bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroprotective function for ramified microglia in hippocampal excitotoxicity
Authors: Vinet Jonathan , van Weering Hilmar RJ , Heinrich Annette , Kälin Roland E , Wegner Anja , Brouwer Nieske , Heppner Frank L , van Rooijen Nico , Boddeke Hendrikus WGM , Biber Knut 
Published: January 2012

Abstract

Background
Most of the known functions of microglia, including neurotoxic and neuroprotective properties, are attributed to morphologically-activated microglia. Resting, ramified microglia are suggested to primarily monitor their environment including synapses. Here, we show an active protective role of ramified microglia in excitotoxicity-induced neurodegeneration.

Methods
Mouse organotypic hippocampal slice cultures were treated with N-methyl-D-aspartic acid (NMDA) to induce excitotoxic neuronal cell death. This procedure was performed in slices containing resting microglia or slices that were chemically or genetically depleted of their endogenous microglia.

Results
Treatment of mouse organotypic hippocampal slice cultures with 10-50 μM N-methyl-D-aspartic acid (NMDA) induced region-specific excitotoxic neuronal cell death with CA1 neurons being most vulnerable, whereas CA3 and DG neurons were affected less. Ablation of ramified microglia severely enhanced NMDA-induced neuronal cell death in the CA3 and DG region rendering them almost as sensitive as CA1 neurons. Replenishment of microglia-free slices with microglia restored the original resistance of CA3 and DG neurons towards NMDA.

Conclusions
Our data strongly suggest that ramified microglia not only screen their microenvironment but additionally protect hippocampal neurons under pathological conditions. Morphological activation of ramified microglia is thus not required to influence neuronal survival.
Gaming control using a wearable and wireless EEG-based brain-computer interface device with novel dry foam-based sensors
Authors: Liao Lun-De , Chen Chi-Yu , Wang I-Jan , Chen Sheng-Fu , Li Shih-Yu , Chen Bo-Wei , Chang Jyh-Yeong , Lin Chin-Teng 
Published: January 2012

Abstract
A brain-computer interface (BCI) is a communication system that can help users interact with the outside environment by translating brain signals into machine commands. The use of electroencephalographic (EEG) signals has become the most common approach for a BCI because of their usability and strong reliability. Many EEG-based BCI devices have been developed with traditional wet- or micro-electro-mechanical-system (MEMS)-type EEG sensors. However, those traditional sensors have uncomfortable disadvantage and require conductive gel and skin preparation on the part of the user. Therefore, acquiring the EEG signals in a comfortable and convenient manner is an important factor that should be incorporated into a novel BCI device. In the present study, a wearable, wireless and portable EEG-based BCI device with dry foam-based EEG sensors was developed and was demonstrated using a gaming control application. The dry EEG sensors operated without conductive gel; however, they were able to provide good conductivity and were able to acquire EEG signals effectively by adapting to irregular skin surfaces and by maintaining proper skin-sensor impedance on the forehead site. We have also demonstrated a real-time cognitive stage detection application of gaming control using the proposed portable device. The results of the present study indicate that using this portable EEG-based BCI device to conveniently and effectively control the outside world provides an approach for researching rehabilitation engineering.
Medical ethnobotany of the Albanian Alps in Kosovo
Authors: Mustafa Behxhet , Hajdari Avni , Krasniqi Feriz , Hoxha Esat , Ademi Hatixhe , Quave Cassandra L , Pieroni Andrea 
Published: January 2012

