bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rescue of nonsense mutations by amlexanox in human cells
Authors: Gonzalez-Hilarion Sara , Beghyn Terence , Jia Jieshuang , Debreuck Nadège , Berte Gonzague , Mamchaoui Kamel , Mouly Vincent , Gruenert Dieter C , Déprez Benoit , Lejeune Fabrice 
Published: September 2012

Abstract

Background
Nonsense mutations are at the origin of many cancers and inherited genetic diseases. The consequence of nonsense mutations is often the absence of mutant gene expression due to the activation of an mRNA surveillance mechanism called nonsense-mediated mRNA decay (NMD). Strategies to rescue the expression of nonsense-containing mRNAs have been developed such as NMD inhibition or nonsense mutation readthrough.

Methods
Using a dedicated screening system, we sought molecules capable to block NMD. Additionally, 3 cell lines derived from patient cells and harboring a nonsense mutation were used to study the effect of the selected molecule on the level of nonsense-containing mRNAs and the synthesis of proteins from these mutant mRNAs.

Results
We demonstrate here that amlexanox, a drug used for decades, not only induces an increase in nonsense-containing mRNAs amount in treated cells, but also leads to the synthesis of the full-length protein in an efficient manner. We also demonstrated that these full length proteins are functional.

Conclusions
As a result of this dual activity, amlexanox may be useful as a therapeutic approach for diseases caused by nonsense mutations.
Neuromuscular effects of G93A-SOD1 expression in zebrafish
Authors: Sakowski Stacey A , Lunn J Simon , Busta Angela S , Oh Sang Su , Zamora-Berridi Grettel , Palmer Madeline , Rosenberg Andrew A , Philip Stephen G , Dowling James J , Feldman Eva L 
Published: September 2012

Abstract

Background
Amyotrophic lateral sclerosis (ALS) is a fatal disorder involving the degeneration and loss of motor neurons. The mechanisms of motor neuron loss in ALS are unknown and there are no effective treatments. Defects in the distal axon and at the neuromuscular junction are early events in the disease course, and zebrafish provide a promising in vivo system to examine cellular mechanisms and treatments for these events in ALS pathogenesis.

Results
We demonstrate that transient genetic manipulation of zebrafish to express G93A-SOD1, a mutation associated with familial ALS, results in early defects in motor neuron outgrowth and axonal branching. This is consistent with previous reports on motor neuron axonal defects associated with familial ALS genes following knockdown or mutant protein overexpression. We also demonstrate that upregulation of growth factor signaling is capable of rescuing these early defects, validating the potential of the model for therapeutic discovery. We generated stable transgenic zebrafish lines expressing G93A-SOD1 to further characterize the consequences of G93A-SOD1 expression on neuromuscular pathology and disease progression. Behavioral monitoring reveals evidence of motor dysfunction and decreased activity in transgenic ALS zebrafish. Examination of neuromuscular and neuronal pathology throughout the disease course reveals a loss of neuromuscular junctions and alterations in motor neuron innervations patterns with disease progression. Finally, motor neuron cell loss is evident later in the disease.

Conclusions
This sequence of events reflects the stepwise mechanisms of degeneration in ALS, and provides a novel model for mechanistic discovery and therapeutic development for neuromuscular degeneration in ALS.
Scrotal cutaneous verruciform xanthoma with monocyte chemoattractant protein-1 immunohistochemical study: a case report
Authors: Ito Chihiro , Kitazawac Riko , Makita Kenji , Watanabe Takafumi , Toda Akihiro , Haraguchi Ryuma , Tanaka Shinji , Kitazawa Sohei 
Published: September 2012

Abstract

Introduction
Verruciform xanthoma is a rare, benign lesion characterized by hyperkeratosis and aggregates of foam cell macrophages. Here, we describe a case of verruciform xanthoma on the scrotum, in which the immunohistochemical localization of monocyte chemoattractant protein-1, a chemokine of the C-C or beta family that has been shown to induce the recruitment of monocytes for injured tissue, was analyzed to determine which cells release chemoattractants for macrophages.

