bluuebunny/crossref_metadata_2025 huggingface dataset:
Long non‐coding RNA Fer‐1‐like protein 4 suppresses oncogenesis and exhibits prognostic value by associating with miR‐106a‐5p in colon cancer
Authors: Yue Ben , Sun Bo , Liu Chenchen , Zhao Senlin , Zhang Dongyuan , Yu Fudong , Yan Dongwang
Published: July 2015

Novel long non‐coding RNA Fer‐1‐like protein 4 (FER1L4) has been confirmed to play crucial regulatory roles in tumor progression. It exerts an impact on tumor suppression and functions as a competing endogenous RNA (ceRNA) by sponging miR‐106a‐5p in gastric cancer. However, its clinical significance in colon cancer is completely unknown. The aim of the present study was to annotate the role of FER1L4 and its clinical value in colon cancer. The results showed the aberrant expression of FER1L4 and miR‐106a‐5p in colon cancer tissues. In addition, significant negative correlation between FER1L4 and miR‐106a‐5p expression levels was observed. Among the colon cancer cell lines, FER1L4 levels were relatively lower, with concurrent high levels of miR‐106a‐5p. Restoration of FER1L4 decreased the expression of miR‐106a‐5p, and had a significant influence on colon cancer cell proliferation, migration and invasion. The FER1L4 expression was correlated with depth of tumor invasion, lymph node metastasis, vascular invasion and clinical stage. Moreover, striking differences in overall survival and disease‐free survival were observed for the cases with both low FER1L4 expression and high miR‐106a‐5p expression compared with cases with high FER1L4 expression and low miR‐106a‐5p expression. Circulating FER1L4 and miR‐106a‐5p levels were decreased and increased, respectively, in colon cancer patients after surgery. Our findings indicated that FER1L4 could exert a tumor suppressive impact on colon cancer, which at least, in part, through suppressing miR‐106a‐5p expression, and depletion of FER1L4, alone or combined with overexpression of miR‐106a‐5p, is predictive of poor prognosis in colon cancer and may play a crucial role in cancer prevention and treatment.
Occupational allergic contact dermatitis caused by epoxy chemicals: occupations, sensitizing products, and diagnosis
Authors: Aalto‐Korte Kristiina , Pesonen Maria , Suuronen Katri
Published: July 2015

Background

Epoxy products are among the most common causes of occupational allergic contact dermatitis. Diglycidyl ether of bisphenol A resin (DGEBA‐R) is the most important sensitizer in epoxy systems.

Objectives

To describe patients with occupational allergic contact dermatitis caused by epoxy products.

Methods

Patients with allergic reactions to epoxy chemicals were chosen from test files (January 1991 to June 2014). Only patients with occupational contact allergy to some component of epoxy resin systems were included. We analysed patch test results, occupation, symptoms, and exposure data.

Results

We found a total of 209 cases with occupational contact allergy to epoxy chemicals. The largest occupational groups were painters (n = 41), floor layers (n = 19), electrical industry workers (n = 19), tile setters (n = 16), and aircraft industry workers (n = 15). A total of 82% of the patients reacted to DGEBA‐R. Diagnosis of the DGEBA‐R‐negative patients required testing with m‐xylylenediamine, N,N′‐tetraglycidyl‐4,4′‐methylenedianiline, 1,4‐butanediol diglycidyl ether, 2,4,6‐tris‐(dimethylaminomethyl)phenol, diglycidyl ether of bisphenol F resin, N,N′‐diglycidyl‐4‐glycidyloxyaniline, isophoronediamine, 4,4′‐diaminodiphenylmethane, diethylenetriamine, and cresyl glycidyl ether. The hands/upper extremities were most commonly affected (69%), but facial symptoms were also frequent (60%).

Conclusions

Allergic contact dermatitis caused by to epoxy products cannot always be diagnosed by the use of commercial test substances. Workplace products need to be tested.
Respiratory mode and gear type are important determinants of elasmobranch immediate and post‐release mortality
Authors: Dapp Derek R , Walker Terence I , Huveneers Charlie , Reina Richard D
Published: July 2015

Estimated declines in shark and ray populations worldwide have raised major, widespread concern about the impacts of global fisheries on elasmobranchs. The mechanisms causing elasmobranch mortality during fisheries’ capture are not fully understood, but we must gain greater clarity on this topic for fisheries managers to develop effective conservation plans to mitigate further population declines. To evaluate how two important factors, respiratory mode and fishing gear type, impact elasmobranch survival, we compiled publicly available data sources on the immediate mortality percentages of 83 species and post‐release mortality percentages of 40 species. Using Bayesian models, we found that sharks and rays captured in longlines had significantly lower immediate mortality than those caught in trawls or gillnets. Our models also predicted the mean total discard mortality (combined immediate and post‐release mortality) percentages of obligate ram‐ventilating elasmobranchs caught in longline, gillnet and trawl gear types to be 49.8, 79.0 and 84.2%, respectively. In contrast, total discard mortality percentages of stationary‐respiring species were significantly lower (longline capture mean = 7.2%, gillnet capture mean = 25.3%, trawl capture mean = 41.9%). Our global meta‐analysis provides the first quantified demonstration of how mortality is affected by these two factors across a broad range of species. Our results and approach can be applied to data‐deficient elasmobranchs and fisheries to identify species that are likely to experience high rates of mortality due to respiratory mode and/or fishing methods used, so that appropriate mitigation measures can be prioritized and investigated.
Biocompatibility of a titanium dioxide‐coating method for denture base acrylic resin
Authors: Tsuji Masashi , Ueda Takayuki , Sawaki Kohei , Kawaguchi Mitsuru , Sakurai Kaoru
Published: July 2015

Objectives

Ease of denture cleaning is of paramount importance in geriatric patients and those with limited dexterity. We have previously investigated methods of coating dentures with titanium dioxide (TiO2) and reported the effects (self‐cleaning and antibacterial) of such treatments in in vitro studies. This study was to verify the biocompatibility of a TiO2‐coated acrylic resin produced by the new coating method with spray‐coating technique.

