bluuebunny/crossref_metadata_2025 huggingface dataset:
A Multi‐Method Database of the Black and White Marbles of Göktepe (Aphrodisias), Including Isotopic, EPR, Trace and Petrographic Data
Authors: Attanasio D. , Bruno M. , Prochaska W. , Yavuz A. B.
Published: December 2013

A database of the ancient marbles of Göktepe near Aphrodisias is reported, and includes 160 white, black and bichrome samples from 13 quarries and two waste deposits. The quarries are grouped into four districts. Districts 1 and 2, to the north, produced exclusively black or dark grey marbles (nero antico). Districts 3 and 4 produced white statuary marble. Nero antico and a black and white stone were also quarried in district 4, where the black marble surfaces again. The samples were characterized using petrography, isotopic analysis, EPR spectroscopy and trace analysis. The Göktepe white exhibits an unparalleled combination of fine grain, low EPR intensity and high strontium concentration that often allows easy identification. The isotopic values are less distinctive and similar to those for Carrara. In most cases, however, they are tightly grouped and also quite indicative. The black marbles exhibit a much weaker metamorphic overprint. With respect to the white marbles, they show analytical similarities but also notable differences. Therefore, establishing their provenance can be more difficult and may require the support of petrographic analysis. The results suggest that the Göktepe marbles were among the most prized and widespread statuary marbles used in Roman times, particularly from the early second century ad onwards.
Interactive models of depression vulnerability: The role of childhood trauma, dysfunctional attitudes, and coping
Authors: Morris Matthew C. , Kouros Chrystyna D. , Fox Kathryn R. , Rao Uma , Garber Judy
Published: December 2013

Objectives

This prospective study investigated whether within‐individual relations between depression vulnerability factors (childhood trauma, dysfunctional attitudes, maladaptive coping) and depressive symptom trajectories varied as a function of the number of prior major depressive episodes (MDEs) experienced in their lifetime.

Design

Participants were 68 young adults who varied with regard to their history of depression; 32 were remitted depressed and 36 were never depressed.

Methods

Depressive symptoms and disorders were assessed using semi‐structured psychiatric interviews conducted twice over a 6‐month period; interviews yielded weekly ratings of depressive symptoms during the follow‐up interval. Childhood trauma, dysfunctional attitudes and coping were assessed with self‐report measures. Data analyses were conducted using time‐lagged multilevel models.

Results

Individuals with more previous MDEs who reported greater childhood trauma exposure, more dysfunctional attitudes, or greater use of maladaptive coping strategies experienced more rapid increases in depressive symptoms during the follow‐up period. A significant interaction of coping, number of previous MDEs, and time was found indicating that among individuals with less adaptive coping (i.e., lower primary or lower secondary control coping scores), depressive symptoms rating (DSR) increased significantly in relation to number of prior depressive episodes; no change in DSR was observed for never‐depressed individuals. Among individuals with higher primary control coping scores, significant increases in DSR scores were observed for individuals with ≥3 prior MDEs only.

Conclusions

Findings highlight the need for treatment and prevention programmes that target stress reactivity and coping strategies early in the course of depression.

Practitioner points

Findings highlight the need to conduct multi‐dimensional assessments of depression vulnerability that examine the interplay among risk factors over time.

Relations between vulnerability factors (childhood trauma, dysfunctional attitudes, maladaptive coping) and depressive symptoms were stronger for individuals with more prior major depressive episodes (MDEs).

Interventions for recurrent depression should focus on secondary control coping strategies that emphasize accommodation to stressful life events.

Future studies should assess high‐risk individuals before their first MDE to determine whether vulnerability factors linked with recurrence are pre‐existing and relatively stable, or if they reflect ‘scars’ from MDEs.
Unexpectedly increased anorexigenic postprandial responses of PYY and GLP‐1 to fast ice cream consumption in adult patients with Prader‐Willi syndrome
Authors: Rigamonti A. E. , Bini S. , Grugni G. , Agosti F. , De Col A. , Mallone M. , Cella S. G. , Sartorio A.
Published: December 2013

Objective

The effect of eating rate on the release of anorexigenic gut peptides in Prader‐Willi syndrome (PWS), a neurogenetic disorder clinically characterized by hyperphagia and excessive obesity, has not been investigated so far.

Design and Patients

Postprandial PYY and GLP‐1 levels to fast (5 min) and slow (30 min) ice cream consumption were measured in PWS adult patients and age‐matched patients with simple obesity and normal‐weighted subjects. Visual analog scales (VASs) were used to evaluate the subjective feelings of hunger and satiety.

Results

Fast ice cream consumption stimulated GLP‐1 release in normal subjects, a greater increase being observed with slow feeding. Fast or slow feeding did not change circulating levels of GLP‐1 in obese patients, while, unexpectedly, fast feeding (but not slow feeding) stimulated GLP‐1 release in PWS patients. Plasma PYY concentrations increased in all groups, irrespective of the eating rate. Slow feeding was more effective in stimulating PYY release in normal subjects, while fast feeding was more effective in PWS patients. Slow feeding evoked a lower hunger and higher satiety compared with fast feeding in normal subjects, this finding being not evident in obese patients. Unexpectedly, fast feeding evoked a lower hunger and higher satiety in PWS patients in comparison with slow feeding.

