bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic Insecurity and Political Trust in the United States
Authors: Wroe Andrew
Published: August 2015

Extant research demonstrates that citizens’ evaluations of national economic performance play an important role in determining trust in politicians and political institutions, whereas evaluations of their own economic situation play a lesser or even negligible role. Utilizing American National Election Studies data and more apposite measures of personal economic privation during an age of globalization and de-industrialization, this article finds that the extent to which citizens perceive themselves and their families to be economically insecure has a statistically significant and substantial negative effect on political trust. Indeed, the effect at least matches those of macro-economic evaluations and party identification. This article therefore adds a new dimension to our understanding of the economy–trust nexus and contributes to the small but growing body of scholarship on insecurity’s effects on political behavior.
Meta-Analysis of Oxaliplatin-Based Chemotherapy Combined With Traditional Medicines for Colorectal Cancer
Authors: Chen Menghua , May Brian H. , Zhou Iris W. , Xue Charlie C. L. , Zhang Anthony L.
Published: August 2015

This meta-analysis evaluates the clinical evidence for the addition of traditional medicines (TMs) to oxaliplatin-based regimens for colorectal cancer (CRC) in terms of tumor response rate (TRR). Eight electronic databases were searched for randomized controlled trials of oxaliplatin-based chemotherapy combined with TMs compared to the same oxaliplatin-based regimen. Data on TRR from 42 randomized controlled trials were analyzed using Review Manager 5.1. Studies were conducted in China or Japan. Publication bias was not evident. The meta-analyses suggest that the combination of the TMs with oxaliplatin-based regimens increased TRR in the palliative treatment of CRC (risk ratio [RR] 1.31 [1.20-1.42], I2 = 0%). Benefits were evident for both injection products (RR 1.36 [1.18-1.57], I2 = 0%) and orally administered TMs (RR 1.27 [1.15-1.41], I2 = 0%). Further sensitivity analysis of specific plant-based TMs found that Paeonia, Curcuma, and Sophora produced consistently higher contributions to the RR results. Compounds in each of these TMs have shown growth-inhibitory effects in CRC cell-line studies. Specific combinations of TMs appeared to produce higher contributions to TRR than the TMs individually. Notable among these was the combination of Hedyotis, Astragalus, and Scutellaria.
Prediction of Balance Compensation After Vestibular Schwannoma Surgery
Authors: Parietti-Winkler Cécile , Lion Alexis , Frère Julien , Perrin Philippe P. , Beurton Renaud , Gauchard Gérome C.
Published: August 2015

Background. Balance compensation after vestibular schwannoma (VS) surgery is under the influence of specific preoperative patient and tumor characteristics. Objective. To prospectively identify potential prognostic factors for balance recovery, we compared the respective influence of these preoperative characteristics on balance compensation after VS surgery. Methods. In 50 patients scheduled for VS surgical ablation, we measured postural control before surgery (BS), 8 (AS8) days after, and 90 (AS90) days after surgery. Based on factors found previously in the literature, we evaluated age, body mass index and preoperative physical activity (PA), tumor grade, vestibular status, and preference for visual cues to control balance as potential prognostic factors using stepwise multiple regression models. Results. An asymmetric vestibular function was the sole significant explanatory factor for impaired balance performance BS, whereas the preoperative PA alone significantly contributed to higher performance at AS8. An evaluation of patients’ balance recovery over time showed that PA and vestibular status were the 2 significant predictive factors for short-term postural compensation (BS to AS8), whereas none of these preoperative factors was significantly predictive for medium-term postoperative postural recovery (AS8 to AS90). Conclusions. We identified specific preoperative patient and vestibular function characteristics that may predict postoperative balance recovery after VS surgery. Better preoperative characterization of these factors in each patient could inform more personalized presurgical and postsurgical management, leading to a better, more rapid balance recovery, earlier return to normal daily activities and work, improved quality of life, and reduced medical and societal costs.
Fitness in Youth
Authors: Ortega Francisco B. , Ruiz Jonatan R.
Published: August 2015

In this issue, Sacheck and Hall discussed the key findings from the Final Report “Fitness Measures and Health Outcomes in Youth” developed by an expert committee appointed by the Institute of Medicine in 2011 and published in 2012. The findings from this report are more valuable when interpreted together with those from the EU-funded ALPHA project (conducted from 2007 to 2010). The ALPHA project aimed to provide an evidence-based set of valid, reliable, feasible, and safe field-based fitness tests for the assessment of health-related physical fitness in youth to be used in public health monitoring in a comparable way within the European Union and around the globe. The ALPHA team conducted 4 reviews (3 of them systematic reviews) and 11 methodological studies, tested the battery in the school setting, and had several meetings with an international expert board to further discuss the development of the work. The evidence-based ALPHA fitness test battery was finally published in 2011. Several important methodological issues related to fitness assessment and its clinical value mainly derived from this project are discussed in the present article: the ALPHA-fitness test battery; Slaughter’s equations and normalization of fat indicators by height; absolute versus relative muscular strength; physical fitness reference data; health-related fitness cut-points; Self-reported fitness assessment: The International FItness Scale-IFIS; and fitness assessment in preschoolers: The PREFIT project.
Computational fluid dynamics evaluation of flow reversal treatment of giant basilar tip aneurysm
Authors: Alnæs Martin Sandve , Mardal Kent-Andre , Bakke Søren , Sorteberg Angelika
Published: August 2015

