Effects of Photoperiod, Water temperature, and Exogenous Hormones on Spawning and Plasma gonadal Steroid in Starry Flounder, Platichthys stellatus

The sexual maturation and spawning of teleosts are regulated by the external environment and the endocrine system. When the environmental conditions are artificially adjusted at a fish farm, the maturity and spawning of fish can be controlled. In this study, sexual maturation and spawning of the starry flounder, Platichthys stellatus, were artificially induced by adjusting the water temperature and photoperiod at a fish farm to accelerate the species’ natural spawning period. One experimental group acted as a control and was exposed to a natural photoperiod and natural water temperature (NPNT). In contrast, another experimental group was exposed to an adjusted environment consisting of a regulated photoperiod and temperature (RPRT). Daylight time was reduced by 10 minutes every 3 days from 13 hours to a duration of 8 hours. The water temperature was first reduced by 1oC every day, starting at 22oC and ending at 8oC, and then raised to 10oC until the spawning period. Both experimental groups were treated with gonadotropin-releasing hormone analog (GnRHa) pellets to induce ovulation. The results show that when the water temperature and photoperiod were artificially controlled, ovulation could be induced 97 days earlier than the natural spawning. Plasma testosterone levels of RPRT and NPNT tended to increase and then decrease 1–2 months before spawning, and plasma levels of 17α,20β-dihydroxy-4-pregnen-3-one increased 1–2 months before spawning. The concentration of estradiol-17β (E2) in plasma was not associated with spawning

Capillary force lithography with impermeable molds

Capillary force lithography (CFL) with impermeable mold is presented. For the CFL to be operative over large area, either the mold or the substrate has to be flexible. With a silicon wafer mold and a flexible substrate, a repeated line and space pattern with a spacing of 30 nm is shown to be well patterned. With a flexible mold and a hard substrate, a similar pattern with a spacing of 60 nm is demonstrated by CFL. The flexibility is needed for the intimate contact that is required between the mold and the substrate for the capillarity to take hold over large area. The forte of CFL with impermeable mold lies in the fact that the driving force for the patterning, which is capillary force, increases with decreasing pattern size.This work was supported by the Korea Foundation Grant funded by MOEHRD (KRF-2005-041-D00250)

Round Cell Variant of Myxoid Liposarcoma in a Japanese Macaque (Macaca fuscata)

A 5-year-old, female, Japanese Macaque (Macaca fuscata) was diagnosed with round cell variant of myxoid liposarcoma. At necropsy, multifocal to coalescing, reddish tan to white nodules, ranging from 0.5 to 1 cm in diameter, were noted throughout the omentum and retroperitoneum. Similar neoplastic nodules were also present in diaphragm, abdominal wall, and on hepatic capsule. Microscopically, neoplastic masses consisted of round to polyhedral cells, which had round, often eccentric nuclei and abundant eosinophilic granular and microvacuolated cytoplasm; Oil red O staining demonstrated large numbers of lipid droplets in the cytoplasm. Ultrastructurally, the cytoplasm of the tumor cells was packed with occasional lipid vacuoles and numerous enlarged mitochondria. Immunohistochemistry revealed tumor cells were positive for vimentin, while negative to cytokeratin, actin, and Factor VIII–related antigen. To the authors' knowledge, this is the first report of round-cell variant of myxoid liposarcoma in nonhuman primate.This study was supported through Brain Korea 21 Program for Veterinary Science

Reduced risk of Barrett’s esophagus in statin users: case–control study and meta-analysis

Background: Use of statins has been associated with a reduced incidence of esophageal adenocarcinoma in population-based studies. However there are few studies examining statin use and the development of Barrett’s esophagus. Aim: The purpose of this study was to examine the association between statin use and the presence of Barrett’s esophagus in patients having their first gastroscopy. Methods: We have performed a case–control study comparing statin use between patients with, and without, an incident diagnosis of non-dysplastic Barrett’s esophagus. Male Barrett’s cases (134) were compared to 268 male age-matched controls in each of two control groups (erosive gastro-esophageal reflux and dyspepsia without significant upper gastrointestinal disease). Risk factor and drug exposure were established using standardised interviews. Logistic regression was used to compare statin exposure and correct for confounding factors. We performed a meta-analysis pooling our results with three other case–control studies. Results: Regular statin use was associated with a significantly lower incidence of Barrett’s esophagus compared to the combined control groups [adjusted OR 0.62 (95 % confidence intervals 0.37–0.93)]. This effect was more marked in combined statin plus aspirin users [adjusted OR 0.43 (95 % CI 0.21–0.89)]. The inverse association between statin or statin plus aspirin use and risk of Barrett’s was significantly greater with longer duration of use. Meta-analysis of pooled data (1098 Barrett’s, 2085 controls) showed that statin use was significantly associated with a reduced risk of Barrett’s esophagus [pooled adjusted OR 0.63 (95 % CI 0.51–0.77)]. Conclusions: Statin use is associated with a reduced incidence of a new diagnosis of Barrett’s esophagus

