Miracle-dz/UniFAR-FTUs huggingface dataset:
The evolution of evolvability in microRNA target sites in vertebrates

The lack of long-term evolutionary conservation of microRNA (miRNA) target sites appears to contradict many analyses of their functions. Several hypotheses have been offered, but an attractive one—that the conservation may be a function of taxonomic hierarchy (vertebrates, mammals, primates, etc.)—has rarely been discussed. For such an analysis, we cannot use evolutionary conservation as a criterion of target identification, and hence, have used high confidence target sites in the cross-linking immunoprecipitation (CLIP) data. Assuming that a proportion, p, of target sites in the CLIP data are conserved, we define the evolvability of miRNA targets as 1-p. Genomic data from vertebrate species show that the evolvability between human and fish is very high, at more than 90%. The evolvability decreases to 50% between birds and mammals, 20% among mammalian orders, and only 6% between human and chimpanzee. Within each taxonomic hierarchy, there is a set of targets that are conserved only at that level of evolution. Extrapolating the evolutionary trend, we find the evolvability in any single species to be close to 0%. Thus, all miRNA target sites identified by the CLIP method are evolutionarily conserved in one species, but the conservation is lost step by step in larger taxonomic groups. The changing evolvability of miRNA targets suggests that miRNA-target interactions may play a role in the evolution of organismal diversity.
Interrater reliability, concurrent validity, responsiveness, and predictive validity of the Melville-Nelson Self-Care Assessment.

OBJECTIVE This study examines psychometric characteristics of the Melville-Nelson Self-Care Assessment (SCA), which is designed for occupational therapists working in skilled nursing facilities (SNFs) and subacute rehabilitation. Like the federally mandated Minimum Data Set, the SCA assesses seven self-care occupations in two ways: self-performance and support needed. METHOD Participants were SNF patients receiving subacute rehabilitation. Primary and secondary diagnoses varied widely; mean age was 76.5 years (SD = 9.8). Using the SCA, the Functional Independence Measure (FIM), and the Klein-Bell Activities of Daily Living Scale, four teams of raters independently and simultaneously assessed 54 women and 14 men at admission and discharge; 40 participants were available for reassessment in their homes after discharge. RESULTS Total self-performance scores on the SCA showed (a) interrater reliability (mean ICC = .94); (b) concurrent validity with relevant areas of the FIM (rho = -.85) and the Klein-Bell (rho = -.86); (c) responsiveness in detecting change from admission to discharge, t(67) = 6.3, p < . 001, with a large effect size of 1.10; and (d) moderate predictive validity of caregiving time in the home (rho = -.44) and overall function in the home as measured by the total FIM (rho = -.55) and total Klein-Bell (rho = -.54) scores. The self-performance and support measures for the seven self-care areas all had acceptable interrater reliability and concurrent validity. Eating, personal hygiene, and bathing showed little or no responsiveness to change from admission to discharge, whereas positive change was substantial in bed mobility, transfers, dressing, and toileting. CONCLUSION This instrument is recommended for use as part of a comprehensive occupational therapy model of practice in SNFs and subacute rehabilitation.
Control of fatty acid desaturation: a mechanism conserved from bacteria to humans

Unsaturated fatty acids (UFAs) have profound effects on the fluidity and function of biological membranes. Microorganisms, plants and animals regulate the synthesis of UFAs during changing environmental conditions as well as in response to nutrients. UFAs homeostasis in many organisms is achieved by feedback regulation of fatty acid desaturase gene transcription through signalling pathways that are governed by sensors embedded in cellular membranes. Here, we review recently discovered components of the regulatory machinery governing the transcription of fatty acid desaturases in bacteria, yeasts and animals that indicate an ancient role of transmembrane signalling mechanisms and integrate membrane composition with lipid biosynthesis.
Prevalence of methicillin-resistant and methicillin-sensitive Staphylococcus aureus nasal colonization among patients at the time of admission to the hospital

BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) is an important agent of hospital-acquired infection. The mode of entry of MRSA in the hospital might be on admission of patients with MRSA infection or nasal colonization. The present study was undertaken to determine the prevalence of MRSA nasal colonization among patients on admission to hospital. METHODS Six hundred patients were screened for nasal colonization of MRSA on admission to hospital. Nasal swabs were cultured on salt mannitol agar and blood agar. Age, sex, previous admission to hospital and antibiotic therapy were recorded. RESULTS S. aureus was isolated from the nasal swabs of 122 patients (20.2%) on admission to hospital. MRSA was isolated from 7 patients (1.1%) and methicillin-sensitive S. aureus (MSSA) from 115 patients (19.1%). Nasal colonization of S. aureus was higher in younger and elderly patients and significantly higher colonization was observed among females. The MRSA strains isolated from nasal swabs had a different antibiotic susceptibility pattern than those isolated from patients having hospital-acquired MRSA infection. Previous admissions to hospital, underlying disease antibiotic therapy were not risk factors for MRSA nasal colonization. CONCLUSION MRSA nasal colonization of patients on admission to hospital is low in this region. The screening of every new admission would not be cost effective, but patients transferred form other institutions should be screened for MRSA. Standard infection control precautions should be strictly implemented to prevent the spread and control of MRSA infections.
Detecting Cross-Lingual Plagiarism Using Simulated Word Embeddings

Cross-lingual plagiarism (CLP) occurs when texts written in one language are translated into a different language and used without acknowledgement. One of the most common methods used for detecting CLP requires online machine translators (such as Google or Microsoft translate) which are not always available, and given that plagiarism detection typically involves large document comparison, the amount of translations would overwhelm an online machine translator, especially when detecting plagiarism over the web. In addition, when translated texts are replaced with their synonyms, using online machine translators to detect CLP would result in poor performance. This paper addresses the problem of cross-lingual plagiarism detection (CLPD) by proposing a model that uses simulated word embeddings to reproduce the predictions of an online machine translator (Google translate) when detecting CLP without relying on online translators. The simulated embeddings comprise of translated words in different languages mapped in a common space, and replicated to increase the prediction probability of retrieving the translations of a word (and their synonyms) from the model. Unlike most existing models, the proposed model does not require parallel corpora, and accommodates multiple languages (multi-lingual). We demonstrated the effectiveness of the proposed model in detecting CLP in standard datasets that contain CLP cases, and evaluated its performance against a state-of-the-art baseline that relies on online machine translator (T+MA model). Evaluation results revealed that the proposed model is not only effective in detecting CLP, it outperformed the baseline. The results indicate that CLP could be detected with state-of-the-art performances by leveraging the prediction accuracy of an internet translator with word embeddings without relying on internet translators.
Obsessive compulsive symptom dimensions and neuroticism: An examination of shared genetic and environmental risk

Individuals with obsessive compulsive disorder can display diverse and heterogeneous patterns of symptoms. Little is known about the relationship between obsessive‐compulsive symptom (OCS) dimensions and normal personality traits, particularly those that increase risk for other internalizing disorders. In this study of 1,382 individuals from female–female twin pairs, we examined the relationship between self‐report OCS dimensions derived from the Padua Inventory and Eysenck's personality traits neuroticism and extraversion. We conducted factor analysis to determine their phenotypic structure followed by twin analyses to determine their genetic and environmental sources of covariation. A three‐factor solution, with dimensions corresponding to checking, aggressive obsessions, and contamination, was the best fit for the Padua OCS items. These dimensions were significantly and somewhat variably associated with neuroticism but negligibly associated with extraversion. The genetic correlations between neuroticism and these three OCS dimensions were moderate to high (0.66 with checking, 0.89 with aggressive obsessions, and 0.40 with contamination). However, the estimated genetic correlation between neuroticism and a unified latent OCS construct was smaller (0.32). Overall this study suggests that genetic, and to a smaller extent environmental, factors underlying neuroticism may act differentially as risk factors for OCS dimensions. © 2014 Wiley Periodicals, Inc.
Acetylation of Histones and Transcription-Related Factors

