bluuebunny/crossref_metadata_2025 huggingface dataset:
Using the plurality of codon positions to identify deleterious variants in human exomes
Authors: Subramanian Sankar
Published: October 2014

Motivation: A codon position could perform different or multiple roles in alternative transcripts of a gene. For instance, a non-synonymous position in one transcript could be a synonymous site in another. Alternatively, a position could remain as non-synonymous in multiple transcripts. Here we examined the impact of codon position plurality on the frequency of deleterious single-nucleotide variations (SNVs) using data from 6500 human exomes.

Results: Our results showed that the proportion of deleterious SNVs was more than 2-fold higher in positions that remain non-synonymous in multiple transcripts compared with that observed in positions that are non-synonymous in one or some transcript(s) and synonymous or intronic in other(s). Furthermore, we observed a positive relationship between the fraction of deleterious non-synonymous SNVs and the number of proteins (alternative splice variants) affected. These results demonstrate that the plurality of codon positions is an important attribute, which could be useful in identifying mutations associated with diseases.

Contact:  s.subramanian@griffith.edu.au

Supplementary Information:  Supplementary data are available at Bioinformatics online
An alternative approach to multiple testing for methylation QTL mapping reduces the proportion of falsely identified CpGs
Authors: Luijk René , Goeman Jelle J. , Slagboom Eline P. , Heijmans Bastiaan T. , van Zwet Erik W.
Published: October 2014

Introduction : An increasing number of studies investigates the influence of local genetic variation on DNA methylation levels, so-called in cis methylation quantitative trait loci (meQTLs). A common multiple testing approach in genome-wide cis meQTL studies limits the false discovery rate (FDR) among all CpG–SNP pairs to 0.05 and reports on CpGs from the significant CpG–SNP pairs. However, a statistical test for each CpG is not performed, potentially increasing the proportion of CpGs falsely reported on. Here, we presented an alternative approach that properly control for multiple testing at the CpG level.

Results : We performed cis meQTL mapping for varying window sizes using publicly available single-nucleotide polymorphism (SNP) and 450 kb data, extracting the CpGs from the significant CpG–SNP pairs ( FDR<0.05 ). Using a new bait-and-switch simulation approach, we show that up to 50% of the CpGs found in the simulated data may be false-positive results. We present an alternative two-step multiple testing approach using the Simes and Benjamini–Hochberg procedures that does control the FDR among the CpGs, as confirmed by the bait-and-switch simulation. This approach indicates the use of window sizes in cis meQTL mapping studies that are significantly smaller than commonly adopted.

Discussion : Our approach to cis meQTL mapping properly controls the FDR at the CpG level, is computationally fast and can also be applied to cis eQTL studies.

Availability and implementation : An examplary R script for performing the Simes procedure is available as supplementary material.

Contact : e.w.van_zwet@lumc.nl or b.t.heijmans@lumc.nl

Supplementary information : Supplementary data are available at Bioinformatics online.
SIST: stress-induced structural transitions in superhelical DNA
Authors: Zhabinskaya Dina , Madden Sally , Benham Craig J.
Published: October 2014

Summary : Supercoiling imposes stress on a DNA molecule that can drive susceptible sequences into alternative non-B form structures. This phenomenon occurs frequently in vivo and has been implicated in biological processes, such as replication, transcription, recombination and translocation. SIST is a software package that analyzes sequence-dependent structural transitions in kilobase length superhelical DNA molecules. The numerical algorithms in SIST are based on a statistical mechanical model that calculates the equilibrium probability of transition for each base pair in the domain. They are extensions of the original stress-induced duplex destabilization (SIDD) method, which analyzes stress-driven DNA strand separation. SIST also includes algorithms to analyze B-Z transitions and cruciform extrusion. The SIST pipeline has an option to use the DZCB trans algorithm, which analyzes the competition among these three transitions within a superhelical domain.

Availability and implementation : The package and additional documentation are freely available at https://bitbucket.org/benhamlab/sist_codes .

Contact : dzhabinskaya@ucdavis.edu
Evaluation of Commercial Kits for Dual Extraction of DNA and RNA from Human Body Fluids,,
Authors: Schweighardt Andrew J. , Tate Courtney M. , Scott Kristina A. , Harper Kathryn A. , Robertson James M.
Published: October 2014

STR typing of DNA evidence can identify the donor with a high power of discrimination but cannot identify the tissue origin of a body‐fluid stain. Using RNA to attribute a crime scene stain to a particular tissue may aid in reconstruction efforts. With blood from 10 donors, four DNA and RNA coextraction kits were evaluated by measuring yields and STR and mRNA profiles. T tests indicated some significant differences in kit performance. The Zymo Research ZR‐Duet™ kit performed best based on average DNA (41.4 ng) and mRNA (4.07 ng) yields and was the only kit to provide complete DNA/RNA profiles for all samples. The consistency of this kit was challenged by data from additional blood and saliva donors. Further testing is advised before a superior kit is unequivocally chosen. Stand‐alone DNA or RNA purification generally offers higher yield, but coextraction may still allow successful STR profiling and tissue source identification.
Columnar‐Thin‐Film‐Assisted Visualization of Depleted Sebaceous Fingermarks on Nonporous Metals and Hard Plastics
Authors: Williams Stephanie F. , Pulsifer Drew P. , Lakhtakia Akhlesh , Shaler Robert C.
Published: October 2014

