Promoter prediction in E. coli based on SIDD profiles and Artificial Neural Networks

<p>Abstract</p> <p>Background</p> <p>One of the major challenges in biology is the correct identification of promoter regions. Computational methods based on motif searching have been the traditional approach taken. Recent studies have shown that DNA structural properties, such as curvature, stacking energy, and stress-induced duplex destabilization (SIDD) are useful in promoter prediction, as well. In this paper, the currently used SIDD energy threshold method is compared to the proposed artificial neural network (ANN) approach for finding promoters based on SIDD profile data.</p> <p>Results</p> <p>When compared to the SIDD threshold prediction method, artificial neural networks showed noticeable improvements for precision, recall, and <it>F</it>-score over a range of values. The maximal <it>F</it>-score for the ANN classifier was 62.3 and 56.8 for the threshold-based classifier.</p> <p>Conclusions</p> <p>Artificial neural networks were used to predict promoters based on SIDD profile data. Results using this technique were an improvement over the previous SIDD threshold approach. Over a wide range of precision-recall values, artificial neural networks were more capable of identifying distinctive characteristics of promoter regions than threshold based methods.</p

The Existence of a Hypnotic State Revealed by Eye Movements

Hypnosis has had a long and controversial history in psychology, psychiatry and neurology, but the basic nature of hypnotic phenomena still remains unclear. Different theoretical approaches disagree as to whether or not hypnosis may involve an altered mental state. So far, a hypnotic state has never been convincingly demonstrated, if the criteria for the state are that it involves some objectively measurable and replicable behavioural or physiological phenomena that cannot be faked or simulated by non-hypnotized control subjects. We present a detailed case study of a highly hypnotizable subject who reliably shows a range of changes in both automatic and volitional eye movements when given a hypnotic induction. These changes correspond well with the phenomenon referred to as the “trance stare” in the hypnosis literature. Our results show that this ‘trance stare’ is associated with large and objective changes in the optokinetic reflex, the pupillary reflex and programming a saccade to a single target. Control subjects could not imitate these changes voluntarily. For the majority of people, hypnotic induction brings about states resembling normal focused attention or mental imagery. Our data nevertheless highlight that in some cases hypnosis may involve a special state, which qualitatively differs from the normal state of consciousness

Selection against Spurious Promoter Motifs Correlates with Translational Efficiency across Bacteria

Because binding of RNAP to misplaced sites could compromise the efficiency of transcription, natural selection for the optimization of gene expression should regulate the distribution of DNA motifs capable of RNAP-binding across the genome. Here we analyze the distribution of the −10 promoter motifs that bind the σ70 subunit of RNAP in 42 bacterial genomes. We show that selection on these motifs operates across the genome, maintaining an over-representation of −10 motifs in regulatory sequences while eliminating them from the nonfunctional and, in most cases, from the protein coding regions. In some genomes, however, −10 sites are over-represented in the coding sequences; these sites could induce pauses effecting regulatory roles throughout the length of a transcriptional unit. For nonfunctional sequences, the extent of motif under-representation varies across genomes in a manner that broadly correlates with the number of tRNA genes, a good indicator of translational speed and growth rate. This suggests that minimizing the time invested in gene transcription is an important selective pressure against spurious binding. However, selection against spurious binding is detectable in the reduced genomes of host-restricted bacteria that grow at slow rates, indicating that components of efficiency other than speed may also be important. Minimizing the number of RNAP molecules per cell required for transcription, and the corresponding energetic expense, may be most relevant in slow growers. These results indicate that genome-level properties affecting the efficiency of transcription and translation can respond in an integrated manner to optimize gene expression. The detection of selection against promoter motifs in nonfunctional regions also confirms previous results indicating that no sequence may evolve free of selective constraints, at least in the relatively small and unstructured genomes of bacteria

Genome-Wide Identification of Transcription Start Sites, Promoters and Transcription Factor Binding Sites in E. coli