Therapeutic parent artery flow reversal is a treatment option for giant, partially thrombosed basilar tip aneurysms. The effectiveness of this treatment has been variable and not yet studied by applying computational fluid dynamics. Computed tomography images and blood flow velocities acquired with transcranial Doppler ultrasonography were obtained prior to and after bilateral endovascular vertebral artery occlusion for a giant basilar tip aneurysm. Patient-specific geometries and velocity waveforms were used in computational fluid dynamics simulations in order to determine the velocity and wall shear stress changes induced by treatment. Therapeutic parent artery flow reversal lead to a dramatic increase in aneurysm inflow and wall shear stress (30 to 170 Pa) resulting in an increase in intra-aneurysmal circulation. The enlargement of the circulated area within the aneurysm led to a re-normalization of the wall shear stress and the aneurysm remained stable for more than 8 years thereafter. Therapeutic parent artery flow reversal can lead to unintended, potentially harmful changes in aneurysm inflow which can be quantified and possibly predicted by applying computational fluid dynamics.
Modelling and analysis of system robustness for mechanical product based on axiomatic design and fuzzy clustering algorithm
Authors: Cheng Xianfu , Zhang Shengcai , Wang Tao
Published: August 2015

Robust performance is the most important concern in the design of any product, especially in system design stage that precedes parameter design, because it actually determines the attainable level of product robustness in the parameter design phase. In this article, a framework of modelling and analysis of system robustness is proposed, which includes system modelling, cluster analysis and design of experiments. In the process of system modelling, the metamodel of general design theory was utilized to describe the function–structure model of product design, and the customer needs are transformed into functional requirements. Based on the independent axiom and zigzag mapping mode of axiomatic design, the functional requirements are mapping to design parameters, and the design matrix is created, which is then converted into design structure matrix by identifying the relationship between functional requirements and the sensitivity of functional requirements to design parameters. The fuzzy clustering algorithm is utilized to cluster the design parameters and to group the system components into modules in design structure matrix, and the interface among modules can be identified and system robustness incidence matrix is developed. Then the incidence parameters are considered as controllable factors, and experimental design techniques are utilized to analyse the influence of incidence parameters on the design objectives, if any, that may result in a robust system. The proposed framework is illustrated with the trolley design of overhead travelling crane.
The effect of individual isometric muscle loading on the alignment of the base of the thumb metacarpal: a cadaveric study
Authors: Mobargha N. , Esplugas M. , Garcia-Elias M. , Lluch A. , Megerle K. , Hagert E.
Published: August 2015

Stability of the thumb carpometacarpal joint relies upon equilibrium between its ligaments, muscular support and joint congruity. We wanted to identify the muscles important in preventing or increasing dorsoradial subluxation of this joint. In ten cadaveric hands, a Fastrak® motion tracking device was used to assess the effects of individual isometric muscle loading on the base of the thumb metacarpal relative to the radius and to the base of the middle finger metacarpal. We found that the first dorsal interosseous muscle caused the least dorsoradial translation and highest distal migration of the base of the first metacarpal, whereas abductor pollicis longus was the primary destabilizer, increasing dorsoradial misalignment. The findings show different impacts of these muscles on joint alignment and stability, which suggests that treatment should be targeted to enhance the action of the primary stabilizing muscle, the first dorsal interosseous muscle.
The association between HIV/AIDS-related knowledge and perception of risk for infection: a systematic review
Authors: Ndugwa Kabwama Steven , Berg-Beckhoff Gabriele
Published: August 2015

This systematic review tries to elucidate the association between what people know about HIV/AIDS and how they perceive their risk of infection. The initial search for articles yielded 1,595 abstracts, 16 of which met the inclusion criteria. Five studies found a positive correlation, four reported a negative correlation and seven found no association between knowledge and risk perception. It was found that the existing psychometrically sound measure of HIV/AIDS risk perception had not been used in any of the studies. The context in which the risk is assessed is pivotal to whether an association between knowledge and the perceived risk is found. Biases in judgement such as optimistic bias, psychological distancing, anchoring bias and overconfidence also explain how knowledge may fail to predict risk perception. It was concluded that the association between HIV/AIDS knowledge and risk perception might follow a continuum from positive to no association and finally to negative. The hypothesis, however, still needs to be studied further.
A Multicenter Performance Evaluation of a Blood Glucose Monitoring System in 21 Leading Hospitals in Spain
Authors: Bedini José Luis , Wallace Jane F. , Petruschke Thorsten , Pardo Scott
Published: August 2015

Background:

Self-monitoring of blood glucose is crucial for the effective self-management of diabetes. The present study evaluated the accuracy of the Contour® XT blood glucose monitoring system (BGMS) compared to the reference method in a large multicenter study under routine lab conditions at each hospital site.

Methods:

This study was conducted at 21 leading hospitals in Spain using leftover whole blood samples (n = 2100). Samples were tested with the BGMS using 1 commercial strip lot and the local laboratory hexokinase method. BGMS accuracy was assessed and results were compared to ISO 15197:2013 accuracy limit criteria and by using mean absolute relative difference analysis (MARD), consensus (Parkes) error grid (CEG), and surveillance error grid analyses (SEG).