Conclusions

Fast feeding leads to higher concentrations of anorexigenic gut peptides and favours satiety in PWS adult patients, this pattern being not evident in age‐matched patients with simple obesity, thus suggesting the existence of a different pathophysiological substrate in these two clinical conditions.
Implant Tooth‐Supported Removable Partial Denture with at Least 15‐Year Long‐Term Follow‐Up
Authors: Mijiritsky Eitan , Lorean Adi , Mazor Ziv , Levin Liran
Published: December 2013

Purpose

The aim of the present report is to describe the long‐term follow‐up of cases treated with implant tooth‐supported removable partial denture (ITSRPD) after at least 15 years.

Materials and Methods

The study sample comprised 20 consecutively partially edentulous patients treated with ITSRPD. Implants were placed in order to improve unfavorable removable partial denture design resulting from unfavorable teeth distribution and biomechanical considerations, esthetic, or periodontal challenges. All patients were followed up every 6 months for the first 2 years and annually thereafter for at least 15 years. Recall visits for professional cleaning and oral hygiene re‐enforcement were scheduled every 3 to 6 mounts.

Results

A total of 42 implants were placed in 20 patients and restored with ITSRPD. All implants and prosthetic devices functioned successfully throughout the 15 years of follow‐up. Three patients had gone through further implant placement several years after ITSRPD was provided, and a fixed implant‐supported restoration was provided on the original and new implants. No implant failure was noted during follow‐up, resulting in a rate for implant survival of 100% for the study. Marginal bone loss around implants ranged between 0 and 2 mm (mean 0.64 ± 0.6 mm). During the follow‐up period, prosthetic complications were minor and included one rest rupture. All patients answered a questionnaire and were satisfied with the prosthesis. They reported good chewing ability and stability of the prosthetic devices.

Conclusions

ITSRPD can be used with predictable long‐term results in carefully selected and well‐maintained population. Patients should be advised of their role in maintenance, and a comprehensive recall system is mandatory to obtain satisfactory long‐term results.
Clinical and Aesthetic Outcome with Post‐Extractive Implants with or without Soft Tissue Augmentation: A 2‐Year Randomized Clinical Trial
Authors: Migliorati Marco , Amorfini Leonardo , Signori Alessio , Biavati Armando Silvestrini , Benedicenti Stefano
Published: December 2013

Background

The aesthetic outcome of an implant‐supported restoration is first of all dependent on the soft tissue volume. Because the labial bone plate resorbs in every direction after tooth extraction, even when an implant is placed immediately, most patients end up with compromised aesthetics.

Materials and Methods

In this parallel‐designed, randomized clinical trial, participants were randomly assigned to the test group (immediate load post‐extractive implant treated with subepithelial connective tissue graft placed using the tunnel technique in the labial area) and control group (immediate load post‐extractive implant treated without raising a flap) with an allocation ratio of 1:1. Both groups received deproteinized bovine bone mineral. Patients were observed at baseline, crown insertion, 1‐year follow‐up, and 2‐year follow‐up. Clinical, radiological and aesthetic parameters were recorded to assess primary treatment outcomes. A random permuted block system was blindly generated ensuring uniformity of the patient allocation during the trial by randomly distributing three participants to the test and three participants to the control group every six treated patients.

Results

At the 2‐year examination, all 47 implants were successfully integrated, demonstrating stability and healthy peri‐implant soft tissues as documented by standard clinical parameters. The results showed a soft tissue remodeling of −10% in thickness and −18% in highness in the non‐grafted group, whereas in the grafted group there was a gain of 35% in thickness and a slight reduction of −11% in highness. Test group reported an increase of aesthetic result (mean pink aesthetic score [PES] 8) compared with control group (mean PES 6.65).

Conclusions

This prospective study demonstrates the effectiveness of placing a soft tissue graft at the time of immediate implant placement in the aesthetic zone. At the 2‐year follow‐up, test group revealed a better aesthetic outcomes and stable facial soft tissues compared with control group.
Recovery of linear and nonlinear heart rate dynamics after coronary artery bypass grafting surgery
Authors: Pantoni Camila Bianca Falasco , Mendes Renata Gonçalves , Di Thommazo‐Luporini Luciana , Simões Rodrigo Polaquini , Amaral‐Neto Othon , Arena Ross , Guizilini Solange , Gomes Walter José , Catai Aparecida Maria , Borghi‐Silva Audrey
Published: December 2013

Background

Conventional coronary artery bypass grafting (C‐CABG) and off‐pump CABG (OPCAB) surgery may produce different patients’ outcomes, including the extent of cardiac autonomic (CA) imbalance. The beneficial effects of an exercise‐based inpatient programme on heart rate variability (HRV) for C‐CABG patients have already been demonstrated by our group. However, there are no studies about the impact of a cardiac rehabilitation (CR) on HRV behaviour after OPCAB. The aim of this study is to compare the influence of both operative techniques on HRV pattern following CR in the postoperative (PO) period.

Methods

Cardiac autonomic function was evaluated by HRV indices pre‐ and post‐CR in patients undergoing C‐CABG (n = 15) and OPCAB (n = 13). All patients participated in a short‐term (approximately 5 days) supervised CR programme of early mobilization, consisting of progressive exercises, from active‐assistive movements at PO day 1 to climbing flights of stairs at PO day 5.

Results

Both groups demonstrated a reduction in HRV following surgery. The CR programme promoted improvements in HRV indices at discharge for both groups. The OPCAB group presented with higher HRV values at discharge, compared to the C‐CABG group, indicating a better recovery of CA function.