Downregulated miR-18b-5p triggers apoptosis by inhibition of calcium signaling and neuronal cell differentiation in transgenic SOD1 (G93A) mice and SOD1 (G17S and G86S) ALS patients

Abstract Background MicroRNAs (miRNAs) are endogenous non-coding RNAs that regulate gene expression at the post-transcriptional level and are key modulators in neurodegenerative diseases. Overexpressed miRNAs play an important role in ALS; however, the pathogenic mechanisms of deregulated miRNAs are still unclear. Methods We aimed to assess the dysfunction of RNAs or miRNAs in fALS (SOD1 mutations). We compared the RNA-seq of subcellular fractions in NSC-34 WT (hSOD1) and MT (hSOD1 (G93A)) cells to find altered RNAs or miRNAs. We identified that Hif1α and Mef2c were upregulated, and Mctp1 and Rarb were downregulated in the cytoplasm of NSC-34 MT cells. Results SOD1 mutations decreased the level of miR-18b-5p. Induced Hif1α which is the target for miR-18b increased Mef2c expression as a transcription factor. Mef2c upregulated miR-206 as a transcription factor. Inhibition of Mctp1 and Rarb which are targets of miR-206 induces intracellular Ca2+ levels and reduces cell differentiation, respectively. We confirmed that miR-18b-5p pathway was also observed in G93A Tg, fALS (G86S) patient, and iPSC-derived motor neurons from fALS (G17S) patient. Conclusions Our data indicate that SOD1 mutation decreases miR-18b-5p, which sequentially regulates Hif1α, Mef2c, miR-206, Mctp1 and Rarb in fALS-linked SOD1 mutation. These results provide new insights into the downregulation of miR-18b-5p dependent pathogenic mechanisms of ALS

PicXAA-R: Efficient structural alignment of multiple RNA sequences using a greedy approach

<p>Abstract</p> <p>Background</p> <p>Accurate and efficient structural alignment of non-coding RNAs (ncRNAs) has grasped more and more attentions as recent studies unveiled the significance of ncRNAs in living organisms. While the Sankoff style structural alignment algorithms cannot efficiently serve for multiple sequences, mostly progressive schemes are used to reduce the complexity. However, this idea tends to propagate the early stage errors throughout the entire process, thereby degrading the quality of the final alignment. For multiple protein sequence alignment, we have recently proposed PicXAA which constructs an accurate alignment in a non-progressive fashion.</p> <p>Results</p> <p>Here, we propose PicXAA-R as an extension to PicXAA for greedy structural alignment of ncRNAs. PicXAA-R efficiently grasps both folding information within each sequence and local similarities between sequences. It uses a set of probabilistic consistency transformations to improve the posterior base-pairing and base alignment probabilities using the information of all sequences in the alignment. Using a graph-based scheme, we greedily build up the structural alignment from sequence regions with high base-pairing and base alignment probabilities.</p> <p>Conclusions</p> <p>Several experiments on datasets with different characteristics confirm that PicXAA-R is one of the fastest algorithms for structural alignment of multiple RNAs and it consistently yields accurate alignment results, especially for datasets with locally similar sequences. PicXAA-R source code is freely available at: <url>http://www.ece.tamu.edu/~bjyoon/picxaa/</url>.</p

Carriage of the V279F Null Allele within the Gene Encoding Lp-PLA2 Is Protective from Coronary Artery Disease in South Korean Males

The Asia-specific PLA2G7 994G-T transversion leads to V279F substitution within the lipoprotein-associated phospholipase-A2 (Lp-PLA₂) and to absence of enzyme activity in plasma. This variant offers a unique natural experiment to assess the role of Lp-PLA₂ in the pathogenesis of coronary artery disease (CAD) in humans. Given conflicting results from mostly small studies, a large two-stage case-control study was warranted.PLA2G7 V279F genotypes were initially compared in 2890 male cases diagnosed with CAD before age 60 with 3128 male controls without CAD at age 50 and above and subsequently in a second independent male dataset of 877 CAD cases and 1230 controls. In the first dataset, the prevalence of the 279F null allele was 11.5% in cases and 12.8% in controls. After adjustment for age, body mass index, diabetes, smoking, glucose and lipid levels, the OR (95% CI) for CAD for this allele was 0.80 (0.66-0.97, p = 0.02). The results were very similar in the second dataset, despite lower power, with an allele frequency of 11.2% in cases and 12.5% in controls, leading to a combined OR of 0.80 (0.69-0.92), p = 0.002. The magnitude and direction of this genetic effect were fully consistent with large epidemiological studies on plasma Lp-PLA₂ activity and CAD risk.Natural deficiency in Lp-PLA₂ activity due to carriage of PLA2G7 279F allele protects from CAD in Korean men. These results provide evidence for a causal relationship between Lp-PLA₂ and CAD, and support pharmacological inhibition of this enzyme as an innovative way to prevent CAD

