bluuebunny/crossref_metadata_2025 huggingface dataset:
Sources of Variation in Ancestral Sequence Reconstruction for HIV-1 Envelope Genes
Authors: Ross Howard A. , Nickle David C. , Liu Yi , Heath Laura , Jensen Mark A. , Rodrigo Allen G. , Mullins James I.
Published: November 2017

We characterized the variation in the reconstructed ancestor of 118 HIV-1 envelope gene sequences arising from the methods used for (a) estimating and (b) rooting the phylogenetic tree, and (c) reconstructing the ancestor on that tree, from (d) the sequence format, and from (e) the number of input sequences. The method of rooting the tree was responsible for most of the sequence variation both among the reconstructed ancestral sequences and between the ancestral and observed sequences. Variation in predicted 3-D structural properties of the ancestors mirrored their sequence variation. The observed sequence consensus and ancestral sequences from center-rooted trees were most similar in all predicted attributes. Only for the predicted number of N-glycosylation sites was there a difference between MP and ML methods of reconstruction. Taxon sampling effects were observed only for outgroup-rooted trees, not center-rooted, reflecting the occurrence of several divergent basal sequences. Thus, for sequences exhibiting a radial phylogenetic tree, as does HIV-1, most of the variation in the estimated ancestor arises from the method of rooting the phylogenetic tree. Those investigating the ancestors of genes exhibiting such a radial tree should pay particular attention to alternate rooting methods in order to obtain a representative sample of ancestors.
Genome Signatures, Self-Organizing Maps and Higher Order Phylogenies: A Parametric Analysis
Authors: Gatherer Derek
Published: November 2017

Genome signatures are data vectors derived from the compositional statistics of DNA. The self-organizing map (SOM) is a neural network method for the conceptualisation of relationships within complex data, such as genome signatures. The various parameters of the SOM training phase are investigated for their effect on the accuracy of the resulting output map. It is concluded that larger SOMs, as well as taking longer to train, are less sensitive in phylogenetic classification of unknown DNA sequences. However, where a classification can be made, a larger SOM is more accurate. Increasing the number of iterations in the training phase of the SOM only slightly increases accuracy, without improving sensitivity. The optimal length of the DNA sequence k-mer from which the genome signature should be derived is 4 or 5, but shorter values are almost as effective. In general, these results indicate that small, rapidly trained SOMs are generally as good as larger, longer trained ones for the analysis of genome signatures. These results may also be more generally applicable to the use of SOMs for other complex data sets, such as microarray data.
Interactions between SNP Alleles at Multiple Loci and Variation in Skin Pigmentation in 122 Caucasians
Authors: Anno Sumiko , Abe Takashi , Sairyo Koichi , Kudo Susumu , Yamamoto Takushi , Ogata Koretsugu , Goel Vijay K.
Published: November 2017

This study was undertaken to clarify the molecular basis for human skin color variation and the environmental adaptability to ultraviolet irradiation, with the ultimate goal of predicting the impact of changes in future environments on human health risk. One hundred twenty-two Caucasians living in Toledo, Ohio participated. Back and cheek skin were assayed for melanin as a quantitative trait marker. Buccal cell samples were collected and used for DNA extraction. DNA was used for SNP genotyping using the Masscode™ system, which entails two-step PCR amplification and a platform chemistry which allows cleavable mass spectrometry tags. The results show gene-gene interaction between SNP alleles at multiple loci (not necessarily on the same chromosome) contributes to inter-individual skin color variation while suggesting a high probability of linkage disequilibrium. Confirmation of these findings requires further study with other ethic groups to analyze the associations between SNP alleles at multiple loci and human skin color variation. Our overarching goal is to use remote sensing data to clarify the interaction between atmospheric environments and SNP allelic frequency and investigate human adaptability to ultraviolet irradiation. Such information should greatly assist in the prediction of the health effects of future environmental changes such as ozone depletion and increased ultraviolet exposure. If such health effects are to some extent predictable, it might be possible to prepare for such changes in advance and thus reduce the extent of their impact.
Selection Effects on the Positioning of Genes and Gene Structures from the Interplay of Replication and Transcription in Bacterial Genomes
Authors: Arakawa Kazuharu , Tomita Masaru
Published: November 2017

Bacterial chromosomes are partly shaped by the functional requirements for efficient replication, which lead to strand bias as commonly characterized by the excess of guanines over cytosines in the leading strand. Gene structures are also highly organized within bacterial genomes as a result of such functional constraints, displaying characteristic positioning and structuring along the genome. Here we analyze the gene structures in completely sequenced bacterial chromosomes to observe the positional constraints on gene orientation, length, and codon usage with regard to the positions of replication origin and terminus. Selection on these gene features is different in regions surrounding the terminus of replication from the rest of the genome, but the selection could be either positive or negative depending on the species, and these positional effects are partly attributed to the A-T enrichment near the terminus. Characteristic gene structuring relative to the position of replication origin and terminus is commonly observed among most bacterial species with circular chromosomes, and therefore we argue that the highly organized gene positioning as well as the strand bias should be considered for genomics studies of bacteria.
The GC Skew Index: A Measure of Genomic Compositional Asymmetry and the Degree of Replicational Selection
Authors: Arakawa Kazuharu , Tomita Masaru
Published: November 2017

