bluuebunny/crossref_metadata_2025 huggingface dataset:
p63‐dependent and independent mechanisms of nectin‐1 and nectin‐4 regulation in the epidermis
Authors: Mollo Maria Rosaria , Antonini Dario , Mitchell Karen , Fortugno Paola , Costanzo Antonio , Dixon Jill , Brancati Francesco , Missero Caterina
Published: November 2014

Nectins are immunoglobulin‐like cell adhesion molecules mainly localized in adherens junctions. The transcription factor p63 is a master regulator of gene expression in stratified epithelia and controls several molecular processes. As mutations in the Pvrl1 and Pvrl4 genes encoding for nectins cause genetic disorders with phenotypes similar to p63‐related syndromes, we investigated whether these proteins might be under p63 transcriptional control. Here, we show that in p63‐null skin, Pvrl1 gene expression is strongly reduced, whereas Pvrl4 expression is unaffected. In human and mouse primary keratinocytes p63 depletion leads to a specific downregulation of the Pvrl1 gene. Consistent with a direct regulation, chromatin immunoprecipitation experiments (ChIP) indicate that p63 binds to two conserved intronic Pvrl1 enhancer regions. Ankyloblepharon–ectodermal defects–cleft lip/palate (AEC) syndrome is a rare autosomal dominant disorder, caused by mutations in p63 gene, mainly characterized by skin fragility. To test whether nectins may be affected in AEC syndrome, their expression was measured in keratinocytes obtained from patients with AEC or from a conditional mouse model for AEC syndrome. Pvrl1 expression was reduced in AEC keratinocytes, consistent with impaired p63 function. Surprisingly, Pvrl4 expression was similarly affected, in parallel with decreased expression of the transcription factor Irf6. Consistent with the well‐characterized role of Irf6 in keratinocyte differentiation and its strong downregulation in AEC syndrome, Irf6 depletion caused reduced expression of Pvrl4 in wild‐type keratinocytes. Taken together, our results indicate that Pvrl1 is a bona fide target gene of the transcription factor p63, whereas Pvrl4 regulation is linked to epidermal differentiation and is under Irf6 control.
Efficacy of the ‘Long‐term Urinary Catheter Management Training Program’: a pilot study
Authors: Maeda Shuko , Takiuti Takako , Komatsu Taeko , Kohno Yumiko , Nakai Hisao
Published: November 2014

In home‐care patients with urinary catheters (hereafter, ‘catheters’), the indwelling periods are sometimes prolonged and can cause various complications. To educate visiting nurses about long‐term catheter management, we conducted ‘The Long‐term Urinary Catheter Management Training Program for Visiting Nurses’ (hereafter, ‘the training program’). We investigated the efficacy of the training program in the present pilot study. The aim of the study was to verify the efficacy of the training program. Forty‐one participants completed a questionnaire survey before and after the training program. The training program's efficacy was verified on the basis of three indices: satisfaction of learning needs, learning achievement and usefulness for visiting nurses. In the satisfaction of learning needs index, more than 50·0% of training participants answered ‘Yes’ for all program content. The participants answered the same questions about long‐term catheter management before and after the training program to assess their learning achievement. The number of correct answers was significantly higher in the post‐training survey than in the pre‐training survey, and the number of correct answers increased for 75·6% of participants. In the usefulness for visiting nurses index, 50·0% or more participants answered ‘Yes’ for all topics but one. The results of this pilot study indicate that the training program was basically effective in educating a relatively small number of participating visiting nurses about long‐term catheter management from a cognitive perspective. However, ‘number of participants,’ ‘method for examining learning achievement,’ ‘number of goals in the program’ and ‘education method’ require improvement.
TheEuroPlusPact: Competitiveness and External Capital Flows in theEUCountries
Authors: Gabrisch Hubert , Staehr Karsten
Published: November 2014