SUMMARY The state of chromatin (the packaging of DNA in eukaryotes) has long been recognized to have major effects on levels of gene expression, and numerous chromatin-altering strategies—including ATP-dependent remodeling and histone modification—are employed in the cell to bring about transcriptional regulation. Of these, histone acetylation is one of the best characterized, as recent years have seen the identification and further study of many histone acetyltransferase (HAT) proteins and their associated complexes. Interestingly, most of these proteins were previously shown to have coactivator or other transcription-related functions. Confirmed and putative HAT proteins have been identified from various organisms from yeast to humans, and they include Gcn5-related N-acetyltransferase (GNAT) superfamily members Gcn5, PCAF, Elp3, Hpa2, and Hat1: MYST proteins Sas2, Sas3, Esa1, MOF, Tip60, MOZ, MORF, and HBO1; global coactivators p300 and CREB-binding protein; nuclear receptor coactivators SRC-1, ACTR, and TIF2; TATA-binding protein-associated factor TAFII250 and its homologs; and subunits of RNA polymerase III general factor TFIIIC. The acetylation and transcriptional functions of these HATs and the native complexes containing them (such as yeast SAGA, NuA4, and possibly analogous human complexes) are discussed. In addition, some of these HATs are also known to modify certain nonhistone transcription-related proteins, including high-mobility-group chromatin proteins, activators such as p53, coactivators, and general factors. Thus, we also detail these known factor acetyltransferase (FAT) substrates and the demonstrated or potential roles of their acetylation in transcriptional processes.
A Rickettsiales symbiont of amoebae with ancient features.

The Rickettsiae comprise intracellular bacterial symbionts and pathogens infecting diverse eukaryotes. Here, we provide a detailed characterization of 'Candidatus Jidaibacter acanthamoeba', a rickettsial symbiont of Acanthamoeba. The bacterium establishes the infection in its amoeba host within 2 h where it replicates within vacuoles. Higher bacterial loads and accelerated spread of infection at elevated temperatures were observed. The infection had a negative impact on host growth rate, although no increased levels of host cell lysis were seen. Phylogenomic analysis identified this bacterium as member of the Midichloriaceae. Its 2.4 Mb genome represents the largest among Rickettsiales and is characterized by a moderate degree of pseudogenization and a high coding density. We found an unusually large number of genes encoding proteins with eukaryotic-like domains such as ankyrins, leucine-rich repeats and tetratricopeptide repeats, which likely function in host interaction. There are a total of three divergent, independently acquired type IV secretion systems, and 35 flagellar genes representing the most complete set found in an obligate intracellular Alphaproteobacterium. The deeply branching phylogenetic position of 'Candidatus Jidaibacter acanthamoeba' together with its ancient features place it closely to the rickettsial ancestor and helps to better understand the transition from a free-living to an intracellular lifestyle.
Catenin Family Genes Are Not Commonly Mutated in Hereditary Diffuse Gastric Cancer

Background: Approximately one third of the hereditary diffuse gastric cancer (HDGC) families carry germline mutations in the E-cadherin gene (CDH1). Risk prediction in members of families with this rare but deadly cancer could be improved by the identification of additional HDGC genes in non-CDH1 families. Methods: Affected individuals from 22 CDH1 mutation-negative families were screened for germline mutations in four catenin genes: CTNNA1, CTNNB1, JUP, and CTNND1. Catenins interact closely with E-cadherin molecules in cells, and are therefore logical candidate genes for mutation screening in HDGC families. Results: No nonsynonymous variants were seen in CTNNA1, CTNNB1, or CTNND1; only JUP contained nonsynonymous variants, of which only two rare variants were predicted to be deleterious. Conclusion: Catenin genes are not commonly mutated in non-CDH1 HDGC families. Impact: Germline mutations in CTNNA1, CTNNB1, JUP, or CTNND1 are unlikely to play a major role in HDGC. Cancer Epidemiol Biomarkers Prev; 21(12); 2272–4. ©2012 AACR.
Alcohol, nightlife and violence: the relative contributions of drinking before and during nights out to negative health and criminal justice outcomes.