A fingermark on a nonporous substrate can be developed by depositing a columnar thin film (CTF) on it, but the CTF technique's sensitivity for low‐quality fingermarks is unknown. The optimized CTF and traditional development of several depletion series of sebaceous‐loaded fingermarks were compared using a split‐print methodology as well as subjective and objective grading schemes, in a limited laboratory trial. CTF development was superior to development with selected traditional techniques on brass, anodized aluminum, black acrylonitrile butadiene styrene (ABS), and white nylon. On white ABS and black nylon, the CTF technique performed poorly but still as well as the best‐performing traditional development technique. The CTF technique was more sensitive on brass and anodized aluminum than, and as sensitive on the four hard plastics and stainless steel as, the best‐performing traditional technique. Thus, the CTF technique is useful to develop friction‐ridge detail from limited fingermark residue on some smooth substrates.
Learning the “Craft” of Auditing: A Dynamic View of Auditors' On‐the‐Job Learning
Authors: Westermann Kimberly D. , Bedard Jean C. , Earley Christine E.
Published: October 2014

We investigate how auditors learn the technical aspects of their professional role while performing client engagements, and how that learning process has been shaped by changes in societal, economic, and regulatory forces. Prior studies explicitly recognize that auditors need social skills and demeanor consistent with professional norms as well as requisite knowledge, but those studies generally focus on the processes through which new auditors are molded toward consistency with social norms. In contrast, we focus on forces affecting the transfer of technical knowledge from supervisor (guide) to subordinate (learner) in the everyday work setting. Our evidence derives from semi‐structured interviews with 30 relatively new and more experienced audit partners at one Big 4 firm, thus spanning multiple “generations” of experience. Results confirm that auditors primarily acquire technical knowledge on the job, through the interactions among individual engagement team members. However, partners express concern about changes in the practice environment that may limit effectiveness of on‐the‐job learning, including characteristics of personnel, the approach to formal training at induction, supervisors' reluctance to provide candid feedback, regulatory and economic pressures, and the increased distraction, and reduced interpersonal contact associated with the use of information technology. At the end of the day, our findings raise implications for practice regarding the difficulty of developing effective learning conditions for auditors in the face of these challenges.
Subgingival bacterial recolonization after scaling and root planing in smokers with chronic periodontitis
Authors: Feres M , Bernal MAC , Matarazzo F , Faveri M , Duarte PM , Figueiredo LC
Published: October 2014

Background

The aim of this study was to compare subgingival bacterial recolonization patterns after scaling and root planing in current smokers and non‐smokers.

Methods

15 smokers and 15 non‐smokers with chronic periodontitis received scaling and root planing in six visits lasting one hour each, over a period of 21 days. Clinical monitoring was performed at baseline and 180 days, and microbiological monitoring was performed at baseline, immediately after scaling and root planing (Day 0) and at 42, 63 and 180 days post‐therapy. Subgingival plaque samples were analysed by checkerboard DNA–DNA hybridization.

Results

An improvement in clinical condition was observed for smokers and non‐smokers; however, non‐smokers showed a greater reduction in mean clinical attachment level in intermediate sites in comparison with smokers (p < 0.05). At Day 0, there was a significant reduction in the mean counts of the three pathogens from the red complex, Eubacterium nodatum and Parvimonas micra only in non‐smokers (p < 0.05). There was a significant increase in the proportion of host‐compatible species in non‐smokers and smokers from baseline to 180 days post‐therapy (p < 0.05). However, a significant decrease in the pathogenic species was observed only in non‐smokers.

Conclusions

Smokers were more susceptible to the re‐establishment of a pathogenic subgingival biofilm than non‐smokers.
Inhibition of transforming growth factor beta/SMAD signal by MiR‐155 is involved in arsenic trioxide‐induced anti‐angiogenesis in prostate cancer
Authors: Ji Hui , Li Yuan , Jiang Fei , Wang Xingxing , Zhang Jianping , Shen Jian , Yang Xiaojun
Published: October 2014

Prostate cancer is the most common cause of cancer‐related deaths in men. Current practices for treatment of prostate cancer are less than satisfactory because of metastasis and recurrence, which are primarily attributed to angiogenesis. Hence, anti‐angiogenesis treatment is becoming a promising new approach for prostate cancer therapy. In addition to treating acute promyelocytic leukemia, arsenic trioxide (As2O3) suppresses other solid tumors, including prostate cancer. However, the effects of As2O3 on angiogenesis in prostate cancer cells, and the underlying molecular mechanisms remain unclear. In the present study, As2O3 attenuated angiogenic ability through microRNA‐155 (miR‐155)‐mediated inhibition of transforming growth factor beta (TGF‐β)/SMAD signal pathway in human prostate cancer PC‐3 and LNCaP cells in vitro and in vivo. Briefly, As2O3 inhibited the activations/expressions of both TGFβ‐induced and endogenous SMAD2/3. Furthermore, As2O3 improved the expression of miR‐155 via DNA‐demethylation. MiR‐155, which targeted the SMAD2‐3′UTR, decreased the expression and function of SMAD2. Knockdown of miR‐155 abolished the As2O3‐induced inhibitions of the TGF‐β/SMAD2 signaling, the vascular endothelial growth factor secretion and angiogenesis. Through understanding a novel mechanism whereby As2O3 inhibits angiogenic potential of prostate cancer cells, our study would help in the development of As2O3 as a potential chemopreventive agent when used alone or in combination with other current anticancer drugs.
Use of a modified Delphi approach to develop research priorities for the Association of Coloproctology of Great Britain and Ireland
Authors: Tiernan J. , Cook A. , Geh I. , George B. , Magill L. , Northover J. , Verjee A. , Wheeler J. , Fearnhead N.
Published: October 2014

Aim

The modified Delphi approach is an established method for reaching a consensus opinion among a group of experts in a particular field. We have used this technique to survey the entire membership of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) to reach a consensus on prioritizing clinical research questions in colorectal disease.

