bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fgf2 improves functional recovery—decreasing gliosis and increasing radial glia and neural progenitor cells after spinal cord injury
Authors: Goldshmit Yona , Frisca Frisca , Pinto Alexander R. , Pébay Alice , Tang Jean‐Kitty K. Y. , Siegel Ashley L. , Kaslin Jan , Currie Peter D. 
Published: January 2014

AbstractObjectivesA major impediment for recovery after mammalian spinal cord injury (SCI) is the glial scar formed by proliferating reactive astrocytes. Finding factors that may reduce glial scarring, increase neuronal survival, and promote neurite outgrowth are of major importance for improving the outcome after SCI. Exogenous fibroblast growth factor (Fgf) has been shown to decrease injury volume and improve functional outcome; however, the mechanisms by which this is mediated are still largely unknown.MethodsIn this study, Fgf2 was administered for 2 weeks in mice subcutaneously, starting 30 min after spinal cord hemisection.ResultsFgf2 treatment decreased the expression of TNF‐a at the lesion site, decreased monocyte/macrophage infiltration, and decreased gliosis. Fgf2 induced astrocytes to adopt a polarized morphology and increased expression of radial markers such as Pax6 and nestin. In addition, the levels of chondroitin sulfate proteoglycans (CSPGs), expressed by glia, were markedly decreased. Furthermore, Fgf2 treatment promotes the formation of parallel glial processes, “bridges,” at the lesion site that enable regenerating axons through the injury site. Additionally, Fgf2 treatment increased Sox2‐expressing cells in the gray matter and neurogenesis around and at the lesion site. Importantly, these effects were correlated with enhanced functional recovery of the left paretic hind limb.ConclusionsThus, early pharmacological intervention with Fgf2 following SCI is neuroprotective and creates a proregenerative environment by the modulation of the glia response.
N‐acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities
Authors: Bavarsad Shahripour Reza , Harrigan Mark R. , Alexandrov Andrei V. 
Published: January 2014

AbstractBackgroundThere is an expanding field of research investigating the benefits of medicines with multiple mechanisms of action across neurological disorders. N‐acetylcysteine (NAC), widely known as an antidote to acetaminophen overdose, is now emerging as treatment of vascular and nonvascular neurological disorders. NAC as a precursor to the antioxidant glutathione modulates glutamatergic, neurotrophic, and inflammatory pathways.Aim and discussionMost NAC studies up to date have been carried out in animal models of various neurological disorders with only a few studies completed in humans. In psychiatry, NAC has been tested in over 20 clinical trials as an adjunctive treatment; however, this topic is beyond the scope of this review. Herein, we discuss NAC molecular, intracellular, and systemic effects, focusing on its potential applications in neurodegenerative diseases including spinocerebellar ataxia, Parkinson's disease, tardive dyskinesia, myoclonus epilepsy of the Unverricht–Lundbor type as well as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease.ConclusionFinally, we review the potential applications of NAC to facilitate recovery after traumatic brain injury, cerebral ischemia, and in treatment of cerebrovascular vasospasm after subarachnoid hemorrhage.
Identification and Characterization of the Carbapenem MM 4550 and its Gene Cluster in Streptomyces argenteolus ATCC 11009
Authors: Li Rongfeng , Lloyd Evan P. , Moshos Kristos A. , Townsend Craig A. 
Published: January 2014

AbstractNearly 50 naturally occurring carbapenem β‐lactam antibiotics, most produced by Streptomyces, have been identified. The structural diversity of these compounds is limited to variance of the C‐2 and C‐6 side chains as well as the stereochemistry at C‐5/C‐6. These structural motifs are of interest both for their antibiotic effects and their biosynthesis. Although the thienamycin gene cluster is the only active gene cluster publically available in this group, more comparative information is needed to understand the genetic basis of these structural differences. We report here the identification of MM 4550, a member of the olivanic acids, as the major carbapenem produced by Streptomyces argenteolus ATCC 11009. Its gene cluster was also identified by degenerate PCR and targeted gene inactivation. Sequence analysis revealed that the genes encoding the biosynthesis of the bicyclic core and the C‐6 and C‐2 side chains are well conserved in the MM 4550 and thienamycin gene clusters. Three new genes, cmmSu, cmm17 and cmmPah were found in the new cluster, and their putative functions in the sulfonation and epimerization of MM 4550 are proposed. Gene inactivation showed that, in addition to cmmI, two new genes, cmm22 and ‐23, encode a two‐component response system thought to regulate the production of MM 4550. Overexpression of cmmI, cmm22 and cmm23 promoted MM 4550 production in an engineered strain. Finally, the involvement and putative roles of all genes in the MM 4550 cluster are proposed based on the results of bioinformatics analysis, gene inactivation, and analysis of disruption mutants. Overall, the differences between the thienamycin and MM 4550 gene clusters are reflected in characteristic structural elements and provide new insights into the biosynthesis of the complex carbapenems.
Regulation of chondrocyte proliferation through GIT1‐Rac1‐mediated ERK1/2 pathway by PDGF
Authors: Xiao Jin , Chen Xuqiong , Xu Lipeng , Zhang Ying , Yin Qingshui , Wang Fei 
Published: January 2014

