Palindromic Decompositions with Gaps and Errors

Identifying palindromes in sequences has been an interesting line of research in combinatorics on words and also in computational biology, after the discovery of the relation of palindromes in the DNA sequence with the HIV virus. Efficient algorithms for the factorization of sequences into palindromes and maximal palindromes have been devised in recent years. We extend these studies by allowing gaps in decompositions and errors in palindromes, and also imposing a lower bound to the length of acceptable palindromes. We first present an algorithm for obtaining a palindromic decomposition of a string of length n with the minimal total gap length in time O(n log n * g) and space O(n g), where g is the number of allowed gaps in the decomposition. We then consider a decomposition of the string in maximal \delta-palindromes (i.e. palindromes with \delta errors under the edit or Hamming distance) and g allowed gaps. We present an algorithm to obtain such a decomposition with the minimal total gap length in time O(n (g + \delta)) and space O(n g).Comment: accepted to CSR 201

Combinatorial RNA Design: Designability and Structure-Approximating Algorithm

In this work, we consider the Combinatorial RNA Design problem, a minimal instance of the RNA design problem which aims at finding a sequence that admits a given target as its unique base pair maximizing structure. We provide complete characterizations for the structures that can be designed using restricted alphabets. Under a classic four-letter alphabet, we provide a complete characterization of designable structures without unpaired bases. When unpaired bases are allowed, we provide partial characterizations for classes of designable/undesignable structures, and show that the class of designable structures is closed under the stutter operation. Membership of a given structure to any of the classes can be tested in linear time and, for positive instances, a solution can be found in linear time. Finally, we consider a structure-approximating version of the problem that allows to extend bands (helices) and, assuming that the input structure avoids two motifs, we provide a linear-time algorithm that produces a designable structure with at most twice more base pairs than the input structure.Comment: CPM - 26th Annual Symposium on Combinatorial Pattern Matching, Jun 2015, Ischia Island, Italy. LNCS, 201

Building development and roads: implications for the distribution of stone curlews across the Brecks

Background: Substantial new housing and infrastructure development planned within England has the potential to conflict with the nature conservation interests of protected sites. The Breckland area of eastern England (the Brecks) is designated as a Special Protection Area for a number of bird species, including the stone curlew (for which it holds more than 60% of the UK total population). We explore the effect of buildings and roads on the spatial distribution of stone curlew nests across the Brecks in order to inform strategic development plans to avoid adverse effects on such European protected sites. Methodology: Using data across all years (and subsets of years) over the period 1988 – 2006 but restricted to habitat areas of arable land with suitable soils, we assessed nest density in relation to the distances to nearest settlements and to major roads. Measures of the local density of nearby buildings, roads and traffic levels were assessed using normal kernel distance-weighting functions. Quasi-Poisson generalised linear mixed models allowing for spatial auto-correlation were fitted. Results: Significantly lower densities of stone curlew nests were found at distances up to 1500m from settlements, and distances up to 1000m or more from major (trunk) roads. The best fitting models involved optimally distance-weighted variables for the extent of nearby buildings and the trunk road traffic levels. Significance : The results and predictions from this study of past data suggests there is cause for concern that future housing development and associated road infrastructure within the Breckland area could have negative impacts on the nesting stone curlew population. Given the strict legal protection afforded to the SPA the planning and conservation bodies have subsequently agreed precautionary restrictions on building development within the distances identified and used the modelling predictions to agree mitigation measures for proposed trunk road developments

A simple, practical and complete O-time Algorithm for RNA folding using the Four-Russians Speedup

<p>Abstract</p> <p>Background</p> <p>The problem of computationally predicting the secondary structure (or folding) of RNA molecules was first introduced more than thirty years ago and yet continues to be an area of active research and development. The basic <it>RNA-folding problem </it>of finding a maximum cardinality, non-crossing, matching of complimentary nucleotides in an RNA sequence of length <it>n</it>, has an <it>O</it>(<it>n</it>³)-time dynamic programming solution that is widely applied. It is known that an <it>o</it>(<it>n</it>³) worst-case time solution is possible, but the published and suggested methods are complex and have not been established to be practical. Significant practical improvements to the original dynamic programming method have been introduced, but they retain the <it>O</it>(<it>n</it>³) worst-case time bound when <it>n </it>is the only problem-parameter used in the bound. Surprisingly, the most widely-used, general technique to achieve a worst-case (and often practical) speed up of dynamic programming, the <it>Four-Russians </it>technique, has not been previously applied to the RNA-folding problem. This is perhaps due to technical issues in adapting the technique to RNA-folding.</p> <p>Results</p> <p>In this paper, we give a simple, complete, and practical Four-Russians algorithm for the basic RNA-folding problem, achieving a worst-case time-bound of <it>O</it>(<it>n</it>³/log(<it>n</it>)).</p> <p>Conclusions</p> <p>We show that this time-bound can also be obtained for richer nucleotide matching scoring-schemes, and that the method achieves consistent speed-ups in practice. The contribution is both theoretical and practical, since the basic RNA-folding problem is often solved multiple times in the inner-loop of more complex algorithms, and for long RNA molecules in the study of RNA virus genomes.</p

Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling

Vascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not fully known. Here we propose a novel role for the mineralisation regulator Ucma/GRP (Upper zone of growth plate and Cartilage Matrix Associated protein/Gla Rich Protein) in phosphate-induced VSMC calcification. We show that Ucma/GRP is present in calcified atherosclerotic plaques and highly expressed in calcifying VSMCs in vitro. VSMCs from Ucma/GRP(-/-) mice showed increased mineralisation and expression of osteo/chondrogenic markers (BMP-2, Runx2, beta-catenin, p-SMAD1/5/8, ALP, OCN), and decreased expression of mineralisation inhibitor MGP, suggesting that Ucma/GRP is an inhibitor of mineralisation. Using BMP signalling inhibitor noggin and SMAD1/5/8 signalling inhibitor dorsomorphin we showed that Ucma/GRP is involved in inhibiting the BMP-2-SMAD1/5/8 osteo/chondrogenic signalling pathway in VSMCs treated with elevated phosphate concentrations. Additionally, we showed for the first time evidence of a direct interaction between Ucma/GRP and BMP-2. These results demonstrate an important role of Ucma/GRP in regulating osteo/chondrogenic differentiation and phosphate-induced mineralisation of VSMCs.NWO ZonMw [MKMD 40-42600-98-13007]; FCT [SFRH/BPD/70277/2010]info:eu-repo/semantics/publishedVersio

A personalized, intense physical rehabilitation program improves walking in people with multiple sclerosis presenting with different levels of disability: A retrospective cohort

Copyright © 2015 Kalron et al.Background: People with multiple sclerosis (PwMS) endure walking limitations. To address this restriction, various physical rehabilitation programs have been implemented with no consensus regarding their efficacy. Our objective was to report on the efficacy of an integrated tailored physical rehabilitation program on walking in people with multiple sclerosis categorized according to their level of neurological disability. Methods: Retrospective data were examined and analyzed. Specifically, data obtained from all patients who participated in the Multiple Sclerosis Center's 3 week rehabilitation program were extracted for in depth exploration. The personalized rehabilitation program included three major components modified according to the patient's specific impairments and functional needs: (a) goal directed physical therapy (b) moderately intense aerobic exercise training on a bicycle ergometer and (c) aquatic therapy chiefly oriented to body structures appropriate to movement. Gait outcome measurements included the 10 meter, 20 meter, Timed up and go and 2 minute walking tests measured pre and post the rehabilitation program. Three hundred and twelve people with relapsing-remitting multiple sclerosis were included in the final analysis. Patients were categorized into mild (n = 87), moderate (n = 104) and severely (n = 121) disabled groups. Results: All clinical walking outcome measurements demonstrated statistically significant improvements, however, only an increase in the 2 minute walking test was above the minimal clinical difference value. The moderate and severe groups considerably improved compared to the mild gait disability group. Mean change scores (%) of the pre-post intervention period of the 2 minute walking test were 19.0 (S.E. = 3.4) in the moderate group, 16.2 (S.E. = 5.4) in the severe group and 10.9 (S.E. = 2.3) in the mild gait disability group. Conclusions: We presented comprehensive evidence verifying the effects of an intense goal-directed physical rehabilitation program on ambulation in people with multiple sclerosis presenting with different neurological impairment levels

