RNA secondary structure prediction from multi-aligned sequences

It has been well accepted that the RNA secondary structures of most functional non-coding RNAs (ncRNAs) are closely related to their functions and are conserved during evolution. Hence, prediction of conserved secondary structures from evolutionarily related sequences is one important task in RNA bioinformatics; the methods are useful not only to further functional analyses of ncRNAs but also to improve the accuracy of secondary structure predictions and to find novel functional RNAs from the genome. In this review, I focus on common secondary structure prediction from a given aligned RNA sequence, in which one secondary structure whose length is equal to that of the input alignment is predicted. I systematically review and classify existing tools and algorithms for the problem, by utilizing the information employed in the tools and by adopting a unified viewpoint based on maximum expected gain (MEG) estimators. I believe that this classification will allow a deeper understanding of each tool and provide users with useful information for selecting tools for common secondary structure predictions.Comment: A preprint of an invited review manuscript that will be published in a chapter of the book `Methods in Molecular Biology'. Note that this version of the manuscript may differ from the published versio

On the Bohr inequality

The Bohr inequality, first introduced by Harald Bohr in 1914, deals with finding the largest radius $r$, $0<r<1$, such that $\sum_{n=0}^\infty |a_n|r^n \leq 1$ holds whenever $|\sum_{n=0}^\infty a_nz^n|\leq 1$ in the unit disk $\mathbb{D}$ of the complex plane. The exact value of this largest radius, known as the \emph{Bohr radius}, has been established to be $1/3.$ This paper surveys recent advances and generalizations on the Bohr inequality. It discusses the Bohr radius for certain power series in $\mathbb{D},$ as well as for analytic functions from $\mathbb{D}$ into particular domains. These domains include the punctured unit disk, the exterior of the closed unit disk, and concave wedge-domains. The analogous Bohr radius is also studied for harmonic and starlike logharmonic mappings in $\mathbb{D}.$ The Bohr phenomenon which is described in terms of the Euclidean distance is further investigated using the spherical chordal metric and the hyperbolic metric. The exposition concludes with a discussion on the $n$-dimensional Bohr radius

Simply longer is not better: reversal of theta burst after-effect with prolonged stimulation

From all rTMS protocols at present, the theta burst stimulation (TBS) is considered the most efficient in terms of number of impulses and intensity required during a given stimulation. The aim of this study was to investigate the effects of inhibitory and excitatory TBS protocols on motor cortex excitability when the duration of stimulation was doubled. Fourteen healthy volunteers were tested under four conditions: intermittent theta bust stimulation (iTBS), continuous theta burst stimulation (cTBS), prolonged intermittent theta bust stimulation (ProiTBS) and prolonged continuous theta burst stimulation (ProcTBS). The prolonged paradigms were twice as long as the conventional TBS protocols. Conventional facilitatory iTBS converted into inhibitory when it was applied for twice as long, while the normally inhibitory cTBS became facilitatory when the stimulation duration was doubled. Our results show that TBS-induced plasticity cannot be deliberately enhanced simply by prolonging TBS protocols. Instead, when stimulating too long, after-effects will be reversed. This finding supplements findings at the short end of the stimulation duration range, where it was shown that conventional cTBS is excitatory in the first half and switches to inhibition only after the full length protocol. It is relevant for clinical applications for which an ongoing need for further protocol improvement is imminent

Invasive characteristics of human prostatic epithelial cells: understanding the metastatic process

Prostate cancer has a predilection to metastasise to the bone marrow stroma (BMS) by an as yet uncharacterised mechanism. We have defined a series of coculture models of invasion, which simulate the blood/BMS boundary and allow the elucidation of the signalling and mechanics of trans-endothelial migration within the complex bone marrow environment. Confocal microscopy shows that prostate epithelial cells bind specifically to bone marrow endothelial-to-endothelial cell junctions and initiate endothelial cell retraction. Trans-endothelial migration proceeds via an epithelial cell pseudopodial process, with complete epithelial migration occurring after 232±43 min. Stromal-derived factor-1 (SDF-1)/CXCR4 signalling induced PC-3 to invade across a basement membrane although the level of invasion was 3.5-fold less than invasion towards BMS (P=0.0007) or bone marrow endothelial cells (P=0.004). Maximal SDF-1 signalling of invasion was completely inhibited by 10 μM of the SDF-1 inhibitor T140. However, 10 μM T140 only reduced invasion towards BMS and bone marrow endothelial cells by 59% (P=0.001) and 29% (P=0.011), respectively. This study highlights the need to examine the potential roles of signalling molecules and/or inhibitors, not just in single-cell models but in coculture models that mimic the complex environment of the bone marrow

Crude oil yield and properties of rice bran oil from different varieties as affected by extraction conditions using soxhterm method