Carriage of the V279F Null Allele within the Gene Encoding Lp-PLA2 Is Protective from Coronary Artery Disease in South Korean Males

The Asia-specific PLA2G7 994G-T transversion leads to V279F substitution within the lipoprotein-associated phospholipase-A2 (Lp-PLA₂) and to absence of enzyme activity in plasma. This variant offers a unique natural experiment to assess the role of Lp-PLA₂ in the pathogenesis of coronary artery disease (CAD) in humans. Given conflicting results from mostly small studies, a large two-stage case-control study was warranted.PLA2G7 V279F genotypes were initially compared in 2890 male cases diagnosed with CAD before age 60 with 3128 male controls without CAD at age 50 and above and subsequently in a second independent male dataset of 877 CAD cases and 1230 controls. In the first dataset, the prevalence of the 279F null allele was 11.5% in cases and 12.8% in controls. After adjustment for age, body mass index, diabetes, smoking, glucose and lipid levels, the OR (95% CI) for CAD for this allele was 0.80 (0.66-0.97, p = 0.02). The results were very similar in the second dataset, despite lower power, with an allele frequency of 11.2% in cases and 12.5% in controls, leading to a combined OR of 0.80 (0.69-0.92), p = 0.002. The magnitude and direction of this genetic effect were fully consistent with large epidemiological studies on plasma Lp-PLA₂ activity and CAD risk.Natural deficiency in Lp-PLA₂ activity due to carriage of PLA2G7 279F allele protects from CAD in Korean men. These results provide evidence for a causal relationship between Lp-PLA₂ and CAD, and support pharmacological inhibition of this enzyme as an innovative way to prevent CAD

miREE: miRNA recognition elements ensemble

Abstract Background Computational methods for microRNA target prediction are a fundamental step to understand the miRNA role in gene regulation, a key process in molecular biology. In this paper we present miREE, a novel microRNA target prediction tool. miREE is an ensemble of two parts entailing complementary but integrated roles in the prediction. The Ab-Initio module leverages upon a genetic algorithmic approach to generate a set of candidate sites on the basis of their microRNA-mRNA duplex stability properties. Then, a Support Vector Machine (SVM) learning module evaluates the impact of microRNA recognition elements on the target gene. As a result the prediction takes into account information regarding both miRNA-target structural stability and accessibility. Results The proposed method significantly improves the state-of-the-art prediction tools in terms of accuracy with a better balance between specificity and sensitivity, as demonstrated by the experiments conducted on several large datasets across different species. miREE achieves this result by tackling two of the main challenges of current prediction tools: (1) The reduced number of false positives for the Ab-Initio part thanks to the integration of a machine learning module (2) the specificity of the machine learning part, obtained through an innovative technique for rich and representative negative records generation. The validation was conducted on experimental datasets where the miRNA:mRNA interactions had been obtained through (1) direct validation where even the binding site is provided, or through (2) indirect validation, based on gene expression variations obtained from high-throughput experiments where the specific interaction is not validated in detail and consequently the specific binding site is not provided. Conclusions The coupling of two parts: a sensitive Ab-Initio module and a selective machine learning part capable of recognizing the false positives, leads to an improved balance between sensitivity and specificity. miREE obtains a reasonable trade-off between filtering false positives and identifying targets. miREE tool is available online at http://didattica-online.polito.it/eda/miREE/</p

Crosstalk between Nuclear Factor I-C and Transforming Growth Factor-β1 Signaling Regulates Odontoblast Differentiation and Homeostasis

Transforming growth factor-β1 (TGF-β1) signaling plays a key role in vertebrate development, homeostasis, and disease. Nuclear factor I-C (NFI-C) has been implicated in TGF-β1 signaling, extracellular matrix gene transcription, and tooth root development. However, the functional relationship between NFI-C and TGF-β1 signaling remains uncharacterized. The purpose of this study was to identify the molecular interactions between NFI-C and TGF-β1 signaling in mouse odontoblasts. Real-time polymerase chain reaction and western analysis demonstrated that NFI-C expression levels were inversely proportional to levels of TGF-β1 signaling molecules during in vitro odontoblast differentiation. Western blot and immunofluorescence results showed that NFI-C was significantly degraded after TGF-β1 addition in odontoblasts, and the formation of the Smad3 complex was essential for NFI-C degradation. Additionally, ubiquitination assay results showed that Smurf1 and Smurf2 induced NFI-C degradation and polyubiquitination in a TGF-β1-dependent manner. Both kinase and in vitro binding assays revealed that the interaction between NFI-C and Smurf1/Smurf2 requires the activation of the mitogen-activated protein kinase pathway by TGF-β1. Moreover, degradation of NFI-C induced by TGF-β1 occurred generally in cell types other than odontoblasts in normal human breast epithelial cells. In contrast, NFI-C induced dephosphorylation of p-Smad2/3. These results show that crosstalk between NFI-C and TGF-β1 signaling regulates cell differentiation and homeostatic processes in odontoblasts, which might constitute a common cellular mechanism