Methods

Specimens were prepared from denture base acrylic resin and polished up to grit #1000. The TiO2‐coating agent was sprayed onto the specimens using an airbrush gun. Specimens were then divided into ‘polymethyl methacrylate (PMMA)’, ‘primer‐coated PMMA’ and ‘TiO2‐coated PMMA’ groups to be evaluated for biological safety using a hamster oral mucosa irritation test, a guinea pig skin sensitisation test and a rabbit intracutaneous test. The biological reaction was scored.

Results

Reaction scores were considerably <1.0, the acceptable limit set by the ISO, in all three tests. Indeed, in most samples, there was no deleterious effect at all.

Conclusion

These results tested on animals demonstrate that denture base resin coated with TiO2 by this method does not cause irritation or sensitisation of the oral mucosa, skin or intracutaneous tissue and is therefore good biocompatibility for use in close proximity to oral mucosa and skin.
Voltage‐dependent anion channel (VDAC‐1) is required for olfactory sensing in Caenorhabditis elegans
Authors: Uozumi Takayuki , Hamakawa Masayuki , Deno Yu‐ki , Nakajo Nobushige , Hirotsu Takaaki
Published: July 2015

The Ras–MAP kinase signaling pathway plays important roles for the olfactory reception in olfactory neurons in Caenorhabditis elegans. However, given the absence of phosphorylation targets of MAPK in the olfactory neurons, the mechanism by which this pathway regulates olfactory function is unknown. Here, we used proteomic screening to identify the mitochondrial voltage‐dependent anion channel VDAC‐1 as a candidate target molecule of MAPK in the olfactory system of C. elegans. We found that Amphid Wing “C” (AWC) olfactory neuron‐specific knockdown of vdac‐1 caused severe defects in chemotaxis toward AWC‐sensed odorants. We generated a new vdac‐1 mutant using the CRISPR‐Cas9 system, with this mutant also showing decreased chemotaxis toward odorants. This defect was rescued by AWC‐specific expression of vdac‐1, indicating that functions of VDAC‐1 in AWC neurons are essential for normal olfactory reception in C. elegans. We observed that AWC‐specific RNAi of vdac‐1 reduced AWC calcium responses to odorant stimuli and caused a decrease in the quantity of mitochondria in the sensory cilia. Behavioral abnormalities in vdac‐1 knockdown animals might therefore be due to reduction of AWC response, which might be caused by loss of mitochondria in the cilia. Here, we showed that the function of VDAC‐1 is regulated by phosphorylation and identified Thr175 as the potential phosphorylation site of MAP kinase.
Sarcopenia is a risk factor for the recurrence of hepatocellular carcinoma after curative treatment
Authors: Kamachi Saori , Mizuta Toshihiko , Otsuka Taiga , Nakashita Shunya , Ide Yasushi , Miyoshi Atsushi , Kitahara Kenji , Eguchi Yuichiro , Ozaki Iwata , Anzai Keizo
Published: July 2015

Background and Aim

Sarcopenia, initially proposed as decreased of muscle mass and strength, is associated with aging and malignant diseases. The aim of the present study was to determine whether there is a correlation between sarcopenia and the recurrence of hepatocellular carcinoma (HCC) after curative treatment.

Methods

We conducted a retrospective analysis of consecutive naive patients with HCC who underwent curative resection or radiofrequency ablation. To eliminate the influence of cause or the severity of liver damage, subjects were limited to those with HCC with hepatitis C‐related cirrhosis and Child–Pugh class A liver function. Patients were assessed using computed tomographic measurement of muscle mass at the level of the third lumbar (L3) vertebrae, the L3 skeletal muscle index (L3 SMI). Sarcopenia was defined by using previously published, sex‐specific cut‐off value.

Results

Sarcopenia was present in 61 of 92 patients. Patients’ median age was 71.5 years (range, 47–84), and the baseline characteristics of patients were comparable between patients with and without sarcopenia except for sex, serum albumin level, prothrombin time, diabetes mellitus and body mass index. Recurrence rates at 1, 3 and 5 years were 39.1%,77.1%,81.7% for patients with sarcopenia and 23.5%,59.5% and 75.7% for patients without sarcopenia, respectively (P = 0.03). Multivariate Cox analysis revealed that sarcopenia and preoperative α‐fetoprotein of more than 40 ng/mL were significant independent factors for recurrence.

Conclusion

Sarcopenia is a risk factor for recurrence in patients with HCC who were treated with curative treatment.
Efficacy of additional radiofrequency ablation after transcatheter arterial chemoembolization for intermediate hepatocellular carcinoma
Authors: Azuma Seishin , Asahina Yasuhiro , Nishimura‐Sakurai Yuki , Kakinuma Sei , Kaneko Shun , Nagata Hiroko , Goto Fumio , Ootani Satoshi , Kawai‐Kitahata Fukiko , Taniguchi Miki , Murakawa Miyako , Watanabe Takako , Tasaka‐Fujita Megumi , Itsui Yasuhiro , Nakagawa Mina , Watanabe Mamoru
Published: July 2015

Aim

For intermediate hepatocellular carcinoma (HCC), transcatheter arterial chemoembolization (TACE) therapy is recommended in the guidelines as a monotherapy, although TACE is a non‐curative therapy. The aims of the present study were to evaluate the efficacy of adding radiofrequency ablation (RFA) to TACE in patients with intermediate HCC, and to identify the factors that were associated with favorable survival in these patients.