Results:

Pooled analysis of 2100 measurements from all sites showed that 99.43% of the BGMS results were within the ranges accepted by the accuracy limit criteria. The overall MARD was 3.85%. MARD was 4.47% for glucose concentrations < 70 mg/dL and 3.81% for concentrations of 70-300 mg/dL. In CEG, most results (99.8%) were within zone A (“no effect on clinical action”); the remaining ones (0.2%) were in zone B (“little to no effect on clinical action”). The SEG analysis showed that most of the results (98.4%) were in the “no risk” zone, with the remaining results in the “slight, lower” risk zone.

Conclusions:

This is the largest multicenter study of Contour XT BGMS to date, and shows that this BGMS meets the ISO 15197:2013 accuracy limit criteria under local routine conditions in 21 leading Spanish hospitals.
Retrospective Analysis of the Effectiveness of Platelet-Rich Plasma in the Treatment of Achilles Tendinopathy
Authors: Oloff Lawrence , Elmi Eman , Nelson Joseph , Crain Jana
Published: August 2015

Platelet-rich plasma (PRP) has been presented as a means of treating Achilles tendinopathy. Over the past dozen years, a plethora of medical articles have advocated this treatment, yet little evidentiary-based research exists in support of this approach. Treatment protocols with PRP have been performed in 2 ways during this time: administered adjunctively during tendon surgery and as a stand-alone injection. The senior author has utilized PRP by both methods to treat Achilles tendinopathy over the past 7 years; 26 patients so treated were able to be recalled, half having undergone Achilles tendon surgery in combination with PRP administration and the other half PRP alone. In this retrospective study, qualified patients had pretreatment and posttreatment magnetic imaging studies and completed a Victorian Institute of Sports Assessment-Achilles questionnaire. In this limited study, PRP showed promise in the treatment of Achilles tendinopathy. Both the stand-alone injection group and surgical/injection groups had statistically significant degrees of improvement in pre-MRI and post-MRI imaging studies. There was no statistically significant difference between the 2 treatment groups. Of interest, it appears that the difference between the MRI scoring correlates with the survey score.

Level of Evidence: Therapeutic, Level, IV: Case series
Role of Foot Abduction and Heel Angle in Equinus Correction in Idiopathic Clubfoot
Authors: Agarwal Anil , Kumar Anubrat , Shaharyar Abbas , Mishra Madhusudan
Published: August 2015

Introduction. The purpose of this study was to determine whether foot abduction and heel angles have any influence on resultant equinus correction and whether hindfoot dorsiflexion can be predicted based on these parameters. Material and Methods. Twenty-four children with 39 unintervened idiopathic clubfeet who completed Ponseti’s casting and percutaneous Achilles tenotomy with satisfactory equinus correction (≥15°) were included. Measurements included foot abduction and heel angle at the beginning of cast treatment, pre-tenotomy, and post-tenotomy along with post-tenotomy hindfoot dorsiflexion. Statistical relationships were calculated using Pearson’s coefficients. Results. The changes in heel angle correlated better with post-tenotomy dorsiflexion achieved than changes in foot abduction. Pre-tenotomy foot abduction or heel angle did not have any statistically significant correlation with post-tenotomy dorsiflexion. Furthermore, there was a significant relationship between post-tenotomy foot abduction and post-tenotomy dorsiflexion. Conclusions. Changes in foot abduction and heel angle (from initial casting to pre-tenotomy measurement) statistically correlated to post-tenotomy hindfoot dorsiflexion achieved. Absolute degree measurements of pre-tenotomy abduction or heel valgus did not correlate with the post-tenotomy hindfoot dorsiflexion achieved. There was also significant correlation between post-tenotomy abduction and post-tenotomy hindfoot dorsiflexion. Correlation between post-tenotomy heel valgus and post-tenotomy hindfoot dorsiflexion was weak.

Levels of Evidence: Prognostic, Level II: Prospective study
The Space Visions, Past and Futures
Authors: Dator James Allen
Published: August 2015

During the first two-thirds of the twentieth century, public expectations for human space travel were high and largely fulfilled by reality. However, support for public space programs now is low, perhaps because although developments in communications have continued at an astonishingly rapid pace, developments in transportation have stood still since the 1970s. At the same time, space fiction movies, television shows, and games continue to feed expectations that are far beyond what is technically possible today. Failed energy, economic, and governing systems along with climate change and other environmental challenges may hinder future space travel.
There are alternatives! Contestation and hope in early childhood education
Authors: Moss Peter
Published: August 2015

In a context of expanding early childhood education, this article begins by adopting a critical approach, exploring the technologies being applied to young children in a contemporary society of control, taking the case of England, a country which has seen a marked change in government’s attitude towards early childhood education over the past 20 years, from indifference to high priority. England also illustrates the relationship between changing state attitudes to early childhood education and the growing influence of neoliberalism on politics and economics. The second part of the article changes tack, from a critique of a powerful discourse of control to the disruptive potential of a discourse of hope. While recognising that ‘everything is dangerous’, not least education and the institution of the school, and that the dangers should never be downplayed, there are alternatives, for example, a discourse of education and the school that foregrounds democracy, emancipation and potentiality, a discourse that many have sought to enact and continue to do so.
Benign metastasizing pleomorphic adenoma in liver mimicking synchronic metastatic disease from colorectal cancer: a case report with emphasis on imaging findings
Authors: Young Victoria Solveig , Viktil Ellen , Løberg Else Marit , Enden Tone
Published: August 2015

