sera from Hunan Province, China, and 47 sera after treatment by praziquantel were used to evaluate the diagnostic validity of LAMP. Meanwhile, 42 sera from healthy individuals in a non-endemic area, and 60 sera from "healthy” residents who were identified as being negative for feces examination and immuno-methods in an endemic area were also examined. The results showed that LAMP could detect S. japonicum DNA in sera from rabbits at 3rd day post-infection. Following administration of praziquantel, the S. japonicum DNA in rabbit sera became negative at 10 weeks post-treatment. Of 110 sera from patients, LAMP showed 95.5% sensitivity, and even for 41 patients with less than 10 EPG, the sensitivity of LAMP still reached to 95.1%. For 47 patients after treatment, the negative conversion rate of S. japonicum DNA in patient sera increased from 23.4%, 61.7% to 83.0% at 3 months, 6 months and 9 months post-treatment, respectively. No false-positive result was obtained for 42 human sera from non-endemic area, while for the 60 “healthy” individuals from endemic area, 10 (16.7%) individuals were positive by LAMP, which suggested that these individuals might be false-negative patients. Conclusions/ Significance: The present study demonstrated that the LAMP assay is sensitive, specific, and affordable, which would help reduce schistosomiasis transmission through targeted treatment of individuals, particularly for those with negative stool examinations who may yet remain infected. The LAMP assay may provide a potential tool to support schistosomiasis control and elimination strategies. [ABSTRACT FROM AUTHOR]