Methods

Fifty‐nine patients with intermediate HCC were enrolled in this retrospective study. Thirty‐nine patients were treated with TACE alone and 20 patients were treated with additional RFA after TACE.

Results

The recurrence‐free survival rates at 0.5, 1 and 2 years for the additional RFA group were 32%, 19% and 13%, respectively, and these were significantly higher than those of the TACE group (8%, 3% and 0%, respectively; log–rank test, P = 0.001). The cumulative survival rates of the additional RFA group were significantly higher than those of the TACE group (log–rank test, P = 0.002), although this significant difference was not found in the subgroup of treatment naive patients because of small sample size. Multivariate analysis indicated male sex, lower total bilirubin, lower α‐fetoprotein, lower des‐γ‐carboxyprothrombin, newly recurrent HCC nodules within the last 12 months and additional RFA as independent factors that were significantly associated with favorable overall survival.

Conclusion

Additional RFA of nodules insufficiently treated by TACE is effective therapy for obtaining favorable disease‐free survival in patients with intermediate HCC, and leads to better overall survival particularly in recurrent patients.
Screening for lupus anticoagulants in patients treated with vitamin K antagonists
Authors: Isert M. , Miesbach W. , Stoever G. , Lindhoff‐Last E. , Linnemann B.
Published: July 2015

Introduction

The dRVVT test for detecting lupus anticoagulants (LA) is difficult to interpret when patients are treated with vitamin K antagonists (VKA).

Methods

We performed LA testing in 33 VKA‐treated patients with definite antiphospholipid syndrome (APS) and compared the results with 100 controls subjects not receiving VKA and 110 APL‐negative patients anticoagulated for reasons other than APS.

Results

Compared with the dRVVT ratio before the initiation of VKA therapy, a higher cutoff value, defined as the 99th percentile, was established for VKA‐treated patients with INR values between 2.0 and 3.5. A dRVVT ratio of >1.7 yielded a sensitivity of 81.3%, specificity of 99.1%, and positive and negative predictive values of 98.7% and 85.8%, respectively, for detecting LA. Cohen's kappa coefficient indicated good agreement for the dRVVT ratio obtained from testing with and without VKA treatment (κ = 0.813; 95% CI: 0.773–0.853), which was higher (κ = 0.941; 95% CI: 0.917–0.965) when the LA diagnosis was based on the results of both the dRVVT and a second test system (i.e., Mixcon‐LA assay).

Conclusions

Lupus anticoagulants testing in VKA‐treated patients with APS according to current guidelines appears to be possible for the majority of patients without discontinuing anticoagulant therapy.
The investigation of circulating microRNAs associated with lipid metabolism in childhood obesity
Authors: Can U. , Buyukinan M. , Yerlikaya F. H.
Published: July 2015

Background

Childhood obesity is an increasing health challenge related to increased risk of chronic diseases. microRNAs (miRNAs) are noncoding short RNA molecules regulating multiple biological processes linked to obesity.

Objectives

We aimed at evaluating the association between circulating miRNA levels and lipid metabolism in obese and non‐obese children and adolescents.

Methods

By constituting study group, 45 obese children and adolescents were recruited. To perform comparisons with study group, 41 lean controls were matched for age and sex. Using real‐time quantitative PCR analysis, circulating miRNAs were evaluated in both groups.

Results

Circulating miR‐335 (P < 0.001), miR‐143 (P = 0.001) and miR‐758 (P = 0.006) in obese children were significantly lower than those of controls. However, circulating miR‐27 (P = 0.032), miR‐378 (P < 0.001) and miR‐370 (P = 0.045) in obese children were significantly higher, compared with those of controls. In addition, circulating miR‐33 in obese children was higher than those of controls, but no significant difference was present (P = 0.687).

Conclusion

Our findings showed that a significant association is present between circulating miR‐370, miR‐33, miR‐378, miR‐27, miR‐335, miR‐143 and miR‐758 values, and childhood obesity. Low levels of miR‐335, miR‐143 and miR‐758, and high levels of miR‐27, miR‐378, miR‐33 and miR‐370 may have been responsible for elevated triglycerides and low‐density lipoprotein (LDL‐C) levels, and low level of high‐density lipoprotein (HDL‐C) in obese subjects. Therefore, miRNAs may be a good novel biomarker for childhood obesity.
Nurses' health‐related behaviours: protocol for a quantitative systematic review of prevalence of tobacco smoking, physical activity, alcohol consumption and dietary habits
Authors: Neall Rosie A. , Atherton Iain M. , Kyle Richard G.
Published: July 2015

Aim

To enumerate nurses' health‐related behaviour by critically appraising studies on tobacco smoking, physical activity, alcohol consumption and dietary habits.

Background

Nurses represent the largest occupational group in healthcare systems internationally and have an established and expanding public health role. Nurses own health‐related behaviour is known to impact nurses' ability and confidence to engage in health promotion, and how patients receive and respond to advice and guidance nurses' give. However, there has been no comprehensive and comparable assessment of evidence on nurses' health‐related behaviours.

