bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apoptosis-inducing factor downregulation increased neuronal progenitor, but not stem cell, survival in the neonatal hippocampus after cerebral hypoxia-ischemia
Authors: Sun Yanyan , Zhang Yu , Wang Xiaoyang , Blomgren Klas , Zhu Changlian 
Published: April 2012

Abstract

Background
A considerable proportion of all newly generated cells in the hippocampus will die before becoming fully differentiated, both under normal and pathological circumstances. The caspase-independent apoptosis-inducing factor (AIF) has not been investigated previously in this context.

Results
Postnatal day 8 (P8) harlequin (Hq) mutant mice, expressing lower levels of AIF, and wild type littermates were injected with BrdU once daily for two days to label newborn cells. On P10 mice were subjected to hypoxia-ischemia (HI) and their brains were analyzed 4 h, 24 h or 4 weeks later. Overall tissue loss was 63.5% lower in Hq mice 4 weeks after HI. Short-term survival (4 h and 24 h) of labeled cells in the subgranular zone was neither affected by AIF downregulation, nor by HI. Long-term (4 weeks) survival of undifferentiated, BLBP-positive stem cells was reduced by half after HI, but this was not changed by AIF downregulation. Neurogenesis, however, as judged by BrdU/NeuN double labeling, was reduced by half after HI in wild type mice but preserved in Hq mice, indicating that primarily neural progenitors and neurons were protected. A wave of cell death started early after HI in the innermost layers of the granule cell layer (GCL) and moved outward, such that 24 h after HI dying cells could be detected in the entire GCL.

Conclusions
These findings demonstrate that AIF downregulation provides not only long-term overall neuroprotection after HI, but also protects neural progenitor cells, thereby rescuing hippocampal neurogenesis.
Thailandepsins are new small molecule class I HDAC inhibitors with potent cytotoxic activity in ovarian cancer cells: a preclinical study of epigenetic ovarian cancer therapy
Authors: Wilson Andrew J , Cheng Yi-Qiang , Khabele Dineo 
Published: April 2012

Abstract

Background
New treatment strategies are emerging to target DNA damage response pathways in ovarian cancer. Our group has previously shown that the class I biased HDAC inhibitor romidepsin (FK228) induces DNA damage response and has potent cytotoxic effects in ovarian cancer cells. Here, we investigated newly discovered HDAC inhibitors, thailandepsin A (TDP-A) and thailandepsin B (TDP-B), to determine the effects on cell viability, apoptosis and DNA damage response in ovarian cancer cells.

Methods
FK228, TDP-A and TDP-B were tested in five ovarian cancer cell lines. Cellular viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Immunofluorescence assays were used to assess activated caspase 3. Western blots were performed to detect protein expression of PARP cleavage, pH2AX, P-glycoprotein and tubulin acetylation.

Results
Treatment with TDPs decreased cell viability at nanonomolar concentrations in four of the five ovarian cancer cell lines studied. Similar to FK228, both TDP compounds exerted minimal effects on NCI/ADR-RES ovarian cancer cells. Across the four cell lines sensitive to the TDPs, TDP-B consistently had a greater inhibitory effect than TDP-A on cell viability. TDP-B also had relatively greater effects on promoting cell apoptosis and induction of pH2AX (a mark of DNA damage response), than TDP-A. These antitumor effects of TDP-B were of similar magnitude to those induced by an equal concentration of FK228. Similar to FK228, the nanomolar concentrations of the TDPs had little effect on tubulin acetylation (a mark of class II HDAC6 inhibition).

Conclusions
The new small molecule HDAC inhibitors TDP-A and TDP-B are FK228 analogues that suppress cell viability and induce apoptosis at nanomolar drug concentrations. TDP-B showed the most similarity to the biological activity of FK228 with greater cytotoxic effects than TDP-A in vitro. Our results indicate that FK228-like small molecule class I HDAC-biased HDAC inhibitors have therapeutic potential for ovarian cancer.
The Sp1 transcription factor is essential for the expression of gliostatin/thymidine phosphorylase in rheumatoid fibroblast-like synoviocytes
Authors: Ikuta Kenji , Waguri-Nagaya Yuko , Kikuchi Kae , Yamagami Takaya , Nozaki Masahiro , Aoyama Mineyoshi , Asai Kiyofumi , Otsuka Takanobu 
Published: April 2012

Abstract
Introduction
Gliostatin/thymidine phosphorylase (GLS/TP) has angiogenic and arthritogenic activities, and aberrant GLS production has been observed in the active synovial membranes of rheumatoid arthritis (RA) patients. The human GLS gene promoter contains at least seven consensus binding sites for the DNA binding protein Sp1. Here we examined whether Sp1 is necessary for GLS production in RA. We also studied the effects of the Sp1 inhibitor mithramycin on GLS production in RA fibroblast-like synoviocytes (FLSs).