AbstractThere are many growth factors contributing to fracture healing after bone fractures. Platelet‐derived growth factor (PDGF) released from platelets is a factor promoting cell division and proliferation, and first appears around the sites of fractures. Culture of chondrocytes in vitro are stimulated by PDGF to proliferation, its presence being upregulated in the extracellular matrix of cartilage; the main components include aggrecan and type II collagen. PDGF induces the expression of G the protein‐coupled receptor kinase interacting protein 1 (GIT1), promoting Rac1 and ERK1/2 phosphorylation. Both knocking down GIT1 expression by siRNA and blocking phosphorylation of Rac1 inhibit this induced proliferation of chondrocyte. GIT1 and Rac1 control each other, having a synergistic effect on activation of the ERK1/2 pathway. The results suggest that PDGF regulates chondrocyte proliferation through activation of ERK1/2 pathway by upregulation of GIT1 expression and Rac1 phosphorylation.
Claudin‐4 immunohistochemistry is highly effective in distinguishing adenocarcinoma from malignant mesothelioma in effusion cytology
Authors: Jo Vickie Y. , Cibas Edmund S. , Pinkus Geraldine S. 
Published: January 2014

BACKGROUNDAdenocarcinoma can be challenging to distinguish from malignant mesothelioma in effusions, and this distinction often requires ancillary studies and clinical correlation. Immunohistochemistry for claudin‐4, a tight‐junction‐associated protein, has recently been shown to distinguish adenocarcinoma from malignant mesothelioma, mostly in surgical specimens. Our aim was to validate and assess the immunoreactivity profile of claudin‐4 in a large series of malignant effusions.METHODSWe evaluated 159 malignant effusions (84 adenocarcinomas and 75 malignant mesotheliomas). Claudin‐4 immunohistochemistry was performed on cell‐block paraffin sections and scored for staining intensity, staining pattern (cytoplasmic versus membranous), and percentage of positive tumor cells. Appropriate positive and negative controls were used throughout.RESULTSAll cases of mesothelioma were negative for claudin‐4 (0 of 64). Eighty‐three of 84 cases of adenocarcinoma were positive (99%); 1 case of serous carcinoma was negative. Most adenocarcinomas showed strong and diffuse membranous staining (71 of 84; 84%); 12 cases (14%) showed membranous staining of moderate intensity. The overall sensitivity for adenocarcinoma was 99% (83 of 84).CONCLUSIONSClaudin‐4 immunohistochemistry effectively distinguishes adenocarcinoma from malignant mesothelioma with high sensitivity and specificity in the evaluation of malignant effusions. Cancer (Cancer Cytopathol) 2014;122:299–306. © 2014 American Cancer Society.
GATA3: A promising marker for metastatic breast carcinoma in serous effusion specimens
Authors: Shield Paul W. , Papadimos David J. , Walsh Michael D. 
Published: January 2014