Circular bacterial chromosomes have highly polarized nucleotide composition in the two replichores, and this genomic strand asymmetry can be visualized using GC skew graphs. Here we propose and discuss the GC skew index (GCSI) for the quantification of genomic compositional skew, which combines a normalized measure of fast Fourier transform to capture the shape of the skew graph and Euclidean distance between the two vertices in a cumulative skew graph to represent the degree of skew. We calculated GCSI for all available bacterial genomes, and GCSI correlated well with the visibility of GC skew. This novel index is useful for estimating confidence levels for the prediction of replication origin and terminus by methods based on GC skew and for measuring the strength of replicational selection in a genome.
Choosing and Using Introns in Molecular Phylogenetics
Authors: Creer Simon
Published: November 2017

Introns are now commonly used in molecular phylogenetics in an attempt to recover gene trees that are concordant with species trees, but there are a range of genomic, logistical and analytical considerations that are infrequently discussed in empirical studies that utilize intron data. This review outlines expedient approaches for locus selection, overcoming paralogy problems, recombination detection methods and the identification and incorporation of LVHs in molecular systematics. A range of parsimony and Bayesian analytical approaches are also described in order to highlight the methods that can currently be employed to align sequences and treat indels in subsequent analyses. By covering the main points associated with the generation and analysis of intron data, this review aims to provide a comprehensive introduction to using introns (or any non-coding nuclear data partition) in contemporary phylogenetics.
Structural Evolution of the ABC Transporter Subfamily B
Authors: Flanagan J.U. , Huber T.
Published: November 2017

The ATP binding cassette containing transporters are a superfamily of integral membrane proteins that translocate a wide range of substrates. The subfamily B members include the biologically important multidrug resistant (MDR) protein and the transporter associated with antigen processing (TAP) complex. Substrates translocated by this subfamily include drugs, lipids, peptides and iron. We have constructed a comprehensive set of comparative models for the transporters from eukaryotes and used these to study the effects of sequence divergence on the substrate translocation pathway. Notably, there is very little structural divergence between the bacterial template structure and the more distantly related eukaryotic proteins illustrating a need to conserve transporter structure. By contrast different properties have been adopted for the translocation pathway depending on the substrate type. A greater level of divergence in electrostatic properties is seen with transporters that have a broad substrate range both within and between species, while a high level of conservation is observed when the substrate range is narrow. This study represents the first effort towards understanding effect of evolution on subfamily B ABC transporters in the context of protein structure and biophysical properties.

Abbreviations

A. thaliana Arabidopsis thaliana D. melanogaster Drosophilia melanogaster S. aureus Staphylococcus aureus ABC ATP binding cassette TAP Transporter associated with antigen processing.
The 2006 NESCent Phyloinformatics Hackathon: A Field Report
Authors: Lapp Hilmar , Bala Sendu , Balhoff James P. , Bouck Amy , Goto Naohisa , Holder Mark , Holland Richard , Holloway Alisha , Katayama Toshiaki , Lewis Paul O. , Mackey Aaron J. , Osborne Brian I. , Piel William H. , Pond Sergei L. Kosakovsky , Poon Art F.Y. , Qiu Wei-Gang , Stajich Jason E. , Stoltzfus Arlin , Thierer Tobias , Vilella Albert J. , Vos Rutger A. , Zmasek Christian M. , Zwickl Derrick J. , Vision Todd J.
Published: November 2017

In December, 2006, a group of 26 software developers from some of the most widely used life science programming toolkits and phylogenetic software projects converged on Durham, North Carolina, for a Phyloinformatics Hackathon, an intense five-day collaborative software coding event sponsored by the National Evolutionary Synthesis Center (NESCent). The goal was to help researchers to integrate multiple phylogenetic software tools into automated workflows. Participants addressed deficiencies in interoperability between programs by implementing “glue code” and improving support for phylogenetic data exchange standards (particularly NEXUS) across the toolkits. The work was guided by use-cases compiled in advance by both developers and users, and the code was documented as it was developed. The resulting software is freely available for both users and developers through incorporation into the distributions of several widely-used open-source toolkits. We explain the motivation for the hackathon, how it was organized, and discuss some of the outcomes and lessons learned. We conclude that hackathons are an effective mode of solving problems in software interoperability and usability, and are underutilized in scientific software development.
Mlcoalsim: Multilocus Coalescent Simulations
Authors: Ramos-Onsins Sebastian E. , Mitchell-Olds Thomas
Published: November 2017