Method

Three rounds of surveys were conducted using a web‐based tool. In the first, the ACPGBI membership was invited to submit research questions. In Rounds 2 and 3 they were asked to score questions on priority. A steering group analysed the results of each round to identify those questions ranked as being of highest priority.

Results

Five hundred and two questions were submitted in Round 1. Following two rounds of voting and analysis, a list of 25 priority questions was produced, including 15 cancer‐related and 10 noncancer‐related questions.

Conclusion

It is anticipated that these results will: (i) set the research agenda over the next few years for the study of colorectal disease in the United Kingdom, (ii) promote development and (iii) define funding of new research and prioritize areas of unmet clinical need where the potential clinical impact is greatest.
Gracilis muscle interposition for rectovaginal and anovaginal fistula repair: a systematic literature review
Authors: Hotouras A. , Ribas Y. , Zakeri S. , Murphy J. , Bhan C. , Chan C. L.
Published: October 2014

Background

Repair of rectovaginal fistula (RVF) is associated with high recurrence. For this reason gracilis muscle interposition is increasingly being used.

Aim

To evaluate the efficacy of this procedure for RVF repair.

Method/Search strategy

A search of PubMed and Medline databases was performed in November 2013 using the text terms and MESH headings ‘rectovaginal fistula/fistulation’, and ‘gracilis muscle’, spanning 1980–2013. The search strategy was restricted to articles written in English with available abstracts. Sample size, aetiology of RVF, previous repair attempts, follow‐up period, healing rates and complications were recorded and analysed.

Results

Seventeen studies involving 106 patients were analysed. The cause of RVF included inflammatory bowel disease (n = 37 [34.9%]: Crohn's disease [34], ulcerative colitis [3]), pelvic surgery (37 [34.9%]), obstetric injury (9 [8.5%]), malignancy (7 [6.6%]), trauma (5 [4.7%]), miscellaneous (idiopathic, endometriosis, radiation: 11 [10.4%]). Patients had undergone a median number of two previous unsuccessful repairs. At a median follow‐up of 21 months, healing had occurred in 33–100% (median 100%) with the largest studies reporting rates between 60% and 90%. Thirteen studies did not report any complications, with the remainder reporting only minor morbidity.

Conclusion

Gracilis interposition appears to have a reasonable success rate for RVF repair with acceptable morbidity. It may be considered as one of the first‐line treatment options for recurrent RVF.
Cardiogenic shock and coronary endothelial dysfunction predict cardiac allograft vasculopathy after heart transplantation
Authors: Lopez‐Fernandez Silvia , Manito‐Lorite Nicolas , Gómez‐Hospital Joan Antoni , Roca Josep , Fontanillas Carles , Melgares‐Moreno Rafael , Azpitarte‐Almagro José , Cequier‐Fillat Angel
Published: October 2014

Cardiac allograft vasculopathy remains one of the major causes of death post‐heart transplantation. Its etiology is multifactorial and prevention is challenging. The aim of this study was to prospectively determine factors related to cardiac allograft vasculopathy after heart transplantation. This research was planned on 179 patients submitted to heart transplant. Performance of an early coronary angiography with endothelial function evaluation was scheduled at three‐month post‐transplant. Patients underwent a second coronary angiography after five‐yr follow‐up. At the 5‐ ± 2‐yr follow‐up, 43% of the patients had developed cardiac allograft vasculopathy (severe in 26% of them). Three independent predictors of cardiac allograft vasculopathy were identified: cardiogenic shock at the time of the transplant operation (OR: 6.49; 95% CI: 1.86–22.7, p = 0.003); early coronary endothelial dysfunction (OR: 3.9; 95% CI: 1.49–10.2, p = 0.006), and older donor age (OR: 1.05; 95% CI: 1.00–1.10, p = 0.044). Besides early endothelial coronary dysfunction and older donor age, a new predictor for development of cardiac allograft vasculopathy was identified: cardiogenic shock at the time of transplantation. In these high‐risk patient subgroups, preventive measures (treatment of cardiovascular risk factors, use of novel immunosuppressive agents such as mTOR inhibitors) should be earlier and much more aggressive.
Cardiophrenic lymph nodes in liver transplant candidates with hepatocellular carcinoma: imaging characteristics and post‐transplant outcomes
Authors: Lee Christopher , Kim Andrew , Santos Idoia , Cen Yong , Alexopoulos Sophoclis , Navarro Shannon , Wallman Melissa , Dhanireddy Kiran , Grant Edward
Published: October 2014

Background

No guidelines exist for the management of cardiophrenic lymph nodes in patients with hepatocellular carcinoma (HCC) being evaluated for liver transplantation.

Methods

One hundred and seventy‐eight patients with HCC listed for liver transplant received both pre‐transplant computed tomography (CT) and follow‐up CT scans. Enlarged cardiophrenic lymph nodes on CT were characterized and followed on subsequent scans; lymph node outcomes were assigned to “reduced” and “not reduced” categories. Tumor and patient characteristics were also recorded.