Conclusion

Our data suggest that patients submitted to OPCAB and an inpatient CR programme present with greater improvement in CA function compared to C‐CABG.
Endoscopic mucosal resection of a rectal malakoplakia in a healthy adult
Authors: Sato Harunobu , Tsukamoto Tetsuya , Mizuno Yoshihisa , Ichikawa Tomoaki , Kotani Yoshihito , Honda Katsuyuki , Hatta Kouhei , Kuroda Makoto
Published: December 2013

Malakoplakia in the gastrointestinal tract is rare in healthy young people without underlying disease. Sufficient tissue is required for accurate diagnosis. We describe a malakoplakia that developed in a healthy young woman and was treated by endoscopic mucosal resection (EMR). A 40‐year‐old woman with a history of taking oral contraceptives until one year earlier was referred to our hospital with anal bleeding and constipation. A colonoscopy carried out at our another hospital 18 months earlier disclosed no abnormal findings. Colonoscopy at presentation revealed a yellowish‐white tumor, 5 mm in diameter, in the rectum. The lesion was slightly protruded and had a smooth flat surface, without erosion or ulceration. EMR was carried out for a definitive diagnosis. Histopathological examination showed that the tumor contained granular histiocytes, positive for CD68 and negative forcytokeratin (AE1/AE3). Several histiocytes contained intracytoplasmic round bodies (Michaelis–Gutmann bodies), which reacted positively with periodic acid‐Schiff and calcium (Von Kossa) stains. Intracytoplasmic Escherichia coli (von Hansemann bodies) were identified by Giemsa staining. Based on these results, the tumor in the rectum was diagnosed as a malakoplakia. Following EMR, the patient did not receive further treatment for malakoplakia because she had no symptoms associated with malakoplakia. She has been well for more than 9 months, with no symptoms of disease. Awareness of colorectal malakoplakia is important in patients taking steroids, including oral contraceptives.
Gene targeting technologies in rats: Zinc finger nucleases, transcription activator‐like effector nucleases, and clustered regularly interspaced short palindromic repeats
Authors: Mashimo Tomoji
Published: December 2013

The laboratory rat has been widely used as an animal model in biomedical science for more than 150 years. Applying zinc‐finger nucleases or transcription activator‐like effector nucleases to rat embryos via microinjection is an efficient genome editing tool for generating targeted knockout rats. Recently, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated endonucleases have been used as an effective tool for precise and multiplex genome editing in mice and rats. In this review, the advantages and disadvantages of these site‐specific nuclease technologies for genetic analysis and manipulation in rats are discussed.
Is constraint‐induced movement therapy harmful in unilateral spastic cerebral palsy with ipsilateral cortico‐spinal projections?
Authors: Staudt Martin , Berweck Steffen
Published: December 2013

This commentary is on the original article by Islam et al. on pages 252–258 of this issue.
Kidney function crucially affects B‐type natriuretic peptide (BNP), N‐terminal proBNP and their relationship
Authors: Takase Hiroyuki , Dohi Yasuaki
Published: December 2013

Background

B‐type natriuretic peptide (BNP) and N‐terminal proBNP (NT‐proBNP) are useful biomarkers in the management of heart failure. Both peptides are secreted into the circulation after cleavage of their precursor proBNP and excreted from the kidney in the active form or as metabolites. We investigated effects of kidney function on the levels and association of these peptides.

Materials and methods

Plasma concentrations of BNP and serum concentrations of NT‐proBNP were measured in 229 outpatients of our cardiology department (male/female = 138/91, mean age= 68 years) and 53 hospital outpatients on chronic haemodialysis (30/23, 68 years). Kidney function in nondialysed patients was assessed by estimated glomerular filtration rate (eGFR; mL/min/1·73 m2) and categorised across five stages. Effects of kidney function on BNP, NT‐proBNP and their relationship were investigated.

Results

Deterioration in kidney function increased BNP and NT‐proBNP levels, as well as the NT‐proBNP/BNP ratio, and these values were highest in patients on haemodialysis. The eGFR inversely correlated with BNP (r = –0·472), NT‐proBNP (r = –0·579), and the NT‐proBNP/BNP ratio (r = –0·454, all P < 0·0001). A significant correlation was observed between BNP and NT‐proBNP at all stages of kidney function including patients on haemodialysis, but the correlation was significantly affected by kidney function.

Conclusions

Although circulating levels of both BNP and NT‐proBNP increased with deteriorating kidney function, the impact of kidney function on NT‐proBNP was much more pronounced than that on BNP. Kidney function should be taken into account when interpreting data on BNP, NT‐proBNP and their relationship.
Exploring host‐associated differentiation in the North American native cranberry fruitworm, Acrobasis vaccinii, from blueberries and cranberries
Authors: Medina R.F. , Szendrei Z. , Harrison K. , Isaacs R. , Averill A. , Malo E.A. , Rodriguez‐Saona C.
Published: December 2013