The Euro Plus Pact was approved by the European Union countries in March 2011. The pact stipulates various measures to strengthen competitiveness with the ultimate aim of preventing accumulation of unsustainable external imbalances. This article uses Granger causality tests to assess the short‐term linkages between changes in relative unit labour costs and changes in the current account balance for the period 1995–2011. The main finding is that changes in the current account balance precede changes in relative unit labour costs, while there is no discernible effect in the opposite direction. This suggests that capital flows from the European core to the periphery contributed to the divergence in unit labour costs across Europe prior to the global financial crisis. The results also suggest that the measures to restrain unit labour costs may have only limited effect on the current account balance in the short term.
Increased reaction time variability in attention‐deficit hyperactivity disorder as a response‐related phenomenon: evidence from single‐trial event‐related potentials
Authors: Saville Christopher W. N. , Feige Bernd , Kluckert Christian , Bender Stephan , Biscaldi Monica , Berger Andrea , Fleischhaker Christian , Henighausen Klaus , Klein Christoph
Published: November 2014

Background

Increased intra‐subject variability (ISV) in reaction times (RTs) is a promising endophenotype for attention‐deficit hyperactivity disorder (ADHD) and among the most robust hallmarks of the disorder. ISV has been assumed to represent an attentional deficit, either reflecting lapses in attention or increased neural noise. Here, we use an innovative single‐trial event‐related potential approach to assess whether the increased ISV associated with ADHD is indeed attributable to attention, or whether it is related to response‐related processing.

Methods

We measured electroencephalographic responses to working memory oddball tasks in patients with ADHD (N = 20, aged 11.3 ± 1.1) and healthy controls (N = 25, aged 11.7 ± 1.1), and analysed these data with a recently developed method of single‐trial event‐related potential analysis. Estimates of component latency variability were computed for the stimulus‐locked and response‐locked forms of the P3b and the lateralised readiness potential (LRP).

Results

ADHD patients showed significantly increased ISV in behavioural ISV. This increased ISV was paralleled by an increase in variability in response‐locked event‐related potential latencies, while variability in stimulus‐locked latencies was equivalent between groups. This result held across the P3b and LRP. Latency of all components predicted RTs on a single‐trial basis, confirming that all were relevant for speed of processing.

Conclusions

These data suggest that the increased ISV found in ADHD could be associated with response‐end, rather than stimulus‐end processes, in contrast to prevailing conceptions about the endophenotype. This mental chronometric approach may also be useful for exploring whether the existing lack of specificity of ISV to particular psychiatric conditions can be improved upon.
Impact of early tumor shrinkage on clinical outcome in wild‐type‐KRAS colorectal liver metastases treated with cetuximab
Authors: Ye Le‐chi , Wei Ye , Zhu De‐xiang , Chen Tao , Xu Jianmin
Published: November 2014

Background and Aim

To evaluate the impact of early tumor shrinkage (ETS) on long‐term outcome in patients with wild‐type Kirsten rat sarcoma viral oncogene homolog (KRAS) unresectable colorectal liver metastases (CLM) receiving cetuximab plus chemotherapy.

Methods

A total of 138 patients in a randomized controlled trial (70 in armA received cetuximab plus chemotherapy, 68 in armB received chemotherapy alone), as previously reported (Ye et al., 2013) were included into this analysis. The cut‐off date updated for overall survival (OS) was June 2014. ETS was defined as a ≥ 20% reduction of the longest diameters of the target lesions compared with baseline at the first evaluation (8 weeks). Outcome measures were progression‐free survival (PFS) and OS.

Results

There were 132 patients available for evaluation, and ETS occurred more frequently in armA than that in armB (P = 0.003). ETS was associated with longer OS (armA: 35.7 vs 19.5 months, P < 0.001; armB 28.7 vs 18.7 months, P = 0.01) and PFS (armA: 13.4 vs 4.2 months, P < 0.001; armB 7.0 vs 4.2 months, P = 0.001) compared with patients with no‐ETS. Among patients with ETS, there was a significant difference between armA and armB in PFS (P = 0.03), but not in OS (P = 0.19). All 23 patients who underwent liver surgery achieved ETS. In armA, for patients without liver surgery, patients observed ETS also gained an increased survival benefit over those no‐ETS in OS (P = 0.02) and PFS (P < 0.001). ETS was an independent predictor of improved OS (hazard ratio 0.56, P = 0.007).

