bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased expression of system large amino acid transporter (LAT)-1 mRNA is associated with invasive potential and unfavorable prognosis of human clear cell renal cell carcinoma
Authors: Betsunoh Hironori , Fukuda Takehiko , Anzai Naohiko , Nishihara Daisaku , Mizuno Tomoya , Yuki Hideo , Masuda Akinori , Yamaguchi Yoshiyuki , Abe Hideyuki , Yashi Masahiro , Fukabori Yoshitatsu , Yoshida Ken-Ichiro , Kamai Takao 
Published: October 2013

Abstract

Background
The system L amino acid transporter (LAT) has an important role in the transport of various amino acids, and there have been reports about the relation of this system to cancer. Although LATs are highly expressed in the kidneys, little is known about their influence on human renal cancer.

Methods
To clarify the role of LATs in human clear cell renal cell carcinoma (RCC), we investigated the expression of mRNAs for LAT1, LAT2, LAT3, LAT4, and 4F2hc in clear cell RCC tissues. The mRNAs of these five genes were analyzed by the real-time reverse transcription polymerase chain reaction in matched sets of tumor and non-tumor tissues obtained at operation from 82 Japanese patients with clear cell RCC. We also measured phosphorylated S6 ribosomal protein (Ser-235/236) proteins levels in 18 paired tumor and non-tumor tissues of the patients by Western blotting.

Results
Expression of LAT1 mRNA was significantly increased in tumor tissue compared with non-tumor tissue, while expression of LAT2 and LAT3 mRNAs was reduced. There was no difference in the expression of LAT4 and 4F2hc mRNAs between tumor and non-tumor tissues. Increased expression of LAT1 mRNA was associated with less differentiated tumors, local invasion, microscopic vascular invasion, and metastasis. Kaplan-Meier survival analysis showed that a higher serum LAT1 mRNA level was associated with a shorter overall survival time. Phosphorylated S6 ribosomal protein levels were associated with metastatic potential. LAT1 mRNA levels positively correlated with phosphorylated S6 ribosomal protein proteins levels in primary tumors.

Conclusions
These findings suggest that LAT1 mRNA is related to the invasive and progressive potential of clear cell RCC.
EXCAVATOR: detecting copy number variants from whole-exome sequencing data
Authors: Magi Alberto , Tattini Lorenzo , Cifola Ingrid , D’Aurizio Romina , Benelli Matteo , Mangano Eleonora , Battaglia Cristina , Bonora Elena , Kurg Ants , Seri Marco , Magini Pamela , Giusti Betti , Romeo Giovanni , Pippucci Tommaso , Bellis Gianluca De , Abbate Rosanna , Gensini Gian Franco 
Published: October 2013

Abstract
Abstract
We developed a novel software tool, EXCAVATOR, for the detection of copy number variants (CNVs) from whole-exome sequencing data. EXCAVATOR combines a three-step normalization procedure with a novel heterogeneous hidden Markov model algorithm and a calling method that classifies genomic regions into five copy number states. We validate EXCAVATOR on three datasets and compare the results with three other methods. These analyses show that EXCAVATOR outperforms the other methods and is therefore a valuable tool for the investigation of CNVs in largescale projects, as well as in clinical research and diagnostics. EXCAVATOR is freely available at http://sourceforge.net/projects/excavatortool/.
NKG2D- and CD28-mediated costimulation regulate CD8+ T cell chemotaxis through different mechanisms: the role of Cdc42/N-WASp
Authors: Serrano-Pertierra Esther , Cernuda-Morollón Eva , López-Larrea Carlos 
Published: October 2013