The factors explaining host‐associated differentiation (HAD) have not yet been fully characterized, especially in agricultural systems. It is thought that certain characteristics within a system may increase the probability for HAD to occur. These characteristics include relatively long‐standing evolutionary relationships between insects and their host plants, endophagy, and allochrony in host‐plant phenologies. We assessed the status of these characteristics as well as the presence of HAD in the cranberry fruitworm, Acrobasis vaccinii Riley (Lepidoptera: Pyralidae), a pest associated with blueberry and cranberry in eastern North America. We reveal the occurrence of two distinct populations of A. vaccinii that are allochronically isolated by the phenological stage of their respective host plants (cranberries or blueberries). Laboratory‐reared A. vaccinii adults collected from blueberries emerge at least 1 week earlier than adults from cranberries and the antennal sensitivity of adults to host‐plant volatiles differs between A. vaccinii collected from blueberry and cranberry. Despite finding characteristics indicative of HAD, we did not detect a genetic signature of HAD in A. vaccinii. These findings suggest that HAD may occur through behavioral and phenological mechanisms before there is sufficient genetic variation to be detected.
A chalcid wasp acts chiefly as a hyperparasitoid by mostly using small uncommon hosts
Authors: Macedo Margarete V. , Monteiro Ricardo F. , da Fonseca Adriana M. , Mayhew Peter J.
Published: December 2013

Although ovipositing insects may predominantly use resources that lead to high offspring quality, exceptions to this rule have considerably aided understanding of oviposition decisions. We report the frequency of host species use by a solitary facultative hyperparasitoid, Brachymeria subrugosa Blanchard (Hymenoptera: Chalcididae). In our samples, the wasp attacks the large pupae of the moth Gonioterma indecora Zeller (Lepidoptera: Elachistidae), as well as the considerably smaller, and rarer, pupae of two of its other parasitoids. Consistent with conditional sex allocation models, the wasp produced mainly female offspring on the largest (moth) host, an unbiased sex ratio on the middle‐sized (parasitoid) host, and only males on the smallest (parasitoid) host. Adult offspring size was correlated with the size of the host attacked. These features strongly suggest that the two smaller, primary parasitoid, hosts produce lower‐quality offspring. Despite being more common, the proportion of hosts from which parasitoids emerged was lowest (14%) on the largest host species, and highest on the rarer middle‐sized (34%) and smallest (30%) hosts. This suggests that costs or constraints on attacking high‐quality primary hosts may be a selective force favouring the evolution of hyperparasitism.
Wheat bulb fly, Delia coarctata, larval attraction to phenolic components of host‐plant root exudates
Authors: Rogers C.D. , Evans K.A.
Published: December 2013

Wheat bulb fly (WBF), Delia coarctata Fallén (Diptera: Anthomyiidae), larvae are a subterranean pest of wheat [Triticum aestivum L. (Poaceae)] and other cereals. Larvae locate host plants through chemotaxis and chemokinesis, utilising the primary plant metabolite carbon dioxide as a ‘search trigger’ and Poaceae‐specific secondary plant metabolites exuded from the plant. The aim of this study was to use arena bioassays to identify further compounds involved in the host‐finding process. The larval behavioural response to four concentrations of syringic and vanillic acid, chemical constituents of host‐plant exudates, were tested. Analysis of the final resting position of D. coarctata larvae by the Rayleigh test of uniformity identified attraction to wheat seedling exudates and to both compounds at the lowest concentrations tested, with syringic acid concentrations being most attractive at 0.1 mg l−1 and vanillic acid being most attractive at 0.001 mg l−1. These results add more detail to the subterranean chemical ecology of this species, allowing a behavioural sequence for host‐plant orientation by WBF larvae to be proposed.
Genetic structure of cherry fruit fly (Rhagoletis cingulata) populations across managed, unmanaged, and natural habitats
Authors: Smith James J. , Powell Thomas H.Q. , Teixeira Luis , Armstrong William O. , McClowry Robert J. , Isaacs Rufus , Hood Glen R. , Feder Jeffrey L. , Gut Larry
Published: December 2013

The cherry fruit fly (CFF),Rhagoletis cingulataLoew (Diptera:Tephritidae:Trypetini), is endemic to easternNorthAmerica andMexico, where its primary native host is black cherry [Prunus serotinaEhrh. (Rosaceae)]. Cherry fruit fly is also a major economic pest of the fruit of cultivated sweet (Prunus aviumL.) and tart (Prunus cerasusL.) cherries. AdultCFFthat attack wild black cherry and introduced, domesticated cherries in commercial and abandoned orchards are active at different times of the summer, potentially generating allochronic isolation that could genetically differentiate native from sweet and tartCFFpopulations. Here, we test for host‐related genetic differences amongCFFpopulations inMichigan attacking cherries in managed, unmanaged, and native habitats by scoring flies for 10 microsatellite loci. Little evidence for genetic differentiation was found across the three habitats or between the northern and southern MichiganCFFpopulations surveyed in the study. Local gene flow between native black cherry, commercial, and abandoned orchards may therefore be sufficient to overcome seasonal differences in adultCFFactivity and prevent differentiation for microsatellites not directly associated with (tightly linked to) genes affecting eclosion time. The results do not support the existence of host‐associated races inCFFand imply that flies attacking native, managed, and unmanaged cherries should be considered to represent a single population for pest management purposes.
Responses and adaptation by Nephotettix virescens to monogenic and pyramided rice lines with Grh‐resistance genes
Authors: Vu Quynh , Quintana Reyuel , Fujita Daisuke , Bernal Carmencita C. , Yasui Hideshi , Medina Celia D. , Horgan Finbarr G.
Published: December 2013