Conclusion

ETS may serve as a predictor of favorable outcome in patients with wild‐type KRAS CLM receiving cetuximab plus chemotherapy.
Effectiveness of the IMPACT:Ability Program to Improve Safety and Self‐Advocacy Skills in High School Students With Disabilities
Authors: Dryden Eileen M. , Desmarais Jeffery , Arsenault Lisa
Published: November 2014

BACKGROUND

Individuals with disabilities experience higher rates of abuse than the nondisabled. Few evidence‐based prevention interventions have been published despite a need for such work. This study evaluated IMPACT:Ability, a safety and self‐advocacy training for individuals with cognitive and/or physical disabilities.

METHODS

A quasi‐experimental design was used to assess change in safety and self‐advocacy knowledge, confidence, and behaviors among special education high school students in Boston, MA. Instruments were interviewer‐administered at 3 time points. Analysis of covariance (ANCOVA) was used to compare change between the intervention (N = 21) and wait‐list (N = 36) groups. Repeated measures analysis was used to test change in the complete sample (N = 57).

RESULTS

Students were diverse (58% males, 82% nonwhite) with a range of disabilities. Significantly greater improvement in key outcomes, including safety and self‐advocacy knowledge, confidence, and behavior, were observed in intervention students compared to the wait‐list group. Results in the complete sample showed evidence of further improvements in students' sense of safety and general self‐efficacy.

CONCLUSIONS

These findings are encouraging given the effects were demonstrated in a heterogeneous urban population. IMPACT:Ability may be an effective safety and self‐advocacy training for students with disabilities. Further research will be required to determine effectiveness within particular subpopulations of students.
Testosterone and Body Composition in Men after Treatment for Rectal Cancer
Authors: Buchli Christian , Tapper John , Bottai Matteo , Holm Torbjörn , Arver Stefan , Blomqvist Lennart , Martling Anna
Published: November 2014

Introduction

Preoperative radiotherapy for rectal cancer may affect Leydig cell function. However, the diagnosis of posttreatment hypogonadism is complicated as sexual symptoms associated to hypogonadism can rely on adverse events of pelvic radiation and surgery.

Aim

The objective of this study was to investigate the association of testosterone levels and body composition. The clinical value of such an association is tested subsequently in the study population.

Methods

This was a longitudinal study with prospective registration during 2010–2012 and 1-year follow up. Men with rectal cancer stage I–III, treated with radiotherapy and surgery, were eligible, and 40 of 53 men were available for analysis.

Main Outcome Measures

The areas of skeletal muscle and adipose tissue were assessed on a defined section of a computed tomography at baseline and after 1 year. Androgen levels were recorded from morning blood samples.

Results

The area of skeletal muscle was related to the level of bioavailable testosterone (P = 0.01) but not to the level of serum testosterone (P = 0.36). The subcutaneous adipose tissue was not related to testosterone levels. Men with posttreatment serum testosterone levels of 8–12 nmol/L and longitudinal loss of psoas muscle area had a significantly increased luteinizing hormone-testosterone ratio compared with those with longitudinal gain of psoas muscle.

Conclusions

The area of psoas muscle is related to the unbound fraction of circulating testosterone in men treated for rectal cancer. The longitudinal loss of psoas muscle in men with borderline levels of serum testosterone seems to be an androgen-related symptom associated with compensatory activation of the pituitary–gonadal axis indicating a testicular failure in this group of patients.
Investigating the molecular underpinnings underlying morphology and changes in carbon partitioning during tension wood formation in Eucalyptus
Authors: Mizrachi Eshchar , Maloney Victoria J. , Silberbauer Janine , Hefer Charles A. , Berger Dave K. , Mansfield Shawn D. , Myburg Alexander A.
Published: November 2014

Tension wood has distinct physical and chemical properties, including altered fibre properties, cell wall composition and ultrastructure. It serves as a good system for investigating the genetic regulation of secondary cell wall biosynthesis and wood formation. The reference genome sequence for Eucalyptus grandis allows investigation of the global transcriptional reprogramming that accompanies tension wood formation in this global wood fibre crop.

