Aerodynamic roughness variation with vegetation: analysis in a suburban neighbourhood and a city park

Local aerodynamic roughness parameters (zero-plane displacement, zd, and aerodynamic roughness length, z0) are determined for an urban park and a suburban neighbourhood with a new morphometric parameterisation that includes vegetation. Inter-seasonal analysis at the urban park demonstrates zd determined with two anemometric methods is responsive to vegetation state and is 1 – 4 m greater during leaf-on periods. The seasonal change and directional variability in the magnitude of zd is reproduced by the morphometric methods, which also indicate z0 can be more than halved during leaf-on periods. In the suburban neighbourhood during leaf-on, the anemometric and morphometric methods have similar directional variability for both zd and z0. Wind speeds at approximately 3 times the average roughness-element height are estimated most accurately when using a morphometric method which considers roughness-element height variability. Inclusion of vegetation in the morphometric parameterisation improves wind speed estimation in all cases. Results indicate that the influence of both vegetation and roughness-element height variability are important for accurate determination of local aerodynamic parameters and the associated wind-speed estimation

FLC expression is down-regulated by cold treatment in Diplotaxis tenuifolia (wild rocket), but flowering time is unaffected

Wild rocket (Diplotaxis tenuifolia) has become a very popular salad leaf due to its peppery taste. It is part of the Brassicaceae family and thus has a high level of homology at the DNA level to other Brassica species including Arabidopsis thaliana. The vernalization and photoperiodic requirements of wild rocket have not been reported to date. Photoperiodic experiments described here demonstrate that rocket is a facultative long day plant. To investigate the vernalization requirement, both seed and young plants were given vernalization treatments at 4 °C for different lengths of time. A rocket homologue of FLOWERING LOCUS C (DtFLC) was isolated and shown to functionally complement the Arabidopsis FRI+flc3 null mutant. Whilst the expression of DtFLC was significantly reduced after just one week of cold treatment, cold treatments of two to eight weeks had no significant effect on bolting time of wild rocket indicating that rocket does not have a vernalization requirement. These findings illustrate that important fundamental differences can exist between model and crop plant species, such as in this case where down-regulation of DtFLC expression does not enable earlier flowering in wild rocket as it does in Arabidopsis and many other Brassica species

The Reproducibility of Lists of Differentially Expressed Genes in Microarray Studies

Reproducibility is a fundamental requirement in scientific experiments and clinical contexts. Recent publications raise concerns about the reliability of microarray technology because of the apparent lack of agreement between lists of differentially expressed genes (DEGs). In this study we demonstrate that (1) such discordance may stem from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion, the lists become much more reproducible, especially when fewer genes are selected; and (3) the instability of short DEG lists based on P cutoffs is an expected mathematical consequence of the high variability of the t-values. We recommend the use of FC ranking plus a non-stringent P cutoff as a baseline practice in order to generate more reproducible DEG lists. The FC criterion enhances reproducibility while the P criterion balances sensitivity and specificity

The balance of reproducibility, sensitivity, and specificity of lists of differentially expressed genes in microarray studies

<p>Abstract</p> <p>Background</p> <p>Reproducibility is a fundamental requirement in scientific experiments. Some recent publications have claimed that microarrays are unreliable because lists of differentially expressed genes (DEGs) are not reproducible in similar experiments. Meanwhile, new statistical methods for identifying DEGs continue to appear in the scientific literature. The resultant variety of existing and emerging methods exacerbates confusion and continuing debate in the microarray community on the appropriate choice of methods for identifying reliable DEG lists.</p> <p>Results</p> <p>Using the data sets generated by the MicroArray Quality Control (MAQC) project, we investigated the impact on the reproducibility of DEG lists of a few widely used gene selection procedures. We present comprehensive results from inter-site comparisons using the same microarray platform, cross-platform comparisons using multiple microarray platforms, and comparisons between microarray results and those from TaqMan – the widely regarded "standard" gene expression platform. Our results demonstrate that (1) previously reported discordance between DEG lists could simply result from ranking and selecting DEGs solely by statistical significance (<it>P</it>) derived from widely used simple <it>t</it>-tests; (2) when fold change (FC) is used as the ranking criterion with a non-stringent <it>P</it>-value cutoff filtering, the DEG lists become much more reproducible, especially when fewer genes are selected as differentially expressed, as is the case in most microarray studies; and (3) the instability of short DEG lists solely based on <it>P</it>-value ranking is an expected mathematical consequence of the high variability of the <it>t</it>-values; the more stringent the <it>P</it>-value threshold, the less reproducible the DEG list is. These observations are also consistent with results from extensive simulation calculations.</p> <p>Conclusion</p> <p>We recommend the use of FC-ranking plus a non-stringent <it>P </it>cutoff as a straightforward and baseline practice in order to generate more reproducible DEG lists. Specifically, the <it>P</it>-value cutoff should not be stringent (too small) and FC should be as large as possible. Our results provide practical guidance to choose the appropriate FC and <it>P</it>-value cutoffs when selecting a given number of DEGs. The FC criterion enhances reproducibility, whereas the <it>P </it>criterion balances sensitivity and specificity.</p

Acute flaccid myelitis:cause, diagnosis, and management

Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of MM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for MM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population

Attenuated IL-2 muteins leverage the TCR signal to enhance regulatory T cell homeostasis and response in vivo