The green leafhopper, Nephotettix virescens (Distant) (Hemiptera: Cicadellidae), occasionally damages rice in Asia either directly, by feeding on the host phloem, or indirectly by transmitting tungro virus. We assessed the nature of resistance against the leafhopper in monogenic and pyramided near‐isogenic rice lines containing the resistance genes Grh2 and Grh4. Only the pyramided line was resistant to leafhopper damage. Leafhopper nymphs and adults had high mortality and low weight gain when feeding on the pyramided line and adults laid few eggs. In contrast, although there was some minor resistance in 45‐day‐old plants that possessed either Grh2 or Grh4 genes, the monogenic lines were generally as susceptible to the leafhopper as the recurrent parent line Taichung65 (T65). Resistance in the pyramided line was stable as the plant aged and under high nitrogen, and affected each of five Philippine leafhopper populations equally. Furthermore, in a selection study, leafhoppers failed to adapt fully to the pyramided resistant line: nymph and adult survival did improve during the first five generations of selection and attained similar levels as on T65, but egg‐laying failed to improve over 10 generations. Our preliminary results suggested that resistance was associated with physiological costs to the plants in some experiments. The results of this study demonstrate the success of pyramiding resistance genes through marker‐assisted breeding, to achieve a strong and potentially durable resistance. We discuss the utility of gene pyramiding and the development of near‐isogenic lines for leafhopper management.
Does Female Personality Determine Mate Choice Through Sexual Cannibalism?
Authors: Rabaneda‐Bueno Rubén , Aguado Sara , Fernández‐Montraveta Carmen , Moya‐Laraño Jordi
Published: December 2013

Animal personalities (e.g. consistent across‐context behavioural differences between individuals) can lead to differences in mate choice. However, evidence for this link remains limited. Pre‐mating sexual cannibalism can be a behavioural syndrome (i.e. a suboptimal personality) in which adaptive female aggression towards heterospecific prey spills over on non‐adaptive aggression towards courting males, independently of the female mating or feeding status (i.e. the ‘aggressive spillover hypothesis’,ASH). On the other hand, sexual cannibalism can also be a form of mate choice by which females selectively kill or mate with males depending on the male phenotype. We introduce the hypothesis that the most aggressive females in the population will not only attack males more frequently, but will be less likely to impose sexual selection on males through sexual cannibalism. Assuming that in a field common garden experiment in which females were fedad libitumthe rate of weight gain by a female may reflect her voracity or aggressiveness, we show that in the cannibalistic burrowing wolf spiderLycosa hispanica(formerlyL. tarantula), voracity towards heterospecific prey predicts a female's tendency towards sexual cannibalism. Unmated females with higher weight gains were more cannibalistic and attacked males regardless of the male phenotype. On the other hand, females that were less voracious tended to be less cannibalistic, and when they did kill a male, they were selective, killing males in poorer condition and mating with those in better condition. Our results demonstrate that females with different phenotypes (growth rates) differently imposed selection on male condition, tentatively supporting the hypothesis that female aggression levels can spill over on sexual selection through sexual cannibalism.
Genetic risk variants for dyslexia on chromosome 18 in a German cohort
Authors: Mueller B. , Ahnert P. , Burkhardt J. , Brauer J. , Czepezauer I. , Quente E. , Boltze J. , Wilcke A. , Kirsten H.
Published: December 2013

Dyslexia is characterized by impaired reading and spelling. The disorder has a prevalence of about 5% in Germany, and a strong hereditary component. Several loci are thought to be involved in the development of dyslexia. Scerri et al. identified eight potential dyslexia‐associated single nucleotide polymorphisms (SNPs) in seven genes on chromosome 18 in an English‐speaking population. Here, we present an association analysis that explores the relevance of these SNPs in a German population comprising 388 dyslexia cases and 364 control cases. In case–control analysis, three nominal SNP associations were replicated. The major alleles of NEDD4L‐rs12606138 and NEDD4L‐rs8094327 were risk associated [odds ratio (OR) = 1.35, 95% confidence interval (CI) = 1.0–1.7, P‐value = 0.017 and OR = 1.39, 95% CI = 1.1–1.7, P‐value = 0.007, respectively], and both SNPs were in strong linkage disequilibrium (r2 = 0.95). For MYO5B‐rs555879, the minor allele was risk associated (OR = 1.31, 95% CI = 1.1–1.6, P‐value = 0.011). The combined analysis of SNP sets using set enrichment analysis revealed a study‐wide significant association for three SNPs with susceptibility for dyslexia. In summary, our results substantiate genetic markers in NEDD4L and MYO5B as risk factors for dyslexia and provide first evidence that the relevance of these markers is not restricted to the English language.
Stability of athlete blood passport parameters during air freight
Authors: Ashenden M. , Sharpe K. , Plowman J. , Allbon G. , Lobigs L. , Baron A. , Gore C. J.
Published: December 2013

Introduction

Fluctuations in ambient temperature and pressure, as well as physical jostling, may affect the stability of whole blood samples transported by air freight. The aim of this study was to characterize the stability of key blood variables during air freight and to investigate whether vibration or reduced pressure alone affected results.

Methods

Over a 72‐h interval, we evaluated the stability of full blood count indices (plus reticulocytes) in tubes that were air‐freighted a total of 2, 10 and 28 h. We also examined the impact of 24 h of reduced atmospheric pressure (750 hpa or approximately 2500 m.a.s.l) and vibration (5 Hz). Samples were measured on a Sysmex XT‐2000i instrument.