We report the first comprehensive analysis of physicochemical wood property changes in tension wood of Eucalyptus measured in a hybrid (E. grandis × Eucalyptus urophylla) clone, as well as genome‐wide gene expression changes in xylem tissues 3 wk post‐induction using RNA sequencing.

We found that Eucalyptus tension wood in field‐grown trees is characterized by an increase in cellulose, a reduction in lignin, xylose and mannose, and a marked increase in galactose. Gene expression profiling in tension wood‐forming tissue showed corresponding down‐regulation of monolignol biosynthetic genes, and differential expression of several carbohydrate active enzymes.

We conclude that alterations of cell wall traits induced by tension wood formation in Eucalyptus are a consequence of a combination of down‐regulation of lignin biosynthesis and hemicellulose remodelling, rather than the often proposed up‐regulation of the cellulose biosynthetic pathway.
Proven Epstein–Barr encephalitis with negative EBV‐DNA load in cerebrospinal fluid after allogeneic hematopoietic stem cell transplantation in a child with acute lymphoblastic leukemia
Authors: Barberi Walter , Perrone Salvatore , Iori Anna Paola , Torelli Giovanni Fernando , Testi Anna Maria , Moleti Maria Luisa , Ceglie Teresa , Papoff Paola , Caresta Elena , Antonelli Manila , Gianno Francesca , Melone Antonio , Badiali Manuela , Giangaspero Felice , Foà Robin , Gentile Giuseppe
Published: November 2014

We report a case of EBV encephalitis in a seven‐yr‐old child with Ph+ ALL. Two months after an allogeneic HSCT from his HLA mismatched mother, the patient showed an altered sensorium, generalized seizures, and a left hemiparesis. Brain MRI demonstrated multiple lesions highly suggestive for viral encephalitis. Blood and CSF PCR analyses were negative for the most common viruses involved in immunocompromised patients including EBV. A cerebral biopsy was performed, which showed intense gliosis and perivascular lymphocytic cuffing. PCR analysis performed on brain tissue was positive only for the EBV genome, while extensive investigations for other viral infections were negative. The patient's neurological symptoms rapidly worsened and he died two months later. This case report suggests that in patients presenting neurological and radiological signs of encephalitis after an HSCT, an EBV involvement should be considered, even in the absence of CSF and blood PCR virus detection.
Cardiovascular risk factors and cardiac disorders in long‐term survivors of pediatric liver transplantation
Authors: Baskar Shankar , George Peggy L. , Eghtesad Bijan , Radhakrishnan Kadakkal , Hupertz Vera , Aziz Peter F. , Alkhouri Naim
Published: November 2014

The MetS and cardiovascular disease are leading causes of late morbidity in adult liver transplantation recipients; however, limited data are available in pediatric liver transplantation. A single‐center retrospective review was undertaken for patients who had a liver transplantation before 18 yr of age and were >5 yr post‐transplantation, to study the prevalence of MetS, its components, and cardiac disorders. Fifty‐eight patients were included in the study with a mean age at transplantation of 6.3 ± 6.1 yr and mean follow‐up of 14.1 ± 6.0 yr. Of the study group, 41.4% were overweight or obese, with ongoing prednisone use and increased duration of follow‐up being significant risk factors. Fifty‐three patients had sufficient data for determining MetS, which was present in 17% of the patients. Although the prevalence of MetS is low in pediatric liver transplant recipients, it is associated with CKD and prednisone therapy (p < 0.05). Echocardiography data were available for 23 patients, of whom 43.4% had LVH and 13% had evidence of PH. The spectrum of cardiac disorders in this population is much wider than in adults.
Platelet transfusion: a systematic review of the clinical evidence
Authors: Kumar Ambuj , Mhaskar Rahul , Grossman Brenda J. , Kaufman Richard M. , Tobian Aaron A.R. , Kleinman Steven , Gernsheimer Terry , Tinmouth Alan T. , Djulbegovic Benjamin ,   AABB Platelet Transfusion Guidelines Panel
Published: November 2014

Background

Platelet (PLT) transfusion is indicated either prophylactically or therapeutically to reduce the risk of bleeding or to control active bleeding. Significant uncertainty exists regarding the appropriate use of PLT transfusion and the optimal threshold for transfusion in various settings. We formulated 12 key questions to assess the role of PLT transfusion.