AIMS To explore differences in alcohol consumption and negative nightlife experiences between young people who drink prior to attending city nightlife venues and those who do not drink until reaching bars and nightclubs. DESIGN, SETTING AND PARTICIPANTS A cross-sectional survey of 380 young people (aged 18-35 years) in bars and nightclubs in a large city centre in the North-west of England. MEASUREMENTS An anonymous questionnaire explored participants' basic demographics; frequency of utilizing nightlife; quantities of alcohol consumed prior to and during a typical night out in the city; and negative experiences in the city's nightlife in the previous year [fighting, being verbally abused, being sexually molested (e.g. groped) and being too drunk to walk]. FINDINGS Participants who reported drinking prior to attending nightlife (e.g. at their own or a friend's home) reported significantly higher total alcohol consumption over a night out than those not drinking until reaching bars and nightclubs. Over a quarter (26.5%) of female and 15.4% of male alcohol consumption over a night out occurred prior to attending nightlife. Individuals who drink before going out were over four times more likely to report drinking >20 units on a usual night out and 2.5 times more likely to have been involved in a fight in the city's nightlife during the previous 12 months. CONCLUSIONS Measures to tackle drunkenness and alcohol-related violence in nightlife should expand beyond those targeted solely at nightlife environments. Continued disparities in pricing and policing of alcohol between on- and off-licensed premises may increase at-home drinking prior to nights out and alcohol-related problems in residential areas.
Microarray analysis of murine retinal light damage reveals changes in iron regulatory, complement, and antioxidant genes in the neurosensory retina and isolated RPE.

PURPOSE The purpose of this study was to investigate light damage-induced transcript changes within neurosensory retina (NSR) and isolated retinal pigment epithelium (RPE). Similar studies have been conducted previously, but were usually limited to the NSR and only a portion of the transcriptome. Herein most of the transcriptome, not just in the NSR but also in isolated RPE, was queried. METHODS Mice were exposed to 10,000 lux cool white fluorescent light for 18 hours and euthanized 4 hours after photic injury. NSR and isolated RPE were collected, and RNA was isolated. DNA microarray hybridization was conducted as described in the Affymetrix GeneChip Expression Analysis Technical Manual. Microarray analysis was performed using probe intensity data derived from the Mouse Gene 1.0 ST Array. For the genes of interest, confirmation of gene expression was done using quantitative real-time PCR. Immunofluorescence assessed protein levels and localization. RESULTS Numerous iron regulatory genes were significantly changed in the light-exposed NSR and RPE. Several of these gene expression changes favored an iron-overloaded state. For example, the transferrin receptor was upregulated in both light-exposed NSR and RPE. Consistent with this, there was stronger transferrin receptor immunoreactivity in the light-exposed retinas. Significant changes in gene expression following light damage were also observed in oxidative stress and complement system genes. CONCLUSIONS The concept of a photooxidative stress-induced vicious cycle of increased iron uptake leading to further oxidative stress was introduced.
A comparison of Bayesian localization methods in the presence of outliers

Localization of a user in a wireless network is challenging in the presence of malfunctioning or malicious reference nodes, since if they are not accounted for, large localization errors can ensue. We evaluate three Bayesian methods to statistically identify outliers during localization: an exact method, an expectation maximization (EM) method proposed earlier, and a new method based on Variational Bayesian EM (VBEM). Simulation results indicate similar performance for the latter two schemes, with the VBEM algorithm able to provide a statistical description of the user location, rather than an estimate as in the simpler EM case. In contrast to previous studies, we find that there is a significant gap between the approximate methods and the exact method, the cause of which is discussed.
Stabilization of a nucleotide-binding domain of the cystic fibrosis transmembrane conductance regulator yields insight into disease-causing mutations