Coalescent theory is a powerful tool for population geneticists as well as molecular biologists interested in understanding the patterns and levels of DNA variation. Using coalescent Monte Carlo simulations it is possible to obtain the empirical distributions for a number of statistics across a wide range of evolutionary models; these distributions can be used to test evolutionary hypotheses using experimental data. The mlcoalsim application presented here (based on a version of the ms program, Hudson, 2002) adds important new features to improve methodology (uncertainty and conditional methods for mutation and recombination), models (including strong positive selection, finite sites and heterogeneity in mutation and recombination rates) and analyses (calculating a number of statistics used in population genetics and P-values for observed data). One of the most important features of mlcoalsim is the analysis of multilocus data in linked and independent regions. In summary, mlcoalsim is an integrated software application aimed at researchers interested in molecular evolution. mlcoalsim is written in ANSI C and is available at: http://www.ub.es/softevol/mlcoalsim .
Evolution of the Influenza A Virus: Some New Advances
Authors: Rabadan Raul , Robins Harlan
Published: November 2017

Influenza is an RNA virus that causes mild to severe respiratory symptoms in humans and other hosts. Every year approximately half a million people around the world die from seasonal Influenza. But this number is substantially larger in the case of pandemics, with the most dramatic instance being the 1918 “Spanish flu” that killed more than 50 million people worldwide. In the last few years, thousands of Influenza genomic sequences have become publicly available, including the 1918 pandemic strain and many isolates from non-human hosts. Using these data and developing adequate bioinformatic and statistical tools, some of the major questions surrounding Influenza evolution are becoming tractable. Are the mutations and reassortments random? What are the patterns behind the virus's evolution? What are the necessary and sufficient conditions for a virus adapted to one host to infect a different host? Why is Influenza seasonal? In this review, we summarize some of the recent progress in understanding the evolution of the virus.
An Insulin-Like Modular Basis for the Evolution of Glucose Transporters (GLUT) with Implications for Diabetes
Authors: Root-Bernstein Robert
Published: November 2017

Glucose transporters (GLUT) are twelve-transmembrane spanning proteins that contain two pores capable of transporting glucose and dehydroascorbate in and out of cells. The mechanism by which transport is effected is unknown. An evolutionarily-based hypothesis for the mechanism of glucose transport is presented here based on reports that insulin has multiple binding sites for glucose. It is proposed that insulin-like peptides were incorporated as modular elements into transmembrane proteins during evolution, resulting in glucose transporting capacity. Homology searching reveals that all GLUT contain multiple copies of insulin-like regions. These regions map onto a model of GLUT in positions that define the glucose transport cores. This observation provides a mechanism for glucose transport involving the diffusion of glucose from one insulin-like glucose-binding region to another. It also suggests a mechanism by which glucose disregulation may occur in both type 1 and type 2 diabetes: insulin rapidly self-glycates under hyperglycemic conditions. Insulin-like regions of GLUT may also self-glycate rapidly, thereby interfering with transport of glucose into cells and disabling GLUT sensing of blood glucose levels. All aspects of the hypothesis are experimentally testable.
Environmental Quality, Developmental Plasticity and the Thrifty Phenotype: A Review of Evolutionary Models
Authors: Wells Jonathan CK
Published: November 2017

The concept of the thrifty phenotype, first proposed by Hales and Barker, is now widely used in medical research, often in contrast to the thrifty genotype model, to interpret associations between early-life experience and adult health status. Several evolutionary models of the thrifty phenotype, which refers to developmental plasticity, have been presented. These include (A) the weather forecast model of Bateson, (B) the maternal fitness model of Wells, (C) the intergenerational phenotypic inertia model of Kuzawa, and (D) the predictive adaptive response model of Gluckman and Hanson. These models are compared and contrasted, in order to assess their relative utility for understanding human ontogenetic development. The most broadly applicable model is model A, which proposes that developing organisms respond to cues of environmental quality, and that mismatches between this forecast and subsequent reality generate significant adverse effects in adult phenotype. The remaining models all address in greater detail what kind of information is provided by such a forecast. Whereas both models B and C emphasise the adaptive benefits of exploiting information about the past, encapsulated in maternal phenotype, model D assumes that the fetus uses cues about the present external environment to predict its probable adult environment. I argue that for humans, with a disproportionately long period between the closing of sensitive windows of plasticity and the attainment of reproductive maturity, backward-looking models B and C represent a better approach, and indicate that the developing offspring aligns itself with stable cues of maternal phenotype so as to match its energy demand with maternal capacity to supply. In contrast, the predictive adaptive response model D over-estimates the capacity of the offspring to predict the future, and also fails to address the long-term parent-offspring dynamics of human development. Differences between models have implications for the design of public health interventions.
The regenerated chacra of the Kichwa-Lamistas: an alternative to permaculture?
Authors: Caradonna Jeremy L , Apffel-Marglin Frederique
Published: November 2017