Results

The two key variables in the context of antidoping (haemoglobin concentration, reticulocytes) remained stable over a 72‐h period regardless of the duration of air freight. Atmospheric pressure and vibration had no discernible effect.

Conclusion

Whole blood samples stored in NanoCool devices can be relied upon to remain stable for at least 72 h despite interim air freight.
Novel and rapid enumeration method of peripheral blood stem cells using automated hematology analyzer
Authors: Tanosaki R. , Kumazawa T. , Yoshida A. , Oguni S. , Nakano A. , Yamagata S. , Takahashi N. , Kurosawa S. , Kim S. W. , Yamashita T. , Mori S. , Heike Y. , Fukuda T. , Hamaguchi Y. , Tsuda H.
Published: December 2013

Introduction

The number of infused CD34+ cells is crucial to the success of peripheral blood stem cell transplantation (PBSCT). Here, we present, for the first time, a new method of enumerating hematopoietic progenitor cells (HPCs) for PBSCT.

Method

This novel method is based on hemolysis and chemical staining, followed by flow cytometry‐based optical detection, conducted using an automated hematology analyzer (XN series, Sysmex). CD34+ cells and HPCs were compared in 76 granulocyte colony‐stimulating factor (G‐CSF)‐mobilized blood or apheresis samples taken from healthy donors (n = 18) or patients undergoing autologous PBSCT (n = 6).

Results

There was a strong correlation between the numbers of HPCs and CD34+ cells (R2 = 0.958). The expected total number of HPCs in the final products, which was estimated from HPCs in pre‐apheresis PB or mid‐apheresis products, also correlated well with the total number of CD34+ cells in the final products. The change in HPCs in PB closely resembled that of CD34+ cells during mobilization. Experiments using immunomagnetic beads suggested that the majority of CD34+ cells existed in HPCs, and vice versa.

Conclusion

Hematopoietic progenitor cells may serve as surrogates for CD34+ cells in PBSCT. However, further investigations are required to verify this.
Developmental origins of complex radular characters in the Muricidae: the bifid rachidian edge
Authors: Pio María José , Herbert Gregory S. , Pastorino Guido
Published: December 2013

Muricid gastropod radulae are more complex than those of most other neogastropods, especially in the number and variety of cusps, denticles, and interlocking mechanisms. How this complexity evolved, however, is unknown. Morphological gaps between higher taxa within the Muricidae are substantial, and there are few unambiguous intermediates. Here, we use developmental data from the Patagonian trophonine muricid Trophon geversianus to investigate the evolution of an unusual condition in which there are two marginal cusps at each end of each central rachidian tooth, rather than one or none as in most muricids. Trophon geversianus begins ontogeny with one marginal cusp (the inner marginal cusp), but a second (the outer marginal cusp) appears later, arising from separation of the rachidian base edge from the radular membrane rather than through bifurcation or lateral migration of pre‐existing cusps. Truncation of development (i.e., paedomorphosis) at this second developmental phase in a trophonine ancestor provides an explanation for the lack of transitional forms between most adult trophonine muricids, which have the plesiomorphic condition of one marginal cusp, and sister group ocenebrine muricids, which have the derived condition of two marginal cusps.
Rhogocytes in gastropod larvae: developmental transformation from protonephridial terminal cells
Authors: Stewart Heather , Westlake Hannah E. , Page Louise R.
Published: December 2013

Rhogocytes, terminal cells of protonephridia, and podocytes of metanephridial systems share an architectural feature that creates an apparent sieving device. The sieve serves to ultrafilter body fluid during the excretion and osmoregulation process carried out by nephridial systems, but its function in rhogocytes is unclear. Rhogocytes are molluscan hemocoelic cells that appear to have various functions related to metabolism of metal ions, including synthesis of hemocyanin in some gastropods and metal detoxification in pteriomorph bivalves. A hypothesis that proposed developmental and possibly evolutionary conversion between protonephridial terminal cells and rhogocytes has never been further explored; indeed, information on the occurrence of rhogocytes in molluscan developmental stages is meager. We used transmission electron microscopy to show that rhogocytes are present within larvae of eight species of gastropods sampled from the three major gastropod clades with a feeding larval stage in the life history. In larvae of a heterobranch gastropod, a rhogocyte was located next to each terminal cell of a pair of protonephridia that flanked the foregut, whereas all six species of caenogastropod larvae and a neritimorph larva that we examined had rhogocytes, but no protonephridia, in this location. We did not find ring‐shaped profiles of hemocyanin decamers within rhogocytes of larvae or pre‐hatch embryos. Rhogocytes in newly released larvae of Nerita melanotragus contained orderly bundles of cylinders, but the diameter of the cylinders was only 70% of the diameter typical of hemocyanin multidecamers. By examining embryos of the caenogastropod Nassarius mendicus at four successive developmental time points that bracketed the occurrence of larval hatching, we found that terminal cells from non‐functional protonephridia in pre‐hatch embryos transformed into rhogocytes around the time of hatching. This empirical evidence of ontogenetic transformation of protonephridial terminal cells into rhogocytes might be interpreted as developmental recapitulation of an evolutionary transition that occurred early in molluscan history.
Species delimitation, patterns of diversification and historical biogeography of the Neotropical frog genus Adenomera (Anura, Leptodactylidae)
Authors: Fouquet Antoine , Santana Cassini Carla , Fernando Baptista Haddad Célio , Pech Nicolas , Trefaut Rodrigues Miguel
Published: December 2013

Aim

For many taxa, inaccuracy of species boundaries and distributions hampers inferences about diversity and evolution. This is particularly true in the Neotropics where prevalence of cryptic species has often been demonstrated. The frog genus Adenomera is suspected to harbour many more species than the 16 currently recognized. These small terrestrial species occur in Amazonia, Atlantic Forest (AF), and in the open formations of the Dry Diagonal (DD: Chaco, Cerrado and Caatinga). This widespread and taxonomically complex taxon provides a good opportunity to (1) test species boundaries, and (2) investigate historical connectivity between Amazonia and the AF and associated patterns of diversification.