Pleomorphic adenoma of the parotid gland with metastases to the liver is a rare etiology of focal liver lesions, and there are no described pathognomonic imaging features. We report a patient who presented with a newly diagnosed rectal cancer and multiple cystic liver lesions suspicious of mucinous synchronous liver metastases. Following chemotherapy no reduction in the number or size of the liver lesions was observed. The patient was re-evaluated and a biopsy of a lesion was performed. The specimen showed a metastasis from a pleomorphic adenoma of the parotid gland for which the patient had been treated 20 years earlier. The case illustrates how a thorough medical history can be crucial when a standard diagnostic imaging workup for colorectal cancer metastases is uncertain, and how a biopsy, though regarded as contraindicated due to the risk of tumor cell dissemination, can be required to secure a correct diagnosis.
The Life History Model of Psychopathology Explains the Structure of Psychiatric Disorders and the Emergence of the p Factor
Authors: Del Giudice Marco
Published: August 2015

In recent years, tremendous progress has been made in mapping the structure of comorbidity between psychiatric disorders. In particular, empirical findings have suggested the existence of a general p factor of susceptibility to psychopathology. In the present study, simulation methods were used to test whether the observed structure of psychiatric disorders can be reproduced by the life history model of psychopathology, a recent classification model based on evolutionary theory. The assumptions of the life history model were used to generate virtual epidemiological samples, which were then analyzed with the methods used by earlier researchers. Analyses of simulated data successfully replicated the key findings by these researchers, including the emergence of the p factor and the switch from positive to negative correlation between internalizing and externalizing symptoms after inclusion of the p factor. These results offer initial support for the validity of the life history model.
Impaired Retrieval Inhibition of Threat Material in Generalized Anxiety Disorder
Authors: Kircanski Katharina , Johnson Douglas C. , Mateen Maria , Bjork Robert A. , Gotlib Ian H.
Published: August 2015

Generalized anxiety disorder (GAD) is characterized by cognitive biases toward threat-relevant information, but the underlying mechanisms are unclear. We translated a retrieval-practice paradigm from cognitive science to investigate impaired inhibition of threat information as one such mechanism. Participants diagnosed with GAD and never-disordered control participants learned a series of cue–target pairs; whereas some cues were associated only with neutral targets, others were associated with both neutral and threat targets. Next, participants practiced retrieving neutral targets, which typically suppresses the subsequent recall of unpracticed associated targets (retrieval-induced forgetting; RIF). Finally, participants were tested on their recall of all targets. Despite showing intact RIF of neutral targets, the GAD group failed to exhibit RIF of threat targets. Furthermore, within the GAD group, less RIF of threat targets correlated with greater pervasiveness of worry. Deficits in inhibitory control over threat-relevant information may underlie the cognitive pathology of GAD, which has important treatment implications.
Uptake and Outcomes Associated with Implementation of a Community-Based Voluntary HIV Counseling and Testing Program in Antigua and Barbuda
Authors: Myers Janet J. , Maiorana Andres , Chaturvedi Shaan D. , Guilin Vincent , Buisker Timothy , Khumalo-Sakutukwa Gertrude , Sealey-Thomas Rhonda , O’Keiffe Colin , Williams Delcora
Published: August 2015

Objective:

To evaluate the implementation of community-based voluntary HIV counseling and testing (CBVCT) in the Eastern Caribbean.

Methods:

A total of 9782 unique HIV testing events performed through a national program of CBVCT in Antigua and Barbuda (2009-2012) were analyzed. The authors describe testers’ demographic characteristics and assess demographic (education, housing, marital status, nationality, and age) and sexual exposure (partner gender, transactional sex, and multiple partners) factors associated with testing HIV-positivity and with condom use.

Results:

Older men and men having sex with women and women with higher education, of Antiguan nationality, and having sex with men were less likely to test positive for HIV. Younger, educated, and unmarried men and women with multiple partners were more likely to report using condoms.

Conclusion:

The CBVCT model can be successfully implemented in Eastern Caribbean. Demographic differences persist in HIV testing, risk behavior, and infection among vulnerable populations and should be considered in HIV prevention intervention design.
Koumine Enhances Spinal Cord 3α-Hydroxysteroid Oxidoreductase Expression and Activity in a Rat Model of Neuropathic Pain
Authors: Qiu Hong-Qiang , Xu Ying , Jin Gui-Lin , Yang Jian , Liu Ming , Li Su-Ping , Yu Chang-Xi
Published: August 2015

Background

Koumine is an alkaloid monomer found abundantly in Gelsemium plants. It has been shown to reverse thermal hyperalgesia and mechanical allodynia induced by sciatic nerve chronic constriction injury (CCI) in rats in a dose-dependent manner. Interestingly, this effect is mediated by elevated allopregnanolone levels in the spinal cord (SC). Since 3α-hydroxysteroid oxidoreductase (3α-HSOR), the key synthetase of allopregnanolone, is responsible for allopregnanolone upregulation in the SC, the objective of the present study was to investigate the role of its expression in the SC in koumine-induced analgesia using a rat model of neuropathic pain following peripheral nerve injury.