Case presentation
A 75-year-old Japanese man with a well-defined nodule on the left scrotum was admitted to the hospital. An excision biopsy revealed epidermal papillary proliferation with parakeratosis, hyperkeratosis, and infiltration of foam cell macrophages, whereby a pathological diagnosis of benign cutaneous verruciform xanthoma was made. Immunohistochemically, monocyte chemoattractant protein-1 was observed predominantly on cytokeratin AE1/AE3-positive differentiating keratinocytes in the prickle cell layer. However, while infiltrating macrophages were densely stained for monocyte chemoattractant protein-1, keratinocytes in the basal and parabasal layers were almost negative.

Conclusions
We demonstrated that keratinocyte-derived monocyte chemoattractant protein-1 plays an important role in the establishment of particular histological features of verruciform xanthoma. However, in the present case, unlike in previous reports, monocyte chemoattractant protein-1 immunostaining in keratinocytes in the basal and parabasal layers was not prominent. We speculate that in the active phase of verruciform xanthoma, when continuous stimuli that release monocyte chemoattractant protein-1 from keratinocytes to the surrounding stromal area are present, the apparent immunostaining of monocyte chemoattractant protein-1 can be underestimated because of the void created by accelerated keratinocyte release from the cytoplasmic fraction.
Non-invasive prenatal diagnostic test accuracy for fetal sex using cell-free DNA a review and meta-analysis
Authors: Wright Caroline F , Wei Yinghui , Higgins Julian PT , Sagoo Gurdeep S 
Published: September 2012

AbstractBackgroundCell-free fetal DNA (cffDNA) can be detected in maternal blood during pregnancy, opening the possibility of early non-invasive prenatal diagnosis for a variety of genetic conditions. Since 1997, many studies have examined the accuracy of prenatal fetal sex determination using cffDNA, particularly for pregnancies at risk of an X-linked condition. Here we report a review and meta-analysis of the published literature to evaluate the use of cffDNA for prenatal determination (diagnosis) of fetal sex. We applied a sensitive search of multiple bibliographic databases including PubMed (MEDLINE), EMBASE, the Cochrane library and Web of Science.ResultsNinety studies, incorporating 9,965 pregnancies and 10,587 fetal sex results met our inclusion criteria. Overall mean sensitivity was 96.6% (95% credible interval 95.2% to 97.7%) and mean specificity was 98.9% (95% CI = 98.1% to 99.4%). These results vary very little with trimester or week of testing, indicating that the performance of the test is reliably high.ConclusionsBased on this review and meta-analysis we conclude that fetal sex can be determined with a high level of accuracy by analyzing cffDNA. Using cffDNA in prenatal diagnosis to replace or complement existing invasive methods can remove or reduce the risk of miscarriage. Future work should concentrate on the economic and ethical considerations of implementing an early non-invasive test for fetal sex.
Load-distributing band improves ventilation and hemodynamics during resuscitation in a porcine model of prolonged cardiac arrest
Authors: Wang Shuo , Wu Jun-Yuan , Li Chun-Sheng 
Published: September 2012

Abstract

Background
The use of mechanical cardiopulmonary resuscitation (CPR) has great potential for the clinical setting. The purpose of present study is to compare the hemodynamics and ventilation during and after the load-distributing band CPR, versus the manual CPR in a porcine model of prolonged cardiac arrest, and to investigate the influence of rescue breathing in different CPR protocols.

Methods
Sixty-four male pigs (n = 16/group), weighing 30 ± 2 kg, were induced ventricular fibrillation and randomized into four resuscitation groups: continuous load-distributing band CPR without rescue ventilation (C-CPR), load-distributing band 30:2 CPR (A-CPR), load-distributing band CPR with continuous rescue breathing (10/min) (V-CPR) or manual 30:2 CPR (M-CPR). Respiratory variables and hemodynamics were recorded continuously; blood gas was analyzed.

Results
Tidal volume produced by compressions in the A-, C- and V-CPR groups were significantly higher compared with the M-CPR group (all p < 0.05). Coronary perfusion pressure of the V-CPR group was significantly lower than the C-CPR group (p < 0.01), but higher than the M-CPR group. The increasing of lung dead space after restoration of spontaneous circulation was significantly greater in the M-CPR group compared with the A-, C- and V-CPR groups (p < 0.01). Blood pH gradually decreased and was lower in the M-CPR group than that in the A-, C- and V-CPR groups (p < 0.01). PaO2 of the A-, C- and V-CPR groups were significantly higher and PaCO2 were significantly lower compared with the M-CPR (both p < 0.05). Cerebral performance categories were better in the A-, C- and V-CPR groups compared with the M-CPR group (p < 0.0001).