Methods
FLSs from RA patients were treated with specific inhibitors. The gene and protein expression of GLS were studied using the quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and an enzyme immunoassay. Intracellular signalling pathway activation was determined by western blotting analysis, a luciferase assay, a chromatin immunoprecipitation (ChIP) assay and a small interfering RNA (siRNA) transfection.

Results
The luciferase and ChIP assays showed that Sp1 binding sites in the GLS promoter were essential for GLS messenger RNA (mRNA) expression. GLS production was suppressed in FLSs by siRNA against Sp1 transfection. Mithramycin decreased GLS promoter activity, mRNA and protein expression in FLSs. Tumour necrosis factor-α (TNF-α) significantly increased GLS expression in RA FLSs; this effect was reduced by pre-treatment with cycloheximide and mithramycin.

Conclusions
Pretreatment of mithramycin and Sp1 silencing resulted in a significant suppression of GLS production in TNF-α-stimulated FLSs compared to controls. GLS gene expression enhanced by TNF-α was partly mediated through Sp1. As physiological concentrations of mithramycin can regulate GLS production in RA, mithramycin is a promising candidate for anti-rheumatic therapy.
Antioxidant micronutrients in the critically ill: a systematic review and meta-analysis
Authors: Manzanares William , Dhaliwal Rupinder , Jiang Xuran , Murch Lauren , Heyland Daren K 
Published: April 2012

Abstract
Introduction
Critical illness is characterized by oxidative stress, which is a major promoter of systemic inflammation and organ failure due to excessive free radical production, depletion of antioxidant defenses, or both. We hypothesized that exogenous supplementation of trace elements and vitamins could restore antioxidant status, improving clinical outcomes.

Methods
We searched computerized databases, reference lists of pertinent articles and personal files from 1980 to 2011. We included randomized controlled trials (RCTs) conducted in critically ill adult patients that evaluated relevant clinical outcomes with antioxidant micronutrients (vitamins and trace elements) supplementation versus placebo.

Results
A total of 21 RCTs met inclusion criteria. When the results of these studies were statistically aggregated (n = 20), combined antioxidants were associated with a significant reduction in mortality (risk ratio (RR) = 0.82, 95% confidence interval (CI) 0.72 to 0.93, P = 0.002); a significant reduction in duration of mechanical ventilation (weighed mean difference in days = -0.67, 95% CI -1.22 to -0.13, P = 0.02); a trend towards a reduction in infections (RR= 0.88, 95% CI 0.76 to 1.02, P = 0.08); and no overall effect on ICU or hospital length of stay (LOS). Furthermore, antioxidants were associated with a significant reduction in overall mortality among patients with higher risk of death (>10% mortality in control group) (RR 0.79, 95% CI 0.68 to 0.92, P = 0.003) whereas there was no significant effect observed for trials of patients with a lower mortality in the control group (RR = 1.14, 95% 0.72 to 1.82, P = 0.57). Trials using more than 500 μg per day of selenium showed a trend towards a lower mortality (RR = 0.80, 95% CI 0.63 to 1.02, P = 0.07) whereas trials using doses lower than 500 μg had no effect on mortality (RR 0.94, 95% CI 0.67 to 1.33, P = 0.75).

Conclusions
Supplementation with high dose trace elements and vitamins may improve outcomes of critically ill patients, particularly those at high risk of death.
Plant odour stimuli reshape pheromonal representation in neurons of the antennal lobe macroglomerular complex of a male moth
Authors: Chaffiol Antoine , Kropf Jan , Barrozo Romina B. , Gadenne Christophe , Rospars Jean-Pierre , Anton Sylvia 
Published: April 2012

