Novel dermaseptin, adenoregulin and caerin homologs from the Central American red-eyed leaf frog, Agalychnis callidryas, revealed by functional peptidomics of defensive skin secretion

By integrating systematic peptidome and transcriptome studies of the defensive skin secretion of the Central American red-eyed leaf frog, Agalychnis callidryas, we have identified novel members of three previously described antimicrobial peptide families, a 27-mer dermaseptin-related peptide (designated DRP-AC4), a 33-mer adenoregulin-related peptide (designated ARP-AC1) and most unusually, a 27-mer caerin-related peptide (designated CRP-AC1). While dermaseptin and adenoregulin were originally isolated from phyllomedusine leaf frogs, the caerins, until now. had only been described in Australian frogs of the genus, Litoria. Both the dermaseptin and adenoregulin were C-terminally amidated and lacked the C-terminal tripeptide of the biosynthetic precursor sequence. In contrast, the caerin-related peptide, unlike the majority of Litoria analogs. was not C-terminally amidated. The present data emphasize the need for structural characterization of mature peptides to ensure that unexpected precursor cleavages and/or post-translational modifications do not produce mature peptides that differ in structure to those predicted from cloned biosynthetic precursor cDNA. Additionally, systematic study of the secretory peptidome can produce unexpected results such as the CRP described here that may have phylogenetic implications. It is thus of the utmost importance in the functional evaluation of novel peptides that the primary structure of the mature peptide is unequivocally established - something that is often facilitated by cloning biosynthetic precursor cDNAs but obviously not reliable using such data alone. (C) 2008 Elsevier Masson SAS. All rights reserved.

Reading the Irishwoman: Studies in Cultural Encounter and Exchange, 1714-1960

In 1700 few Irishwomen were literate. Most lived in a rural environment, rarely encountered a book or a play or ventured much beyond their own domestic space. By 1960 literacy was universal, all Irishwomen attended primary school, had access to a variety of books, magazines, newspapers and other forms of popular media and the wider world was now part of their every-day life. This study seeks to examine the cultural encounters and exchanges inherent in this transformation. It analyses reading and popular and consumer culture as sites of negotiation of gender roles. This is not an exhaustive treatment of the theme but focusses on three key points of cultural encounter: the Enlightenment, emigration and modernism. The writings and intellectual discourse generated by the Enlightenment was one of the most influential forces shaping western society. It set the agenda for scientific, political and social thought for the eighteenth and nineteenth centuries. The migration of peoples to north America was another key historical marker in the development of the modern world. Emigration altered and shaped American society as well as the lives of those who remained behind. By the twentieth century, aesthetic modernism suspicious of enlightenment rationalism and determined to produce new cultural forms developed in a complex relationship with the forces of industrialisation, urbanisation and social change. This study analyses the impact of these three key forces in Western culture on changing roles and perceptions of Irish women from 1700 to 1960.

Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies

Objectives: We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD).
Background: Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers.
Methods: The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports.
Results: A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of <2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups.
Conclusions: The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study.

Implications for Powering Biomarker Discovery Studies

This study examined variations in gene expression between FFPE blocks within tumors of individual patients. Microarray data were used to measure tumor heterogeneity within and between patients and disease states. Data were used to determine the number of samples needed to power biomarker discovery studies. Bias and variation in gene expression were assessed at the intrapatient and interpatient levels and between adenocarcinoma and squamous samples. A mixed-model analysis of variance was fitted to gene expression data and model signatures to assess the statistical significance of observed variations within and between samples and disease states. Sample size analysis, adjusted for sample heterogeneity, was used to determine the number of samples required to support biomarker discovery studies. Variation in gene expression was observed between blocks taken from a single patient. However, this variation was considerably less than differences between histological characteristics. This degree of block-to-block variation still permits biomarker discovery using either macrodissected tumors or whole FFPE sections, provided that intratumor heterogeneity is taken into account. Failure to consider intratumor heterogeneity may result in underpowered biomarker studies that may result in either the generation of longer gene signatures or the inability to identify a viable biomarker. Moreover, the results of this study indicate that a single biopsy sample is suitable for applying a biomarker in nonsmall-cell lung cancer. © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology.

Experimental studies of the advanced fast ignitor scheme

Guided compression offers an attractive route to explore some of the physics issues of hot electron heating and transport in the fast ignition route to inertial confinement fusion, whilst avoiding the difficulties associated with establishing the stability of the channel formation pulse. X-ray images are presented that show that the guided foil remains hydrodynamically stable during the acceleration phase, which is confirmed by two-dimensional simulations. An integrated conical compression/fast electron heating experiment is presented that confirms that this approach deserves detailed study. (C) 2000 American Institute of Physics. [S1070-664X(00)02809-3].

Family-based association studies of lipid gene polymorphisms in coronary artery disease

Dysfunction of lipid-metabolizing proteins is implicated in the pathogenesis of coronary artery disease. Single nucleotide polymorphisms in genes that encode sterol regulatory binding protein-la, adenosine triphosphate binding cassette-A1, hepatic lipase, lipoprotein lipase, and cholesteryl ester transfer protein were assessed as potential markers of disease susceptibility in a family-based study of 1,012 patients from 386 families. Association between single nucleotide polymorphisms and coronary artery disease was tested by the combined transmission disequilibrium test/sib transmission disequilibrium test and pedigree disequilibrium test. After Bonferroni's correction, the pedigree disequilibrium test demonstrated significant excess transmission (p < 0.0083) to affected patients of the hepatic lipase -514 T allele, which suggests that this may constitute a novel disease-susceptibility locus. (c) 2005 Elsevier Inc. All rights reserved.