This article compares Western permaculture theory and practice with the indigenous agricultural system of the Kichwa-Lamistas in the Department of San Martin in High Amazon Peru. It draws on indigenous theory and collaborations with the Kichwa-Lamistas to argue that the bioculture of the latter represents an alternative not only to modern, industrialized agriculture but also to permaculture. The article profiles the agroecological system used by the Kichwa-Lamistas, which employs agroforestry, the use of anthropogenic Terra Preta soils, and other sustainable practices. Although both the Kichwa-Lamista chacra (farm) and the permaculture farm or garden represent, in theory, two forms of closed-loop, polycultural, agroforestry-based subsistence farming, we argue that the enactments of reciprocity and other spiritual components of Kichwa-Lamista bioculture constitute an alternative to permaculture’s rootedness in scientific, materialist, and universalist traditions, which ultimately treat the natural world as other.
Evaluation of Two Outlier-Detection-Based Methods for Detecting Tissue-Selective Genes from Microarray Data
Authors: Kadota Koji , Konishi Tomokazu , Shimizu Kentaro
Published: November 2017

Large-scale expression profiling using DNA microarrays enables identification of tissue-selective genes for which expression is considerably higher and/or lower in some tissues than in others. Among numerous possible methods, only two outlier-detection-based methods (an AIC-based method and Sprent's non-parametric method) can treat equally various types of selective patterns, but they produce substantially different results. We investigated the performance of these two methods for different parameter settings and for a reduced number of samples. We focused on their ability to detect selective expression patterns robustly. We applied them to public microarray data collected from 36 normal human tissue samples and analyzed the effects of both changing the parameter settings and reducing the number of samples. The AIC-based method was more robust in both cases. The findings confirm that the use of the AIC-based method in the recently proposed ROKU method for detecting tissue-selective expression patterns is correct and that Sprent's method is not suitable for ROKU.
Practical Lessons from Theoretical Models about the Somitogenesis
Authors: González Aitor , Kageyama Ryoichiro
Published: November 2017

Vertebrae and other mammalian repetitive structures are formed from embryonic organs called somites. Somites arise sequentially from the unsegmented presomitic mesoderm (PSM). In mice, a new bilateral pair of somites arise every two hours from the rostral PSM. On the other hand, cells are added to the caudal side of the PSM due to cell proliferation of the tail bud. Somite formation correlates with cycles of cell-autonomous expression in the PSM of genes like Hes7. Because the somitogenesis is a highly dynamic and coordinated process, this event has been subjected to extensive theoretical modeling. Here, we describe the current understanding about the somitogenesis in mouse embryos with an emphasis on insights gained from computer simulations. It is worth noting that the combination of experiments and computer simulations has uncovered dynamical properties of the somitogenesis clock such as the transcription/translation delays, the half-life and the synchronization mechanism across the PSM. Theoretical models have also been useful to provide predictions and rigorous hypothesis about poorly understood processes such as the mechanisms by which the temporal PSM oscillations are arrested and converted into an spatial pattern. We aim at reviewing this theoretical literature in such a way that experimentalists might appreciate the resulting conclusions.
Insulin Sensitizing Pharmacology of Thiazolidinediones Correlates with Mitochondrial Gene Expression rather than Activation of PPARγ
Authors: Bolten Charles W. , Blanner Patrick M. , McDonald William G. , Staten Nicholas R. , Mazzarella Richard A. , Arhancet Graciela B. , Meier Martin F. , Weiss David J. , Sullivan Patrick M. , Hromockyj Alexander E. , Kletzien Rolf F. , Colca Jerry R.
Published: November 2017

Insulin sensitizing thiazolidinediones (TZDs) are generally considered to work as agonists for the nuclear receptor peroxisome proliferative activated receptor-gamma (PPARγ). However, TZDs also have acute, non-genomic metabolic effects and it is unclear which actions are responsible for the beneficial pharmacology of these compounds. We have taken advantage of an analog, based on the metabolism of pioglitazone, which has much reduced ability to activate PPARγ. This analog (PNU-91325) was compared to rosiglitazone, the most potent PPARγ activator approved for human use, in a variety of studies both in vitro and in vivo. The data demonstrate that PNU-91325 is indeed much less effective than rosiglitazone at activating PPARγ both in vitro and in vivo. In contrast, both compounds bound similarly to a mitochondrial binding site and acutely activated PI-3 kinase-directed phosphorylation of AKT, an action that was not affected by elimination of PPARγ activation. The two compounds were then compared in vivo in both normal C57 mice and diabetic KKAy mice to determine whether their pharmacology correlated with biomarkers of PPARγ activation or with the expression of other gene transcripts. As expected from previous studies, both compounds improved insulin sensitivity in the diabetic mice, and this occurred in spite of the fact that there was little increase in expression of the classic PPARγ target biomarker adipocyte binding protein-2 (aP2) with PNU-91325 under these conditions. An examination of transcriptional profiling of key target tissues from mice treated for one week with both compounds demonstrated that the relative pharmacology of the two thiazolidinediones correlated best with an increased expression of an array of mitochondrial proteins and with expression of PPARγ coactivator 1-alpha (PGC1α), the master regulator of mitochondrial biogenesis. Thus, important pharmacology of the insulin sensitizing TZDs may involve acute actions, perhaps on the mitochondria, that are independent of direct activation of the nuclear receptor PPARγ. These findings suggest a potential alternative route to the discovery of novel insulin sensitizing drugs.
Role of SP-1 in SDS-Induced Adipose Differentiation Related Protein Synthesis in Human Keratinocytes
Authors: Corsini Emanuela , Zancanella Omar , Lucchi Laura , Viviani Barbara , Marinovich Marina , Galli Corrado L.
Published: November 2017

Skin irritation is a complex phenomenon, and keratinocytes play an important role in it. We have recently characterized the expression and protective role of adipose differentiation related protein (ADRP) in skin irritation. In particular, ADRP expression is induced to recover functional cell membrane following the cell damage caused by skin irritants.