SUMMARY
Male moths are confronted with complex odour mixtures in a natural environment when flying towards a female-emitted sex pheromone source. Whereas synergistic effects of sex pheromones and plant odours have been observed at the behavioural level, most investigations at the peripheral level have shown an inhibition of pheromone responses by plant volatiles, suggesting a potential role of the central nervous system in reshaping the peripheral information. We thus investigated the interactions between sex pheromone and a behaviourally active plant volatile, heptanal, and their effects on responses of neurons in the pheromone-processing centre of the antennal lobe, the macroglomerular complex, in the moth Agrotis ipsilon. Our results show that most of these pheromone-sensitive neurons responded to the plant odour. Most neurons responded to the pheromone with a multiphasic pattern and were anatomically identified as projection neurons. They responded either with excitation or pure inhibition to heptanal, and the response to the mixture pheromone + heptanal was generally weaker than to the pheromone alone, showing a suppressive effect of heptanal. However, these neurons responded with a better resolution to pulsed stimuli. The other neurons with either purely excitatory or inhibitory responses to all three stimuli did not exhibit significant differences in responses between stimuli. Although the suppression of the pheromone responses in AL neurons by the plant odour is counter-intuitive at first glance, the observed better resolution of pulsed stimuli is probably more important than high sensitivity to the localization of a calling female.
A long-latency aversive learning mechanism enables locusts to avoid odours associated with the consequences of ingesting toxic food
Authors: Simões Patrício M. V. , Ott Swidbert R. , Niven Jeremy E. 
Published: April 2012

SUMMARYAvoiding food that contains toxins is crucial for the survival of many animals, particularly herbivores, because many plants defend themselves with toxins. Some animals can learn to avoid food containing toxins not through its taste but by the toxins’ effects following ingestion, though how they do so remains unclear. We studied how desert locusts (Schistocerca gregaria), which are generalist herbivores, form post-ingestive aversive memories and use them to make appropriate olfactory-based decisions in a Y-maze. Locusts form an aversion gradually to an odour paired with food containing the toxin nicotine hydrogen tartrate (NHT), suggesting the involvement of a long-latency associative mechanism. Pairing of odour and toxin-free food accompanied by NHT injections at different latencies showed that locusts could form an association between an odour and toxic malaise, which could be separated by up to 30 min. Tasting but not swallowing the food, or the temporal separation of odour and food, prevents the formation of these long-latency associations, showing that they are post-ingestive. A second associative mechanism not contingent upon feeding operates only when odour presentation is simultaneous with NHT injection. Post-ingestive memory formation is not disrupted by exposure to a novel odour alone but can be if the odour is accompanied by simultaneous NHT injection. Thus, the timing with which food, odour and toxin are encountered whilst foraging is likely to influence memory formation and subsequent foraging decisions. Therefore, locusts can form specific long-lasting aversive olfactory associations that they can use to avoid toxin-containing foods whilst foraging.
Book Reviews
Authors: Rand Graham K. 
Published: April 2012

In Book Reviews, we review an extensive and diverse range of books. They cover theory and applications in operations research, statistics, management science, econometrics, mathematics, computers, and information systems. In addition, we include books in other fields that emphasize technical applications. The editor will be pleased to receive an e-mail from those willing to review a book, with an indication of specific areas of interest. If you are aware of a specific book that you would like to review, or that you think should be reviewed, please contact the editor. The following books are reviewed in this issue of Interfaces, 42(2), March-April 2012: Red Plenty: Industry! Progress! Abundance! – Inside the Fifties' Soviet Dream, Francis Spufford; Sports Data Mining, Robert P. Schumaker, Osama K. Solieman, and Hsinchun Chen; Foundations of Optimization, Osman Güler; Stochastic Processes with Applications to Reliability Theory, Toshio Nakagawa; Data Mining and Knowledge Discovery via Logic-Based Methods, Evangelos Triantaphyllou; Random-Like Multiple Objective Decision Making, Jiuping Xu and Liming Yao.
Thin Film Coil Design Considerations for Wireless Power Transfer in Flat Panel Display
Authors: Yu Jun , Ying Kai , Hasko David , Lee Sungsik , Ahnood Arman , Milne W. I. , Nathan Arokia 
Published: April 2012

AbstractWireless power transfer is experimentally demonstrated by transmission between an AC power transmitter and receiver, both realised using thin film technology. The transmitter and receiver thin film coils are chosen to be identical in order to promote resonant coupling. Planar spiral coils are used because of the ease of fabrication and to reduce the metal layer thickness. The energy transfer efficiency as a function of transfer distance is analysed along with a comparison between the theoretical and the experimental results.
Tamoxifen and CYP2D6: A Contradiction of Data
Authors: Hertz Daniel L. , McLeod Howard L. , Irvin William J. 
Published: April 2012