Results

Seventy‐one of one hundred and seventy‐eight patients (39.9%) had at least one cardiophrenic lymph node larger than 8 mm in diameter on pre‐transplant CT. One hundred and sixty‐six total lymph nodes were characterized. Six lymph nodes (3.6%) in two patients increased in size on follow‐up imaging; all six cardiophrenic lymph nodes were presumed to represent metastases. There was a statistically significant reduction in lymph node size in patients who were transplanted vs. those who were not transplanted. Furthermore, a statistically significant association was found between increasing Model for End‐Stage Liver Disease score and lymph node size reduction. There were no significant differences in post‐transplant survival between patients with different lymph node outcomes.

Conclusion

In the absence of metastatic disease in other sites, these lymph nodes are probably reactive; further workup is likely not necessary.
The development of route learning in Down syndrome, Williams syndrome and typical development: investigations with virtual environments
Authors: Purser Harry R.M. , Farran Emily K. , Courbois Yannick , Lemahieu Axelle , Sockeel Pascal , Mellier Daniel , Blades Mark
Published: October 2014

The ability to navigate new environments has a significant impact on the daily life and independence of people with learning difficulties. The aims of this study were to investigate the development of route learning in Down syndrome (N= 50), Williams syndrome (N= 19), and typically developing children between 5 and 11 years old (N= 108); to investigate use of landmarks; and to relate cognitive functions to route‐learning ability in these groups. Overall, measures of attention and long‐term memory were strongly associated with route learning, even once non‐verbal ability was controlled for. All of the groups, including 5‐ to 6‐year‐oldTDchildren, demonstrated the ability to make use of all landmark types to aid route learning; those near junctions, those further from junctions, and also distant landmarks (e.g. church spire, radio mast). Individuals withWSperformed better than a matched subset ofTDchildren on more difficult routes; we suggest that this is supported by relatively strong visual feature recognition in the disorder. Participants withDSwho had relatively high levels of non‐verbal ability performed at a similar level toTDparticipants.
Biochemical characterization of the water‐soluble squalene synthase from Methylococcus capsulatus and the functional analyses of its two DXXD(E)D motifs and the highly conserved aromatic amino acid residues
Authors: Ohtake Kana , Saito Naoki , Shibuya Satoshi , Kobayashi Wakako , Amano Ryosuke , Hirai Takumi , Sasaki Shinji , Nakano Chiaki , Hoshino Tsutomu
Published: October 2014

Information regarding squalene synthases (SQSs) from prokaryotes is scarce. We aimed to characterize the SQS from Methylococcus capsulatus. We studied its reaction mechanism by kinetic analysis and evaluated the structure of the substrate/inhibitor‐binding sites via homology modeling. The cloned M. capsulatus SQS was expressed in Escherichia coli and purified by nickel‐nitrilotriacetic acid column chromatography. Interestingly, M. capsulatus SQS was water‐soluble and did not require any detergent for its higher activity, unlike other SQSs studied previously; supplementation of any type of detergent inhibited enzyme activity. The specific activity and the kinetic values (Km and kcat) for the substrate farnesyl diphosphate and NADPH are reported. The substrate analog farnesyl methylenediphosphonate showed potent inhibition toward the enzyme. We prepared the site‐specific mutants directed at potential active‐site residues 58DXX61E62D (S1 site) and 213DXX216D217D (S2 site), which were assumed to be involved in the binding of the substrate farnesyl diphosphate through the Mg2+ ion. We first demonstrated that the S1 site and the two basic residues (R55 and K212) were responsible for the binding of farnesyl diphosphate. Furthermore, we examined the catalytic roles of the highly conserved aromatic residues and demonstrated that the Y164 residue abstracts the proton of cation 5, which is produced during the first half‐reaction (Scheme 1), to afford presqualene diphosphate, and that the W224 residue stabilizes the intermediary cation 5 via the cation–π interaction. Furthermore, we confirm for the first time that the F32 and the Y51 residues also stabilize the carbocation intermediate(s) generated during the second half‐reaction.
Structural basis for the binding of the membrane‐proximal C‐terminal region of chemokine receptor CCR2 with the cytosolic regulator FROUNT
Authors: Esaki Kaori , Yoshinaga Sosuke , Tsuji Tatsuichiro , Toda Etsuko , Terashima Yuya , Saitoh Takashi , Kohda Daisuke , Kohno Toshiyuki , Osawa Masanori , Ueda Takumi , Shimada Ichio , Matsushima Kouji , Terasawa Hiroaki
Published: October 2014

The membrane‐proximal C‐terminal region (Pro‐C) is important for the regulation of G‐protein‐coupled receptors (GPCRs), but the binding of the Pro‐C region to a cytosolic regulator has not been structurally analyzed. The chemokine receptor CCR2 is a member of the GPCR superfamily, and the Pro‐C region of CCR2 binds to the cytosolic regulator FROUNT. Studying the interaction between CCR2 Pro‐C and FROUNT at an atomic level provides a basis for understanding the signal transduction mechanism via GPCRs. NOE‐based NMR experiments showed that, when bound to FROUNT, CCR2 Pro‐C adopted a helical conformation, as well as when embedded in dodecylphosphocholine micelles. A comparison of two types of cross‐saturation‐based NMR experiments, applied to a three‐component mixture of Pro‐C, FROUNT and micelles or a two‐component mixture of Pro‐C and micelles, revealed that the hydrophobic binding surface on Pro‐C for FROUNT mostly overlapped with the binding site for micelles, suggesting competitive binding of Pro‐C between FROUNT and micelles. Leu316 was important for both FROUNT and micelle binding. Phe319 was newly identified to be crucial for FROUNT binding, by NMR and mutational analyses. The association and dissociation rates of CCR2 Pro‐C for lipid bilayer biomembranes were faster than those for FROUNT. We previously reported that FROUNT binding to CCR2 is detectable even in unstimulated cells and increases in response to chemokine stimulation. Taken together, these results support a model of CCR2 equilibrium: chemokine binding changes the conformational equilibrium of CCR2 toward the active state, and Pro‐C switches its binding partner from the membrane to FROUNT.