Effect of the Glycemic Index of Carbohydrates on Acne vulgaris

Acne vulgaris may be improved by dietary factors that increase insulin sensitivity. We hypothesized that a low-glycemic index diet would improve facial acne severity and insulin sensitivity. Fifty-eight adolescent males (mean age ± standard deviation 16.5 ± 1.0 y and body mass index 23.1 ± 3.5 kg/m2) were alternately allocated to high or low glycemic index diets. Severity of inflammatory lesions on the face, insulin sensitivity (homeostasis modeling assessment of insulin resistance), androgens and insulin-like growth factor-1 and its binding proteins were assessed at baseline and at eight weeks, a period corresponding to the school term. Forty-three subjects (n = 23 low glycemic index and n = 20 high glycemic index) completed the study. Diets differed significantly in glycemic index (mean ± standard error of the mean, low glycemic index 51 ± 1 vs. high glycemic index 61 ± 2, p = 0.0002), but not in macronutrient distribution or fiber content. Facial acne improved on both diets (low glycemic index −26 ± 6%, p = 0.0004 and high glycemic index −16 ± 7%, p = 0.01), but differences between diets did not reach significance. Change in insulin sensitivity was not different between diets (low glycemic index 0.2 ± 0.1 and high glycemic index 0.1 ± 0.1, p = 0.60) and did not correlate with change in acne severity (Pearson correlation r = −0.196, p = 0.244). Longer time frames, greater reductions in glycemic load or/and weight loss may be necessary to detect improvements in acne among adolescent boys

Whey protein lowers systolic blood pressure and Ca-caseinate reduces serum TAG after a high-fat meal in mildly hypertensive adults

Epidemiological studies show an inverse association between dairy consumption and blood pressure (BP) but there are few data on the postprandial effects of milk proteins. This study examined their effects, compared to maltodextrin, on postprandial BP and other CVD risk markers in volunteers with mild and pre-hypertension over an 8 h period. In this double-blinded, randomised, cross-over, controlled study 27 adults ingested a high-fat, isoenergetic breakfast and lunch with 28 g whey protein, 28 g Ca-caseinate or 27 g maltodextrin. Whey protein reduced systolic BP compared with Ca-caseinate (−15.2 ± 13.6 mmHg) and maltodextrin (−23.4 ± 10.5 mmHg) up to 5 h post-ingestion. There was an improvement in arterial stiffness after whey protein compared with maltodextrin (incremental Area Under the Curve- iAUC0–8h: +14.4 ± 6.2%). Despite similar glucose levels after both whey protein and Ca-caseinate, whey protein induced a higher insulin response than Cacaseinate (iAUC0–8h: +219.5 ± 54.6 pmol/L). Ca-caseinate induced less suppression of non-esterified fatty acids than whey protein (iAUC0–5h: −58.9 ± 135.5 μmol/L) and maltodextrin (iAUC0–5h: −106.9 ± 89.4 μmol/L) and induced a smaller postprandial triacylglycerol response than whey protein (iAUC0–8h: −1.68 ± 0.6 mmol/L). Milk proteins co-ingestion with high-fat meals may have the potential to maintain or improve CVD risk factors

Endogenous laminin is required for human airway smooth muscle cell maturation

BACKGROUND: Airway smooth muscle (ASM) contraction underlies acute bronchospasm in asthma. ASM cells can switch between a synthetic-proliferative phenotype and a contractile phenotype. While the effects of extracellular matrix (ECM) components on modulation of ASM cells to a synthetic phenotype have been reported, the role of ECM components on maturation of ASM cells to a contractile phenotype in adult lung is unclear. As both changes in ECM components and accumulation of contractile ASM are features of airway wall remodelling in asthma, we examined the role of the ECM protein, laminin, in the maturation of contractile phenotype in human ASM cells. METHODS: Human ASM cells were made senescence-resistant by stable expression of human telomerase reverse transcriptase. Maturation to a contractile phenotype was induced by 7-day serum deprivation, as assessed by immunoblotting for desmin and calponin. The role of laminin on ASM maturation was investigated by comparing the effects of exogenous laminin coated on culture plates, and of soluble laminin peptide competitors. Endogenous expression of laminin chains during ASM maturation was also measured. RESULTS: Myocyte binding to endogenously expressed laminin was required for ASM phenotype maturation, as laminin competing peptides (YIGSR or GRGDSP) significantly reduced desmin and calponin protein accumulation that otherwise occurs with prolonged serum deprivation. Coating of plastic cell culture dishes with different purified laminin preparations was not sufficient to further promote accumulation of desmin or calponin during 7-day serum deprivation. Expression of α2, β1 and γ1 laminin chains by ASM cells was specifically up-regulated during myocyte maturation, suggesting a key role for laminin-2 in the development of the contractile phenotype. CONCLUSION: While earlier reports suggest exogenously applied laminin slows the spontaneous modulation of ASM to a synthetic phenotype, we show for the first time that endogenously expressed laminin is required for ASM maturation to the contractile phenotype. As endogenously expressed laminin chains α2, β1 and γ1 are uniquely increased during myocyte maturation, these laminin chains may be key in this process. Thus, human ASM maturation appears to involve regulated endogenous expression of a select set of laminin chains that are essential for accumulation of contractile phenotype myocytes