bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternating evolutionary pressure in a genetic algorithm facilitates protein model selection
Authors: Offman Marc N , Tournier Alexander L , Bates Paul A 
Published: August 2008

AbstractBackgroundAutomatic protein modelling pipelines are becoming ever more accurate; this has come hand in hand with an increasingly complicated interplay between all components involved. Nevertheless, there are still potential improvements to be made in template selection, refinement and protein model selection.ResultsIn the context of an automatic modelling pipeline, we analysed each step separately, revealing several non-intuitive trends and explored a new strategy for protein conformation sampling using Genetic Algorithms (GA). We apply the concept of alternating evolutionary pressure (AEP), i.e. intermediate rounds within the GA runs where unrestrained, linear growth of the model populations is allowed.ConclusionThis approach improves the overall performance of the GA by allowing models to overcome local energy barriers. AEP enabled the selection of the best models in 40% of all targets; compared to 25% for a normal GA.
An approach to analyse the specific impact of rapamycin on mRNA-ribosome association
Authors: Genolet Raphael , Araud Tanguy , Maillard Laetitia , Jaquier-Gubler Pascale , Curran Joseph 
Published: August 2008

AbstractBackgroundRecent work, using both cell culture model systems and tumour derived cell lines, suggests that the differential recruitment into polysomes of mRNA populations may be sufficient to initiate and maintain tumour formation. Consequently, a major effort is underway to use high density microarray profiles to establish molecular fingerprints for cells exposed to defined drug regimes. The aim of these pharmacogenomic approaches is to provide new information on how drugs can impact on the translational read-out within a defined cellular background.MethodsWe describe an approach that permits the analysis of de-novo mRNA-ribosome association in-vivo during short drug exposures. It combines hypertonic shock, polysome fractionation and high-throughput analysis to provide a molecular phenotype of translationally responsive transcripts. Compared to previous translational profiling studies, the procedure offers increased specificity due to the elimination of the drugs secondary effects (e.g. on the transcriptional read-out). For this pilot "proof-of-principle" assay we selected the drug rapamycin because of its extensively studied impact on translation initiation.ResultsHigh throughput analysis on both the light and heavy polysomal fractions has identified mRNAs whose re-recruitment onto free ribosomes responded to short exposure to the drug rapamycin. The results of the microarray have been confirmed using real-time RT-PCR. The selective down-regulation of TOP transcripts is also consistent with previous translational profiling studies using this drug.ConclusionThe technical advance outlined in this manuscript offers the possibility of new insights into mRNA features that impact on translation initiation and provides a molecular fingerprint for transcript-ribosome association in any cell type and in the presence of a range of drugs of interest. Such molecular phenotypes defined pre-clinically may ultimately impact on the evaluation of a particular drug in a living cell.
The Alternative Splicing Mutation Database: a hub for investigations of alternative splicing using mutational evidence
Authors: Bechtel Jason M , Rajesh Preeti , Ilikchyan Irina , Deng Ying , Mishra Pankaj K , Wang Qi , Wu Xiaochun , Afonin Kirill A , Grose William E , Wang Ye , Khuder Sadik , Fedorov Alexei 
Published: August 2008

Abstract

Background
Some mutations in the internal regions of exons occur within splicing enhancers and silencers, influencing the pattern of alternative splicing in the corresponding genes. To understand how these sequence changes affect splicing, we created a database of these mutations.

Findings
The Alternative Splicing Mutation Database (ASMD) serves as a repository for all exonic mutations not associated with splicing junctions that measurably change the pattern of alternative splicing. In this initial published release (version 1.2), only human sequences are present, but the ASMD will grow to include other organisms, (see Availability and requirements section for the ASMD web address).
This relational database allows users to investigate connections between mutations and features of the surrounding sequences, including flanking sequences, RNA secondary structures and strengths of splice junctions. Splicing effects of the mutations are quantified by the relative presence of alternative mRNA isoforms with and without a given mutation. This measure is further categorized by the accuracy of the experimental methods employed. The database currently contains 170 mutations in 66 exons, yet these numbers increase regularly.
We developed an algorithm to derive a table of oligonucleotide Splicing Potential (SP) values from the ASMD dataset. We present the SP concept and tools in detail in our corresponding article.