Results

Time-course investigations of immunohistochemistry and real-time polymerase chain reaction revealed that the immunoreactivity and mRNA expression of 3α-HSOR markedly increased in a time-dependent manner in the SC of koumine-treated CCI rats. Furthermore, 3α-HSOR activity in the SC of koumine-treated CCI rats increased by 15.8% compared to the activity in untreated CCI rats. Intrathecal injection of medroxyprogesterone acetate, a selective 3α-HSOR inhibitor, reversed the analgesic effect of koumine on CCI-induced mechanical pain perception. Our results confirm that koumine alleviates neuropathic pain in rats with CCI by enhancing 3α-HSOR mRNA expression and bioactivity in the SC.

Conclusion

This study demonstrates that 3α-HSOR is an important molecular target of koumine for alleviating neuropathic pain. Koumine may prove a promising compound for the development of novel analgesic agents effective against intractable neuropathic pain.
Common fixed point theorems for hybrid contractive pairs with the $(\mathit{CLR})$-property
Authors: Abdou Afrah AN
Published: August 2015

In this work, we introduce the $(\mathit{CLR})$
(
CLR
)
-property for the hybrid pairs of single-valued and multi-valued mappings and give some coincidence and common fixed point theorems for the hybrid pairs of some contractive conditions. Also, we will give some examples to illustrate the main results in this paper. Our results extend and improve some results given by some authors.
Impaired innate immune response of leukocytes from ascitic fluid of patients with spontaneous bacterial peritonitis
Authors: Nieto Juan Camilo , Sánchez Elisabet , Romero Cristina , Román Eva , Poca Maria , Guarner Carlos , Juárez Cándido , Soriano Germán , Vidal Silvia
Published: August 2015

An ascitic microenvironment can condition the immune response of cells from cirrhotic patients with spontaneous bacterial peritonitis. To characterize this response, we determined the cytokine concentrations in ascitic fluid and analyzed the phenotype and function of ascitic leukocytes at diagnosis and after antibiotic-induced resolution in sterile ascites and ascitic fluid of 2 spontaneous bacterial peritonitis variants: positive and negative bacteriological culture. At diagnosis, a high concentration was found of IL-6 and IL-10 in the ascitic fluid from negative and positive bacteriological culture. The IL-6 concentration correlated with the percentage of neutrophils (R = 0.686, P < 0.001). In this context, positive and negative culture neutrophils had an impaired oxidative burst, and, after the antibiotic, the negative culture spontaneous bacterial peritonitis burst was fully recovered. Higher concentrations of IL-6 and IL-10 correlated with the presence of low granular CD 14low macrophages (R = −0.436, P = 0.005 and R = 0.414, P = 0.007, respectively). Positive culture spontaneous bacterial peritonitis macrophages expressed the lowest levels of CD16, CD86, CD11b and CD206, and HLA-DR, suggesting an impaired global function. Treatment increased all markers on the positive culture macrophages and CD11b and CD86 on negative culture macrophages. In negative culture spontaneous bacterial peritonitis, this increase was accompanied by phagocytic function recovery. The antibiotics then reverted the marker levels on positive and negative culture macrophages to the levels on sterile ascitis macrophages and restored ascitic negative culture cell function.
Xenoestrogens Ethinyl Estradiol and Zearalenone Cause Precocious Puberty in Female Rats via Central Kisspeptin Signaling
Authors: Kriszt Rókus , Winkler Zsuzsanna , Polyák Ágnes , Kuti Dániel , Molnár Csilla , Hrabovszky Erik , Kalló Imre , Szőke Zsuzsanna , Ferenczi Szilamér , Kovács Krisztina J.
Published: August 2015

Xenoestrogens from synthetic or natural origin represent an increasing risk of disrupted endocrine functions including the physiological activity of the hypothalamo-pituitary-gonad axis. Ethinyl estradiol (EE2) is a synthetic estrogen used in contraceptive pills, whereas zearalenone (ZEA) is a natural mycoestrogen found with increasing prevalence in various cereal crops. Both EE2 and ZEA are agonists of estrogen receptor-α and accelerate puberty. However, the neuroendocrine mechanisms that are responsible for this effect remain unknown. Immature female Wistar rats were treated with EE2 (10 μg/kg), ZEA (10 mg/kg), or vehicle for 10 days starting from postnatal day 18. As a marker of puberty, the vaginal opening was recorded and neuropeptide and related transcription factor mRNA levels were measured by quantitative real time PCR and in situ hybridization histochemistry. Both ZEA and EE2 accelerated the vaginal opening, increased the uterine weight and the number of antral follicles in the ovary, and resulted in the increased central expression of gnrh. These changes occurred in parallel with an earlier increase of kiss1 mRNA in the anteroventral and rostral periventricular hypothalamus and an increased kisspeptin (KP) fiber density and KP-GnRH appositions in the preoptic area. These changes are compatible with a mechanism in which xenoestrogens overstimulate the developmentally unprepared reproductive system, which results in an advanced vaginal opening and an enlargement of the uterus at the periphery. Within the hypothalamus, ZEA and EE2 directly activate anteroventral and periventricular KP neurons to stimulate GnRH mRNA. However, GnRH and gonadotropin release and ovulation are disrupted due to xenoestrogen-mediated inhibitory KP signaling in the arcuate nucleus.
Osteoblast de- and redifferentiation is controlled by a dynamic response to retinoic acid during zebrafish fin regeneration
Authors: Blum Nicola , Begemann Gerrit
Published: August 2015