Study Design and Methods

We performed a systematic review (SR) of randomized controlled trials (RCTs) and observational studies. A comprehensive search of PubMed, Web of Science, and Cochrane registry of controlled trials was performed. Methodologic quality of included studies was assessed and a meta‐analysis was performed if more than two studies with similar designs were identified for a specific question.

Results

Seventeen RCTs and 55 observational studies were included in the final SR. Results from RCTs showed a beneficial effect of prophylactic compared with therapeutic transfusion for the prevention of significant bleeding in patients with hematologic disorders undergoing chemotherapy or stem cell transplantation. We found no difference in significant bleeding events related to the PLT count threshold for transfusion or the dose of PLTs transfused. Overall methodologic quality of RCTs was moderate. Results from observational studies showed no evidence that PLT transfusion prevented significant bleeding in patients undergoing central venous catheter insertions, lumbar puncture, or other surgical procedures. The methodologic quality of observational studies was very low.

Conclusion

We provide a comprehensive assessment of evidence on the use of PLT transfusions in a variety of clinical settings. Our report summarizes current knowledge and identifies gaps to be addressed in future research.
Studies on atomic layer deposition of IRMOF-8 thin films
Authors: Salmi Leo D. , Heikkilä Mikko J. , Vehkamäki Marko , Puukilainen Esa , Ritala Mikko , Sajavaara Timo
Published: November 2014

Deposition of IRMOF-8 thin films by atomic layer deposition was studied at 260–320 °C. Zinc acetate and 2,6-naphthalenedicarboxylic acid were used as the precursors. The as-deposited amorphous films were crystallized in 70% relative humidity at room temperature resulting in an unknown phase with a large unit cell. An autoclave with dimethylformamide as the solvent was used to recrystallize the films into IRMOF-8 as confirmed by grazing incidence x-ray diffraction. The films were further characterized by high temperature x-ray diffraction (HTXRD), field emission scanning electron microscopy, Fourier transform infrared spectroscopy (FTIR), time-of-flight elastic recoil detection analysis (TOF-ERDA), nanoindentation, and energy-dispersive x-ray spectroscopy. HTXRD measurements revealed similar behavior to bulk IRMOF-8. According to TOF-ERDA and FTIR, composition of the films was similar to IRMOF-8. Through-porosity was confirmed by loading the films with palladium using Pd(thd)2 (thd = 2,2,6,6-tetramethyl-3,5-heptanedionato) as the precursor.
Semen enhances HIV infectivity and impairs the antiviral efficacy of microbicides
Authors: Zirafi Onofrio , Kim Kyeong-Ae , Roan Nadia R. , Kluge Silvia F. , Müller Janis A. , Jiang Shibo , Mayer Benjamin , Greene Warner C. , Kirchhoff Frank , Münch Jan
Published: November 2014

Endogenous amyloids in semen impair the antiretroviral efficacy of drugs targeting HIV directly, but do not impair maraviroc, which targets the cellular CCR5 receptor.
Catastrophic Childhood Epilepsy: A Recent Convergence of Basic and Clinical Neuroscience
Authors: Katsnelson Alla , Buzsáki Gyorgy , Swann John W.
Published: November 2014

Advances in understanding the genetics and underlying pathology of the catastrophic childhood epilepsies are pointing toward treatments.
Tau-Chopping Enzyme Adds Fuel to the Neurodegeneration Fire
Authors: Musiek Erik S.
Published: November 2014

A new enzyme slices tau into toxic fragments that may mediate tangle formation and neurodegeneration in Alzheimer’s disease.
A Tug of War in the Periphery
Authors: Chitalia Vipul
Published: November 2014