AbstractBackgroundEthnobotanical studies are crucial in South-Eastern Europe for fostering local development and also for investigating the dynamics of Traditional Environmental Knowledge (TEK) related to plants in one of the most crucial European hotspots for biocultural diversity. The current medico-ethnobotanical survey was conducted in rural alpine communities in Kosovo. The aims of the study were twofold: 1) to document the state of TEK of medicinal plants in these communities; 2) to compare these findings with that of similar field studies previously conducted among local populations inhabiting the Montenegrin and Albanian side of the same Alpine range.MethodsField research was conducted in 36 villages on the Kosovar side of the Albanian Alps. Snowball sampling techniques were used to recruit 91 elderly informants (≥ 50 years-old) for participation in semi-structured interviews and structured surveys regarding the use of the local flora for medicinal and food purposes. Standard ethnobotanical methods were employed and prior informed consent was obtained for all study participants.Results and ConclusionThe uses of 98 plants species belonging to 39 families were recorded; the most quoted botanical families were Rosaceae, Asteraceae, and Lamiaceae. Mainly decoctions and infusions were quoted as folk medicinal preparations and the most common uses referred to gastrointestinal and respiratory disorders, as well as illnesses of the uro-genital system. Among the most uncommon medicinal taxa quoted by the informants, Carduus nutansL.,Echinops bannaticusRochel ex Schrad., andOrlaya grandifloraHoffm. may merit phytochemical and phytopharmacological investigations.Comparison of the data with other ethnobotanical field studies recently conducted on the Albanian and Montenegrin sides of the same Alps has shown a remarkable link between the medical ethnobotany of Montenegrin and Kosovar side of the Albanian Alps. Moreover, folk uses of the most quoted wild medicinal taxa recorded in Kosovo often include those recorded both in Albania and in Montenegro, thus suggesting a hybrid character of the Kosovar local plant knowledge. This may be also explained with the fact that Montenegro and Kosovo, despite their differences in the ethnic composition, have shared a common history during the last Century.
ATP-dependent chromatin remodeling in the DNA-damage response
Authors: Lans Hannes , Marteijn Jurgen A , Vermeulen Wim 
Published: January 2012

Abstract
The integrity of DNA is continuously challenged by metabolism-derived and environmental genotoxic agents that cause a variety of DNA lesions, including base alterations and breaks. DNA damage interferes with vital processes such as transcription and replication, and if not repaired properly, can ultimately lead to premature aging and cancer. Multiple DNA pathways signaling for DNA repair and DNA damage collectively safeguard the integrity of DNA. Chromatin plays a pivotal role in regulating DNA-associated processes, and is itself subject to regulation by the DNA-damage response. Chromatin influences access to DNA, and often serves as a docking or signaling site for repair and signaling proteins. Its structure can be adapted by post-translational histone modifications and nucleosome remodeling, catalyzed by the activity of ATP-dependent chromatin-remodeling complexes. In recent years, accumulating evidence has suggested that ATP-dependent chromatin-remodeling complexes play important, although poorly characterized, roles in facilitating the effectiveness of the DNA-damage response. In this review, we summarize the current knowledge on the involvement of ATP-dependent chromatin remodeling in three major DNA repair pathways: nucleotide excision repair, homologous recombination, and non-homologous end-joining. This shows that a surprisingly large number of different remodeling complexes display pleiotropic functions during different stages of the DNA-damage response. Moreover, several complexes seem to have multiple functions, and are implicated in various mechanistically distinct repair pathways.
Extracellular nicotinamide phosphoribosyltransferase (NAMPT/visfatin) inhibits insulin-like growth factor-1 signaling and proteoglycan synthesis in human articular chondrocytes
Authors: Yammani Raghunatha R , Loeser Richard F 
Published: January 2012

Abstract

Introduction

Obesity is one of the major risk factors for the development of osteoarthritis (OA). Although the mechanical factors appear to be critical, recent studies have suggested a role for adipokines in cartilage degradation. Chondrocytes from osteoarthritic cartilage respond poorly to insulin-like growth factor-1 (IGF-1) and the molecular mechanism(s) involved is not clearly understood. The purpose of the present study was to determine the role of extracellular nicotinamide phosphoribosyltransferase (eNAMPT/visfatin), a newly described adipokine, in regulating IGF-1 function in chondrocytes.

Methods

Human articular chondrocytes isolated from normal ankle cartilage were pretreated with eNAMPT (0.1 to 5.0 μg/ml) overnight followed by stimulation with IGF-1 (50 ng/ml) for 24 hours, and proteoglycan synthesis was measured by [35S]sulfate incorporation. Chondrocytes were pretreated with eNAMPT overnight followed by IGF-1 for 10 minutes, and the cell lysates were immunoblotted for various signaling proteins that are activated by IGF-1 using phosphospecific antibodies. In addition, chondrocytes were pretreated with mitogen-activated protein kinase kinase inhibitor (U0126) prior to stimulation with eNAMPT and IGF-1.