Zebrafish restore amputated fins by forming tissue-specific blastema cells that coordinately regenerate the lost structures. Fin amputation triggers the synthesis of several diffusible signaling factors that are required for regeneration, raising the question of how cell lineage specific programs are protected from regenerative crosstalk between neighboring fin tissues. During fin regeneration, osteoblasts revert from a non-cycling, mature state to a cycling, preosteoblastic state to establish a pool of progenitors within the blastema. After several rounds of proliferation, preosteoblasts redifferentiate to produce new bone. Blastema formation and proliferation are driven by the continued synthesis of retinoic acid (RA). Here we find that osteoblast dedifferentiation and redifferentiation are inhibited by RA signaling and uncover how the bone regenerative program is achieved against a background of massive RA synthesis. Stump osteoblasts manage to contribute to the blastema by upregulating expression of the RA degrading enzyme cyp26b1. Redifferentiation is controlled by a presumptive gradient of RA, in which high RA-levels towards the distal tip of the blastema suppress redifferentiation. We show that this might be achieved through a mechanism involving repression of Bmp signaling and promotion of Wnt/β-catenin signaling. In turn, cyp26b1-positive fibroblast-derived blastema cells in the more proximal regenerate serve as a sink to reduce RA levels, thereby allowing differentiation of neighboring preosteoblasts. Our findings reveal a mechanism explaining how the osteoblast regenerative program is protected from adverse crosstalk with neighboring fibroblasts that advances our understanding of the regulation of bone repair by RA.
Protein phosphatase 2A promotes the transition to G0 during terminal differentiation in Drosophila
Authors: Sun Dan , Buttitta Laura
Published: August 2015

Protein phosphatase type 2A complex (PP2A) has been known as a tumor suppressor for over two decades, but it remains unclear exactly how it suppresses tumor growth. Here we provide data indicating a novel role for PP2A in promoting the transition to quiescence upon terminal differentiation in vivo. Using Drosophila eyes and wings as a model, we find that compromising PP2A activity during the final cell cycle prior to a developmentally controlled cell cycle exit leads to extra cell divisions and delayed entry into quiescence. By systematically testing the regulatory subunits of Drosophila PP2A, we find that the B56 family member widerborst (wdb) is required for the role of PP2A in promoting the transition to quiescence. Cells in differentiating tissues with compromised PP2A retain high Cdk2 activity when they should be quiescent, and genetic epistasis tests demonstrate that ectopic CyclinE/Cdk2 activity is responsible for the extra cell cycles caused by PP2A inhibition. The loss of wdb/PP2A function cooperates with aberrantly high Cyclin E protein, allowing cells to bypass a robust G0 late in development. This provides an example of how loss of PP2A can cooperate with oncogenic mutations in cancer. We propose that the wdb/PP2A complex plays a novel role in differentiating tissues to promote developmentally controlled quiescence through the regulation of CyclinE/Cdk2 activity.
Meis1 coordinates a network of genes implicated in eye development and microphthalmia
Authors: Marcos Séverine , González-Lázaro Monica , Beccari Leonardo , Carramolino Laura , Martin-Bermejo Maria Jesus , Amarie Oana , Martín Daniel Mateos-San , Torroja Carlos , Bogdanović Ozren , Doohan Roisin , Puk Oliver , de Angelis Martin Hrabě , Graw Jochen , Gomez-Skarmeta Jose Luis , Casares Fernando , Torres Miguel , Bovolenta Paola
Published: August 2015

Microphthalmos is a rare congenital anomaly characterized by reduced eye size and visual deficits of variable degrees. Sporadic and hereditary microphthalmos has been associated to heterozygous mutations in genes fundamental for eye development. Yet, many cases are idiopathic or await the identification of molecular causes. Here we show that haploinsufficiency of Meis1, a transcription factor with an evolutionary conserved expression in the embryonic trunk, brain and sensory organs, including the eye, causes microphthalmic traits and visual impairment, in adult mice. By combining the analysis of Meis1 loss-of-function and conditional Meis1 functional rescue with ChIP-seq and RNA-seq approaches we show that, in contrast to Meis1 preferential association with Hox-Pbx binding sites in the trunk, Meis1 binds to Hox/Pbx-independent sites during optic cup development. In the eye primordium, Meis1 coordinates, in a dose-dependent manner, retinal proliferation and differentiation by regulating genes responsible for human microphthalmia and components the Notch signalling pathway. In addition, Meis1 is required for eye patterning by controlling a set of eye territory-specific transcription factors, so that in Meis1−/− embryos boundaries among the different eye territories are shifted or blurred. We thus propose that Meis1 is at the core of a genetic network implicated in eye patterning/microphthalmia, itself representing an additional candidate for syndromic cases of these ocular malformations.
Regenerated leg segment patterns are regulated epigenetically by histone H3K27 methylation in the cricket Gryllus bimaculatus
Authors: Hamada Yoshimasa , Bando Tetsuya , Nakamura Taro , Ishimaru Yoshiyasu , Mito Taro , Noji Sumihare , Tomioka Kenji , Ohuchi Hideyo
Published: August 2015