The metabolic syndrome, a strong risk factor for peripheral artery disease, increases the antiangiogenic VEGF-A
165b
isoform, impeding the development of new blood vessels in ischemic limbs.
High prevalence of hepatitis B virus infection among pregnant women attending antenatal care: a cross-sectional study in two hospitals in northern Uganda
Authors: Bayo Pontius , Ochola Emmanuel , Oleo Caroline , Mwaka Amos Deogratius
Published: November 2014

Objective

To determine the prevalence of the hepatitis B viral (HBV) infection and hepatitis B e antigen (HBeAg) positivity among pregnant women attending antenatal clinics in two referral hospitals in northern Uganda.

Design

Cross-sectional observational study.

Setting

Two tertiary hospitals in a postconflict region in a low-income country.

Participants

Randomly selected 402 pregnant women attending routine antenatal care in two referral hospitals. Five women withdrew consent for personal reasons. Data were analysed for 397 participants.

Primary outcome

Hepatitis B surface antigen (HBsAg) positivity.

Results

Of 397 pregnant women aged 13–43 years, 96.2% were married or cohabiting. 47 (11.8%) tested positive for HBsAg; of these, 7 (14.9%) were HBeAg positive. The highest HBsAg positivity rate was seen in women aged 20 years or less (20%) compared with those aged above 20 years (8.7%), aOR=2.54 (95% CI 1.31 to 4.90). However, there was no statistically significant difference between women with positive HBsAg and those with negative tests results with respect to median values of liver enzymes, haemoglobin level, absolute neutrophil counts and white cell counts. HIV positivity, scarification and number of sexual partners were not predictive of HBV positivity.

Conclusions

One in eight pregnant women attending antenatal care in the two study hospitals has evidence of hepatitis B infection. A significant number of these mothers are HBeAg positive and may be at increased risk of transmitting hepatitis B infection to their unborn babies. We suggest that all pregnant women attending antenatal care be tested for HBV infection; exposed babies need to receive HBV vaccines at birth.
An evaluation of combat application tourniquets on training military personnel: changes in application times and success rates in three successive phases
Authors: Unlu Aytekin , Kaya E , Guvenc I , Kaymak S , Cetinkaya R A , Lapsekili E O , Ozer M T , Guler A , Yildiz R , Petrone P , Harlak A , Kilic S
Published: November 2014

Introduction

Haemorrhage from the injured extremity is a significant cause of preventable death in military settings. This study evaluated the effect of training on the efficacy of the combat application tourniquet (CAT) and to define standards for military personnel.

Method

Participants from a training tank battalion were randomised. Data collected included age, body mass index, mean arterial pressure, hand dominance, femoral artery diameter and skin thickness. The study involved tourniquet application times (AT) and application success rates in basic, after-training and eyes-closed phases. Doppler ultrasound was used to identify the presence or absence of popliteal, radial and ulnar artery pulses.

Results

A total of 102 trainees participated. In the after-training phase, the left and right upper extremity ATs were 35±13.1 s, and 34.8±13.5 s and the right and left lower extremity ATs were 20.6±6.0 s and 20.5±5.5 s, respectively. The overall tourniquet success rates in three successive study phases were 69.6%, 82.4% and 91.2%, respectively. A negative significant relationship was found between extremity circumference and tourniquet success.

Discussion

The results show that the efficacy of CAT application increases with training. Further studies are required to investigate the reasons underlying application failures. This single group prospective randomised study involves level of evidence 4.
Ambient temperature influences adult size and life span in jumbo squid (Dosidicus gigas)
Authors: Arkhipkin Alexander , Argüelles Juan , Shcherbich Zhanna , Yamashiro Carmen
Published: November 2014