Database

Protein Data Bank submission codes of FROUNT‐bound form and DPC micelle‐bound form are PDB ID 2MLQ and PDB ID 2MLO, respectively. Biological Magnetic Resonance Bank submission codes of the samples of 800 μm 13C/15N‐labeled CCR2 Pro‐C mixed with 8 μm unlabeled FROUNT and the samples of 200 μm 13C/15N‐labeled CCR2 Pro‐C mixed with 10 mm DPC‐d38 are BMRB ID 19829 and BMRB ID 19828, respectively.

Structured digital abstract

FROUNT binds to CCR2 Pro-C by surface plasmon resonance (1, 2)

FROUNT and CCR2 Pro-C bind by nuclear magnetic resonance (View interaction)
An update on anal neoplasia
Authors: Fléjou Jean‐François
Published: October 2014

Although anal cancer remains a relatively uncommon tumour its frequency is rising, especially in high‐risk groups. It is now well recognized that anal squamous cell carcinoma, the largely predominant tumour type, shares many similarities with cancer of the uterine cervix, with a major role for oncogenic human papilloma viruses in both tumours. Anal squamous precancerous lesions have now to be classified with the same criteria and terminology as their cervical counterparts, by using the Lower Anogenital Squamous Terminology (LAST) proposal. Only p16 protein is a useful marker in this setting at the present time. As most cases of anal cancer are treated by non‐surgical procedures, pathology has a limited role in the staging of the disease, except for early lesions treated by local excision, and when the sentinel lymph node procedure is undertaken that is still under evaluation. A variety of other tumour types can occur more rarely, with difficult diagnostic issues, solved in most cases by immunohistochemistry.
CBCT‐based volume of simulated root resorption – influence of FOV and voxel size
Authors: Da Silveira P. F. , Fontana M. P. , Oliveira H. W. , Vizzotto M. B. , Montagner F. , Silveira H. L. , Silveira H. E.
Published: October 2014

Aim

To examine the influence of the field of view (FOV) and voxel size on the measurement of the volume of simulated internal root resorption (IRR) lesions through cone‐beam computed tomography (CBCT).

Methodology

Eleven single‐rooted teeth with IRR simulated by acid demineralization were studied. CBCT images were acquired using large FOV (voxel sizes of 0.200, 0.250 and 0.300 mm) and limited FOV (voxel sizes of 0.076, 0.100 and 0.200 mm). The IRR volumes were calculated using the Dolphin® software. Volumetric measurements were validated using IRR silicone putty casts. The analysis of variance (anova) for randomized block design complemented with the Tukey's test was employed.

Results

IRR volumes obtained using voxel sizes of 0.200 and 0.250 mm were similar (P > 0.05). However, both these values were significantly different from that obtained using the 0.300‐mm voxel (P < 0.05). There was no significant difference between IRR volumes measured through voxel sizes of 0.076 and 0.100 mm (P > 0.05), but both differed significantly from that obtained through the 0.200‐mm voxel (P < 0.05). There was no significant difference between the volumetric measurements of the 0.200‐mm voxel images of the restricted and large FOV protocols. The mean volumes of the silicone casts were smaller than those calculated using a 0.200‐mm voxel, but were similar to those obtained using voxel sizes of 0.076 and 0.300 mm.

Conclusions

Despite the FOV protocol, voxel size can influence measurement of simulated IRR volumes. The importance of standardization of CBCT image acquisition protocols is emphasized, especially during follow‐up of an IRR lesion, to prevent misinterpretation of its extent, which can create a bias in clinical decisions.
Human T helper type 1 dichotomy: origin, phenotype and biological activities
Authors: Annunziato Francesco , Cosmi Lorenzo , Liotta Francesco , Maggi Enrico , Romagnani Sergio
Published: October 2014

The great variety of pathogens present in the environment has obliged the immune system to evolve different mechanisms for tailored and maximally protective responses. Initially, two major types of CD4+ T helper (Th) effector cells were identified, and named as type 1 (Th1) and type 2 (Th2) cells because of the different cytokines they produce. More recently, a third type of CD4+ Th effectors has been identified and named as Th17 cells. Th17 cells, however, have been found to exhibit high plasticity because they rapidly shift into the Th1 phenotype in the inflammatory sites. Therefore, in these sites there is usually a dichotomous mixture of classic and non‐classic (Th17‐derived) Th1 cells. In humans, non‐classic Th1 cells express CD161, as well as the retinoic acid orphan receptor C, interleukin‐17 receptor E (IL‐17RE), IL‐1RI, CCR6, and IL‐4‐induced gene 1 and Tob‐1, which are all virtually absent from classic Th1 cells. The possibility to distinguish between these two cell subsets may allow the opportunity to better establish their respective pathogenic role in different chronic inflammatory disorders. In this review, we discuss the different origin, the distinctive phenotypic features and the major biological activities of classic and non‐classic Th1 cells.
Morphological Study of the Encystment and Excystment of Vermamoeba vermiformis Revealed Original Traits
Authors: Fouque Emilie , Yefimova Marina , Trouilhé Marie‐Cécile , Quellard Nathalie , Fernandez Béatrice , Rodier Marie‐Hélène , Thomas Vincent , Humeau Philippe , Héchard Yann
Published: October 2014