The purpose of this study was to characterize in a human keratinocyte cells line (NCTC 2544) the biochemical events that lead to ADRP expression following SDS treatment, and in particular, to investigate the role of transcription factor SP-1. Analysis of ADRP promoter region revealed the presence of a potential binding site for the transcription factor SP-1 close to the start site. Evaluated by measuring the DNA binding activity, we found that SDS induced a dose and time related SP-1 activation, which was correlated with SDS-induced ADRP mRNA expression. Furthermore, SDS-induced SP-1 activation, ADRP mRNA expression and lipid droplets accumulation could be modulated by mithramycin A, an antibiotic that selectively binds to the GC box preventing SP-1 binding and gene expression. This demonstrated that SDS-induced ADRP expression was mediated in part through the transcription factor SP-1. In addition, SDS-induced SP-1 activation and ADRP expression could be modulated by the calcium chelator BAPTA, indicating a role of calcium in ADRP-induction.

Thus, every time an irritant perturbs the membrane barrier, it renders the membrane leaky and allows extracellular calcium to enter the cells, an event that provides the upstream mechanisms initiating the signaling cascade that triggers the activation of SP-1 and culminates in the enhancement of ADRP expression, which helps to restore the normal homeostasis and ultimately repairs the to membrane.
Variability of DNA Microarray Gene Expression Profiles in Cultured Rat Primary Hepatocytes
Authors: Xu Jun , Deng Xutao , Chan Victor , Kelley-Loughnane Nancy , Harker Brent W , Shi Leming , Hussain Saber M. , Frazier John M. , Wang Charles
Published: November 2017

DNA microarray is a powerful tool in biomedical research. However, transcriptomic profiling using DNA microarray is subject to many variations including biological variability. To evaluate the different sources of variation in mRNA gene expression profiles, gene expression profiles were monitored using the Affymetrix RatTox U34 arrays in cultured primary hepatocytes derived from six rats over a 26 hour period at 6 time points (0h, 2h, 5h, 8h, 14h and 26h) with two replicate arrays at each time point for each animal. In addition, the impact of sample size on the variability of differentially expressed gene lists and the consistency of biological responses were also investigated. Excellent intra-animal reproducibility was obtained at all time points with 0 out of 370 present probe sets across all time points showing significant difference between the 2 replicate arrays (3-way ANOVA, p ≤ 0.0001). However, large inter-animal biological variation in mRNA expression profiles was observed with 337 out of 370 present probe sets showing significant differences among 6 animals (3-way ANOVA, p ≤ 0.05). Principal Component Analysis (PCA) revealed that time effect (PC1) in this data set accounted for 47.4% of total variance indicating the dynamics of transcriptomics. The second and third largest effects came from animal difference, which accounted for 16.9% (PC2 and PC3) of the total variance. The reproducibility of gene lists and their functional classification was declined considerably when the sample size was decreased. Overall, our results strongly support that there is significant inter-animal variability in the time-course gene expression profiles, which is a confounding factor that must be carefully evaluated to correctly interpret microarray gene expression studies. The consistency of the gene lists and their biological functional classification are also sensitive to sample size with the reproducibility decreasing considerably under small sample size.
Vectors Encoding Seven Oikosin Signal Peptides Transfected into CHO Cells Differ Greatly in Mediating Gaussia luciferase and Human Endostatin Production although mRNA Levels are Largely Unaffected
Authors: Tröße Christiane , Ravneberg Hanne , Stern Beate , Pryme Ian F.
Published: November 2017

The signal peptide of the luciferase secreted by the marine copepod Gaussia princeps has been shown to promote high-level protein synthesis/secretion of recombinant proteins, being far superior to mammalian counterparts. The main aim of the present study was to investigate the effects of seven selected signal peptides derived from oikosins, house proteins of the marine organism Oikopleura dioica, on synthesis/secretion of recombinant proteins. Vector constructs were made in which the coding regions of two naturally secreted proteins, Gaussia luciferase and human endostatin (hEndostatin), were “seamlessly” fused to the signal peptide coding sequences of interest. CHO cells were transfected with the plasmids and populations of stably transfected cells established. The amounts of reporter proteins in cell extract and medium samples were determined and the results compared to those obtained from cells stably transfected with a reference vector construct. In addition, the amounts of luciferase or hEndostatin encoding mRNAs in the cells were determined and related to the protein levels obtained. The levels of reporter protein produced varied greatly among the seven oikosin signal peptides tested. Whereas the oikosin 1 signal peptide resulted in about 40% production of Gaussia luciferase compared to the reference construct, oikosins 2–7 were extremely ineffective (<1%). mRNA levels were not dramatically affected such that inadequate availability of transcript for translation was not the underlying reason for the observations. The oikosin 1 signal peptide was also the most effective regarding synthesis/secretion of hEndostatin. No secreted product was observed using the oikosin 3 signal peptide. Interestingly, the molecular weight of hEndostatin in cell extracts prepared from cells transfected with oikosin 2 and 3 constructs was higher than that using the oikosin 1 signal peptide. The overall findings indicate that the signal peptide affects the efficiency of protein synthesis and secretion through a mechanism operating at the post-transcriptional level. The results described here provide substantial support to our previous observations which suggested that the choice of the signal peptide is imperative when aiming to achieve optimal synthesis and secretion of a recombinant protein using transfected mammalian cells.
Genomic Loci Modulating the Retinal Transcriptome in Wound Healing
Authors: Vázquez-Chona Félix R. , Lu Lu , Williams Robert W. , Geisert Eldon E.
Published: November 2017