Design

Quantitative systematic review of prevalence of tobacco smoking, physical activity, alcohol consumption and dietary habits.

Methods

Systematic searches for literature published between January 2000 and February 2015 and indexed in Medical Literature Analysis and Retrieval System, Cumulative Index to Nursing and Allied Health Literature and Psychological Information. Eligibility criteria will be applied to titles and abstracts by two reviewers independently. Full text will be reviewed and the same criteria and process applied. Two reviewers will independently assess study quality guided by the Joanna Briggs Institute handbook for the systematic review of prevalence and incidence data. Discrepancies in eligibility or quality assessment will be resolved through discussion and, where required, a third reviewer. Data synthesis will be conducted and findings reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses checklist.

Discussion

Enumerating prevalence of nurses' health‐related behaviours is crucial to direct future research, inform public health policy, particularly around health promotion and to better support the nursing workforce through the development of behaviour change interventions.

PROSPERO registration: CRD42015016751.
The role of pigment based plumage traits in resolving conflicts
Authors: Young Catherine Mary , Cain Kristal Elaine , Svedin Nina , Backwell Patricia Ruth Yvonne , Pryke Sarah Rosalind
Published: July 2015

The role of melanin ‘badges of status’, in male–male competition has been well‐studied, in contrast, carotenoid based plumage has largely been examined in the context of female mate choice. Recent work has shown that carotenoid signals can also function in male–male competition, although the functions of the two types of signals is currently unclear. Here, we examine the relationships between colouration, dominance and aggression in the crimson finch Neochmia phaeton, a species where males have both conspicuous red carotenoid plumage and a black melanin patch. We examined the importance of carotenoid and melanin based signals in three contexts: 1) among free‐living birds interacting at a feeding station: we found that neither colour signal influenced the outcome of interactions; 2) in staged dyadic contest in captivity: we found that coloration from carotenoid pigments was positively related to the probability of winning a contest, while the size of the melanin plumage patch was not related to winning; and 3) in staged dyadic contests where male plumage colour had been masked: we found that the number of interactions required to determine dominance increased. While the underlying natural plumage colour was still important in these contests, birds with more intense carotenoid colouration were now more likely to lose. These results confirm carotenoid‐based signalling in male–male contests. However this signal is used in conjunction with other factors such as self‐assessment and body condition. Contrary to traditional expectations, the black melanin patch was not found to be important in this context.
Immature spinal cord neurons are dynamic regulators of adult nociceptive sensitivity
Authors: Rusanescu Gabriel , Mao Jianren
Published: July 2015

Chronic pain is a debilitating condition with unknown mechanism. Nociceptive sensitivity may be regulated by genetic factors, some of which have been separately linked to neuronal progenitor cells and neuronal differentiation. This suggests that genetic factors that interfere with neuronal differentiation may contribute to a chronic increase in nociceptive sensitivity, by extending the immature, hyperexcitable stage of spinal cord neurons. Although adult rodent spinal cord neurogenesis was previously demonstrated, the fate of these progenitor cells is unknown. Here, we show that peripheral nerve injury in adult rats induces extensive spinal cord neurogenesis and a long‐term increase in the number of spinal cord laminae I–II neurons ipsilateral to injury. The production and maturation of these new neurons correlates with the time course and modulation of nociceptive behaviour, and transiently mimics the cellular and behavioural conditions present in genetically modified animal models of chronic pain. This suggests that the number of immature neurons present at any time in the spinal cord dorsal horns contributes to the regulation of nociceptive sensitivity. The continuous turnover of these neurons, which can fluctuate between normal and injured states, is a dynamic regulator of nociceptive sensitivity. In support of this hypothesis, we find that promoters of neuronal differentiation inhibit, while promoters of neurogenesis increase long‐term nociception. TrkB agonists, well‐known promoters of nociception in the short‐term, significantly inhibit long‐term nociception by promoting the differentiation of newly produced immature neurons. These findings suggest that promoters of neuronal differentiation may be used to alleviate chronic pain.
Value of a facilitated quality improvement initiative on cardiovascular disease risk: findings from an evaluation of the Aggressively Treating Global Cardiometabolic Risk Factors to Reduce Cardiovascular Events (AT GOAL)
Authors: Losby Jan L. , Osuji Thearis A. , House Marnie J. , Davis Rachel , Boyce Simone Peart , Greenberg Michael Canter , Whitehill John M.
Published: July 2015

Rationale, aims and objectives

In the United States, cardiovascular disease (CVD) is the leading cause of death. The US Centers for Disease Control and Prevention contracted an evaluation of the Aggressively Treating Global Cardiometabolic Risk Factors to Reduce Cardiovascular Events (AT GOAL) programme as part of its effort to identify strategies to address CVD risk factors.

Methods

This study analysed patient‐level data from 7527 patients in 43 primary care practices. The researchers assessed average change in control rates for CVD‐related measures across practices, and then across patients between baseline and a patient's last visit during the practice's tenure in the programme (referred to as ‘end line’) using repeated measures analysis of variance and random effects generalized least squares, respectively.

Results

Among non‐diabetic patients, there were significant increases in control rates for overall blood pressure (74.3% to 78.0%, P = 0.0002), systolic blood pressure (70.3% to 80.6%, P = 0.0099), diastolic blood pressure (90.1% to 92.7%, P = 0.0001) and low‐density lipoprotein (LDL; 48.6% to 53.1%, P = 0.0001) between baseline and end line. Among diabetic patients, there was a significant increase in diastolic blood pressure control (59.8% to 61.9%, P = 0.0141). While continuous CVD‐related outcomes show an overall trend between baseline and end line, patients with uncontrolled measures at baseline showed a decrease between baseline and end line relative to their counterparts who were controlled at baseline.