Conclusions
The load-distributing band CPR significantly improved respiratory parameters during resuscitation by augmenting passive ventilation, and significantly improved coronary perfusion pressure. The volume of ventilation produced by the load-distributing band CPR was adequate to maintain sufficient gas exchange independent of rescue breathing.
Is the lag screw sliding effective in the intramedullary nailing in A1 and A2 AO-OTA intertrochanteric fractures? A prospective study of Sliding and None-sliding lag screw in Gamma-III nail
Authors: Zhu Yi , Meili Severin , Zhang Changqing , Luo Congfeng , Zeng Bing-fang 
Published: September 2012

AbstractObjectTo compare the Sliding with Non-sliding lag screw of a gamma nail in the treatment of A1 and A2 AO-OTA intertrochanteric fractures.Materials and methods80 patients were prospectively collected. In each group, AO/OTA 31-A were classified into group A. AO/OTA 31-A2.1 was classified as group B. We classified the A2.2 and A2.3 as group C. According to the set-screw locking formation of Gamma-III, the cases were randomly allocated to Sliding subgroup and Non-sliding subgroup in A, B and C groups. Follow-ups were performed 1, 3, 6 and 12 months postoperatively.ResultsIn the Sliding group, the bone healing rate 3, 6, 12 months postoperatively reached 85.00%, 97.50%, 100% in group A, B and C. Meanwhile, in Non-sliding group, postoperatively, bone healing rate were 90.00%, 95.00% and 97.50% in group A, B and C, respectively. Both differences were not significant. Lower limb discrepancy between Sliding and Non-sliding pattern was significantly different in group C which represent fracture types of AO/OTA 31-A2.2 and A2.3 (0.573 ± 0.019 mm in Non-sliding group, 0.955 mm ± 0.024 mm in Sliding group, P < 0.001 ). Difference of sliding distance among the three groups was significant among group A, B and C: 0.48 mm ± 0.04 mm, 0.62 mm ± 0.07 mm and 0.92 mm ± 0.04 mm (P < 0.001). Differences in average healing time and Harris scores also presented no significance in the three groups.ConclusionsAs a result, we can conclude that the sliding distance is minimal in Gamma nails and it is related to the comminuted extent of the intertrochanteric area in A1 and A2 AO-OTA intertrochanteric fractures. For treating these kinds of fractures, the sliding of the lag screw of an Gamma nail does not improve any clinical results and in certain cases, such as highly comminuted A1 and A2 fractures, can therefore even benefit from a locked lag screw by tightening the set-screw.
Challenges and opportunities in patient‐specific, motion‐managed and PET/CT‐guided radiation therapy of lung cancer: review and perspective
Authors: Bowen Stephen R , Nyflot Matthew J , Gensheimer Michael , Hendrickson Kristi R G , Kinahan Paul E , Sandison George A , Patel Shilpen A 
Published: September 2012

AbstractThe increasing interest in combined positron emission tomography (PET) and computed tomography (CT) to guide lung cancer radiation therapy planning has been well documented. Motion management strategies during treatment simulation PET/CT imaging and treatment delivery have been proposed to improve the precision and accuracy of radiotherapy. In light of these research advances, why has translation of motion‐managed PET/CT to clinical radiotherapy been slow and infrequent? Solutions to this problem are as complex as they are numerous, driven by large inter‐patient variability in tumor motion trajectories across a highly heterogeneous population. Such variation dictates a comprehensive and patient‐specific incorporation of motion management strategies into PET/CT‐guided radiotherapy rather than a one‐size‐fits‐all tactic. This review summarizes challenges and opportunities for clinical translation of advances in PET/CT‐guided radiotherapy, as well as in respiratory motion‐managed radiotherapy of lung cancer. These two concepts are then integrated into proposed patient‐specific workflows that span classification schemes, PET/CT image formation, treatment planning, and adaptive image‐guided radiotherapy delivery techniques.
Introducing the Forensic Research/Reference on Genetics knowledge base, FROG-kb
Authors: Rajeevan Haseena , Soundararajan Usha , Pakstis Andrew J , Kidd Kenneth K 
Published: September 2012

Abstract

Background
Online tools and databases based on multi-allelic short tandem repeat polymorphisms (STRPs) are actively used in forensic teaching, research, and investigations. The Fst value of each CODIS marker tends to be low across the populations of the world and most populations typically have all the common STRP alleles present diminishing the ability of these systems to discriminate ethnicity. Recently, considerable research is being conducted on single nucleotide polymorphisms (SNPs) to be considered for human identification and description. However, online tools and databases that can be used for forensic research and investigation are limited.