Purpose

The present study predicts and tests genetic networks that modulate gene expression during the retinal wound-healing response.

Methods

Upstream modulators and target genes were defined using meta-analysis and bioinformatic approaches. Quantitative trait loci (QTLs) for retinal acute phase genes (Vazquez-Chona et al. 2005) were defined using QTL analysis of CNS gene expression (Chesler et al. 2005). Candidate modulators were defined using computational analysis of gene and motif sequences. The effect of candidate genes on wound healing was tested using animal models of gene expression.

Results

A network of early wound-healing genes is modulated by a locus on chromosome 12. The genetic background of the locus altered the wound-healing response of the retina. The C57BL/6 allele conferred enhanced expression of neuronal marker Thy1 and heat-shock-like crystallins, whereas the DBA/2J allele correlated with greater levels of the classic marker of retinal stress, glial fibrillary acidic protein (GFAP). Id2 and Lpin1 are candidate upstream modulators as they strongly correlated with the segregation of DBA/2J and C57BL/6 alleles, and their dosage levels correlated with the enhanced expression of survival genes ( Thy1 and crystallin genes).

Conclusion

We defined a genetic network associated with the retinal acute injury response. Using genetic linkage analysis of natural transcript variation, we identified regulatory loci and candidate modulators that control transcript levels of acute phase genes. Our results support the convergence of gene expression profiling, QTL analysis, and bioinformatics as a rational approach to discover molecular pathways controlling retinal wound healing.
TAK1 mRNA Expression in the Tumor Tissue of Locally Advanced Head and Neck Cancer Patients
Authors: Honorato Beatriz , Alcalde Juan , Martinez-Monge Rafael , Zabalegui Natalia , Garcia-Foncillas Jesús
Published: November 2017

Resistance to radio and chemotherapy is one of the major drawbacks in the progression of head and neck squamous cell cancer (HNSCC) patients, evidencing the importance of finding optimum molecular prognosis markers to develop personalized treatment schedules. TGF-β effector TAK1 activity has been related to a greater aggressiveness in several types of cancer (Kondo et al. 1998; Edlund et al. 2003; Kaur et al. 2005) and, although there has been described no significant implication of TAK1 in HNSCC development, we have further examined the role of its mRNA expression as a marker of prognosis in HNSCC. Fifty-nine advanced HNSCC patients were recruited for the study. The tumor expression of TAK1 mRNA was analyzed with RT-PCR using Taqman technology and its relationship with the clinical outcome of the patients studied. TAK1 mRNA expression was lower in patients that relapsed than in those that did not, but the difference was only significant between the patients that showed response to treatment (p < 0.001). ROC curve analyses pointed a 0.5 expression ratio TAK1/B2M value as an optimum cut-off point for relapse and response. Our data suggest the TAK1 mRNA analysis by Taqman RT-PCR can predict the risk of relapse in HNSCC patients.
Australian students’ activity preferences, perceived physical risk and interest in vacationing in Japan
Authors: Tkaczynski Aaron , Nagai Hayato , Rundle-Thiele Sharyn R
Published: November 2017

The purpose of this study was to identify Australian students’ activity preferences, perceived physical risk and interest in Japan as a vacation destination. Based on a sample of 422 Australian students, five activity factors were determined. These were labeled as cultural, outdoor, excitement, built attractions and personal. Australian students were extremely interested in vacationing in Japan and they generally perceived few physical risks of a Japanese vacation. Hygiene risk significantly contributed to variance in interest in vacationing in Japan. Four activity types significantly contributed to interest in travel to Japan and perceived physical risk did not mediate the activity preference and interest relationship. Theoretical and practical implications for this research are outlined and limitations and opportunities for future research are provided.
Prolonged Exposure Therapy for Comorbid Psychogenic Nonepileptic Seizures and Posttraumatic Stress Disorder
Authors: Myers Lorna , Zandberg Laurie
Published: November 2017