Free‐living amoebae are ubiquitous protozoa commonly found in water. Among them, Acanthamoeba and Vermamoeba (formerly Hartmannella) are the most represented genera. In case of stress, such as nutrient deprivation or osmotic stress, these amoebae initiate a differentiation process, named encystment. It leads to the cyst form, which is a resistant form enabling amoebae to survive in harsh conditions and resist disinfection treatments. Encystment has been thoroughly described in Acanthamoeba but poorly in Vermamoeba. Our study was aimed to follow the encystment/excystment processes by microscopic observations. We show that encystment is quite rapid, as mature cysts were obtained in 9 h, and that cyst wall is composed of two layers. A video shows that a locomotive form is likely involved in clustering cysts together during encystment. As for Acanthamoeba, autophagy is likely active during this process. Specific vesicles, possibly involved in ribophagy, were observed within the cytoplasm. Remarkably, mitochondria rearranged around the nucleus within the cyst, suggesting high needs in energy. Unlike Acanthamoeba and Naegleria, no ostioles were observed in the cyst wall suggesting that excystment is original. During excystment, large vesicles, likely filled with hydrolases, were found in close proximity to cyst wall and digest it. Trophozoite moves inside its cyst wall before exiting during excystment. In conclusion, Vermamoeba encystment/excystment displays original trends as compare to Acanthamoeba.
Phylogenetic Analysis and the Evolution of the 18S rRNA Gene Typing System of Acanthamoeba
Authors: Fuerst Paul A. , Booton Gregory C. , Crary Monica
Published: October 2014

Species of Acanthamoeba were first described using morphological characters including cyst structure and cytology of nuclear division. More than 20 nominal species were proposed using these methods. Morphology, especially cyst shape and size, has proven to be plastic and dependent upon culture conditions. The DNA sequence of the nuclear small‐subunit (18S) rRNA, the Rns gene, has become the most widely accepted method for rapid diagnosis and classification of Acanthamoeba. The Byers–Fuerst lab first proposed an Rns typing system in 1996. Subsequent refinements, with an increasing DNA database and analysis of diagnostic fragments within the gene, have become widely accepted by the Acanthamoeba research community. The development of the typing system, including its current state of implementation is illustrated by three cases: (i) the division between sequence types T13 and T16; (ii) the diversity within sequence supertype T2/T6, and (iii) verification of a new sequence type, designated T20. Molecular studies make clear the disconnection between phylogenetic relatedness and species names, as applied for the genus Acanthamoeba. Future reconciliation of genetic types with species names must become a priority, but the possible shortcomings of the use of a single gene when reconstructing the evolutionary history of the acanthamoebidae must also be resolved.
Synechococcus: 3 billion years of global dominance
Authors: Dvořák Petr , Casamatta Dale A. , Poulíčková Aloisie , Hašler Petr , Ondřej Vladan , Sanges Remo
Published: October 2014

Cyanobacteria are among the most important primary producers on the Earth. However, the evolutionary forces driving cyanobacterial species diversity remain largely enigmatic due to both their distinction from macro‐organisms and an undersampling of sequenced genomes. Thus, we present a new genome of a Synechococcus‐like cyanobacterium from a novel evolutionary lineage. Further, we analyse all existing 16S rRNA sequences and genomes of Synechococcus‐like cyanobacteria. Chronograms showed extremely polyphyletic relationships in Synechococcus, which has not been observed in any other cyanobacteria. Moreover, most Synechococcus lineages bifurcated after the Great Oxidation Event, including the most abundant marine picoplankton lineage. Quantification of horizontal gene transfer among 70 cyanobacterial genomes revealed significant differences among studied genomes. Horizontal gene transfer levels were not correlated with ecology, genome size or phenotype, but were correlated with the age of divergence. All findings were synthetized into a novel model of cyanobacterial evolution, characterized by serial convergence of the features, that is multicellularity and ecology.
Multilocus evidence for globally distributed cryptic species and distinct populations across ocean gyres in a mesopelagic copepod
Authors: Andrews Kimberly R. , Norton Emily L. , Fernandez‐Silva Iria , Portner Elan , Goetze Erica
Published: October 2014

Zooplanktonic taxa have a greater number of distinct populations and species than might be predicted based on their large population sizes and open‐ocean habitat, which lacks obvious physical barriers to dispersal and gene flow. To gain insight into the evolutionary mechanisms driving genetic diversification in zooplankton, we developed eight microsatellite markers to examine the population structure of an abundant, globally distributed mesopelagic copepod, Haloptilus longicornis, at 18 sample sites across the Atlantic and Pacific Oceans (n = 761). When comparing our microsatellite results with those of a prior study that used a mtDNA marker (mtCOII, n = 1059, 43 sample sites), we unexpectedly found evidence for the presence of a cryptic species pair. These species were globally distributed and apparently sympatric, and were separated by relatively weak genetic divergence (reciprocally monophyletic mtCOII lineages 1.6% divergent; microsatellite FST ranging from 0.28 to 0.88 across loci, P < 0.00001). Using both mtDNA and microsatellite data for the most common of the two species (n = 669 for microsatellites, n = 572 for mtDNA), we also found evidence for allopatric barriers to gene flow within species, with distinct populations separated by continental landmasses and equatorial waters in both the Atlantic and Pacific Ocean basins. Our study shows that oceanic barriers to gene flow can act as a mechanism promoting allopatric diversification in holoplanktonic taxa, despite the high potential dispersal abilities and pelagic habitat for these species.
Inspection of Feasible Calibration Conditions for UV Radiometer Detectors with the KI/KIO3 Actinometer
Authors: Qiang Zhimin , Li Wentao , Li Mengkai , Bolton James R. , Qu Jiuhui
Published: October 2014