BACKGROUNDThe usefulness of GATA3 (GATA‐binding protein 3 to DNA sequence [A/T]GATA[A/G]) as a marker for metastatic breast carcinoma in serous effusion specimens was investigated.METHODSCell block sections from 74 serous effusion specimens (32 ascitic, 2 pericardial, and 40 pleural fluids) were stained with an anti‐GATA3 murine monoclonal antibody. The specimens included 62 confirmed metastatic carcinomas from the breast (30 specimens), female genital tract (13 specimens), gastrointestinal tract (7 specimens), lung adenocarcinoma (9 specimens), pancreas (1 specimen), kidney (1 specimen), and bladder (1 specimen). The breast carcinoma cases included 15 ductal carcinomas and 8 lobular carcinomas; the histology subtype was not available for 7 specimens. Twelve cases containing florid reactive mesothelial cells were also stained. The breast carcinoma cases were also stained for mammaglobin and gross cystic disease fluid protein of 15 kilodaltons (GCDFP‐15) to compare their sensitivity with GATA3.RESULTSPositive nuclear staining for GATA3 was found to be present in 90% of metastatic breast carcinoma specimens (27 of 30 specimens). All nonbreast metastatic carcinomas tested were negative with the exception of the single case of metastatic urothelial carcinoma. No staining was observed in any of the benign reactive cases or in benign mesothelial cells present in the malignant cell block preparations. Two cases demonstrated weak positivity of benign lymphoid cells. Staining results were unambiguous because all positive cases demonstrated intense nuclear staining in > 50% of tumor cells. Mammaglobin (57% staining; 17 of 30 cases) and GCDFP‐15 (33% staining; 10 of 30 cases) were found to be less sensitive markers of breast carcinoma. If used in a panel, mammaglobin and GCFP‐15 staining would have identified only 1 additional case compared with those stained with GATA3.CONCLUSIONSGATA3 may be a useful addition to immunostaining panels for serous effusion specimens when metastatic breast carcinoma is a consideration. Cancer (Cancer Cytopathol) 2014;122:307–312. © 2014 American Cancer Society.
A physically motivated constitutive model for 3D numerical simulation of skeletal muscles
Authors: Weickenmeier J. , Itskov M. , Mazza E. , Jabareen M. 
Published: January 2014

SUMMARYA detailed numerical implementation within the FEM is presented for a physically motivated three‐dimensional constitutive model describing the passive and active mechanical behaviors of the skeletal muscle. The derivations for the Cauchy stress tensor and the consistent material tangent are provided. For nearly incompressible skeletal muscle tissue, the strain energy function may be represented either by a coupling or a decoupling of the distortional and volumetric material response. In the present paper, both functionally different formulations are introduced allowing for a direct comparison between the coupled and decoupled isochoric‐volumetric approach. The numerical validation of both implementations revealed significant limitations for the decoupled approach. For an extensive characterization of the model response to different muscle contraction modes, a benchmark model is introduced. Finally, the proposed implementation is shown to provide a reliable tool for the analysis of complex and highly nonlinear problems through the example of the human mastication system by studying bite force and three‐dimensional muscle shape changes during mastication. Copyright © 2014 John Wiley & Sons, Ltd.
Habitat dynamics, marine reserve status, and the decline and recovery of coral reef fish communities
Authors: Williamson David H. , Ceccarelli Daniela M. , Evans Richard D. , Jones Geoffrey P. , Russ Garry R. 
Published: January 2014

AbstractSevere climatic disturbance events often have major impacts on coral reef communities, generating cycles of decline and recovery, and in some extreme cases, community‐level phase shifts from coral‐ to algal‐dominated states. Benthic habitat changes directly affect reef fish communities, with low coral cover usually associated with low fish diversity and abundance. No‐take marine reserves (NTRs) are widely advocated for conserving biodiversity and enhancing the sustainability of exploited fish populations. Numerous studies have documented positive ecological and socio‐economic benefits of NTRs; however, the ability of NTRs to ameliorate the effects of acute disturbances on coral reefs has seldom been investigated. Here, we test these factors by tracking the dynamics of benthic and fish communities, including the important fishery species, coral trout (Plectropomus spp.), over 8 years in both NTRs and fished areas in the Keppel Island group, Great Barrier Reef, Australia. Two major disturbances impacted the reefs during the monitoring period, a coral bleaching event in 2006 and a freshwater flood plume in 2011. Both disturbances generated significant declines in coral cover and habitat complexity, with subsequent declines in fish abundance and diversity, and pronounced shifts in fish assemblage structure. Coral trout density also declined in response to the loss of live coral, however, the approximately 2:1 density ratio between NTRs and fished zones was maintained over time. The only post‐disturbance refuges for coral trout spawning stocks were within the NTRs that escaped the worst effects of the disturbances. Although NTRs had little discernible effect on the temporal dynamics of benthic or fish communities, it was evident that the post‐disturbance refuges for coral trout spawning stocks within some NTRs may be critically important to regional‐scale population persistence and recovery.
Morphological abnormalities in gall‐forming aphids in a radiation‐contaminated area near Fukushima Daiichi: selective impact of fallout?
Authors: Akimoto Shin‐ichi 
Published: January 2014