Hemimetabolous insects such as the cricket Gryllus bimaculatus regenerate lost tissue parts using blastemal cells, which is a population of dedifferentiated-proliferating cells. The gene expression of several epigenetic factors is upregulated in the blastema compared with the expression in differentiated tissue, suggesting that epigenetic changes in gene expression may control the differentiation status of blastema cells during regeneration. To clarify the molecular basis of epigenetic regulation during regeneration, we focused on the function of the Gryllus Enhancer of zeste (Gb’E(z)) and Ubiquitously-transcribed tetratricopeptide repeat gene on the X chromosome (Gb’Utx) homologues that regulate the methylation and demethylation on histone H3 27th lysine residue (H3K27), respectively. Methylated histone H3K27 in the regenerating leg was diminished by Gb’E(z)RNAi and was increased by Gb’UtxRNAi. Regenerated Gb’E(z)RNAi cricket legs exhibited extra leg segment formation between the tibia and tarsus, and regenerated Gb’UtxRNAi cricket legs showed leg joint formation defects in the tarsus. In the Gb’E(z)RNAi-regenerating leg, the Gb’dac expression domain expanded in the tarsus. In contrast, in the Gb’UtxRNAi-regenerating leg, Gb’Egfr expression in the middle of the tarsus was diminished. These results suggest that regulation of the histone H3K27 methylation state is involved in the repatterning process during leg regeneration among cricket species via the epigenetic regulation of leg patterning gene expression.
Kinesin-1 interacts with Bucky ball to form germ cells and is required to pattern the zebrafish body axis
Authors: Campbell Philip D. , Heim Amanda E. , Smith Mordechai Z. , Marlow Florence L.
Published: August 2015

In animals, specification of the primordial germ cells (PGCs), the stem cells of the germline, is required to transmit genetic information from one generation to the next. Bucky ball (Buc) is essential for germ plasm (GP) assembly in oocytes and its overexpression results in excess PGCs in zebrafish embryos. However, the mechanistic basis for the excess PGCs in response to Buc overexpression, and whether endogenous Buc functions during embryogenesis are unknown. Here we show that endogenous Buc, like GP and overexpressed Buc-GFP, accumulates at embryonic cleavage furrows. Furthermore, we show that the maternally expressed zebrafish Kinesin-1 Kif5Ba is a binding partner of Buc and that maternal kif5Ba (Mkif5Ba) plays an essential role in germline specification in vivo. Specifically, Mkif5Ba is required to recruit GP to cleavage furrows and thereby specifies PGCs. Moreover, Mkif5Ba is required to enrich Buc at cleavage furrows and for Buc’s ability to promote excess PGCs, providing mechanistic insight into how Buc functions to assemble embryonic GP. In addition, we show that Mkif5Ba is also essential for dorsoventral (DV) patterning. Specifically, Mkif5Ba promotes formation of the parallel vegetal microtubule array required to asymmetrically position dorsal determinants (DDs) towards the prospective dorsal side. Interestingly, while Syntabulin and wnt8a translocation depend on kif5Ba, grip2a translocation does not, providing evidence for two distinct mechanisms by which DDs may be asymmetrically distributed. These studies identify essential roles for maternal Kif5Ba in PGC specification and DV patterning and provide mechanistic insight into Buc functions during early embryogenesis.
How do treadmill speed and terrain visibility influence neuromuscular control of guinea fowl locomotion?
Authors: Gordon Joanne C. , Rankin Jeffery W. , Daley Monica A.
Published: August 2015

Locomotor control mechanisms must flexibly adapt to both anticipated and unexpected terrain changes to maintain movement and avoid a fall. Recent studies revealed that ground birds alter movement in advance of overground obstacles, but not treadmill obstacles, suggesting context-dependent shifts in use of anticipatory control. We hypothesized that differences between overground and treadmill obstacle negotiation relate to differences in visual sensory information, which influence the ability to execute anticipatory manoeuvres. We explored two possible explanations: 1) previous treadmill obstacles may have been visually imperceptible, as they were low contrast to the tread, and 2) treadmill obstacles are visible for a shorter time compared to runway obstacles, limiting time available for visuomotor adjustments. To investigate these factors, we measured electromyographic activity in 8 hindlimb muscles of the guinea fowl (Numida meleagris, n=6) during treadmill locomotion at two speeds (0.7ms−1 and 1.3ms−1) and three terrain conditions at each speed: (i) level, (ii) repeated 5cm low contrast obstacles (<10% contrast, black/black), and (iii) repeated 5cm high contrast obstacles (>90% contrast, black/white). We hypothesized that anticipatory changes in muscle activity would be higher for 1) high contrast obstacles, and 2) the slower treadmill speed, when obstacle viewing time is longer. We found that treadmill speed significantly influenced obstacle negotiation strategy, but obstacle contrast did not. At the slower speed, we observed earlier and larger anticipatory increases in muscle activity and shifts in kinematic timing. We discuss possible visuomotor explanations for the observed context-dependent use of anticipatory strategies.
Physiological, pharmacological, and behavioral evidence for a TRPA1 channel that can elicit defensive responses in the medicinal leech
Authors: Summers Torrie , Wang Yanqing , Hanten Brandon , Burrell Brian D.
Published: August 2015