UV radiometers are widely employed for irradiance measurements, but their periodical calibrations not only induce an extra cost but also are time‐consuming. In this study, the KI/KIO3 actinometer was applied to calibrate UV radiometer detectors at 254 nm with a quasi‐collimated beam apparatus equipped with a low‐pressure UV lamp, and feasible calibration conditions were identified. Results indicate that a washer constraining the UV light was indispensable, while the size (10 or 50 mL) of a beaker containing the actinometer solution had little influence when a proper washer was used. The absorption or reflection of UV light by the internal beaker wall led to an underestimation or overestimation of the irradiance determined by the KI/KIO3 actinometer, respectively. The proper range of the washer internal diameter could be obtained via mathematical analysis. A radiometer with a longer service time showed a greater calibration factor. To minimize the interference from the inner wall reflection of the collimating tube, calibrations should be conducted at positions far enough away from the tube bottom. This study demonstrates that after the feasible calibration conditions are identified, the KI/KIO3 actinometer can be applied readily to calibrate UV radiometer detectors at 254 nm.
Photostability of Cosmetic UV Filters on Mammalian Skin Under UV Exposure
Authors: Stiefel Constanze , Schwack Wolfgang , Nguyen Yen‐Thi Hai
Published: October 2014

Previous studies showed that the common UV filter substances benzophenone‐3 (BP–3), butyl methoxydibenzoylmethane (BM–DBM), octocrylene (OCR), ethylhexyl methoxycinnamate (EHMC), ethylhexyl salicylate (EHS) and ethylhexyl triazone (EHT) were able to react with amino side chains of different proteins in vitro. To transfer the results to mammalian skin conditions, sunscreen products were applied on both prepared fresh porcine skin and glass plates, followed by UV irradiation and the determination of depletion of the respective UV filters. Significantly lower recoveries of the UV filters extracted from skin samples than from glass plates indicated the additional reaction of the UV filters with skin constituents, when proteins will be the most important reactants. Among the products tested, BP‐3 showed the greatest differences in recoveries between glass and skin samples of about 13% and 24% after 2 and 4 h of irradiation, respectively, followed by EHS > BM‐DBM > OCR > EHMC > EHT. The obtained results raise the question, whether the common in vitro evaluations of sunscreens, using inert substrate materials like roughened quartz or polymethyl methacrylate (PMMA) plates are really suitable to fully replace in vivo methods, as they cannot include skin‐typical reactions.
Localization and seasonal variation of blue pigment (sandercyanin) in walleye (Sander vitreus)
Authors: Schaefer Wayne F. , Schmitz Mark H. , Blazer Vicki S. , Ehlinger Timothy J. , Berges John A.
Published: October 2014

Several fish species, including the walleye (Sander vitreus), have “yellow” and “blue” color morphs. In S. vitreus, one source of the blue color has been identified as a bili-binding protein pigment (sandercyanin), found in surface mucus of the fish. Little is known about the production of the pigment or about its functions. We examined the anatomical localization and seasonal variation of sandercyanin in S. vitreus from a population in McKim Lake, northwestern Ontario, Canada. Skin sections were collected from 20 fish and examined histologically. Mucus was collected from 306 fish over 6 years, and the amount of sandercyanin was quantified spectrophotometrically. Sandercyanin was found solely on dorsal surfaces of the fish and was localized to novel cells in the epidermis, similar in appearance to secretory sacciform cells. Sandercyanin concentrations were significantly higher in fish collected in summer versus other seasons. Yellow and blue morphs did not differ in amounts of sandercyanin, suggesting that the observed blue color, in fact, arises from lack of yellow pigmentation in blue morphs. The function of the sandercyanin remains unclear, but roles in photoprotection and countershading are consistent with available data.
If You Go Down to the Soak Today: Symbolism and Structure in an Arandic Children’s Story
Authors: Green Jennifer , Turpin Myfany
Published: October 2014

In an Aboriginal children’s story from Central Australia, small creatures such as dragon lizards and ground-dwelling insect larvae known as ant lions convey rich symbolic meanings. This article analyzes the story, song, and graphic schema of a story that reinforces the dangers of being alone and the unpredictable incarnations of malevolent characters. By comparing versions in several Arandic languages, we elucidate the network of social and cultural meanings of the story and the poetic and artistic devices used to express them. We suggest that formalized children’s “play” routines such as this story perform an important role in socialization in Arandic society.
‘A Mayde, and Last of Youre Blood’: Galahad’s Asexuality and its Significance in Le Morte Darthur
Authors: Arkenberg Megan
Published: October 2014

Reading the ‘virginité and chastité’ of Galahad in Malory’s Morte Darthur as asexuality , a subjectivity defined by lack of sexual desire, reveals a logic at work in the text that rejects a futurity based on desire and heterosexual reproduction.
Geoffrey of Monmouth’s Sources for the Cador and Camblan Narratives
Authors: Pace Edwin
Published: October 2014