AbstractTo evaluate the impact of fallout from the Fukushima Daiichi Nuclear Power Plant accident on organisms, this study compared the morphology and viability of gall‐forming aphids between the Fukushima population and control populations from noncontaminated areas. This study, in particular, focused on the morphology of first‐instar gall formers derived from the first sexual reproduction after the accident. Of 164 first instars from Tetraneura sorini galls collected 32 km from Fukushima Daiichi in spring 2012, 13.2% exhibited morphological abnormalities, including four conspicuously malformed individuals (2.4%). In contrast, in seven control areas, first instars with abnormal morphology accounted for 0.0–5.1% (on average, 3.8%). The proportions of abnormalities and mortality were significantly higher in Fukushima than in the control areas. Similarly, of 134 first instars from T. nigriabdominalis galls, 5.9% exhibited morphological abnormalities, with one highly malformed individual. However, of 543 second‐generation larvae produced in T. sorini galls, only 0.37% had abnormalities, suggesting that abnormalities found in the first generation were not inherited by the next generation. Although investigation is limited to one study site, this result suggests that radioactive contamination had deleterious effects on embryogenesis in eggs deposited on the bark surface, but a negligible influence on the second generation produced in closed galls. Furthermore, analysis of both species samples collected in spring 2013 indicated that the viability and healthiness of the aphids were significantly improved compared to those in the 2012 samples. Thus, the results of this study suggest the possibility that a reduced level of radiation and/or selection for radiation tolerance may have led to the improved viability and healthiness of the Fukushima population.
Design of a Multiagent‐Based Voltage Control System in Peer‐to‐Peer Networks for Smart Grids
Authors: Rohbogner Gregor , Fey Simon , Benoit Pascal , Wittwer Christof , Christ Andreas 
Published: January 2014

AbstractEnergy management in distribution grids is one of the key challenges that needs to be overcome to increase the share of fluctuating renewable energies. Current control systems for energy management mainly demonstrate centralized‐ or decentralized‐hierarchical control structures. Very few systems manifest a fully decentralized multiagent‐based control structure. Multiagent‐based control systems promise to be an advantageous approach for the future distributed energy supply system because no central control entity is necessary, which eases parameterization in case of grid topology changes, and the agents are more stable against failures and changes of control topologies. Research is necessary to prove these benefits. In this study, we introduce a design of a multiagent‐based voltage control system for low‐voltage grids. In detail we introduce cooperative decision‐making processes and software solutions that allow the agents to perceive and control their environment, the agent‐discovery and localization in different types of communication networks, agent‐to‐agent communication, and the integration of the multiagent system in existing grid‐control infrastructures. Furthermore, the study proposes how different existing technologies can be combined into an applicable multiagent‐based voltage control system: the Java/OSGi‐based OpenMUC framework allows a generic field–device interaction; peer‐to‐peer discovery and session establishment functionalities are combined with the agent communication defined by the Foundation for Intelligent Physical Agents (FIPA). The ripple control‐signal technology is applied as a fallback communication between the agent and a central grid‐control center.
A double‐blind, randomized, placebo‐controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment
Authors: Serpell M. , Ratcliffe S. , Hovorka J. , Schofield M. , Taylor L. , Lauder H. , Ehler E. 
Published: January 2014