Results

Pretreatment of chondrocytes with eNAMPT inhibited IGF-1-stimulated proteoglycan synthesis in a dose-dependent manner. Treatment of chondrocytes with eNAMPT inhibited IGF-1-induced phosphorylation of signaling molecules, including insulin receptor substrate-1 and AKT. Interestingly, pretreatment of chondrocytes with eNAMPT did not inhibit IGF-1-mediated phosphorylation of the IGF-1 receptor; however, it stimulated a sustained phosphorylation of the extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signaling pathway. Inhibition of the ERK/MAPK signaling pathway restored IGF-1-mediated insulin receptor substrate-1 and AKT phosphorylation.

Conclusions

Our study demonstrates that eNAMPT/visfatin inhibits IGF-1 function in articular chondrocytes by activating the ERK/MAPK pathway independent of the IGF-1 receptor. Since eNAMPT levels are elevated in the synovial fluid of OA patients, the signaling pathway activated by eNAMPT could contribute to IGF-1 resistance in OA.
SpliceGrapher: detecting patterns of alternative splicing from RNA-Seq data in the context of gene models and EST data
Authors: Rogers Mark F , Thomas Julie , Reddy Anireddy SN , Ben-Hur Asa 
Published: January 2012

AbstractWe propose a method for predicting splice graphs that enhances curated gene models using evidence from RNA-Seq and EST alignments. Results obtained using RNA-Seq experiments in Arabidopsis thaliana show that predictions made by our SpliceGrapher method are more consistent with current gene models than predictions made by TAU and Cufflinks. Furthermore, analysis of plant and human data indicates that the machine learning approach used by SpliceGrapher is useful for discriminating between real and spurious splice sites, and can improve the reliability of detection of alternative splicing. SpliceGrapher is available for download at http://SpliceGrapher.sf.net.
Donor-derived, tolerogenic dendritic cells suppress immune rejection in the indirect allosensitization-dominant setting of corneal transplantation
Authors: Hattori Takaaki , Saban Daniel R , Emami-naeini Parisa , Chauhan Sunil K , Funaki Toshinari , Ueno Hiroki , Dana Reza 
Published: January 2012

ABSTRACTSignificant interest has been focused on the use of ex vivo-manipulated DCs to optimally induce transplant tolerance and promote allograft survival. Although it is understood that donor-derived, tolerogenic DCs suppress the direct pathway of allosensitization, whether such DCs can similarly suppress the indirect pathway remains unclear. We therefore used the murine model of corneal transplantation to address this, as these allografts are rejected in an indirect pathway-dominant manner. Interestingly, recipients administered with donor bone marrow-derived DCregs, generated via culturing with GM-CSF, IL-10, and TGF-β1, significantly prolonged survival of corneal allografts. Correspondingly, these recipients demonstrated a potent reduction in the frequency of indirectly allosensitized T cells, as determined by ELISPOT. Examination of DCregs relative to mDCs or iDCs showed a resistance to up-regulation of MHC-II and costimulatory molecules, as well as an impaired capacity to stimulate MLRs. In vivo, DCreg administration in corneal-allografted recipients led to inhibition of CD4+IFN-γ+ T cell frequencies and an associated increase in Foxp3 expression in the Treg compartment. We conclude that donor-derived, tolerogenic DCs significantly suppress the indirect pathway, thereby identifying a novel regulatory mechanism for these cells in transplantation.
Impact of FLT3 Internal Tandem Duplication on the Outcome of Related and Unrelated Hematopoietic Transplantation for Adult Acute Myeloid Leukemia in First Remission: A Retrospective Analysis
Authors: Brunet Salut , Labopin Myriam , Esteve Jordi , Cornelissen Jan , Socié Gerard , Iori Anna P. , Verdonck Leo F. , Volin Liisa , Gratwohl Alois , Sierra Jorge , Mohty Mohamad , Rocha Vanderson 
Published: January 2012