Characterization of the second nucleotide-binding domain (NBD2) of the cystic fibrosis transmembrane conductance regulator (CFTR) has lagged behind research into the NBD1 domain, in part because NBD1 contains the F508del mutation, which is the dominant cause of cystic fibrosis. Research on NBD2 has also been hampered by the overall instability of the domain and the difficulty of producing reagents. Nonetheless, multiple disease-causing mutations reside in NBD2, and the domain is critical for CFTR function, because channel gating involves NBD1/NBD2 dimerization, and NBD2 contains the catalytically active ATPase site in CFTR. Recognizing the paucity of structural and biophysical data on NBD2, here we have defined a bioinformatics-based method for manually identifying stabilizing substitutions in NBD2, and we used an iterative process of screening single substitutions against thermal melting points to both produce minimally mutated stable constructs and individually characterize mutations. We present a range of stable constructs with minimal mutations to help inform further research on NBD2. We have used this stabilized background to study the effects of NBD2 mutations identified in cystic fibrosis (CF) patients, demonstrating that mutants such as N1303K and G1349D are characterized by lower stability, as shown previously for some NBD1 mutations, suggesting a potential role for NBD2 instability in the pathology of CF.
The Integrated Use of Alternative Methods in Toxicological Risk Evaluation

The ECVAM Task Force on Integrated Testing Strategies was established in December 1996, with the remit of assessing the current status of integrated toxicity testing, and of making proposals regarding the design and implementation of integrated testing strategies. The first step in an integrated testing strategy is usually to determine the chemical functionality of a substance, on the basis of its structure and physicochemical properties. The biokinetic and dynamic behaviours of the chemical in various in vitro systems are then assessed. The various elements are then integrated, in either a parallel or a stepwise fashion, to make predictions of the local or systemic toxicity of the chemical of interest. In this report, a generic scheme for local/systemic toxicity, and a specific scheme for target organ toxicity, are proposed. The scope and limitations of the approaches are discussed. The task force hopes that its proposals will stimulate a discussion on the feasibility of this type of approach and it welcomes any feedback. It is planned that the discussion points will be elaborated in a second task force report.
The prognostic significance of multiple morphologic features and biologic markers in ductal carcinoma in situ of the breast

A number of conventional histopathologic features have been associated with recurrence of ductal carcinoma in situ (DCIS) after surgery alone and are included in the Van Nuys Pathologic Classification and Prognostic Index. To the authors' knowledge, very little is known regarding the prognostic significance of the many biologic markers that have been studied in DCIS in the past decade.
Statistical methods for characterizing diversity of microbial communities by analysis of terminal restriction fragment length polymorphisms of 16S rRNA genes.

The analysis of terminal restriction fragment length polymorphisms (T-RFLP) of 16S rRNA genes has proven to be a facile means to compare microbial communities and presumptively identify abundant members. The method provides data that can be used to compare different communities based on similarity or distance measures. Once communities have been clustered into groups, clone libraries can be prepared from sample(s) that are representative of each group in order to determine the phylogeny of the numerically abundant populations in a community. In this paper methods are introduced for the statistical analysis of T-RFLP data that include objective methods for (i) determining a baseline so that 'true' peaks in electropherograms can be identified; (ii) a means to compare electropherograms and bin fragments of similar size; (iii) clustering algorithms that can be used to identify communities that are similar to one another; and (iv) a means to select samples that are representative of a cluster that can be used to construct 16S rRNA gene clone libraries. The methods for data analysis were tested using simulated data with assumptions and parameters that corresponded to actual data. The simulation results demonstrated the usefulness of these methods in their ability to recover the true microbial community structure generated under the assumptions made. Software for implementing these methods is available at http://www.ibest. uidaho.edu/tools/trflp_stats/index.php.