Conclusions

Findings from the AT GOAL evaluation support the value of a facilitated quality improvement (QI) initiative on managing CVD risk.
Cyclic Loading Effect on Color Stability of Unshaded versus Shaded Zirconia
Authors: Spyropoulou Panagiota‐Eirini , Kamposiora Phophi , Eliades George , Papavasiliou George , Razzoog Michael E. , Bayne Stephen C.
Published: July 2015

Statement of Problem

Shaded versions of dental zirconia may improve initial color matching to teeth, but might change color with cyclic mechanical loading.

Purpose

The purpose of this study was to measure the color of unshaded and shaded zirconia dental ceramic before and after cyclic mechanical loading and calculate color differences (ΔE).

Material and Methods

Disk‐shaped specimens (N = 30, Nobel Procera, 0.8 mm thick, 12 mm diameter) of unshaded or shaded zirconia (intrinsically shaded by small oxide modifications) were fabricated by the Nobel Biocare using standard CAD‐CAM processing. Milled surfaces were polished. CIE L*a*b* values were measured (Konica Minolta spectrophotometer) before and after mechanical cycling (custom modified Leinfelder test machine, biaxial flexure loading, load = 80 N × 500,000 cycles, dry), and L*a*b* individual differences and ΔE color differences were calculated and compared (ANOVA, p < 0.05).

Results

Mean L*a*b* values for the unshaded group before (U1 = 86.165, −0.887, 0.372) and after (U2 = 84.860, −0.805, 0.097) cyclic loading were compared to the shaded group before (S1 = 75.281, −0.679, 23.251) and after (S2 = 74.961, −1.233, 22.439) cyclic loading. All color variables for both unshaded and shaded groups were significantly different between before and after cyclic loading (p < .004) except for the L* value of the shaded group. The ΔE for unshaded (1.441 ± 0.495) versus shaded (1.252 ± 0.363) were statistically different but clinically the change would not be detectable at this point.

Conclusions

The color of the unshaded and shaded zirconia specimens was influenced by cyclic loading (p < 0.05). Color changes were detectable but small at levels up to 500,000 cycles, and remained clinically acceptable at that point.

Clinical Significance

It is important to acknowledge any possible color changes that might occur in zirconia restorations, especially in the esthetic zone. Minor color changes that are individually imperceptible to the human eye within different restorative components may be compounded to produce clinically significant color change that is not aesthetically acceptable.
The use of wave propagation and reduced complexity inundation models and metamodels for coastal flood risk assessment
Authors: Rueda A. , Gouldby B. , Méndez F.J. , Tomás A. , Losada I.J. , Lara J.L. , Díaz‐Simal P.
Published: July 2015

To estimate coastal risk it is necessary to integrate the joint probability density function, including extremes, of the sea condition variables over a function that defines the consequences, typically economic damage. The use of Monte Carlo methods is common practice to undertake this integration; however, it can introduce a high computational burden for use in practical applications. Hence, a simplifying assumption of full dependence between the sea condition variables is often made. This paper describes a method that overcomes this simplifying assumption through the use of two techniques. A hybrid emulator of the simulating waves nearshore model is used to increase the computational efficiency associated with the wave transformations. In addition, a computationally efficient dynamic inundation model has been incorporated to further reduce the computational burden. To demonstrate the system, it has been applied to an urban coastal area located in northern Spain.
Lack of the scavenger receptor CD36 alters microglial phenotypes after neonatal stroke
Authors: Li Fan , Faustino Joel , Woo Moon‐Sook , Derugin Nikita , Vexler Zinaida S.
Published: July 2015

The stage of brain development at the time of stroke has a major impact on the pathophysiological mechanisms of ischemic damage, including the neuroinflammatory response. Microglial cells have been shown to contribute to acute and subchronic injury in adult stroke models, whereas in neonatal rodents we showed that microglial cells serve as endogenous neuroprotectants early following transient middle cerebral artery occlusion, limiting neuroinflammation and injury. In the neonate, microglial depletion or lack of the scavenger receptor CD36 exacerbates injury. In this study we asked if lack of CD36 affects microglial phenotypes after neonatal stroke. Using RT‐PCR we characterized the patterns of gene expression in microglia isolated from injured regions following acute transient middle cerebral artery occlusion in postnatal day 10 mice and showed that expression of several pro‐inflammatory genes, including Toll‐like receptors, remains largely unaffected in activated microglia in injured regions. Using multiple biochemical assays we demonstrated that lack of CD36 alters several functions of microglia in acutely injured neonatal brain: it further enhances accumulation of the chemokine MCP‐1, affects the number of CD11b+/CD45+ cells, along with protein expression of its co‐receptor, Toll‐like receptor 2, but does not affect accumulation of superoxide in microglia or the cytokines TNFα and IL‐1β in injured regions.