In Situ Single-Crystal Diffraction Studies of the Structural Transition of Metal-Organic Framework Copper 5-Sulfoisophthalate, Cu-SIP-3

The flexibility of the metal-organic framework Cu-2(OH)(C8H3O7S)(H2O)center dot 2H(2)O (Cu-SIP-3) toward reversible single-crystal to single-crystal transformations is demonstrated using in situ diffraction methods at variable temperature. At temperatures below a dehydration-induced phase transition (T < 370 K) the structure is confirmed as being hydrated. In the temperature range where the transition takes place (370 K < T < 405 K) no discrete, sharp Bragg peaks can be seen in the single-crystal X-ray diffraction pattern, indicating significant loss of long-range order. At temperatures higher than 405 K, the Bragg peaks return and the structure can be refined as dehydrated Cu-SIP-3. The loss of guest water molecules can be followed at temperatures below the phase transition giving insight into the mechanism of the dehydration. Addition of nitric oxide gas to the material above the gating opening pressure of 275 mbar also leads to loss of Bragg scattering in the diffraction pattern.

The quality of reporting of diagnostic accuracy studies published in ophthalmic journals

Aim: To evaluate the quality of reporting of all diagnostic studies published in five major ophthalmic journals in the year 2002 using the Standards for Reporting of Diagnostic Accuracy (STARD) initiative parameters. Methods: Manual searching was used to identify diagnostic studies published in 2002 in five leading ophthalmic journals, the American Journal of Ophthalmology (AJO), Archives of Ophthalmology (Archives), British Journal of Ophthalmology (BJO), Investigative Ophthalmology and Visual Science (IOVS), and Ophthalmology. The STARD checklist of 25 items and flow chart was used to evaluate the quality of each publication. Results: A total of 16 publications were included (AJO = 5, Archives = 1, BJO = 2, IOVS = 2, and Ophthalmology = 6). More than half of the studies (n = 9) were related to glaucoma diagnosis. Other specialties included retina (n = 4) cornea (n = 2), and neuro-ophthalmology (n = 1). The most common description of diagnostic accuracy was sensitivity and specificity values, published in 13 articles. The number of fully reported items in evaluated studies ranged from eight to 19. Seven studies reported more than 50% of the STARD items. Conclusions: The current standards of reporting of diagnostic accuracy tests are highly variable. The STARD initiative may be a useful tool for appraising the strengths and weaknesses of diagnostic accuracy studies.

The Quality of Reporting of Diagnostic Accuracy Studies of Optical Coherence Tomography in Glaucoma

Objective: To evaluate the quality of reporting of diagnostic accuracy studies using optical coherence tomography (OCT) in glaucoma. Design: Descriptive series of published studies. Participants: Published studies reporting a measure of the diagnostic accuracy of OCT for glaucoma. Methods: Review of English language papers reporting measures of diagnostic accuracy of OCT for glaucoma. Papers were identified from a Medline literature search performed in June 2006. Articles were appraised using the 25 items provided by the Standards for Reporting of Diagnostic Accuracy (STARD) initiative. Each item was recorded as full, partially, or not reported. Main Outcome Measures: Degree of compliance with the STARD guidelines. Results: Thirty papers were appraised. Eight papers (26.7%) fully reported more than half of the STARD items. The lowest number of fully reported items in a study was 5 and the highest was 17. Descriptions of key aspects of methodology frequently were missing. For example, details of participant sampling (e.g., consecutive or random selection) were described in only 8 (26.7%) of 30 publications. Measures of statistical uncertainty were reported in 18 (60%) of 30 publications. No single STARD item was fully reported by all the papers. Conclusions: The standard of reporting of diagnostic accuracy studies in glaucoma using OCT was suboptimal. It is hoped that adoption of the STARD guidelines will lead to an improvement in reporting of diagnostic accuracy studies, enabling clearer evidence to be produced for the usefulness of OCT for the diagnosis of glaucoma. © 2007 American Academy of Ophthalmology.

Sample size in studies on diagnostic accuracy in ophthalmology:A literature survey

Aim: To assess the sample sizes used in studies on diagnostic accuracy in ophthalmology. Design and sources: A survey literature published in 2005. Methods: The frequency of reporting calculations of sample sizes and the samples' sizes were extracted from the published literature. A manual search of five leading clinical journals in ophthalmology with the highest impact (Investigative Ophthalmology and Visual Science, Ophthalmology, Archives of Ophthalmology, American Journal of Ophthalmology and British Journal of Ophthalmology) was conducted by two independent investigators. Results: A total of 1698 articles were identified, of which 40 studies were on diagnostic accuracy. One study reported that sample size was calculated before initiating the study. Another study reported consideration of sample size without calculation. The mean (SD) sample size of all diagnostic studies was 172.6 (218.9). The median prevalence of the target condition was 50.5%. Conclusion: Only a few studies consider sample size in their methods. Inadequate sample sizes in diagnostic accuracy studies may result in misleading estimates of test accuracy. An improvement over the current standards on the design and reporting of diagnostic studies is warranted.