Location

Tropical South America east of the Andes.

Methods

We used molecular data (four loci) to estimate phylogenetic relationships among 320 Adenomera samples. These results were integrated with other lines of evidence to propose a conservative species delineation. We subsequently used an extended dataset (seven loci) and investigated ancestral area distributions, dispersal–vicariance events, and the temporal pattern of diversification within Adenomera.

Results

Our conservative delineation identified 31 Confirmed Candidate Species (four remaining unconfirmed) representing a 94% increase in species richness. The biogeographical analysis suggested an Amazonian origin of Adenomera with as many as three dispersals to the DD and one to the AF during the Miocene. These dispersals were associated with habitat shifts from forest towards open habitats.

Main conclusions

The DD played a major role in the history of Adenomera in limiting dispersal and favouring diversification of open‐habitat lineages. Moreover, a forest bridge during the Miocene Climatic Optimum may have permitted dispersal from Amazonia towards the AF and subsequent diversification. Uncovering species boundaries and distributions might drastically change inferences based on currently perceived distribution patterns.
Secretory units of islets in transplantation index is a useful predictor of insulin requirement in Japanese type 2 diabetic patients
Authors: Iwata Minoru , Matsushita Yumi , Fukuda Kazuhito , Wakura Tatsurou , Okabe Keisuke , Koshimizu Yukiko , Fukushima Yasuo , Kobashi Chikaaki , Yamazaki Yu , Honoki Hisae , Suzuki Hikari , Kigawa Mika , Tobe Kazuyuki
Published: December 2013

Aims/Introduction

The objective of the present study was to clarify the validity of β‐cell function‐related parameters for predicting the insulin requirement of Japanese type 2 diabetic patients.

Materials and Methods

In 188 patients with type 2 diabetes who had been admitted to the University of Toyama Hospital (Toyama, Japan) without receiving insulin therapy, we carried out a cross‐sectional study examining the relationship between the homeostasis model assessment of β‐cell function (HOMA‐β) and C‐peptide‐based indices, and also carried out a retrospective study to examine the utility for predicting insulin requirement of several β ‐cell function‐related indices using a receiver operating characteristic (ROC) curve analysis.

Results

The secretory units of islets in transplantation index (SUIT) had the strongest correlation with HOMA‐β, followed by the fasting serum C‐peptide immunoreactivity index (CPI); the fasting serum C‐peptide immunoreactivity itself (F‐CPR) had the least correlation. The CPI, HOMA‐β and SUIT were significantly lower in the insulin‐requiring group than in the non‐insulin‐requiring group, even after adjustments for confounding factors (P < 0.01). The areas under the ROC curve for insulin requirement were 0.622, 0.774, 0.808, and 0.759 for F‐CPR, CPI, SUIT, and HOMA‐β, respectively. The cut‐off values of SUIT, CPI, and HOMA‐β for an over 80% specificity for the prediction of insulin therapy were 23.5, 1.00, and 14.9, respectively.

Conclusions

The present study shows that SUIT is the best predictor of insulin requirement among these β‐cell function‐related markers.
Extrahepatic effects of nucleoside and nucleotide analogues in chronic hepatitis B treatment
Authors: Fung James , Seto Wai‐Kay , Lai Ching‐Lung , Yuen Man‐Fung
Published: December 2013

Oral nucleoside/nucleotide analogues (NAs) are the mainstay of therapy for patients with chronic hepatitis B and are generally well tolerated. Despite this, the safety profile of NAs is of paramount importance since the majority of patients will require long‐term treatment. All NAs can potentially affect human DNA polymerase with decrease in mitochondrial DNA, leading to manifestations of mitochondrial toxicity. As a class effect, therefore, NAs can potentially cause extrahepatic conditions, such as myopathy, nephropathy, neuropathy, and lactic acidosis. Indeed, effects on muscles, including myopathy and creatine kinase elevations, have been described with clevudine and telbivudine use. Both adefovir and tenofovir are associated with dose‐dependent nephropathy, predominantly affecting the proximal renal tubules. Neuropathy appears to be rare, and most commonly reported in patients receiving combination therapy with telbivudine and interferon. Increased risk of lactic acidosis has also been described for those with impaired liver and renal function taking entecavir. Loss of bone mineral density and hypophosphatemia have been described with the use of NAs, although the overwhelming studies have been with human immunodeficiency virus‐infected patients. However, not all extrahepatic effects are detrimental. Recent evidence has suggested a potential renal beneficial effect with the use of telbivudine. The effect of NAs on pregnancy appears to be minimal for all NAs, with telbivudine and tenofovir having a more favorable category B rating. Ongoing pharmacovigilance is essential to identify new and monitor existing extrahepatic effects associated with NA use.
Research misconduct: A grand global challenge for the 21st Century
Authors: Farthing Michael J G
Published: December 2013