Despite almost 40 years of molecular genetics research in Escherichia coli a major fraction of its Transcription Start Sites (TSSs) are still unknown, limiting therefore our understanding of the regulatory circuits that control gene expression in this model organism. RegulonDB (http://regulondb.ccg.unam.mx/) is aimed at integrating the genetic regulatory network of E. coli K12 as an entirely bioinformatic project up till now. In this work, we extended its aims by generating experimental data at a genome scale on TSSs, promoters and regulatory regions. We implemented a modified 5′ RACE protocol and an unbiased High Throughput Pyrosequencing Strategy (HTPS) that allowed us to map more than 1700 TSSs with high precision. From this collection, about 230 corresponded to previously reported TSSs, which helped us to benchmark both our methodologies and the accuracy of the previous mapping experiments. The other ca 1500 TSSs mapped belong to about 1000 different genes, many of them with no assigned function. We identified promoter sequences and type of σ factors that control the expression of about 80% of these genes. As expected, the housekeeping σ70 was the most common type of promoter, followed by σ38. The majority of the putative TSSs were located between 20 to 40 nucleotides from the translational start site. Putative regulatory binding sites for transcription factors were detected upstream of many TSSs. For a few transcripts, riboswitches and small RNAs were found. Several genes also had additional TSSs within the coding region. Unexpectedly, the HTPS experiments revealed extensive antisense transcription, probably for regulatory functions. The new information in RegulonDB, now with more than 2400 experimentally determined TSSs, strengthens the accuracy of promoter prediction, operon structure, and regulatory networks and provides valuable new information that will facilitate the understanding from a global perspective the complex and intricate regulatory network that operates in E. coli

Visual Search Strategies of Soccer Players Executing a Power vs. Placement Penalty Kick

Introduction: When taking a soccer penalty kick, there are two distinct kicking techniques that can be adopted; a ‘power’ penalty or a ‘placement’ penalty. The current study investigated how the type of penalty kick being taken affected the kicker’s visual search strategy and where the ball hit the goal (end ball location). Method: Wearing a portable eye tracker, 12 university footballers executed 2 power and placement penalty kicks, indoors, both with and without the presence of a goalkeeper. Video cameras were used to determine initial ball velocity and end ball location. Results: When taking the power penalty, the football was kicked significantly harder and more centrally in the goal compared to the placement penalty. During the power penalty, players fixated on the football for longer and more often at the goalkeeper (and by implication the middle of the goal), whereas in the placement penalty, fixated longer at the goal, specifically the edges. Findings remained consistent irrespective of goalkeeper presence. Discussion/conclusion: Findings indicate differences in visual search strategy and end ball location as a function of type of penalty kick. When taking the placement penalty, players fixated and kicked the football to the edges of the goal in an attempt to direct the ball to an area that the goalkeeper would have difficulty reaching and saving. Fixating significantly longer on the football when taking the power compared to placement penalty indicates a greater importance of obtaining visual information from the football. This can be attributed to ensuring accurate foot-to-ball contact and subsequent generation of ball velocity. Aligning gaze and kicking the football centrally in the goal when executing the power compared to placement penalty may have been a strategy to reduce the risk of kicking wide of the goal altogether

Evaluating hospital websites in Kuwait to improve consumer engagement and access to health information:a cross-sectional analytical study

Abstract Background Current advances in information and communication technology have made accessing and obtaining health-related information easier than ever before. Today, many hospital websites use a patient-centric approach to promote engagement and encourage learning for better health-related decision making. However, little is known about the current state of hospital websites in the State of Kuwait. This study aims to evaluate hospital websites in Kuwait and offer recommendations to improve patient engagement and access to health information. Methods This study employs a cross-sectional analytical approach to evaluate hospital websites in Kuwait in 2017. The websites of hospitals that provide in-patient services were identified through a structured search. Only active websites that were available in either English or Arabic were considered. The evaluation of the websites involved a combination of automated and expert- based evaluation methods and was performed across four dimensions: Accessibility, Usability, Presence, and Content. Results Nine hospitals met the inclusion criteria. Most of the websites fell short in all four dimensions. None of the websites passed the accessibility guidelines. The usability of websites varied between hospitals. Overall, the majority of hospitals in Kuwait have rudimentary online presence and their websites require careful reassessment with respect to design, content, and user experience. The websites focus primarily on promoting services provided by the hospital rather than engaging and communicating with patients or providing evidence-based information. Conclusions Healthcare organization and website developers should follow best-practices to improve their websites taking into consideration the quality, readability, objectivity, coverage and currency of the information as well as the design of their websites. Hospitals should leverage social media to gain outreach and better engagement with consumers. The websites should be offered in additional languages commonly spoken by people living in Kuwait. Efforts should be made to ensure that health information on hospital websites are evidence-based and checked by healthcare professionals