Psychogenic nonepileptic seizures (PNES) superficially resemble epileptic seizures but are not associated with epileptic discharges in the brain. Instead, these episodes, which tend to occur with alterations in consciousness and body movements, are thought to be the result of mechanisms of conversion and dissociation. Psychological trauma and PTSD are very prevalent among patients with PNES. PNES can be conceived of as an extreme avoidance mechanism that serves the function of modulating distress and, in some cases, eliminating the precipitant stressor. Avoidance is also an essential component of PTSD. In patients who carry a dual diagnosis of PNES and PTSD, it is sensible that an empirically validated treatment for PTSD such as prolonged exposure (PE) therapy which targets avoidance by promoting exposure might be a useful approach to treat these patients. In this report, we present the case of a 52-year-old male with a 7-year history of PNES. His seizures, which were characterized by intense body shaking and loud guttural outbursts, were occurring up to 15 times per day. Because of these symptoms, he lost his employment and was ostracized by his family. Upon completion of a course of intensive outpatient PE, he achieved full remission of all psychogenic symptoms. Except for three brief seizures, he has maintained his health for 2 years. This constitutes the first detailed report of PE therapy used to effectively treat comorbid PNES and posttraumatic stress symptoms.
Good Things Are Not Eternal: How Consideration Leadership and Initiating Structure Influence the Dynamic Nature of Organizational Justice and Extra-Role Behaviors at the Collective Level
Authors: Tremblay Michel , Gaudet Marie-Claude , Parent-Rocheleau Xavier
Published: November 2017

The objective of this study was to test the linear and curvilinear influence of initiating structure (IS) and consideration leadership on the variability of extra-role behaviors over time, through the mediating effect of within-store level of distributive (DJ) and procedural justice (PJ). Data from 1,857 employees in 116 business units of a Canadian retailer collected over four waves were analyzed using random coefficient modeling. Our results show that IS and consideration have significant linear and curvilinear effects on within-unit PJ and DJ climates over time, and an indirect influence on the within-unit variability of extra-role behaviors through the mediating effect of DJ and PJ climates. Results underline the complexity of the effects of both leadership dimensions on PJ and DJ climates. While consideration is associated with an increase of both justice climates over time, low and high levels of IS are associated with a decrease in PJ climate over time, and a moderate level of IS was related to an increase of PJ climate. Moreover, the positive effects of leadership behaviors on extra-role behaviors shift completely after a certain time threshold. Surprisingly, while unit-level extra-role behaviors increased over time under high structure leadership, such behaviors decreased under high consideration. Finally, the results showed that the positive influence of PJ and DJ climates on unit-level extra-role behaviors decreases over time, and that low fairness units experience a more dramatic decrease of extra-role behaviors with time.
Seeking Ways to Inform the Uninformed: Improving the Informed Consent Process in Online Social Science Research
Authors: Perrault Evan K. , Keating David M.
Published: November 2017

Participants often do not read consent forms in social science research. This is not surprising, especially for online studies, given they do not typically offer greater risk than what is encountered in daily life. However, if no one is reading, are participants really informed? This study used previous research to craft experimentally manipulated consent forms utilizing different visual presentations (e.g., greater use of line spacing, bullets, bolding, diagrams). Participants ( n = 547) were randomly exposed to one of seven form variations. Results found no significant differences between forms in reading or comprehension. Open-ended questions asked participants why they do not read consent forms and what would influence them to read the forms. Participants most frequently stated forms need to be shorter, and important information needs to be highlighted. We suggest improvements to informed consent forms, including removing much of the information that is constant across forms, and only including unique aspects of studies.
Regional Variations of Medicare Physician Payments for Hand Surgery Procedures in the United States
Authors: Veltre David R. , Yakavonis Mark , Curry Emily J. , Cusano Antonio , Parisien Robert L. , Eichinger Josef K. , Duncan Scott F.M. , Stein Andrew B. , Li Xinning
Published: November 2017

Background: Medicare reimbursement is known to exhibit geographic variation for inpatient orthopedic procedures. This study determined whether US geographic variations also exist for commonly performed hand surgeries. Methods: Using the Medicare Provider Utilization and Payment Data (2012-2013) from Centers for Medicare & Medicaid Services, we analyzed regional physician charges/payments for common outpatient hand surgeries. Results: The most commonly performed procedures in the United States were open carpal tunnel release (n = 21 944), trigger finger release (n = 15 345), endoscopic carpal tunnel release (n = 7106), and basal joint arthroplasty/ligament reconstruction and tendon interposition (n = 2408). A range of average Medicare physician reimbursements existed based on geographic region for basal joint arthroplasty ($669-$571), endoscopic carpal tunnel release ($400-$317), open carpal tunnel release ($325-$261), and trigger finger release ($215-$167). The latter three exhibited statistically significant variation across geographic regions with regard to both charges and physician reimbursement. However, the overall percentage physician reimbursement (70%-79%) to charges was similar across all geographic regions. Conclusions: In conclusion, further research is warranted to determine why regional or geographic variations in physician payments exist in the United States for commonly performed hand surgeries.
Lifestyle Choices Can Augment Female Sexual Well-Being
Authors: Finley Nicola
Published: November 2017