Abstract

Learning Objectives:
After completing this course, the reader will be able to: Describe the significant heterogeneity among the published studies on the link between CYP2D6 genotype and tamoxifen treatment efficacy.Explain the role of CYP2D6 metabolism in the conversion of tamoxifen to its active metabolite, endoxifen, and the potential importance of CYP2D6 polymorphisms to this process.Discuss the role that insufficient genotyping, CYP2D6 inhibition, and tamoxifen combination treatment may have had in the inconsistent findings of past pharmacogenetic studies.
CME This article is available for continuing medical education credit at CME.TheOncologist.com
Tamoxifen is an effective antiestrogen used in the treatment of hormone receptor–positive breast cancer. Bioconversion of tamoxifen to endoxifen, its most abundant active metabolite, is primarily dependent on the activity of cytochrome P450 2D6 (CYP2D6), which is highly polymorphic. Over 20 published studies have reported on the potential association between CYP2D6 polymorphism and tamoxifen treatment outcome, with highly inconsistent results. The purpose of this review is to explore differences among 17 independent studies to identify factors that may have contributed to the discrepant findings. This report discusses six putative factors that are grouped into two categories: (a) clinical management criteria: hormone receptor classification, menopausal status, and tamoxifen combination therapy; (b) pharmacologic criteria: genotyping comprehensiveness, CYP2D6 inhibitor coadministration, and tamoxifen adherence. Comparison of these factors between the positive and negative studies suggests that tamoxifen combination therapy, genotyping comprehensiveness, and CYP2D6 inhibitor coadministration may account for some of the contradictory results. Future association studies on the link between CYP2D6 genotype and tamoxifen treatment efficacy should account for combination therapy and CYP2D6 inhibition, and interrogate as many CYP2D6 alleles as possible.
Effects of acepromazine maleate on platelet function assessed by use of adenosine diphosphate activated– and arachidonic acid– activated modified thromboelastography in healthy dogs
Authors: Conner Bobbi J. , Hanel Rita M. , Hansen Bernard D. , Motsinger-Reif Alison A. , Asakawa Makoto , Swanson Clifford R. 
Published: April 2012

Abstract
Objective—To evaluate the effect of acepromazine maleate administered IV on platelet function assessed in healthy dogs by use of a modified thromboelastography assay.
Animals—6 healthy adult mixed-breed dogs.
Procedures—Dogs received each of 3 treatments (saline [0.9% NaCl] solution [1 to 2 mL, IV] and acepromazine maleate [0.05 and 0.1 mg/kg, IV]) in a randomized crossover study with a minimum 3-day washout period between treatments. From each dog, blood samples were collected via jugular venipuncture immediately before and 30 and 240 minutes after administration of each treatment. A modified thromboelastography assay, consisting of citrated kaolin–activated (baseline assessment), reptilase-ADP–activated (ADP-activated), and reptilase-arachidonic acid (AA)–activated (AA-activated) thromboelastography, was performed for each sample. Platelet inhibition was evaluated by assessing the percentage change in maximum amplitude for ADP-activated or AA-activated samples, compared with baseline values. Percentage change in maximum amplitude was analyzed by use of Skillings-Mack tests with significance accepted at a family-wise error rate of P < 0.05 by use of Bonferroni corrections for multiple comparisons.
Results—No significant differences were found in the percentage change of maximum amplitude from baseline for ADP-activated or AA-activated samples among treatments at any time.
Conclusions and Clinical Relevance—Platelet function in dogs, as assessed by use of a modified thromboelastography assay, was not inhibited by acepromazine at doses of 0.05 or 0.1 mg/kg, IV. This was in contrast to previous reports in which it was suggested that acepromazine may alter platelet function via inhibition of ADP and AA.
Effect of a zinc l-carnosine compound on acid-induced injury in canine gastric mucosa ex vivo
Authors: Hill Tracy L. , Blikslager Anthony T. 
Published: April 2012