image

Microglial cells contribute to acute and sub‐chronic injury in adult stroke models, whereas in neonatal rodents they serve as endogenous neuroprotectants early following transient middle cerebral artery occlusion (tMCAO), limiting neuroinflammation and injury. In the neonate, microglial depletion or lack of the scavenger receptor CD36 exacerbates injury. In this study we asked if lack of CD36 affects microglial phenotypes after neonatal stroke. Expression of several pro‐inflammatory genes, including Toll‐like receptors (TLR), remains largely unaffected in activated microglia in injured regions. Lack of CD36 alters several functions of microglia in acutely injured neonatal brain: it affects, among others, protein expression of its co‐receptor, TLR2, but does not affect accumulation of superoxide in microglia or the cytokines TNFα and IL‐1β in injured regions. We propose that TLR2 function (2&3) in part depends on CD36 function (2).
Genes associated with Parkinson's disease: regulation of autophagy and beyond
Authors: Beilina Alexandra , Cookson Mark R
Published: July 2015

Substantial progress has been made in the genetic basis of Parkinson's disease (PD). In particular, by identifying genes that segregate with inherited PD or show robust association with sporadic disease, and by showing the same genes are found on both lists, we have generated an outline of the cause of this condition. Here, we will discuss what those genes tell us about the underlying biology of PD. We specifically discuss the relationships between protein products of PD genes and show that common links include regulation of the autophagy–lysosome system, an important way by which cells recycle proteins and organelles. We also discuss whether all PD genes should be considered to be in the same pathway and propose that in some cases the relationships are closer, whereas in other cases the interactions are more distant and might be considered separate.

image

Beilina and Cookson review the links between genes for Parkinson's disease (red) and the autophagy–lysosomal system. They propose the hypothesis that many of the known PD genes can be assigned to pathways that affect (I) turnover of mitochondria via mitophagy (II) turnover of several vesicular structures via macroautophagy or chaperone‐mediated autophagy or (III) general lysosome function.

This article is part of a special issue on Parkinson disease.
Circulating chromosome 19 miRNA cluster microRNAs in pregnant women with severe pre‐eclampsia
Authors: Miura Kiyonori , Higashijima Ai , Murakami Yuko , Tsukamoto Ozora , Hasegawa Yuri , Abe Shuhei , Fuchi Naoki , Miura Shoko , Kaneuchi Masanori , Masuzaki Hideaki
Published: July 2015

Aim

To clarify the association between circulating chromosome 19 miRNA cluster (C19MC) microRNAs in maternal plasma and severe pre‐eclampsia.

Method

Maternal blood samples (7 mL) at 27–34 weeks of gestation were obtained from 20 pregnant women with severe pre‐eclampsia (sPE group) and from 20 uncomplicated pregnant women (NP group). Twenty cases of severe pre‐eclampsia were classified into late onset (sPELO group; n = 14) and early onset (sPEEO group; n = 6). Plasma concentration of C19MC microRNAs (miR‐518b, ‐1323, ‐516b, ‐516a‐5p, ‐525‐5p, ‐515‐5p, ‐520 h, ‐520a‐5p, ‐519d and ‐526b) was measured on quantitative real‐time reverse transcription–polymerase chain reaction.

Results

The circulating levels of all 10 C19MC microRNAs in maternal plasma were significantly increased in the sPE group compared with the NP group. Plasma concentration of all 10 C19MC microRNAs tested was significantly increased in the sPEEO group compared with the NP group, while plasma concentration of nine miRNAs, except for miR‐519d, was significantly increased in the sPELO group compared with the NP group. Of the 10 C19MC microRNAs measured, plasma concentration of eight miRNAs, except for miR‐518b and miR‐519d, was significantly increased in the sPEEO group compared with the sPELO group.

Conclusions

Increased levels of C19MC microRNAs in maternal plasma are a characteristic phenomenon of established severe pre‐eclampsia, and it has been shown for the first time that the upregulation of C19MC miRNAs occurred as a consequence of, not in advance of, the onset of pre‐eclampsia.
External iliac artery thrombosis after common iliac artery balloon occlusion during cesarean hysterectomy for placenta accreta in cervico‐isthmic pregnancy
Authors: Matsueda Sayaka , Hidaka Nobuhiro , Kondo Yukiko , Fujiwara Arisa , Fukushima Kotaro , Kato Kiyoko
Published: July 2015

Although the role of interventional radiology in the field of obstetrical hemorrhage has been widely reported upon recently, the rate of procedure‐related complications has not been fully determined. We present the case of a patient who developed an external iliac artery thrombosis, a rarely reported complication associated with prophylactic common iliac artery balloon occlusion (CIABO). After CIABO, we found that the dorsalis pedis artery of the right foot was weak and the foot was cold, despite the fact that the patient had no complaints. Computed tomography demonstrated a linear thrombus in the right external iliac artery. We managed the patient conservatively using a heparin drip without the need for thromboembolectomy. Our experience suggests that it is important to consider the risk of thrombosis formation after CIABO. Physical examination post‐procedure is key to identifying this complication early.
Prenatal diagnosis and follow‐up of a case of branchio‐oto‐renal syndrome displays renal growth impairment after the second trimester
Authors: Bertucci Emma , Mazza Vincenzo , Lugli Licia , Ferrari Fabrizio , Stanghellini Ilaria , Percesepe Antonio
Published: July 2015

Branchio‐oto‐renal syndrome combines branchial arch defects, hearing impairment and renal malformations or hypoplasia. Due to the high phenotypic variability, prenatal diagnosis has a limited prognostic value in mutation‐positive cases. We report the first branchio‐oto‐renal syndrome molecular prenatal diagnosis and ultrasonographic follow‐up, showing a normal renal growth until the 24th week of pregnancy, a growth deceleration during the third trimester and a renal volume recovery during the first months of life.
Circulating annexin A5 predicts mortality in patients with heart failure
Authors: Schurgers L. J. , Burgmaier M. , Ueland T. , Schutters K. , Aakhus S. , Hofstra L. , Gullestad L. , Aukrust P. , Hellmich M. , Narula J. , Reutelingsperger C. P.
Published: July 2015

Background

Natriuretic peptides are currently used to predict mortality in patients with heart failure (HF). However, novel independent biomarkers are needed to improve risk stratification in these patients. We hypothesized that annexin A5 (anxA5) would be highly expressed by organs which are generally affected by HF and that circulating anxA5 levels would predict mortality in HF patients.