Conclusion
The current data set demonstrates that mutations affecting splicing are located throughout exons and might be enriched within local RNA secondary structures. Exons from the ASMD have below average splicing junction strength scores, but the difference is small and is judged not to be significant.
Intervertebral disc cells as competent phagocytes in vitro: implications for cell death in disc degeneration
Authors: Jones Philip , Gardner Lucy , Menage Janis , Williams Gwyn T , Roberts Sally 
Published: August 2008

Abstract
Introduction
Apoptosis has been reported to occur in the intervertebral disc. Elsewhere in the body, apoptotic cells are cleared from the system via phagocytosis by committed phagocytes such as macrophages, reducing the chance of subsequent inflammation. These cells, however, are not normally present in the disc. We investigated whether disc cells themselves can be induced to become phagocytic and so have the ability to ingest and remove apoptotic disc cells, minimising the damage to their environment.

Method
Bovine nucleus pulposus cells from caudal intervertebral discs were grown in culture and exposed to both latex particles (which are ingested by committed phagocytes) and apoptotic cells. Their response was monitored via microscopy, including both fluorescent and video microscopy, and compared with that seen by cell lines of monocytes/macrophages (THP-1 and J774 cells), considered to be committed phagocytes, in addition to a nonmacrophage cell line (L929 fibroblasts). Immunostaining for the monocyte/macrophage marker, CD68, was also carried out.

Results
Disc cells were able to ingest latex beads at least as efficiently, if not more so, than phagocytic THP-1 and J774 cells. Disc cells ingested a greater number of beads per cell than the committed phagocytes in a similar time scale. In addition, disc cells were able to ingest apoptotic cells when cocultured in monolayer with a UV-treated population of HeLa cells. Apoptotic disc cells, in turn, were able to stimulate phagocytosis by the committed macrophages. CD68 immunostaining was strong for THP-1 cells but negligible for disc cells, even those that had ingested beads.

Conclusion
In this study, we have shown that intervertebral disc cells are capable of behaving as competent phagocytes (that is, ingesting latex beads) and apoptotic cells. In terms of number of particles, they ingest more than the monocyte/macrophage cells, possibly due to their greater size. The fact that disc cells clearly can undergo phagocytosis has implications for the intervertebral disc in vivo. Here, where cell death is reported to be common yet there is normally no easy access to a macrophage population, the endogenous disc cells may be encouraged to undergo phagocytosis (for example, of neighbouring cells within cell clusters).
On the Relation between Syphilis and General Paralysis. The difficulty of distinguishing General Paralysis from certain Syphilitic changes of the Brain
Authors: Foville Achille 
Published: August 2008

In the article on General Paralysis in the “Nouveau Dictionnaire de Médicine et de Chirurgie Pratiques “(vol. xvi, p. 89., 1878), I thought I had settled the differential diagnosis of this affection when I said:—“Multiple tumours of the brain, especially those of a syphilitic character, may be accompanied by motor and mental symptoms identical with those of general paralysis. More than once we have observed cases of this kind, and we believe that some do occur in which the differential diagnosis is impossible, except, perhaps, by means of the history. The autopsy alone discloses the error which has existed during the whole duration of the affection.”
The Increase of General Paralysis in England and Wales: Its Carnation and Significance
Authors: Stewart R. S. 
Published: August 2008

No Disproportionate Increase of Insanity.The increase of the total living insane in England and Wales during the intercensal period 1881–91 was 15·24 per cent., while the corresponding increase of population was only 11·7.SummaryI.—There is no evidence of increasing liability to insanity on the part of the English race.II.—There is evidence of an increasing tendency to general paralysis.III.—This is most pronounced among males, in whom the increase is nineteen times what it is in women.IV.—Among males the increase in private patients is more than twice that in pauper patients; in the former it is steadily progressive, in the latter it is a diminishing increase. Among females the increase in paupers is slight. In private female patients there is a steadily maintained diminution.V.—The age at which the increase of general paralysis attains its maximum is the decade 35 to 44; in other forms of insanity the increase occurs at ages over 45 and is greatest at ages over 55.VI.—The increase is greatest among married men, being five times that which occurs in unmarried men, and sixty times that in married women.VII.—The greatest increase is found in large urban centres, most so in sea-ports and in particular coal-exporting towns; the next greatest in coal-mining counties and manufacturing towns, while in agricultural counties there is a decrease. A close parallel, as regards geographical distribution, is to be traced between the increase of general paralysis and the occurrence of the offence of drunkenness.VIII.—The etiological factors most responsible for the increase are alcoholic intemperance, sexual excess, and venereal disease. The causes connected with the reproductive life of women are diminishing as factors in the production of general paralysis. The increase finds its origin in causes related to the self-regarding, not the altruistic, instinct.IX.—The increasing prevalence of general paralysis indicates a change in the type of insanity, a reversion to a lower form of brain disease, increasing moral and physical decadence, lessening power of resistance and diminishing vitality, and increasing tendency to premature and rapid racial decay.X.—The affection being absolutely fatal, and the causes being to a very large extent controllable, the only direction in which the remedy is to be sought is in that of prevention.
Atypical and Unusual Brain-Forms, especially in Relation to Mental Status: a Study on Brain-Surface Morphology
Authors: Mickle W. Julius 
Published: August 2008