Abstract
Objective—To examine whether a zinc l-carnosine compound used for treatment of suspected gastric ulcers in dogs ameliorates acid-induced injury in canine gastric mucosa.
Sample—Gastric mucosa from 6 healthy dogs.
Procedures—Mucosa from the gastric antrum was harvested from 6 unadoptable shelter dogs immediately after euthanasia and mounted on Ussing chambers. The tissues were equilibrated for 30 minutes in neutral Ringer's solution prior to incubation with acidic Ringer's solution (HCl plus Ringer's solution [final pH, 1.5 to 2.5]), acidic Ringer's solution plus zinc l-carnosine compound, or zinc l-carnosine compound alone. Tissues were maintained for 180 minutes in Ussing chambers, during which permeability was assessed by measurement of transepithelial electrical resistance. After the 180-minute treatment period, tissues were removed from Ussing chambers and labeled with immunofluorescent anti–active caspase-3 antibody as an indicator of apoptosis.
Results—Permeability of the gastric mucosa was significantly increased in a time-dependent manner by addition of HCl, whereas control tissues maintained viability for the study period. Change in permeability was detected within the first 15 minutes after acid application and progressed over the subsequent 150 minutes. The zinc l-carnosine compound had no significant effect on this increase in permeability. Apoptosis was evident in acid-treated tissues but not in control tissues. The zinc l-carnosine compound did not protect against development of apoptosis.
Conclusions and Clinical Relevance—Addition of HCl caused a dose-dependent increase in gastric permeability over time and apparent induction of apoptosis as determined on the basis of immunofluorescence. However, there was no significant protective effect of a zinc l-carnosine compound. Nonetheless, results suggested the utility of this method for further studies of canine gastric injury.
Evaluation of a B-cell leukemia-lymphoma 2-specific radiolabeled peptide nucleic acid–peptide conjugate for scintigraphic detection of neoplastic lymphocytes in dogs with B-cell lymphoma
Authors: Statham-Ringen Kimberly A. , Selting Kimberly A. , Lattimer Jimmy C. , Henry Carolyn J. , Green Jonathan A. , Bryan Jeffrey N. , Jia Fang , Lewis Michael R. 
Published: April 2012

Abstract
Objective—To evaluate use of a radiolabeled peptide nucleic acid–peptide conjugate (RaPP) targeting B-cell leukemia-lymphoma 2 (BCL2) mRNA for scintigraphic detection of neoplastic lymphocytes in dogs with B-cell lymphoma and to assess associations among RaPP uptake, time to tumor progression (TTP), and BCL2 mRNA expression.
Animals—11 dogs with B-cell lymphoma and 1 clinically normal dog.
Procedures—Scintigraphic images were acquired 1 hour after IV injection of the RaPP. Regions of interest (ROIs) were drawn around lymph nodes, liver, and spleen; ROI intensity (relative to that of an equally sized region of muscle in the same image) was measured. Each ROI was also subjectively categorized as positive or negative for increased RaPP uptake. Expression of BCL2 mRNA was determined via quantitative reverse transcriptase PCR assay of a lymph node sample from dogs with lymphoma. Associations among imaging results, TTP, and BCL2 mRNA expression were evaluated.
Results—Increased RaPP uptake was detected in affected tissues of dogs with lymphoma. Dogs with superficial cervical lymph node ROIs categorized as negative (n = 8) for increased RaPP uptake had a significantly longer TTP than did dogs for which this ROI was considered positive (2). Measured intensity of mandibular and superficial cervical lymph node ROIs was negatively associated with TTP. Associations among BCL2 mRNA and ROI intensity or TTP were not significant.
Conclusions and Clinical Relevance—Increased RaPP uptake at mandibular or superficial cervical lymph node ROIs may be a negative prognostic indicator in dogs with lymphoma. A larger investigation is needed to determine clinical value of the RaPP for disease detection and prognostication.
Treatment of spinal fractures using Lubra plates
Authors: Theyse L. F. H. , Tryfonidou M. A. , Hazewinkel H. A. W. , Meij B. P. , Krauss M. W. 
Published: April 2012

SummaryThe purpose of this retrospective study was to review the clinical use along with the shortand long-term outcome in patients treated with Lubra plates to stabilize spinal fracture and dislocations that were considered unstable at time of surgery according to the ‘three compartment theory’. The data that were collected included breed, age, gender, body weight of the patients, cause of injury, neurological grade (pre- and postoperative), radiographic findings, surgical treatment, and clinical and radiological outcome. Thirteen dogs and two cats were included with thoracic (1 case), thoracolumbar (3 cases), midlumbar (5 cases) and caudal lumbar (6 cases) vertebral fractures. For stabilization, the small-sized (3 cases), medium-sized (6 cases), and large-sized (6 cases) Lubra plates were used. The clinical outcome was excellent in 10/15 patients, functional in 2/15 and poor in 3/15 with a median follow-up period of nine years (range 2 months to 12 years). The fractures eventually stabilized by ventral spondylosis. No implant failure was seen, however demineralization of the spinous processes necessitated implant removal in one case. Our results suggest that Lubra plating is an appropriate technique for thoracolumbar and lumbar vertebral fractures as well as luxations in dogs and cats. The prognosis for neurological recovery was excellent when the animal had a neurological grade of 3 and was not paralyzed.