The eastern Pacific jumbo squid (Dosidicus gigas) is one of the largest and most abundant squid of the world ocean. To reveal possible interannual variability in the life span, statoliths were used to determine the age of mature females belonging to two modal size groups (<490 and >500 mm mantle length) collected before (1991–1996), during (1997–1998), and after (1999–2011) a strong El Niño event in Peruvian waters. We found that water temperatures encountered between the third and sixth months of ontogenesis had the strongest negative effect on age. Together with a weaker but significant negative effect of temperatures encountered during early life (first to third months) and later ontogenesis (seventh and eighth months), these temperature parameters (along with other environmental factors) were important in determining whether a given animal had a 1-year life cycle (early maturation and small size) or a 1.5- to 2-year life cycle (delayed maturation and large size). The possible cause of a sudden increase in abundance of large D. gigas in 2000–2001 is discussed.
Robust Classifiers Using Imprecise Probability Models and Importance of Classes
Authors: Utkin Lev V. , Zhuk Yulia A.
Published: November 2014

A framework for constructing robust classification models is proposed in the paper. An assumption about importance of one of the classes in comparison with other classes is incorporated into the models. It often takes place in the real application, for example, in reliability, in medical diagnostic, etc. A main idea underlying the models is to consider a set of probability distributions on training examples produced by the imprecise probability models such as linear-vacuous mixture and constant odd-ratio contaminated models. Extreme points of the sets of probability distributions are a main tool for constructing the robust classifiers. It is shown that algorithms for computing optimal classification parameters are reduced to a finite number of weighted support vector machines with weights determined by the extreme points. Experimental results with synthetic and real data illustrate the proposed models.
Role of neuronal nitric oxide synthase in the estrogenic attenuation of cannabinoid-induced changes in energy homeostasis
Authors: Borgquist Amanda , Meza Cecilia , Wagner Edward J.
Published: November 2014

Since estradiol attenuates cannabinoid-induced increases in energy intake, energy expenditure, and transmission at proopiomelanocortin (POMC) synapses in the hypothalamic arcuate nucleus (ARC), we tested the hypothesis that neuronal nitric oxide synthase (nNOS) plays an integral role. To this end, whole animal experiments were carried out in gonadectomized female guinea pigs. Estradiol benzoate (EB; 10 μg sc) decreased incremental food intake as well as O2 consumption, CO2 production, and metabolic heat production as early as 2 h postadministration. This was associated with increased phosphorylation of nNOS (pnNOS), as evidenced by an elevated ratio of pnNOS to nNOS in the ARC. Administration of the cannabinoid receptor agonist WIN 55,212-2 (3 μg icv) into the third ventricle evoked hyperphagia as early as 1 h postadministration, which was blocked by EB and restored by the nonselective NOS inhibitor N-nitro-l-arginine methyl ester hydrochloride (l-NAME; 100 μg icv) when the latter was combined with the steroid. Whole cell patch-clamp recordings showed that 17β-estradiol (E2; 100 nM) rapidly diminished cannabinoid-induced decreases in miniature excitatory postsynaptic current frequency, which was mimicked by pretreatment with the NOS substrate l-arginine (30 μM) and abrogated by l-NAME (300 μM). Furthermore, E2 antagonized endocannabinoid-mediated depolarization-induced suppression of excitation, which was nullified by the nNOS-selective inhibitor N5-[imino(propylamino)methyl]-l-ornithine hydrochloride (10 μM). These effects occurred in a sizable number of identified POMC neurons. Taken together, the estradiol-induced decrease in energy intake is mediated by a decrease in cannabinoid sensitivity within the ARC feeding circuitry through the activation of nNOS. These findings provide compelling evidence for the need to develop rational, gender-specific therapies to help treat metabolic disorders such as cachexia and obesity.
Characterization of a Selenium-Tolerant Rhizosphere Strain from a Novel Se-Hyperaccumulating PlantCardamine hupingshanesis
Authors: Tong Xinzhao , Yuan Linxi , Luo Lei , Yin Xuebin
Published: November 2014