Methods
The back end DBMS (Database Management System) for FROG-kb is Oracle version 10. The front end is implemented with specific code using technologies such as Java, Java Servlet, JSP, JQuery, and GoogleCharts.

Results
We present an open access web application, FROG-kb (Forensic Research/Reference on Genetics-knowledge base, http://frog.med.yale.edu), that is useful for teaching and research relevant to forensics and can serve as a tool facilitating forensic practice. The underlying data for FROG-kb are provided by the already extensively used and referenced ALlele FREquency Database, ALFRED (http://alfred.med.yale.edu). In addition to displaying data in an organized manner, computational tools that use the underlying allele frequencies with user-provided data are implemented in FROG-kb. These tools are organized by the different published SNP/marker panels available. This web tool currently has implemented general functions possible for two types of SNP panels, individual identification and ancestry inference, and a prediction function specific to a phenotype informative panel for eye color.

Conclusion
The current online version of FROG-kb already provides new and useful functionality. We expect FROG-kb to grow and expand in capabilities and welcome input from the forensic community in identifying datasets and functionalities that will be most helpful and useful. Thus, the structure and functionality of FROG-kb will be revised in an ongoing process of improvement. This paper describes the state as of early June 2012.
Comparison of five equations for estimating resting energy expenditure in Chinese young, normal weight healthy adults
Authors: Rao Zhi-yong , Wu Xiao-ting , Liang Bin-miao , Wang Mao-yun , Hu Wen 
Published: September 2012

AbstractBackgroundMost resting energy expenditure (REE) predictive equations for adults were derived from research conducted in western populations; whether they can also be used in Chinese young people is still unclear. Therefore, we conducted this study to determine the best REE predictive equation in Chinese normal weight young adults.MethodsForty-three (21 male, 22 female) healthy college students between the age of 18 and 25 years were recruited. REE was measured by the indirect calorimetry (IC) method. Harris-Benedict, World Health Organization (WHO), Owen, Mifflin and Liu’s equations were used to predictREE (REEe). REEe that was within 10% of measured REE (REEm) was defined as accurate. Student’s ttest, Wilcoxon Signed Ranks Test, McNemar Test and the Bland-Altman method were used for data analysis.ResultsREEm was significantly lower (P < 0.05 orP < 0.01) than REEe from equations, except for Liu’s, Liu’s-s, Owen, Owen-s and Mifflin in men and Liu’s and Owen in women. REEe calculated by ideal body weight was significantly higher than REEe calculated by current body weight (P < 0.01), the only exception being Harris-Benedict equation in men. Bland-Altman analysis showed that the Owen equation with current body weight generated the least bias. The biases of REEe from Owen with ideal body weight and Mifflin with both current and ideal weights were also lower.ConclusionsLiu’s, Owen, and Mifflin equations are appropriate for the prediction of REE in young Chinese adults. However, the use of ideal body weight did not increase the accuracy of REEe.
Immature murine NKT cells pass through a stage of developmentally programmed innate IL-4 secretion
Authors: Dickgreber Nina , Farrand Kathryn J , van Panhuys Nicholas , Knight Deborah A , McKee Sara J , Chong Mei L , Miranda-Hernandez Socorro , Baxter Alan G , Locksley Richard M , Le Gros Graham , Hermans Ian F 
Published: September 2012

Abstract
NKT cells undergo a phase of IL-4 secretion as they mature, with the potential to condition surrounding cells as they develop in the thymus.
We assessed the production of the canonical Th2 cytokine IL-4 by NKT cells directly in vivo using IL-4-substituting strains of reporter mice that provide faithful and sensitive readouts of cytokine production without the confounding effects of in vitro stimulation. Analysis in naïve animals revealed an “innate” phase of IL-4 secretion that did not need to be triggered by administration of a known NKT cell ligand. This secretion was by immature NKT cells spanning Stage 1 of the maturation process in the thymus (CD4+ CD44lo NK1.1− cells) and Stage 2 (CD4+ CD44hi NK1.1− cells) in the spleen. Like ligand-induced IL-4 production by mature cells, this innate activity was independent of an initial source of IL-4 protein and did not require STAT6 signaling. A more sustained level of innate IL-4 production was observed in animals on a BALB/c background compared with a C57BL/6 background, suggesting a level of genetic regulation that may contribute to the “Th2-prone” phenotype in BALB/c animals. These observations indicate a regulated pattern of IL-4 expression by maturing NKT cells, which may endow these cells with a capacity to influence the development of surrounding cells in the thymus.
Motor planning modulates sensory-motor control of collision avoidance behavior in the bullfrog, Rana catesbeiana
Authors: Nakagawa Hideki , Nishida Yuuya 
Published: September 2012