Methods

We prospectively determined the diagnostic value of anxA5, N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), C‐reactive protein (CRP) and estimated glomerular filtration rate (eGFR) to predict mortality in 180 HF patients during a median follow‐up of 3.6 years. Studies were conducted with anxA5−/− mice to investigate the underlying mechanisms.

Results

AnxA5 levels were significantly elevated in HF patients compared to healthy control subjects. Cox regression analysis demonstrated that anxA5, NT‐proBNP and eGFR all predict mortality independently. AnxA5 significantly improved the diagnostic efficiency of NT‐proBNP alone (improvement of c‐statistic from 0.662 to 0.705, P < 0.001) and also combined with eGFR and CRP (improvement of c‐statistic from 0.675 to 0.738, P < 0.001) to predict mortality in the Cox regression model. Receiver operating characteristic curve analysis showed that anxA5 predicted 3‐year survival (area under curve 0.708) with an optimal cut‐off value of 2.24 ng mL−1. Using anxA5−/− mice, we demonstrated that anxA5 is highly expressed in organs that are often affected by HF including lung, kidney, liver and spleen. Lysis of these organs in vitro resulted in a marked and significant increase in anxA5 concentrations.

Conclusion

AnxA5 improves the diagnostic efficiency of conventional biomarkers to predict mortality in HF patients. Whereas natriuretic peptides originate from the myocardium, high circulating anxA5 levels in patients with HF are likely to reflect peripheral organ damage secondary to HF.
What Factors Affect the Persistence of an Innovation Advantage?
Authors: Madsen Tammy L. , Leiblein Michael J.
Published: July 2015

Factors that affect a firm's ability to achieve an advantage may differ from those that affect its ability to sustain that advantage. Moreover, if advantage is a relative concept then studies that relate resource stocks to ‘absolute’ outcomes say little about how resources contribute to enduring differences among firms. We explore these issues in the global semiconductor industry by analyzing how a firm's resource stocks contribute to the persistence of an innovation advantage (a relative outcome). The findings demonstrate that a firm's own production experience and the experience held by its partners contribute to temporary innovation advantages. The results also show that a firm's own production experience yields a more durable innovation advantage as compared to the experience held by a firm's partners and that the experience held by a firm's partners provides a more enduring advantage than a firm's patent stock.
1.688 g/cm3 satellite‐related repeats: a missing link to dosage compensation and speciation
Authors: Gallach Miguel
Published: July 2015

Despite the important progress that has been made on dosage compensation (DC), a critical link in our understanding of the X chromosome recognition mechanisms is still missing. Recent studies in Drosophila indicate that the missing link could be a family of DNA repeats populating the euchromatin of the X chromosome. In this opinion article, I discuss how these findings add a new fresh twist on the DC problem. In the following sections, I first summarize our understanding of DC in Drosophila and integrate these recent discoveries into our knowledge of the X chromosome recognition problem. Next, I introduce a model according to which, 1.688 g/cm3 satellite‐related (SR) repeats would be the primary recognition elements for the dosage compensation complex. Contrary to the current belief, I suggest that the DC system in Drosophila is not conserved and static, but it is continuously co‐evolving with the target SR repeats. The potential role of the SR repeats in hybrid incompatibilities and speciation is also discussed.
The complex phylogeography of the Indo‐Malayan Alophoixus bulbuls with the description of a putative new ring species complex
Authors: Fuchs Jérôme , Ericson Per G.P. , Bonillo Céline , Couloux Arnaud , Pasquet Eric
Published: July 2015

The Indo‐Malayan bioregion has provided some of the most spectacular discoveries of new vertebrate species (e.g. saola, khanyou, bare‐faced bulbul) over the last 25 years. Yet, very little is known about the processes that led to the current biodiversity in this region. We reconstructed the phylogeographic history of a group of closely related passerines, the Alophoixus bulbuls. These birds are continuously distributed in Indo‐Malaya around the Thailand lowlands such that their distribution resembles a ring. Our analyses revealed a single colonization event of the mainland from Sundaland with sequential divergence of taxa from southwest to northeast characterized by significant gene flow between parapatric taxa, and reduced or ancient gene flow involving the two taxa at the extremities of the ring. We detected evidence of population expansion in two subspecies, including one that was involved in the closing of the ring. Hence, our analyses indicate that the diversification pattern of Alophoixus bulbuls fits a ring species model driven by geographic isolation. To our knowledge, the Alophoixus bulbuls represent the first case of a putative broken ring species complex in Indo‐Malaya. We also discuss the implications of our results on our understanding of the biogeography in Indo‐Malaya.
Fifteen years of genomewide scans for selection: trends, lessons and unaddressed genetic sources of complication
Authors: Haasl Ryan J. , Payseur Bret A.
Published: July 2015