ABSTRACTThe activating receptor NKG2D is mainly expressed in NK cells and CD8+ T cells. NKG2D and CD28 recruit the p85 subunit of PI3K to propagate their signals through the YXXM signaling motif. The function of CD28 as a costimulatory molecule is well-established in T cells. Ligation of NKG2D on T cells costimulates TCR signaling, although the intracellular signaling pathways triggered by the two receptors may not be identical. In this study, we analyzed the function of the NKG2D receptor in human CD8+ T cell chemotaxis toward a CXCL12 gradient. We found that costimulation of the TCR together with CD28 or NKG2D impairs cell migration, although the signaling pathways responsible for this effect differ. Whereas the Rho GTPase Rac1 is activated upon TCR and costimulation via CD28 and NKG2D, the activity of Cdc42 is increased only upon CD3/NKG2D activation. Moreover, knockdown of N-WASp expression with siRNA rescues migration rates after NKG2D-mediated costimulation but not after CD3/CD28 activation. CD28- and NKG2D-mediated costimulation induces cofilin activation by dephosphorylation. Inhibition of N-WASp by wiskostatin further decreases phosphorylation levels of cofilin, although this effect is especially severe upon CD3/NKG2D activation. Thus, our findings reveal new differences in the signaling pathways between CD28- and NKG2D-mediated costimulation in the regulation of cell chemotaxis in human CD8+ T cells.
Eukaryotic ribosome biogenesis at a glance
Authors: Thomson Emma , Ferreira-Cerca Sébastien , Hurt Ed 
Published: October 2013

Summary
Ribosomes play a pivotal role in the molecular life of every cell. Moreover, synthesis of ribosomes is one of the most energetically demanding of all cellular processes. In eukaryotic cells, ribosome biogenesis requires the coordinated activity of all three RNA polymerases and the orchestrated work of many (&gt;200) transiently associated ribosome assembly factors. The biogenesis of ribosomes is a tightly regulated activity and it is inextricably linked to other fundamental cellular processes, including growth and cell division. Furthermore, recent studies have demonstrated that defects in ribosome biogenesis are associated with several hereditary diseases. In this Cell Science at a Glance article and the accompanying poster, we summarise the current knowledge on eukaryotic ribosome biogenesis, with an emphasis on the yeast model system.
Boron Diffusion in Surface-Treated Framing Lumber
Authors: Lebow Patricia K. , Lebow Stan T. , Halverson Steven A. 
Published: October 2013

Abstract
The extent of boron penetration in framing lumber treated by spray applications during construction is not well quantified. This study evaluated the effect of formulation and concentration on diffusion of boron in lumber specimens that were equilibrated in conditions that produced wood moisture contents of 18 to 21 percent. One set of specimens was pressure treated with water before equilibration. Borate solutions were prepared from powdered disodium octaborate tetrahydrate (DOT) or from two commercial glycol-borate formulations and applied with a garden-type sprayer. The DOT solution was applied at a 15 percent concentration, while the glycol-borate formulations were applied at 15 and 23 percent concentrations. Boron penetration was evaluated after 6, 13, and 26 weeks and boron retention after 26 weeks of diffusion. Boron penetration was observed for all treatments and progressed for the duration of the study. There was no significant penetration difference between the powdered DOT and glycol-borate solutions when they were applied at the same (15%) DOT concentration. However, after 6 weeks, the glycol-borate solutions applied at the 23 percent DOT concentration produced significantly greater depth of penetration than the solutions applied at the 15 percent concentration. The exception was the 15 percent DOT solution applied to the specimens that had been wetted and then dried down to equilibrium conditions. These specimens had the greatest penetration, possibly as a result of their higher equilibrium moisture content. Retention analysis revealed that the glycol-borate solutions applied at the 23 percent DOT concentration yielded significantly greater boron retentions in the outer assay zone. This effect was less apparent for the inner assay zones. Although boron retentions in the outer assay zone were below those standardized for pressure-treated wood, in some cases they exceeded reported concentrations needed for protection against termites and decay fungi.
Circulating Fetuin-A and Risk of Ischemic Stroke in Women
Authors: Jiménez Monik C , Sun Qi , Schürks Markus , Hu Frank B , Manson JoAnn E , Rexrode Kathryn M 
Published: October 2013

Abstract

BACKGROUND
Fetuin-A, a protein secreted primarily by the liver, has been associated with nonalcoholic fatty liver disease and insulin resistance. In a recent study, higher circulating fetuin-A was associated with cardiovascular events, particularly ischemic stroke. However, these data have not been replicated.

METHODS
A nested case control design was used to examine the relationship between fetuin-A and ischemic stroke among female participants of the Nurses' Health Study. Fetuin-A was measured in blood samples collected and stored between 1989 and 1990. A total of 459 incident cases of ischemic stroke were identified and confirmed by medical records according to the National Survey of Stroke criteria between 1990 and 2006 and matched to 459 controls by age, race/ethnicity, date of sample collection, menopausal status, postmenopausal hormone use, and smoking status. The association between fetuin-A and ischemic stroke was modeled using conditional logistic regression.