Purpose Patients with acute myeloid leukemia (AML) and FLT3/internal tandem duplication (FLT3/ITD) have poor prognosis if treated with chemotherapy only. Whether this alteration also affects outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) remains uncertain. Patients and Methods We analyzed 206 patients who underwent HLA-identical sibling and matched unrelated HSCTs reported to the European Group for Blood and Marrow Transplantation with a diagnosis of AML with normal cytogenetics and data on FLT3/ITD (present: n = 120, 58%; absent: n = 86, 42%). Transplantations were performed in first complete remission (CR) after myeloablative conditioning. Results Compared with FLT3/ITD-negative patients, FLT3/ITD-positive patients had higher median leukocyte count at diagnosis (59 v 21 × 109/L; P < .001) and shorter interval from CR to transplantation (87 v 99 days; P = .04). Other characteristics were similar in the two groups. At 2 years, relapse incidence (RI; ± standard deviation) was higher (30% ± 5% v 16% ± 5%; P = .006) and leukemia-free survival (LFS) lower (58% ± 5% v 71% ± 6%; P = .04) in FLT3/ITD-positive compared with FLT3/ITD-negative patients. In multivariate analyses, FLT3/ITD led to increased RI (hazard ratio [HR], 3.4; 95% CI, 1.46 to 7.94; P = .005), as did older age, female sex, shorter interval between CR and transplantation, and higher number of chemotherapy courses before achieving CR. FLT3/ITD positivity was associated with decreased LFS (HR, 0.37; 95% CI, 0.19 to 0.73; P = .002), along with older age and higher number of chemotherapy courses before achieving CR. Conclusion FLT3/ITD adversely affected the outcome of HSCT in the same direction it does after chemotherapy; despite this, more than half of the patients harboring this mutation who received transplants were alive and leukemia free at 2 years. To further improve the results, use of FLT3 inhibitors before or after HSCT deserves investigation.
Phase I Trial of Anti-CS1 Monoclonal Antibody Elotuzumab in Combination With Bortezomib in the Treatment of Relapsed/Refractory Multiple Myeloma
Authors: Jakubowiak Andrzej J. , Benson Don M. , Bensinger William , Siegel David S.D. , Zimmerman Todd M. , Mohrbacher Ann , Richardson Paul G. , Afar Daniel E.H. , Singhal Anil K. , Anderson Kenneth C. 
Published: January 2012

Purpose To evaluate the maximum-tolerated dose (MTD), safety, and efficacy of elotuzumab in combination with bortezomib in patients with relapsed or relapsed and refractory multiple myeloma (MM). Patients and Methods Elotuzumab (2.5, 5.0, 10, or 20 mg/kg intravenously [IV]) and bortezomib (1.3 mg/m2 IV) were administered on days 1 and 11 and days 1, 4, 8, and 11, respectively, in 21-day cycles by using a 3 + 3 dose-escalation design. Patients with stable disease or better after four cycles could continue treatment until disease progression or unexpected toxicity. Responses were assessed during each cycle by using European Group for Blood and Marrow Transplantation (EBMT) criteria. Results Twenty-eight patients with a median of two prior therapies were enrolled; three patients each received 2.5, 5.0, and 10 mg/kg of elotuzumab and 19 received 20 mg/kg (six during dose escalation and 13 during an expansion phase). No dose-limiting toxicities were observed during cycle 1 of the dose-escalation phase, and the MTD was not reached up to the maximum planned dose of 20 mg/kg. The most frequent grade 3 to 4 adverse events (AEs) were lymphopenia (25%) and fatigue (14%). Two elotuzumab-related serious AEs of chest pain and gastroenteritis occurred in one patient. An objective response (a partial response or better) was observed in 13 (48%) of 27 evaluable patients and in two (67%) of three patients refractory to bortezomib. Median time to progression was 9.46 months. Conclusion The combination of elotuzumab and bortezomib was generally well-tolerated and showed encouraging activity in patients with relapsed/refractory MM.
Age-Related Prognostic Impact of Different Types of DNMT3A Mutations in Adults With Primary Cytogenetically Normal Acute Myeloid Leukemia
Authors: Marcucci Guido , Metzeler Klaus H. , Schwind Sebastian , Becker Heiko , Maharry Kati , Mrózek Krzysztof , Radmacher Michael D. , Kohlschmidt Jessica , Nicolet Deedra , Whitman Susan P. , Wu Yue-Zhong , Powell Bayard L. , Carter Thomas H. , Kolitz Jonathan E. , Wetzler Meir , Carroll Andrew J. , Baer Maria R. , Moore Joseph O. , Caligiuri Michael A. , Larson Richard A. , Bloomfield Clara D. 
Published: January 2012