Genomewide scans for natural selection (GWSS) have become increasingly common over the last 15 years due to increased availability of genome‐scale genetic data. Here, we report a representative survey of GWSS from 1999 to present and find that (i) between 1999 and 2009, 35 of 49 (71%) GWSS focused on human, while from 2010 to present, only 38 of 83 (46%) of GWSS focused on human, indicating increased focus on nonmodel organisms; (ii) the large majority of GWSS incorporate interpopulation or interspecific comparisons using, for example FST, cross‐population extended haplotype homozygosity or the ratio of nonsynonymous to synonymous substitutions; (iii) most GWSS focus on detection of directional selection rather than other modes such as balancing selection; and (iv) in human GWSS, there is a clear shift after 2004 from microsatellite markers to dense SNP data. A survey of GWSS meant to identify loci positively selected in response to severe hypoxic conditions support an approach to GWSS in which a list of a priori candidate genes based on potential selective pressures are used to filter the list of significant hits a posteriori. We also discuss four frequently ignored determinants of genomic heterogeneity that complicate GWSS: mutation, recombination, selection and the genetic architecture of adaptive traits. We recommend that GWSS methodology should better incorporate aspects of genomewide heterogeneity using empirical estimates of relevant parameters and/or realistic, whole‐chromosome simulations to improve interpretation of GWSS results. Finally, we argue that knowledge of potential selective agents improves interpretation of GWSS results and that new methods focused on correlations between environmental variables and genetic variation can help automate this approach.
Habitat use by southern right whales, Eubalaena australis (Desmoulins, 1822), in their main northernmost calving area in the western South Atlantic
Authors: Seyboth Elisa , Groch Karina R. , Secchi Eduardo R. , Dalla Rosa Luciano
Published: July 2015

The subtropical and temperate coastal waters of the western South Atlantic are an important calving ground for southern right whales, Eubalaena australis. From 2002 to 2008, data on right whale distribution and habitat characteristics were collected in 14 bays along the coastline of Santa Catarina State, Brazil. Generalized linear models with a negative binomial error distribution were used to determine which environmental (beach morphotype, bay mouth width, bay inclination angle, north‐south and east‐west wind components), and temporal (month and year) variables best explained the aggregation pattern of individuals. Our results suggested that both cow‐calf pairs and adults unaccompanied by calves prefer bays with dissipative beaches, and that cow‐calf pairs apparently avoid bays facing southeast during days of strong east‐west winds. The number of sightings peaked in September and tended to increase over the study period. One particular embayment (Ribanceira beach) had considerably higher numbers of animals and may be considered a preferred spot in this calving ground. Our findings contribute to a better understanding of the species' habitat use and ecological requirements and should be taken into account if new management measures are implemented to further increase protection of southern right whales in the region.
Pleiotropy and the evolution of floral integration
Authors: Smith Stacey D.
Published: July 2015

Floral traits often show correlated variation, both within and across species. One explanation for this pattern of floral integration is that different elements of floral phenotypes are controlled by the same genes, that is, that the genetic architecture is pleiotropic. Recent studies from a range of model systems suggest that the pleiotropy is common among the loci responsible for floral divergence. Moreover, the effects of allelic substitutions at these loci are overwhelmingly aligned with direction of divergence, suggesting that the nature of the pleiotropic effects was adaptive. Molecular genetic studies have revealed the functional basis for some of these effects, although much remains to be discovered with respect to the molecular, biochemical and developmental mechanisms underlying most quantitative trait loci (QTL) responsible for floral differences. Developing a detailed understanding of the nature of pleiotropic mutations and their phenotypic consequences is crucial for modeling how the genetic architecture of trait variation influences the tempo and trajectory of floral evolution.

Contents

Summary
80

I.
Introduction
80

II.
Extent and nature of pleiotropy in floral trait architecture
81

III.
The evolution of pleiotropy
83

IV.
Pleiotropy as an impediment or facilitator of phenotypic evolution
83

Acknowledgements
84

References
84
Prevalence of Chronic Pain in a Large Integrated Healthcare Delivery System in the U.S.A
Authors: Lamerato Lois E. , Dryer Richard D. , Wolff Greg G. , Hegeman‐Dingle Rozelle , Mardekian Jack , Park Peter W. , Zlateva Gergana
Published: July 2015

Background

There is a paucity of published data on the prevalence of chronic pain conditions within large, integrated healthcare organizations in the U.S.A. Such data are essential to inform the development of appropriate treatment programs.

Methods

Twenty‐five selected pain conditions were used to identify patients receiving care within the Henry Ford Health System (HFHS) who were enrolled in the Health Alliance Plan (HAP), a subsidiary of HFHS. Patients aged ≥ 18 years, enrolled in HAP in 2010, and having ≥ 2 encounters, ≥ 30 days apart, with an ICD‐9‐CM diagnosis code for a pain condition of interest during 2010 were counted. Variables included in the study were as follows: age, gender, body mass index (BMI), and Charlson comorbidity conditions and index score.

Results

Altogether, 14,784 persons (11.6% of the total adult population) met the criteria for having a chronic pain condition. Overall, the study population was 64.4% female and had mean age (SD) of 61.2 (15.6) years and mean BMI of 31.4 (7.2) kg/m2. Musculoskeletal pain conditions were the most common diagnoses, comprising 75.4% of all pain diagnoses. Diabetes and chronic pulmonary disease were the most common medical comorbidities.

Conclusions

In this comprehensive analysis of 2 years of data from a large, vertically integrated metropolitan health system, chronic pain was identified in 12% of adult patients. Approximately 75% of chronic pain conditions were musculoskeletal. The triad of age ≥ 60 years, BMI ≥ 30, and female sex were the most salient demographic characteristics of patients with chronic pain conditions. These diagnostic and demographic data may be used to inform treatment program development.