Research misconduct is now acknowledged to be an important global issue for both researchers and the wider community. Guidance on the responsible conduct of research is now widespread, but many are still concerned by the apparent rising tide of serious cases of research misconduct, and perhaps the more worrying widespread presence of questionable research practices. I would suggest that guidance and training, while essential, are not sufficient. Additional interventions, including enhanced monitoring of research outputs and random audit using the available technology should be considered, as should the desirability of having a register of “licensed researchers.” In addition, I would support a culture change in the research community in which researchers are encouraged to admit their mistakes; this should be accompanied by a spirit of forgiveness and programmed rehabilitation for the individual concerned. For multiple “premier league” offenders who are reluctant to face their misdemeanors, it is difficult to see how they could continue in the role of a researcher, and their “registration” should be revoked. Research is increasingly undertaken by researchers who cross national boundaries. The globalization of research demands greater collaboration between organizations that are responsible for ensuring standards of research integrity; the need for international standards and guidance has never been greater.
Potential of adenovirus‐mediated REIC/Dkk‐3 gene therapy for use in the treatment of pancreatic cancer
Authors: Uchida Daisuke , Shiraha Hidenori , Kato Hironari , Nagahara Teruya , Iwamuro Masaya , Kataoka Junro , Horiguchi Shigeru , Watanabe Masami , Takaki Akinobu , Nouso Kazuhiro , Nasu Yasutomo , Yagi Takahito , Kumon Hiromi , Yamamoto Kazuhide
Published: December 2013

Background and Aim

The reduced expression in immortalized cells REIC/the dickkopf 3 (Dkk‐3) gene, tumor suppressor gene, is downregulated in various malignant tumors. In a prostate cancer study, an adenovirus vector carrying the REIC/Dkk‐3 gene (Ad‐REIC) induces apoptosis. In the current study, we examined the effects of REIC/Dkk‐3 gene therapy in pancreatic cancer.

Methods

REIC/Dkk‐3 expression was assessed by immunoblotting and immunohistochemistry in the pancreatic cancer cell lines (ASPC1, MIAPaCa2, Panc1, BxPC3, SUIT‐2, KLM1, and T3M4) and pancreatic cancer tissues. The Ad‐REIC agent was used to investigate the apoptotic effect in vitro and antitumor effects in vivo. We also assessed the therapeutic effects of Ad‐REIC therapy with gemcitabine.

Results

The REIC/Dkk‐3 expression was lost in the pancreatic cancer cell lines and decreased in pancreatic cancer tissues. Ad‐REIC induced apoptosis and inhibited cell growth in the ASPC1 and MIAPaCa2 lines in vitro, and Ad‐REIC inhibited tumor growth in the mouse xenograft model using ASPC1 cells. The antitumor effect was further enhanced in combination with gemcitabine. This synergistic effect may be caused by the suppression of autophagy via the enhancement of mammalian target of rapamycin signaling.

Conclusions

Ad‐REIC induces apoptosis and inhibits tumor growth in pancreatic cancer cell lines. REIC/Dkk‐3 gene therapy is an attractive therapeutic tool for pancreatic cancer.
Synergistic effect of simvastatin plus NS398 on inhibition of proliferation and survival in hepatocellular carcinoma cell line
Authors: Lee Sun Jae , Hwang Ji Won , Yim Hyungshin , Yim Hyung Joon , Woo Sang Uk , Suh Sang Jun , Hyun Jong Jin , Jung Sung Woo , Koo Ja Seol , Kim Ji Hoon , Seo Yeon Seok , Yeon Jong Eun , Lee Sang Woo , Byun Kwan Soo , Um Soon Ho
Published: December 2013

Background and Aims

NS398, a selective cyclooxygenase‐2 inhibitor, and simvastatin, a 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitor, both exert an anticancer effect on hepatocellular carcinoma cells, but the effect of co‐administration of the two drugs remains unknown. We aimed to investigate the synergistic in vitro anticancer effect of co‐administration of NS398 and simvastatin and its mechanism.

Methods

The Hep3B and Huh‐7 cell lines were cultured. Cells were treated with simvastatin, NS398, or a combination. 5‐bromo‐2′‐deoxyuridine ELISA assay, flow cytometry, Western blot analyses, and immunofluorescence assay were performed.

Results

In both cell lines, co‐administration of simvastatin and NS398 resulted in a greater effect on proliferation and apoptosis. In Hep3B cells, co‐administration of the two drugs resulted in a greater decrease in procaspase 3 and Bcl‐2 and an increase in cleaved caspase 9 than that noted with monotherapy. In Huh‐7 cells, co‐administration of the two drugs resulted in a greater decrease in procaspase 3 and cyclin D1 and an increase in cleaved caspase 9. Expression of NF‐κB and Akt were also decreased to a greater extent when the two drugs were co‐administered in both cell lines. Immunofluorescence assay showed suppression of the nuclear localization of NF‐κB by simvastatin or NS398. The effect was greater by co‐administration.

Conclusions

The co‐administration of NS398 and simvastatin produced greater antiproliferative and proapoptotic effects against Hep3B cells and Huh‐7 cells. Inhibition of the NF‐κB and Akt pathway and activation of caspase cascade, which are considered as the major mechanism of synergistic anticancer properties, were observed in both cell lines.