RESULTS
Circulating fetuin-A was higher in women (P &lt; 0.01) who reported increased body mass index (BMI) of ≥25 kg/m2, total cholesterol ≥200 mg/dL, high-sensitivity C-reactive protein ≥3 mg/L, and current hormone use at baseline. Significant partial Spearman correlations (P &lt; 0.001), adjusted for matching factors, were found between measured concentrations of fetuin-A and triglycerides (r = 0.20), C-reactive protein (r = 0.14), and BMI (r = 0.15). Fetuin-A quartiles were not significantly associated with increased risk of incident ischemic stroke when adjusted for matching factors (relative risk, 1.03; 95% CI, 0.69–1.54, extreme quartiles); additional adjustment for lifestyle factors or cardiovascular disease risk factors and biomarkers did not alter results.

CONCLUSIONS
In this sample of women, fetuin-A was not significantly associated with risk of ischemic stroke. Further research is needed to explore this association.
Axonal Recordings from Medial Superior Olive Neurons Obtained from the Lateral Lemniscus of the Chinchilla (Chinchilla laniger)
Authors: Bremen Peter , Joris Philip X. 
Published: October 2013

Interaural time differences (ITDs) are a major cue for localizing low-frequency (<1.5 kHz) sounds. Sensitivity to this cue first occurs in the medial superior olive (MSO), which is thought to perform a coincidence analysis on its monaural inputs. Extracellular single-neuron recordings in MSO are difficult to obtain because (1) MSO action potentials are small and (2) a large field potential locked to the stimulus waveform hampers spike isolation. Consequently, only a limited number of studies report MSO data, and even in these studies data are limited in the variety of stimuli used, in the number of neurons studied, and in spike isolation. More high-quality data are needed to better understand the mechanisms underlying neuronal ITD-sensitivity.We circumvented these difficulties by recording from the axons of MSO neurons in the lateral lemniscus (LL) of the chinchilla, a species with pronounced low-frequency sensitivity. Employing sharp glass electrodes we successfully recorded from neurons with ITD sensitivity: the location, response properties, latency, and spike shape were consistent with an MSO axonal origin. The main difficulty encountered was mechanical stability. We obtained responses to binaural beats and dichotic noise bursts to characterize the best delay versus characteristic frequency distribution, and compared the data to recordings we obtained in the inferior colliculus (IC). In contrast to most reports in other rodents, many best delays were close to zero ITD, both in MSO and IC, with a majority of the neurons recorded in the LL firing maximally within the presumed ethological ITD range.
A Retrospective Evaluation of the Survival Rates of Splinted and Non‐Splinted Short Dental Implants in Posterior Partially Edentulous Jaws
Authors: Mendonça Jose Alfredo , Francischone Carlos Eduardo , Senna Plinio Mendes , Matos de Oliveira Ana Elisa , Sotto‐Maior Bruno Salles 
Published: October 2013

Background: The aim of the present study is to evaluate the survival rate and bone loss around short implants (≤10 mm) supporting splinted or non‐splinted posterior prostheses during a follow‐up period of 3 to 16 years.Methods: A total of 453 implants from 198 patients was divided into splinted or non‐splinted groups. Implant survival rate was calculated for each group, and potential risk was represented as odds ratio (OR). The final linear distance from implant platform level to the first bone‐to‐implant contact was compared to this same reference just after loading by digital periapical radiographs to determine the marginal bone loss (BL).Results: The splinted group comprised 219 implants in 86 patients, whereas the non‐splinted group included 234 implants from 112 patients. The mean follow‐up period was 9.7 ± 3.7 years. Although different success rates were found for splinted (97.7%) and non‐splinted (93.2%) groups, they exhibited similar BL (1.22 ± 0.95 mm and 1.27 ± 1.15 mm, respectively). The success of splinted implants was associated with no other variable, whereas non‐splinted implants exhibited higher risk of failure when placed in men (OR = 3.2) and when implants shorter than 10 mm were used (OR = 3.6 and 4.1 for 8.5 mm and 7 mm, respectively). Regardless of group, 71.4% of the unsuccessful implants failed before the end of the first year after loading.Conclusion: Non‐splinted posterior short implants had a somewhat lower success rate than splinted short implants, and the failure rate in non‐splinted short implants appeared to be greater in males as well as in implants ≤10 mm.
Demineralization of the Contacting Surfaces in Autologous Onlay Bone Grafts Improves Bone Formation and Bone Consolidation
Authors: Rezende Maria L. , Consolaro Alberto , Sant'Ana Adriana C. , Damante Carla A. , Greghi Sebastião L. , Passanezi Euloir 
Published: October 2013