AbstractBackgroundPeripheral neuropathic pain (PNP) associated with allodynia poses a significant clinical challenge. The efficacy of Δ9‐tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray, a novel cannabinoid formulation, was investigated in this 15‐week randomized, double‐blind, placebo‐controlled parallel group study.MethodsIn total, 303 patients with PNP associated with allodynia were screened; 128 were randomized to THC/CBD spray and 118 to placebo, in addition to their current analgesic therapy. The co‐primary efficacy endpoints were the 30% responder rate in PNP 0–10 numerical rating scale (NRS) score and the mean change from baseline to the end of treatment in this score. Various key secondary measures of pain and functioning were also investigated.ResultsAt the 30% responder level, there were statistically significant treatment differences in favour of THC/CBD spray in the full analysis (intention‐to‐treat) dataset [p = 0.034; 95% confidence interval (CI): 1.05–3.70]. There was also a reduction in mean PNP 0–10 NRS scores in both treatment groups that was numerically higher in the THC/CBD spray group, but which failed to reach statistical significance. Secondary measures of sleep quality 0–10 NRS score (p = 0.0072) and Subject Global Impression of Change (SGIC) (p = 0.023) also demonstrated statistically significant treatment differences in favour of THC/CBD spray treatment.ConclusionsThese findings demonstrate that, in a meaningful proportion of otherwise treatment‐resistant patients, clinically important improvements in pain, sleep quality and SGIC of the severity of their condition are obtained with THC/CBD spray. THC/CBD spray was well tolerated and no new safety concerns were identified.
Perceived Burdensomeness and Suicide‐Related Behaviors in Clinical Samples: Current Evidence and Future Directions
Authors: Hill Ryan M. , Pettit Jeremy W. 
Published: January 2014

ContextThe interpersonal‐psychological theory of suicide identifies perceived burdensomeness as a primary component of suicidal desire and a possible point of intervention for suicide prevention. A growing literature has explored the relationship between perceived burdensomeness and suicide‐related behaviors.ObjectiveThe aim of this review is to integrate the evidence, identify critical gaps in the evidence‐base, and explore implications for translation to prevention and intervention science.MethodsPapers published that reported on the association between perceived burdensomeness and suicide‐related behaviors were included.ResultsThe literature indicates (a) significant cross‐sectional associations between perceived burdensomeness and suicidal ideation and suicide attempts and (b) that perceived burdensomeness acts as either a moderator or a mediator of the association between risk and protective factors and suicide‐related behaviors.ConclusionResearch is needed to examine the longitudinal association between perceived burdensomeness and suicide‐related behaviors, develop additional measurement approaches, generalize findings to other samples, and begin translating findings to prevention and intervention science.
Reference values of maternal ophthalmic artery doppler variables in the first trimester of normal pregnancy
Authors: Alves Júlio Augusto Gurgel , Yang Bruna , de Sousa Paulo Cesar Praciano , Bezerra Maia e Holanda Moura Sammya , Kane Stefan , da Silva Costa Fabrício 
Published: January 2014

ABSTRACTBackgroundThe aim of this study was to establish normative data for ophthalmic artery Doppler variables in the first trimester of normal pregnancy.MethodsMaternal ophthalmic artery Doppler signals were recorded in 409 singleton pregnancies at 11–14 weeks' gestation, in mothers presenting consecutively for routine antenatal care. Pulsatility and resistance indices (PI, RI), peak systolic velocity (PSV), first peak diastolic velocity (PD1), and peak ratio (PR) were measured. Quartile regression was used to estimate reference ranges in the late first trimester of pregnancy.ResultsMean ± SD values for maternal ophthalmic artery Doppler parameters between 11 and 14 weeks' gestation were RI = 0.81 ± 0.12, PI = 2.06 ± 0.57, PSV = 36.41 ± 12.1, PD1 = 21.07 ± 7.62, and PR = 0.58 ± 0.11. All clinical and Doppler variables were normally distributed. PD1 values were higher in patients who smoked, and in those with diabetes or a history of pre‐eclampsia. PR values were higher in patients with diabetes and chronic hypertension, and lower in the nulliparous; these values declined as gestation advanced from 11 to 14 weeks, whereas the other variables remained unchanged.ConclusionsWe provide reference values for maternal ophthalmic artery Doppler variables in the first trimester of normal pregnancy. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 42:199–204, 2014
Molecular aspects of cholangiocarcinoma
Authors: Kiguchi Kaoru 
Published: January 2014

Abstract Novel targets for therapeutic or chemopreventive approaches against cholangiocarcinoma (CCA) are urgently needed. In this review article, we discuss the molecular aspects of CCA including the role of erbB receptor tyrosine kinases (RTKs), downstream signaling pathways of these erbB RTKs, inflammatory mediators during gallbladder carcinogenesis and bile acids based on our study using a mouse model for human CCA (BK5.erbB2 mice) as well as additional information in the literature.