The current study was employed to investigate the effect of solvent type, extraction time and bran ratio on the rice bran oil (RBO) properties from three varieties of rice bran namely Bario, lowland and upland rice. RBO was extracted by using soxtherm extraction method using methanol solvent at different extraction time (3, 4 and 5 h) and bran ratio (10, 20 and 30 g). Free fatty acid (FFA), total phenolic content (TPC) and antioxidant properties were assessed. Solvent that has low polarity exhibited the attraction of polar component of oil with the highest yield by ethanol (16.16%), followed by methanol (15.38%). FFA contents occurred higher in lowland types of rice bran in all types of solvents at P<0.05 with ethanol (12.73%), methanol (11.96%) and hexane (11.13%), while the total phenolic content and antioxidant properties were influenced by the types of rice bran and solvents used for extracting components out of the bran. The highest phenolic content in the crude oil was extracted using ethanol in lowland (0.509 mg/ml), and the lowest was extracted by hexane in Bario (0.061 mg/ml). The highest antioxidant activity was observed in RBO extracted using methanol of lowland (73.74%) and RBO extracted using ethanol of upland (73.65%), while the lowest were observed in RBO extracted using hexane. The different types of solvent have the significant impact on the crude oil yield and properties of crude oil extracted

Chronic hyperglycemia induces trans-differentiation of human pancreatic stellate cells and enhances the malignant molecular communication with human pancreatic cancer cells

BACKGROUND: Diabetes mellitus is linked to pancreatic cancer. We hypothesized a role for pancreatic stellate cells (PSC) in the hyperglycemia induced deterioration of pancreatic cancer and therefore studied two human cell lines (RLT-PSC, T3M4) in hyperglycemic environment. METHODOLOGY/PRINCIPAL FINDINGS: The effect of chronic hyperglycemia (CHG) on PSCs was studied using mRNA expression array with real-time PCR validation and bioinformatic pathway analysis, and confirmatory protein studies. The stress fiber formation (IC: αSMA) indicated that PSCs tend to transdifferentiate to a myofibroblast-like state after exposure to CHG. The phosphorylation of p38 and ERK1/2 was increased with a consecutive upregulation of CDC25, SP1, cFOS and p21, and with downregulation of PPARγ after PSCs were exposed to chronic hyperglycemia. CXCL12 levels increased significantly in PSC supernatant after CHG exposure independently from TGF-β1 treatment (3.09-fold with a 2.73-fold without TGF-β1, p<0.05). The upregualtion of the SP1 transcription factor in PSCs after CHG exposure may be implicated in the increased CXCL12 and IGFBP2 production. In cancer cells, hyperglycemia induced an increased expression of CXCR4, a CXCL12 receptor that was also induced by PSC's conditioned medium. The receptor-ligand interaction increased the phosphorylation of ERK1/2 and p38 resulting in activation of MAP kinase pathway, one of the most powerful stimuli for cell proliferation. Certainly, conditioned medium of PSC increased pancreatic cancer cell proliferation and this effect could be partially inhibited by a CXCR4 inhibitor. As the PSC conditioned medium (normal glucose concentration) increased the ERK1/2 and p38 phosphorylation, we concluded that PSCs produce other factor(s) that influence(s) pancreatic cancer behaviour. CONCLUSIONS: Hyperglycemia induces increased CXCL12 production by the PSCs, and its receptor, CXCR4 on cancer cells. The ligand-receptor interaction activates MAP kinase signaling that causes increased cancer cell proliferation and migration

Lack of association of genetic variation in chromosome region 15q14-22.1 with type 2 diabetes in a Japanese population

<p>Abstract</p> <p>Background</p> <p>Chromosome 15q14-22.1 has been linked to type 2 diabetes (T2D) and its related traits in Japanese and other populations. The presence of T2D disease susceptibility variant(s) was assessed in the 21.8 Mb region between <it>D15S118 </it>and <it>D15S117 </it>in a Japanese population using a region-wide case-control association test.</p> <p>Methods</p> <p>A two-stage association test was performed using Japanese subjects: The discovery panel (Stage 1) used 372 cases and 360 controls, while an independent replication panel (Stage 2) used 532 cases and 530 controls. A total of 1,317 evenly-spaced, common SNP markers with minor allele frequencies > 0.10 were typed for each stage. Captured genetic variation was examined in HapMap JPT SNPs, and a haplotype-based association test was performed.</p> <p>Results</p> <p>SNP2140 (rs2412747) (<it>C/T</it>) in intron 33 of the ubiquitin protein ligase E3 component n-recognin 1 (<it>UBR1</it>) gene was selected as a landmark SNP based on repeated significant associations in Stage 1 and Stage 2. However, the marginal <it>p </it>value (<it>p </it>= 0.0043 in the allelic test, OR = 1.26, 95% CI = 1.07–1.48 for combined samples) was weak in a single locus or haplotype-based association test. We failed to find any significant SNPs after correcting for multiple testing.</p> <p>Conclusion</p> <p>The two-stage association test did not reveal a strong association between T2D and any common variants on chromosome 15q14-22.1 in 1,794 Japanese subjects. A further association test with a larger sample size and denser SNP markers is required to confirm these observations.</p