Interleukin-2 (IL-2), along with T-cell receptor (TCR) signaling, are required to control regulatory T cell (Treg) homeostasis and function in vivo. Due to the heightened sensitivity to IL-2, Tregs retain the ability to respond to low-dose or attenuated forms of IL-2, as currently being developed for clinical use to treat inflammatory diseases. While attenuated IL-2 increases Treg selectivity, the question remains as to whether a weakened IL-2 signal sufficiently enhances Treg suppressive function(s) toward disease modification. To understand this question, we characterized the in vivo activity and transcriptomic profiles of two different attenuated IL-2 muteins in comparison with wildtype (WT) IL-2. Our study showed that, in addition to favoring Tregs, the attenuated muteins induced disproportionately robust effects on Treg activation and conversion to effector Treg (eTreg) phenotype. Our data furthermore suggested that Tregs activated by attenuated IL-2 muteins showed reduced dependence on TCR signal, at least in part due to the enhanced ability of IL-2 muteins to amplify the TCR signal in vivo. These results point to a new paradigm wherein IL-2 influences Tregs’ sensitivity to antigenic signal, and that the combination effect may be leveraged for therapeutic use of attenuated IL-2 muteins

Constitutive phosphorylation of the FOXO1 transcription factor in gastric cancer cells correlates with microvessel area and the expressions of angiogenesis-related molecules

<p>Abstract</p> <p>Background</p> <p>Although FOXO transcription factors may have an anti-angiogenic role, little is known about their role in tumor angiogenesis. The present study was performed to investigate the correlation between the constitutive expression of phosphorylated FOXO1 (pFOXO1) and angiogenesis in gastric cancer.</p> <p>Methods</p> <p>Immunohistochemistry was performed on tissue array slides containing 272 gastric carcinoma specimens, and the correlations between the cytoplasmic pFOXO1 expression in gastric cancer cells and CD34-immunopositive microvessel area (MVA) or the expressions of angiogenesis-related molecules were analyzed. <it>In vitro </it>analyses with Western blotting and semiquantitative reverse transcription-polymerase chain reaction were performed using the stable SNU-638 gastric cancer cell line transfected with lentivirus-delivered FOXO1 short hairpin RNA.</p> <p>Results</p> <p>The cytoplasmic expression of pFOXO1 in tumor cells was observed in 85% of gastric carcinoma cases, and was found to be positively associated with higher MVA (<it>P </it>= 0.048). Moreover, pFOXO1 expression was positively correlated with the expressions of several angiogenesis-related proteins, including hypoxia inducible factor-1α (HIF-1α, <it>P </it>= 0.003), vessel endothelial growth factor (<it>P </it>= 0.004), phosphorylated protein kinase B (<it>P </it>< 0.001), and nuclear factor-κB (<it>P </it>= 0.040). In contrast, the expression of pFOXO1 was not correlated with that of phosphorylated signal transducer and activator of transcription 3 or β-catenin. In addition, cell culture experiments showed that FOXO1 suppression increased the mRNA and protein expressions of HIF-1α.</p> <p>Conclusion</p> <p>Our results suggest that pFOXO1 expression in cancer cells plays a role in gastric cancer angiogenesis via mechanisms involving various angiogenesis-related molecules. Animal experiments are needed to confirm the anti-angiogenic role of FOXO1 in human gastric cancer.</p

Genetic Susceptibility on CagA-Interacting Molecules and Gene-Environment Interaction with Phytoestrogens: A Putative Risk Factor for Gastric Cancer

OBJECTIVES: To evaluate whether genes that encode CagA-interacting molecules (SRC, PTPN11, CRK, CRKL, CSK, c-MET and GRB2) are associated with gastric cancer risk and whether an interaction between these genes and phytoestrogens modify gastric cancer risk. METHODS: In the discovery phase, 137 candidate SNPs in seven genes were analyzed in 76 incident gastric cancer cases and 322 matched controls from the Korean Multi-Center Cancer Cohort. Five significant SNPs in three genes (SRC, c-MET and CRK) were re-evaluated in 386 cases and 348 controls in the extension phase. Odds ratios (ORs) for gastric cancer risk were estimated adjusted for age, smoking, H. pylori seropositivity and CagA strain positivity. Summarized ORs in the total study population (462 cases and 670 controls) were presented using pooled- and meta-analysis. Plasma concentrations of phytoestrogens (genistein, daidzein, equol and enterolactone) were measured using the time-resolved fluoroimmunoassay. RESULTS: SRC rs6122566, rs6124914, c-MET rs41739, and CRK rs7208768 showed significant genetic effects for gastric cancer in both the pooled and meta-analysis without heterogeneity (pooled OR = 3.96 [95% CI 2.05-7.65], 1.24 [95% CI = 1.01-1.53], 1.19 [95% CI = 1.01-1.41], and 1.37 [95% CI = 1.15-1.62], respectively; meta OR = 4.59 [95% CI 2.74-7.70], 1.36 [95% CI = 1.09-1.70], 1.20 [95% CI = 1.00-1.44], and 1.32 [95% CI = 1.10-1.57], respectively). Risk allele of CRK rs7208768 had a significantly increased risk for gastric cancer at low phytoestrogen levels (p interaction<0.05). CONCLUSIONS: Our findings suggest that SRC, c-MET and CRK play a key role in gastric carcinogenesis by modulating CagA signal transductions and interaction between CRK gene and phytoestrogens modify gastric cancer risk