Resolving the Ortholog Conjecture: Orthologs Tend to Be Weakly, but Significantly, More Similar in Function than Paralogs

The function of most proteins is not determined experimentally, but is extrapolated from homologs. According to the “ortholog conjecture”, or standard model of phylogenomics, protein function changes rapidly after duplication, leading to paralogs with different functions, while orthologs retain the ancestral function. We report here that a comparison of experimentally supported functional annotations among homologs from 13 genomes mostly supports this model. We show that to analyze GO annotation effectively, several confounding factors need to be controlled: authorship bias, variation of GO term frequency among species, variation of background similarity among species pairs, and propagated annotation bias. After controlling for these biases, we observe that orthologs have generally more similar functional annotations than paralogs. This is especially strong for sub-cellular localization. We observe only a weak decrease in functional similarity with increasing sequence divergence. These findings hold over a large diversity of species; notably orthologs from model organisms such as E. coli, yeast or mouse have conserved function with human proteins

A report of laryngeal adenocystic carcinoma metastatic to the spleen and the role of splenectomy in the management of metastatic disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>Adenoid cystic carcinoma (ACC) of the larynx is a rare malignancy characterized by an indolent course and late pulmonary metastases. Metastases from the larynx to the spleen are an unusual event. In the present report, we discuss a patient with adenoid cystic carcinoma of the larynx metastatic to the spleen. A review of the literature did not yield any other such incidents. We review the clinical presentation and course of adenoid cystic carcinoma, as well as the role of splenectomy for metastases.</p> <p>Case presentation</p> <p>We present a case of laryngeal adenoid cystic carcinoma in a 26-year-old Caucasian man treated with total laryngectomy and ionizing radiation. He initially developed asynchronous pulmonary metastases, which were resected. Our patient subsequently presented with a symptomatic splenic lesion consistent with metastatic disease, for which he underwent laparoscopic splenectomy.</p> <p>Conclusions</p> <p>Splenectomy might be indicated for isolated metastases. A splenectomy effectively addresses symptoms and serves as a cytoreduction modality.</p

Individual and Situational Factors Related to Young Women’s Likelihood of Confronting Sexism in Their Everyday Lives

Factors related to young women’s reported likelihood of confronting sexism were investigated. Participants were 338 U.S. female undergraduates (M = 19 years) attending a California university. They were asked to complete questionnaire measures and to write a personal narrative about an experience with sexism. Approximately half (46%) the women reported confronting the perpetrator. Individual factors (prior experience with sexism, feminist identification, collective action) and situational factors (familiarity and status of perpetrator, type of sexism) were tested as predictors in a logistic regression. Women were less likely to report confronting sexism if (1) they did not identify as feminists, (2) the perpetrator was unfamiliar or high-status/familiar (vs. familiar/equal-status), or (3) the type of sexism involved unwanted sexual attention (vs. sexist comments)

Dietary Protein Intake and Incidence of Type 2 Diabetes in Europe: The EPIC-INTERACT Case-Cohort Study

OBJECTIVEThe long-term association between dietary protein and type 2 diabetes incidence is uncertain. We aimed to investigate the association between total, animal, and plant protein intake and the incidence of type 2 diabetes.RESEARCH DESIGN AND METHODSThe prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 individuals from eight European countries, with an average follow-up time of 12.0 years. Pooled country-specific hazard ratios (HRs) and 95% CI of prentice-weighted Cox regression analyses were used to estimate type 2 diabetes incidence according to protein intake.RESULTSAfter adjustment for important diabetes risk factors and dietary factors, the incidence of type 2 diabetes was higher in those with high intake of total protein (per 10 g: HR 1.06 [95% CI 1.02-1.09], Ptrend 30 kg/m(2) (per 10 g animal protein: 1.19 [1.09-1.32]), and nonsignificant in men. Plant protein intake was not associated with type 2 diabetes (per 10 g: 1.04 [0.93-1.16], Ptrend = 0.098).CONCLUSIONSHigh total and animal protein intake was associated with a modest elevated risk of type 2 diabetes in a large cohort of European adults. In view of the rapidly increasing prevalence of type 2 diabetes, limiting iso-energetic diets high in dietary proteins, particularly from animal sources, should be considered