Transient receptor potential ankyrin subtype 1 (TRPA1) channels are chemosensitive to compounds such as allyl isothiocyanate (AITC, the active component of mustard oil) and other reactive electrophiles and may also be thermodetectors in many animal phyla. In this study we provide the first pharmacological evidence of a putative TRPA1-like channel in the medicinal leech. The leech's polymodal nociceptive neuron was activated by both peripheral and central application of the TRPA1 agonist AITC in a concentration-dependent manner. Responses to AITC were inhibited by the selective TRPA1 antagonist HC030031, but also by the TRPV1 antagonist SB366791. Other TRPA1 activators, N-methylmaleimide (NMM) and cinnamaldehyde (CIN), also activated this nociceptive neuron, although HC030031 only inhibited NMM's effects. The polymodal nociceptive neurons responded to moderately cold thermal stimuli (<17°C) and these responses were blocked by HC030031. AITC sensitivity was also found in the pressure-sensitive sensory neurons and was blocked by HC030031, but not by SB366791. AITC elicited a nocifensive withdrawal of the posterior sucker in a concentration-dependent manner that could be attenuated with HC030031. Peripheral application of AITC in vivo also produced swimming-like behavior that was attenuated by HC030031. These results suggest the presence of a TRPA1-like channel in the medicinal leech nervous system that responds to cold temperatures and may interact with the leech TRPV-like channel.
Hypercapnia and low pH induce neuroepithelial cell proliferation and emersion behaviour in the amphibious fish Kryptolebias marmoratus
Authors: Robertson Cayleih , Turko Andy J. , Jonz Michael G. , Wright Patricia A.
Published: August 2015

Aquatic hypercapnia may have helped drive ancestral vertebrate invasion of land. We tested the hypothesis that amphibious fishes sense and respond to elevated aquatic PCO2 by behavioural avoidance mechanisms, and by morphological changes at the chemoreceptor level. Mangrove rivulus (Kryptolebias marmoratus) were exposed to 1 week of normocapnic control water (pH 8), air, hypercapnia (5% CO2, pH 6.8) or isocapnic acidosis (pH 6.8). We found that the density of CO2/H+ chemoreceptive neuroepithelial cells (NECs) was increased in hypercapnia or isocapnic acidosis-exposed fish. Projection area (a measure of cell size) was unchanged. Acute exposure to progressive hypercapnia induced the fish to emerse (leave water) at water pH values ∼6.1, whereas addition of HCl to water caused a more variable response with a lower pH threshold (∼pH 5.5). These results support our hypothesis and suggest that aquatic hypercapnia provides an adequate stimulus for extant amphibious fishes to temporarily transition from aquatic to terrestrial habitats.
Physiological responses of ectotherms to daily temperature variation
Authors: Kern Pippa , Cramp Rebecca L. , Franklin Craig E.
Published: August 2015

Daily thermal fluctuations (DTF) impact the capacity of ectotherms to maintain performance and energetic demands due to thermodynamic effects on physiological processes. Mechanisms which reduce the thermal sensitivity of physiological traits may buffer ectotherms from the consequences of DTF. Species which experience varying degrees of DTF in their environments may differ in their responses to thermally variable conditions, if thermal performance curves reflect environmental conditions. We tested the hypothesis that in response to DTF tadpoles from habitats characterised by small DTF would show greater plasticity in the thermal sensitivity physiological processes than tadpoles from environments characterised by large DTF. We tested the thermal sensitivity of physiological traits in tadpoles of three species which differ naturally in their exposure to DTF raised in control (24°C) and DTF treatments (20-30°C and 18-38°C). DTF reduced growth in all species. Development of tadpoles experiencing DTF was increased for tadpoles from highly thermally variable habitats (∼15%), and slower in tadpoles from less thermally variable habitats (∼30%). In general, tadpoles were unable to alter the thermal sensitivity of physiological processes, although DTF induced plasticity in metabolic enzyme activity in all species, although to a greater extent in species from less thermally variable environments. DTF increased upper thermal limits in all species (between 0.89-1.6°C). Our results suggest that the impact of increased thermal variability may favour some species while others are negatively impacted. Species that cannot compensate for increased variability by buffering growth and development will likely be most affected.
Forelimb kinematics during hopping and landing in toads (Bufo marinus)
Authors: Cox S. , Gillis G.
Published: August 2015

Coordinated landing in a variety of animals involves the re-positioning of limbs prior to impact to safely decelerate the body. However, limb kinematics strategies for landing vary considerably among species. For example, human legs are increasingly flexed before impact as drop height increases while in turkeys, legs are increasingly extended before impact with increasing drop height. In anurans, landing typically involves the use of forelimbs to decelerate the body after impact. Few detailed, quantitative descriptions of anuran forelimb kinematics during jumping exist and it isn't known if they prepare for larger landing forces by changing forelimb kinematics. In this study, we used high-speed video of 51 hops from five cane toads (Bufo marinus) to test the hypothesis that forelimb kinematics change predictably with distance. We measured excursions of the elbow (flexion/extension) and humerus (protraction/retraction and elevation/depression) throughout every hop. Results indicate that elbow and humeral excursions leading up to impact increase significantly with hop length, but do so without any change in the rate of movement. Instead, because the animal is in the air longer during longer hops, near-constant velocity movements lead to the larger excursions. These larger excursions in elbow extension result in animals hitting the ground with more extended forelimbs in longer hops, which in turn allows animals to decelerate over a greater distance.