Background: Autologous bone grafts are usually well consolidated after 4 to 5 months but can be incompletely interlocked with the native bone. This study investigated the effect of acid demineralization of the graft–bed interface on graft consolidation.Methods: Onlay bone grafts were performed on the calvaria of 36 guinea pigs. Half of the animals had the graft–bed contacting surfaces demineralized with 50% citric acid (pH 1.0) for 3 minutes (test group). The other half received no demineralization (control group). The bone grafts were immobilized by a resorbable membrane glued to the recipient bed with cyanoacrylate. After 7, 30, and 90 days, specimens (n = 6) were obtained for light microscopy. Data from qualitative analysis and computerized histomorphometry were statistically processed at a significance level of 5%.Results: Osteogenesis was not seen at the interface after 7 days. After 30 days, the test group showed 34.39% ± 13.4% of the interface area filled with mineralized tissue, compared to 17.14% ± 8.6% in the control group (P = 0.026). After 90 days, the mean percentages of mineralized tissue at the interface in the test and control specimens were 54.00% ± 11.23% and 38.65% ± 7.76% (P = 0.041), respectively. Within groups, a higher percentage of the area filled with mineralized tissue was seen at 90 days compared to 30 days (P = 0.004 for control and 0.041 for test).Conclusions: Demineralization of the contacting surfaces between autologous bone graft and bone bed improved new bone formation and bone consolidation. These data need to be confirmed in humans.
Alternative Splicing Generates a Diacylglycerol Kinase α Transcript That Acts as a Dominant‐Negative Modulator of Superoxide Production in Localized Aggressive Periodontitis
Authors: Batista Eraldo L. , Kantarci Alpdogan I. , Hasturk Hatice , Van Dyke Thomas E. 
Published: October 2013

Background: Diacylglycerol (DAG), levels of which are tightly regulated by diacylglycerol kinases (DGKs), is a lipid mediator linked to key biologic functions. Members of the DGK family undergo alternative splicing, generating the protein diversity necessary to control different intracellular DAG pools. DGKα function is altered in polymorphonuclear neutrophils (PMNs) of patients with localized aggressive periodontitis (LAgP), suggesting a genetic basis. Here, the authors assess DGKα spliced transcripts in human LAgP neutrophils.Methods: In an expression library of a patient with LAgP, PMNs were screened for different DGKα transcripts. Real‐time polymerase chain reaction and in vitro expression assays were performed to assess the fate of different transcripts on protein translocation and superoxide production in human leukemia cells (HL‐60) and COS‐7 cells.Results: A DGKα transcript that lacks exon 10 (DGKαΔ10) and generates a premature stop codon and a truncated protein was identified as being upregulated in LAgP neutrophils. In vitro assays revealed that DGKαΔ10 translocation occurred even in the absence of important regulatory motifs. Transfection of HL‐60 neutrophil‐like cells with the DGKαΔ10 spliced variant induced an increase in the stimulated production of superoxide anion replicating the phenotype of LAgP PMNs.Conclusion: DGKαΔ10 can act as a dominant‐negative transcript that can modulate superoxide production and provides an example of genetic regulation of the inflammatory response that may be relevant to human inflammatory diseases such as LAgP.
Case Report: Meningioma with Intra-tumoural Haemorrhage Secondary to Ruptured Distal Anterior Cerebral Artery Aneurysm
Authors: Alnaami Ibrahim , Ho Ping , Lu Jian-Qiang , Wheatley Blaise 
Published: October 2013

Background:
Brain tumours that are associated with cerebral aneurysms are rare occurrences, whereas the coexistence of brain tumours and intra-tumoural aneurysms is even rarer. There have been 12 brain tumour cases that have been reported in the literature that describe an aneurysm within a brain tumour, with 4 of these tumours being meningiomas.