Chapter IX.A Standard of Aberrant Conformations of Gyres and Furrows framed as a Test, and constituting a stigma, of Hereditary Mental Degeneracy. A Standard of Deviation and Defect.And, in Chapter XI.,The results of the Application of the Standard of Deviation and Defect in Comparisons between the Gyres and Furrows in several forms of Mental Disease, and those in the Standard Group of Cases.Introductory Remarks.∗In the deviations from usual form or type already described—both the new and those adopted from other observers—the material is provided for tests or criteria of various forms of defective or aberrant brain development; and the standard about to be described has its material derived from those sources, and is directly drawn from certain brains.∗ With little change, these preliminary remarks are taken from part of my Presidential Address, in July, 1895, in the Section of Psychology at the Annual Meeting of the British Medical Association in London. (British Medical Journal, Sept. 28, 1895.)
The Evolution of Asylum Architecture, and the Principles which ought to control Modern Construction
Authors: Steen R. H. 
Published: August 2008

“The recovery of the curable, the improvement of the incurable, the comfort and happiness of all the patients, should steadily be kept in view by the architect from the moment in which he commences his plan.”—Conolly, Construction and Government of Lunatic Asylums, p. 1.IN the present day the great increase in the number of certified lunatics has raised the question of asylum architecture to one of primary importance. New asylums are being built and planned in all parts of the country, and the managing authorities are keen to provide the best possible accommodation for the suffering ones under their care.
Further Observations on Experimental Toxi-Infection of the Central Nervous System
Authors: Orr David , Rows  
Published: August 2008

This communication is a continuation of our experimental work on the action of bacterial poisons upon the nervous system.In 1914 (2), after several series of experiments, we drew attention to the differences between lymphogenous and haematogenous infection. The first was induced by infecting the ascending lymph stream of nerves ; the second by placing celloidin capsules containing a culture of bacteria in the abdominal cavity.
The Rôle of Auto-intoxication or Auto-infection in Mental Disorders
Authors: Watson Chalmers 
Published: August 2008

I greatly appreciate the honour which the Society has done me in asking me to read a paper by way of introducing a general discussion on the treatment of mental disorders. My remarks will deal with the relationship of physical disorder to mental symptoms. The main point to which I will more particularly draw your attention is to the need for a closer study of the extent to which mental symptoms are the result of some auto-intoxication or infection from one or other of the free mucous surfaces of the body, the gastro-intestinal tract being, in virtue of its size and function, the most important channel. If the relationship is a close one our outlook on mental disorders necessitates greater attention being directed to the investigation and treatment of our patients with the aid of modern methods, than has hitherto been done. The literature of the subject contains many references of a general kind to what is called the toxic factor in the ætiology of insanity, but the systematic investigation of mental disorders from this point of view has not yet been carried out with the reasonable degree of completeness which modern medicine demands. In this connection it is right to refer to the valuable and suggestive work carried out by Lewis Bruce many years ago, the probable significance and value of which has, I think, been largely lost sight of. There is little new in the conception of the aetiology and treatment of mental disorders, which I am going to present for your consideration. It is, however, largely new in the sense that it has not yet been adequately tested. Prof. Robertson has lately drawn my attention to the interesting fact that the leading alienists in France more than 100 years ago entertained the view that the primary cause of mental disorders was to be found in visceral changes. Pinal in his classical text-book on mental disorders in 1809 wrote as follows:“It seems that the primitive seat of insanity generally is in the region of the stomach and intestines, and it is from that centre that the disorder of intelligence propagates itself as by a species of irradiation.”
Therapeutic Malarialization of General Paralytics in the Tropics
Authors: Smith A. W. H. 
Published: August 2008

During the last few years, in which pyretotherapy has figured so largely in the treatment of general paralysis of the insane, the question must have arisen in many minds whether general paralysis occurs in communities where malaria is indigenous, and if so, whether satisfactory results would be obtained from further malarialization on artificial lines.The Central Mental Hospital of the Federated Malay States has over 2,500 patients in residence, and draws its cases from the whole of the Malay Peninsula. Many races are represented besides the native Malay and associated races—Chinese, Japanese, Siamese, Indian, etc.—and malaria is indigenous over the whole territory.
Snapback Primer Genotyping with Saturating DNA Dye and Melting Analysis
Authors: Zhou Luming , Errigo Roscoe J , Lu Hongzhe , Poritz Mark A , Seipp Michael T , Wittwer Carl T 
Published: August 2008