A survey of Geoffrey’s Historia Regum Britanniae suggests that it is a work transmitted over many centuries, incorporating narratives mis-sychronized from different periods. Accounts from earlier known exemplars display a consistent variation, with those farthest in time from the twelfth century displaying the greatest degree of change.
Representations of Health, Embodiment, and Experience in Graphic Memoir
Authors: Donovan Courtney
Published: October 2014

This essay focuses on the importance of incorporating graphic memoirs in feminist considerations of health, embodiment, and experience. It argues that graphic memoirs refine feminist engagement with these questions by demonstrating the complexity of embodied health experiences with both visual and written text. Like personal accounts, memoirs, and autobiographical writings on health and medicine, graphic memoirs provide valid and important empirical information for dealing with questions of health and medical questions in medical practice and research. The essay draws on Ellen Forney’s graphic memoir Marbles to illustrate its point, which centers on her experience with bipolar disorder. Embodiment is central not only to Forney’s experience of bipolar disorder, but also to her written and visual narratives; specifically, she emphasizes how the contrasting moods of mania and depression create distinct embodied experiences.
“I have more Sight than Sense”: The Sensorium in Taylor’s Meditations 38-40
Authors: Honegger Mark
Published: October 2014

This essay examines the sensory references in three poems by Edward Taylor, based on a relativistic approach to the sensorium, which may vary in different cultures and at different eras. The essay argues that abstract-to-abstract metaphorical mappings, as are found more often in poetry than in other genres, should better inform cognitive linguistic theorizing about metaphor.
Peut-on déplier les pilules de papier de Sherwood Anderson?
Authors: Thomières Daniel
Published: October 2014

Cet essai est une interrogation sur la lecture, dépli-ement, expli-cation, compli-cation, multipli-cation, etc. Il porte sur une analyse de la nouvelle de Sherwood Anderson « Paper Pills », extraite de Winesburg, Ohio .
Maungawhau and Maungakiekie: Reinterpreting the Cultural Landscape
Authors: Lewthwaite Gordon R.
Published: October 2014

The "mountain of the whau tree" ( Entelea arborescens ) now called Mount Eden, and the "mountain of the kiekie" ( Freycinetia banksii ), now known as One Tree Hill, are ancient Maori pas or fortresses preserved by rare foresight in the heart of Auckland, New Zealand. The vicinity, described by one authority as perhaps the most populous of any region occupied by Neolithic man, reveals much of Maori ecology. Shellfish middens, rectangular cultivation plots, sweetpotato storage pits, and groves of fruiting karaka trees stipple the volcanic slopes, and the crater-complexes are carved into suites of house-terraces. Archaeology has uncovered the stumps of defensive stockades, but uncertainties remain: the extent of the occupied area, the numbers involved, and relationships to nearby pas and economic resources still pose difficult questions of interpretation.
Changing Uses of Rural Churches: Examples from Minnesota and Manitoba
Authors: Foster Richard H.
Published: October 2014

With the occupation of North America by settlers of European origin, churches were established almost immediately. They were among the most important cultural cornerstones in communities across Canada and the United States. That was the case in rural parts of both Minnesota and Manitoba, whether churches served people in the countryside, in villages, or in small towns. Many of those rural churches gradually have ceased being used for regular worship services during the past few decades. That has been the result of migration and other demographic changes, along with geographic, social, and economic factors. While discontinuance of regular worship services has caused disappointment among area residents, the possibility of using closed churches for strictly secular purposes often sparks controversy. In both rural Minnesota and rural Manitoba, churches have been found to be significant not only for religious/cultural reasons but also because of the personal attachment many families have to them and their role in local history.
Richard Hugo's "Triggering Towns": A Poet's Landscape of Montana
Authors: Cragg Barbara Taylor
Published: October 2014

The late Richard Hugo looked to the small towns and daily life of Montana's people for subjects which triggered his poetic genius. His passion for the ordinary, the neglected, and the lonely, takes form against the backdrop of ranches, bars, and main streets along the two-lane highways of the West. Much of his poetry reflects the bleakness of western landscapes; at the same time, it reaffirms the bond between people and place and the enduring significance that the American West holds for all Americans.
Vegetation and Land Cover Change in the Willamette River Greenway in Benton and Linn Counties, Oregon: 1972-1981
Authors: Frenkel Robert E. , Wickramaratne S. Nimal , Heinitz Eric F.
Published: October 2014

Change in vegetation and land cover was determined from a time sequence of aerial photographs. Riparian vegetation and land cover in the legislatively defined Willamette River Greenway was classified as: Coniferous Forest, Tall Deciduous Forest, Low Deciduous Forest, Narrowleaf Shrub, Broadleaf Shrub, Grassland, Sand/Gravel Bar, Agriculture, Development, and Water. These types were mapped at 1:12,000 on a set of 29 sheets based on 1976 natural color imagery. A second set of 29 vegetation and land cover change maps was drawn based on interpretation and analysis of 1972 and 1981 aerial photographs using five mapping categories: aggregated vegetation cover; agriculture; development (including sand and gravel operations); cobble, silt, and sand bar; and water. Total Greenway area studied encompassed 12,813 acres (5,185 hectares). A total of 726 acres (294 hectares) of aggregated riparian vegetation was converted to agriculture and development from 1972 to 1981. The legislatively mandated Willamette River Greenway program may not be an effective approach to protecting riparian zone resources.