Case description:
A 34-year-old male patient presented with sudden-onset headache, and an inter-hemispheric meningioma with intra-tumoural bleeding was found due to a ruptured embedded anterior cerebral artery aneurysm. The aneurysm was diagnosed incidentally on the third cerebral angiogram, while the initial 2 angiograms were negative. The patient was treated with endovascular aneurysm embolisation that was followed by tumour resection.

Conclusion:
This paper is the first case report to describe the coexistence of a meningioma and an aneurysm, which presented with intra-tumoural haemorrhage that was negative on the initial cerebral angiogram. Unlike previous case reports, the aneurysm in this case was located with an anterior cerebral artery distribution.
Magnitude of the Dawn Phenomenon and Its Impact on the Overall Glucose Exposure in Type 2 Diabetes
Authors: Monnier Louis , Colette Claude , Dejager Sylvie , Owens David 
Published: October 2013

OBJECTIVE
To assess the magnitude of the dawn phenomenon and its impact on the total glucose exposure in type 2 diabetes.

RESEARCH DESIGN AND METHODS
A total of 248 noninsulin-treated persons with type 2 diabetes who underwent continuous glucose monitoring were divided into three groups selected by treatments: diet alone (n = 53); insulin sensitizers alone (n = 82); and insulin secretagogues alone or in combination with insulin sensitizers (n = 113). The dawn phenomenon (∂ glucose, mg/dL) was quantified by its absolute increment from nocturnal nadir to prebreakfast value. The participants were secondarily divided into two paired subsets after they had been separated by the presence/absence of a dawn phenomenon based on a threshold of 20 mg/dL and matched for glucose nadir. The impact of the dawn phenomenon was assessed on HbA1c and 24-h mean glucose.

RESULTS
The median of ∂ glucose (interquartile range) was 16.0 (0–31.5 mg/dL) in the 248 subjects, and no differences were observed across groups selected by HbA1c or treatments. In the overall population, the mean impacts on HbA1c and 24-h mean glucose were 4.3 ± 1.3 mmol/mol (0.39 ± 0.12%) and 12.4 ± 2.4 mg/dL, respectively. The mean impact on 24-h mean glucose was not statistically different between those on diet alone (16.7 ± 5.9 mg/dL) compared with the two subsets treated with oral hypoglycemic agents (11.2 ± 5.3 and 8.5 ± 7.5 mg/dL).

CONCLUSIONS
The impact of the dawn phenomenon on overall glycemic control in type 2 diabetes, as depicted by the HbA1c level, was ∼0.4% and not eliminated by any of the currently available armamentarium of oral antidiabetes agents.
Reductions in Regimen Distress Are Associated With Improved Management and Glycemic Control Over Time
Authors: Hessler Danielle , Fisher Lawrence , Glasgow Russell E. , Strycker Lisa A. , Dickinson L. Miriam , Arean Patricia A. , Masharani Umesh 
Published: October 2013

OBJECTIVE
Cross-sectional and longitudinal associations among regimen distress (RD), self-management, and glycemic control were undertaken to explore mechanisms of operation among these variables.

RESEARCH DESIGN AND METHODS
In a behavioral randomized control trial (RCT) to reduce RD, 392 adults with type 2 diabetes were assessed for RD, diet, exercise, medication adherence, and HbA1c at baseline and at 4 and 12 months. Associations among RD, self-management, and HbA1c were examined in cross-sectional analyses at baseline, in prospective analyses using baseline values to predict change over time, and in time-varying analyses.

RESULTS
At baseline, greater RD and poorer medication adherence were independently associated with higher HbA1c (P = 0.05 and P &lt; 0.001, respectively), and greater RD was associated with poorer medication adherence (P = 0.03). No consistent pattern of significant prospective associations was found. Significant time-varying findings showed that decreases in RD were associated with improvements in medication adherence (P &lt; 0.01), physical activity (P &lt; 0.001), and HbA1c (P = 0.02) over time following intervention. Changes in self-management were not associated with changes in HbA1c over time.

CONCLUSIONS
In the context of an RCT to reduce distress, RD, self-management, and HbA1c were interrelated in cross-sectional and time-varying analyses. Decreases in RD were associated with improvements in both self-management and HbA1c over 12 months. Findings point to the complex and likely multifaceted pathways of association among these key constructs, with results indicating significant linkages between RD and both self-management and glycemic control over time.