Abstract
Background: DNA hairpins have been used in molecular analysis of PCR products as self-probing amplicons. Either physical separation or fluorescent oligonucleotides with covalent modifications were previously necessary.
Methods: We performed asymmetric PCR for 40–45 cycles in the presence of the saturating DNA dye, LCGreen Plus, with 1 primer including a 5′ tail complementary to its extension product, but without any special covalent modifications. Samples were amplified either on a carousel LightCycler for speed or on a 96/384 block cycler for throughput. In addition to full-length amplicon duplexes, single-stranded hairpins were formed by the primer tail “snapping back” and hybridizing to its extension product. High-resolution melting was performed on a HR-1 (for capillaries) or a LightScanner (for plates).
Results: PCR products amplified with a snapback primer showed both hairpin melting at lower temperature and full-length amplicon melting at higher temperature. The hairpin melting temperature was linearly related to the stem length (6–28 bp) and inversely related to the log of the loop size (17–135 bases). We easily genotyped heterozygous and homozygous variants within the stem, and 100 blinded clinical samples previously typed for F5 1691G&gt;A (Leiden) were completely concordant by snapback genotyping. We distinguished 7 genotypes in 2 regions of CFTR exon 10 with symmetric PCR using 2 snapback primers followed by product dilution to favor intramolecular hybridization.
Conclusions: Snapback primer genotyping with saturating dyes provides the specificity of a probe with only 2 primers that are free of special covalent labels in a closed-tube system.
Influence of Having Breakfast on Cognitive Performance and Mood in 13- to 20-Year-Old High School Students: Results of a Crossover Trial
Authors: Widenhorn-Müller Katharina , Hille Katrin , Klenk Jochen , Weiland Ulrike 
Published: August 2008

OBJECTIVE. The goal was to determine whether breakfast had effects on the cognitive performance and mood of high school students.
METHODS. A crossover trial was performed in boarding schools, involving 104 students between 13 and 20 years of age. The participants were randomly assigned to 2 equal-size groups on the morning of the first testing day. One half of the total sample received a standardized breakfast, whereas the other half received no breakfast. Seven days later, the treatment order was reversed. Measurements of cognitive function included standardized tests of attention and concentration, as well as tests of verbal and spatial memory. In addition, mood was rated with a self-administered questionnaire covering the dimensions of positive and negative affect, information uptake, arousal, and alertness. Statistical analysis consisted of repeated-measures analysis of variance.
RESULTS. Breakfast had no effect on sustained attention among high school students. Visuospatial memory was improved in male students. Self-reported alertness improved significantly in the entire study population. Male students reported feeling more positive after consuming breakfast, compared with the fasting condition.
CONCLUSIONS. This crossover trial demonstrated positive short-term effects of breakfast on cognitive functioning and self-reported alertness in high school students.
Exposure of US Adolescents to Extremely Violent Movies
Authors: Worth Keilah A. , Gibson Chambers Jennifer , Nassau Daniel H. , Rakhra Balvinder K. , Sargent James D. 
Published: August 2008

OBJECTIVE. Despite concerns about exposure to violent media, there are few data on youth exposure to violent movies. In this study we examined such exposure among young US adolescents.
METHODS. We used a random-digit-dial survey of 6522 US adolescents aged 10 to 14 years fielded in 2003. Using previously validated methods, we determined the percentage and number of US adolescents who had seen each of 534 recently released movies. We report results for the 40 that were rated R for violence by the Motion Picture Association of America, UK 18 by the British Board of Film Classification and coded for extreme violence by trained content coders.
RESULTS. The 40 violent movies were seen by a median of 12.5% of an estimated 22 million US adolescents aged 10 to 14 years. The most popular violent movie, Scary Movie, was seen by &gt;10 million (48.1%) children, 1 million of whom were 10 years of age. Watching extremely violent movies was associated with being male, older, nonwhite, having less-educated parents, and doing poorly in school. Black male adolescents were at particularly high risk for seeing these movies; for example Blade, Training Day, and Scary Movie were seen, respectively, by 37.4%, 27.3%, and 48.1% of the sample overall versus 82.0%, 81.0%, and 80.8% of black male adolescents. Violent movie exposure was also associated with measures of media parenting, with high-exposure adolescents being significantly more likely to have a television in their bedroom and to report that their parents allowed them to watch R-rated movies.
CONCLUSIONS. This study documents widespread exposure of young US adolescents to movies with extreme graphic violence from movies rated R for violence and raises important questions about the effectiveness of the current movie-rating system.