Summary
In this study, we examined the collision avoidance behavior of the frog, Rana catesbeiana to an approaching object in the upper visual field. The angular velocity of the frog's escape turn showed a significant positive correlation with the turn angle (r2 = 0.5741, P&lt;0.05). A similar mechanism of velocity control has been known in head movements of the owl and in human saccades. By analogy, this suggests that the frog planned its escape velocity in advance of executing the turn, to make the duration of the escape behavior relatively constant. For escape turns less than 60°, the positive correlation was very strong (r2 = 0.7097, P&lt;0.05). Thus, the frog controlled the angular velocity of small escape turns very accurately and completed the behavior within a constant time. On the other hand, for escape turns greater than 60°, the same correlation was not significant (r2 = 0.065, P&gt;0.05). Thus, the frog was not able to control the velocity of the large escape turns accurately and did not complete the behavior within a constant time. In the latter case, there was a small but significant positive correlation between the threshold angular size and the angular velocity (r2 = 0.1459, P&lt;0.05). This suggests that the threshold is controlled to compensate for the insufficient escape velocity achieved during large turn angles, and could explain a significant negative correlation between the turn angle and the threshold angular size (r2 = 0.1145, P&lt;0.05). Thus, it is likely that the threshold angular size is also controlled by the turn angle and is modulated by motor planning.
Cortactin depletion results in short tubulobulbar complexes and spermiation failure in rat testes
Authors: Young J'Nelle S. , De Asis Marc , Guttman Julian , Vogl A. Wayne 
Published: September 2012

Summary
Tubulobulbar complexes are actin-related endocytic structures that form at sites of intercellular attachment in the seminiferous epithelium and are proposed to internalize intact junctions. In this study, we test the prediction that altering the structure/function of tubulobulbar complexes results in failure to release mature spermatids from Sertoli cells. We used an in vivo knockdown strategy to target cortactin, a component of tubulobulbar complexes, in Sprague Dawley rats. In each animal, one testis was surgically injected with cortactin siRNA reagents and the other testis was injected with non-targeting siRNA. After three days, experimental and control testes were processed for immunoblotting, electron microscopy or immunofluorescence microscopy. In testis sections immunostained for cortactin or labeled for filamentous actin, fluorescence microscopy revealed that tubulobulbar complexes were shorter in siRNA-treated testes relative to controls. Significantly, in the knockdown testes, spermiation was delayed in some tubules and had failed in others. When evaluated by electron microscopy, adhesion complexes (ectoplasmic specializations) remained associated with mature spermatids that failed to be released from Sertoli cells. Immunoblots both of whole testis lysates and of isolated seminiferous epithelial lysates confirmed that cortactin expression was knocked-down in experimental testes and in the seminiferous epithelium respectively, relative to controls. Moreover, in testes injected with siRNA reagents with a dye modification on one of the four targeting siRNA sequences, dye clusters were detected at the base of the epithelium confirming that the reagents entered Sertoli cells. Our results are consistent with the hypothesis that tubulobulbar complexes internalize intercellular junctions and that they are a significant component of the sperm release mechanism.
Specific Amino Acid Sensing Using a Single Acridone-labeled DNA Aptamer
Authors: Ozaki Hiroaki , Hagiwara Yasuhisa , Kuwahara Masayasu 
Published: September 2012

Abstract
Acridone is an attractive fluorescent molecule for use in DNA probes. Sensing molecule, which has acridone as a signaling moiety and DNA aptamer as a recognition moiety, was prepared by postsynthetic modification method. The fluorescence of this sensing molecule changed depending on the DNA structure and l-argininamide could be detected by this molecule. This strategy could provide a quencher-free aptamer beacon.