Purpose To determine the frequency of DNMT3A mutations, their associations with clinical and molecular characteristics and outcome, and the associated gene- and microRNA-expression signatures in primary cytogenetically normal acute myeloid leukemia (CN-AML). Patients and Methods Four hundred fifteen previously untreated adults were analyzed for DNMT3A mutations and established prognostic gene mutations and expression markers. Gene- and microRNA-expression profiles were derived using microarrays. Results Younger (< 60 years; n = 181) and older (≥ 60 years; n = 234) patients had similar frequencies of DNMT3A mutations (35.3% v 33.3%). Missense mutations affecting arginine codon 882 (R882-DNMT3A) were more common (n = 92; 62%) than those affecting other codons (non–R882-DNMT3A). DNMT3A-mutated patients did not differ regarding complete remission rate, but had shorter disease-free survival (DFS; P = .03) and, by trend, overall survival (OS; P = .07) than DNMT3A–wild-type patients. In multivariable analyses, DNMT3A mutations remained associated with shorter DFS (P = .01), but not with shorter OS. When analyzed separately, the two DNMT3A mutation types had different significance by age group. Younger patients with non–R882-DNMT3A mutations had shorter DFS (P = .002) and OS (P = .02), whereas older patients with R882-DNMT3A mutations had shorter DFS (P = .005) and OS (P = .002) after adjustment for other clinical and molecular prognosticators. Gene- and microRNA-expression signatures did not accurately predict DNMT3A mutational status. Conclusion DNMT3A mutations are frequent in CN-AML, and their clinical significance seems to be age dependent. DNMT3A-R882 mutations are associated with adverse prognosis in older patients, and non–R882-DNMT3A mutations are associated with adverse prognosis in younger patients. Low accuracy of gene- and microRNA-expression signatures in predicting DNMT3A mutation status suggested that the role of these mutations in AML remains to be elucidated.
Ndel1-derived peptides modulate bidirectional transport of injected beads in the squid giant axon
Authors: Segal Michal , Soifer Ilya , Petzold Heike , Howard Jonathon , Elbaum Michael , Reiner Orly 
Published: January 2012

Summary
Bidirectional transport is a key issue in cellular biology. It requires coordination between microtubule-associated molecular motors that work in opposing directions. The major retrograde and anterograde motors involved in bidirectional transport are cytoplasmic dynein and conventional kinesin, respectively. It is clear that failures in molecular motor activity bear severe consequences, especially in the nervous system. Neuronal migration may be impaired during brain development, and impaired molecular motor activity in the adult is one of the hallmarks of neurodegenerative diseases leading to neuronal cell death. The mechanisms that regulate or coordinate kinesin and dynein activity to generate bidirectional transport of the same cargo are of utmost importance. We examined how Ndel1, a cytoplasmic dynein binding protein, may regulate non-vesicular bidirectional transport. Soluble Ndel1 protein, Ndel1-derived peptides or control proteins were mixed with fluorescent beads, injected into the squid giant axon, and the bead movements were recorded using time-lapse microscopy. Automated tracking allowed for extraction and unbiased analysis of a large data set. Beads moved in both directions with a clear bias to the anterograde direction. Velocities were distributed over a broad range and were typically slower than those associated with fast vesicle transport. Ironically, the main effect of Ndel1 and its derived peptides was an enhancement of anterograde motion. We propose that they may function primarily by inhibition of dynein-dependent resistance, which suggests that both dynein and kinesin motors may remain engaged with microtubules during bidirectional transport.
Radon capture with silver exchanged zeolites
Authors: Hedström Hanna , Foreman Mark , Ekberg Christian , Ramebäck Henrik 
Published: January 2012

Abstract
To enable laboratory work with larger amounts of 226Ra and its decay products, e.g., 222Rn and its daughters, these need to be captured in order to avoid unnecessary alpha contamination of the laboratory work space and ventilation systems.
In this study, radon gas was pumped through a column filled with the silver exchanged zeolite called “silver exchanged molecular sieves 13X” (Ag84Na2[(AlO2)86(SiO2)106]·xH2O). After exposure to radon, the radioactivity of the zeolite was measured repeatedly using high resolution gamma spectrometry. It was shown that radon was captured and retained in the silver exchanged zeolite. The zeolites´ ability to retain radon was decreased by formation of metallic silver, caused by ionizing radiation. However, the zeolite was regenerated by heating and its radon capture ability was restored. The daughters of radon are not in gas phase and will hence stay on the column.