Female sexual wellbeing is complex and it’s an important part of a comprehensive approach to women’s health. Unfortunately, this aspect of health often is not discussed during medical appointments which can be isolating for female patients. Low libido is the most common female sexual dysfunction. There are multiple causes of low libido that may be physical, cultural, emotional, medical psychological or due to her relationship with her partner. A healthy lifestyle is one way to help women overcome low libido and a few examples include exercise, mindfulness and yoga. Ultimately, these lifestyle approaches can enhance sexual satisfaction.
Direct puncture Onyx embolization of a large calvarial metastasis with intracranial extension: Case report
Authors: Zhou Minerva H , Dunn Gavin P , Osbun Joshua W , Cross DeWitte T , Moran Christopher J , Dacey Ralph G , Kansagra Akash P
Published: November 2017

We report a case of renal cell carcinoma (RCC) metastasis to the calvarium and describe a strategy for percutaneous embolization of hypervascular calvarial tumors with intracranial extension. An elderly patient with history of RCC presented with left-sided weakness. Imaging studies showed a large right frontoparietal calvarial mass with intra- and extracranial extension. The tumor was devascularized by direct puncture tumor embolization using Onyx 18, allowing subsequent operative resection without significant blood loss or the need for flap reconstruction of the scalp. Compared to more common endovascular approaches, direct-needle puncture embolization of transcalvarial masses may offer lower risk of injury to scalp vessels and underlying brain parenchyma.
Risk factors associated with periprosthetic joint infection after total elbow arthroplasty
Authors: Somerson Jeremy S. , Boylan Matthew R. , Hug Kevin T. , Naziri Qais , Paulino Carl B. , Huang Jerry I.
Published: November 2017

Background

For patients undergoing total elbow arthroplasty (TEA), the present study aimed to investigate: (i) what risk factors are associated with periprosthetic elbow infection; (ii) what is the incidence of infection after TEA; and (iii) what is the acuity with which these infections present?

Methods

The Statewide Planning and Research Cooperative System database was used to identify all patients who underwent TEA between 2003 and 2012 in New York State. Admissions for prosthetic joint infection (PJI) were identified using ICD-9 (International Classification of Diseases, Ninth Revision, Clinical Modification) diagnosis code 996.66. Multivariate analysis was used to determine risk factors that were independently prognostic for PJI.

Results

Significant risk factors for PJI included hypothyroidism [odds ratio (OR) = 2.04; p = 0.045], tobacco use disorder (OR = 3.39; p = 0.003) and rheumatoid arthritis (OR = 3.31; p < 0.001). Among the 1452 patients in the study period who underwent TEA, 3.7% ( n = 54) were admitted postoperatively for PJI. There were 30 (56%) early infections, 17 (31%) delayed infections and seven (13%) late infections.

Conclusions

Pre-operative optimization of thyroid function, smoking cessation and management of rheumatoid disease may be considered in surgical candidates for TEA. The results of the present study add prognostic data to the literature that may be helpful with patient selection and risk profile analysis.

Level of evidence

Level III: prognostic study
What if Marx was an anarchist?
Authors: Wainwright Joel
Published: November 2017

This essay responds to David Harvey (2017, ‘Listen, Anarchist!’ a personal response to Simon Springer’s ‘Why a radical geography must be anarchist’. Dialogues in Human Geography) by proposing that Karl Marx could be considered an anarchist. To make this argument, I draw on Kojin Karatani’s Transcritique: On Kant and Marx (2005, Cambridge: MIT Press).
Spinal Dural Repair: A Canadian Questionnaire
Authors: Oitment Colby , Aref Mohammed , Almenawar Saleh , Reddy Kesava
Published: November 2017

Study Design:

Questionnaire.

Objectives:

Iatrogenic dural tear is a complication of spinal surgery with significant morbidity and cost to the health care system. The optimal management is unclear, and therefore we aimed to survey current practices among Canadian practitioners.

Methods:

A questionnaire was administered to members of the Canadian Neurological Surgical Society designed to explore methods of closure of iatrogenic durotomy.

Results:

Spinal surgeons were surveyed anonymously with a 55% response rate (n = 91). For pinhole-sized tears, there is no agreement in the methods of closure, with a trend toward sealant fixation (36.7%). Medium- and large-sized tears are predominantly closed with sutures and sealant (67% and 80%, respectively). Anterior tears are managed without primary closure (40.2%), or using sealant alone (48%). Posterior tears are treated with a combination of sutures and sealant (73.8%). Nerve root tears are treated with either sealant alone (50%), or sutures and sealant (37.8%). Tisseal is the preferred sealant (79.7%) over alternatives. With the exception of pin-hole sized tears (39.5%) most respondents recommended bed rest for at least 24 hours in the setting of medium (73.2%) and large (89.1%) dural tears.

Conclusions:

This study elucidates the areas of uncertainty with regard to iatrogenic dural tear management. There is disagreement regarding management of anterior and nerve root tears, pinhole-sized tears in any location of the spine, and whether patients should be admitted to hospital or should be on bed rest following a pinhole-sized dural tear. There is a need for a robust comparative research study of dural repair strategies.