A novel selenium- (Se-) hyperaccumulating plant,Cardamine hupingshanesis, accumulating Se as a form of SeCys2, was discovered in Enshi, Hubei, China, which could not be explained by present selenocysteine methyltransferase (SMT) theory. However, it is interesting to investigate if rhizosphere bacteria play some roles during SeCys2accumulation. Here, one Se-tolerant rhizosphere strain,Microbacterium oxydans, was isolated fromC. hupingshanesis. Phylogenetic analysis and 16S rRNA gene sequences determined the strain as a kind of Gram positive bacillus and belonged to the familyBrevibacterium frigoritolerans. Furthermore, Se tolerance test indicated the strain could grow in extreme high Se level of 15.0 mg Se L−1. When exposed to 1.5 mg Se L−1, SeCys2was the predominant Se species in the bacteria, consistent with the Se species inC. hupingshanesis. This coincidence might reveal that this strain played some positive effect in SeCys2accumulation ofC. hupingshanesis. Moreover, when exposed to 1.5 mg Se L−1or 15.0 mg Se L−1, As absorption diminished in the logarithmic phase. In contrast, As absorption increased when exposed to 7.5 mg Se L−1, indicating As metabolism processes could be affected by Se on this strain. The present study provided a sight on the role of rhizosphere bacteria during Se accumulation for Se-hyperaccumulating plant.
Effects of ExperimentalSarcocystis neurona-Induced Infection on Immunity in an Equine Model
Authors: Lewis S. Rochelle , Ellison Siobhan P. , Dascanio John J. , Lindsay David S. , Gogal Robert M. , Werre Stephen R. , Surendran Naveen , Breen Meghan E. , Heid Bettina M. , Andrews Frank M. , Buechner-Maxwell Virginia A. , Witonsky Sharon G.
Published: November 2014

Sarcocystis neuronais the most common cause of Equine Protozoal Myeloencephalitis (EPM), affecting 0.5–1% horses in the United States during their lifetimes. The objective of this study was to evaluate the equine immune responses in an experimentally inducedSarcocystis neuronainfection model. Neurologic parameters were recorded prior to and throughout the 70-day study by blinded investigators. Recombinant SnSAG1 ELISA for serum and CSF were used to confirm and track disease progression. All experimentally infected horses displayed neurologic signs after infection. Neutrophils, monocytes, and lymphocytes from infected horses displayed significantly delayed apoptosis at some time points. Cell proliferation was significantly increased inS. neurona-infected horses when stimulated nonspecifically with PMA/I but significantly decreased when stimulated withS. neuronacompared to controls. Collectively, our results suggest that horses experimentally infected withS. neuronamanifest impaired antigen specific response toS. neurona, which could be a function of altered antigen presentation, lack of antigen recognition, or both.
Genetic Variability ofAspergillus flavusIsolates from a Mississippi Corn Field
Authors: Solorzano Cesar D. , Abbas Hamed K. , Zablotowicz Robert M. , Chang Perng-Kuang , Jones Walker A.
Published: November 2014

A nontoxigenicAspergillus flavusstrain, K49, is currently being tested as a biological control agent in corn fields in the Mississippi Delta. However, little is known about the overall genetic diversity ofA. flavusfrom year to year in corn fields and specifically in Mississippi. Our objective was to assess the genetic variability ofA. flavusisolates from different seasons, inoculum sources, and years, from a no-till corn field. Of the 175A. flavusisolates examined, 74 and 97 had the typicalnorB-cypAtype I (1.5 kb) and type II (1.0 kb) deletion patterns, respectively. Variability in the sequence of theomtAgene of the majority of the field isolates (n=118) was compared to strain K49. High levels of haplotypic diversity (24omtAhaplotypes; Hd = 0.61 ± 0.04) were found. Among the 24 haplotypes, two were predominant, H1 (n=71), which consists of mostly toxigenic isolates, and H49 (n=18), which consists of mostly atoxigenic isolates including K49. Toxigenic isolates were prevalent (60%) in this natural population. Nonetheless, about 15% of the population likely shared the same ancestral origin with K49. This study provides valuable information on the diversity ofA. flavus. This knowledge can be further used to develop additional biological control strains.
An Unusual Presentation of a Myocardial Crypt in Hypertrophic Cardiomyopathy
Authors: van de Sande Danny A. J. P. , Hoogsteen Jan , Theunissen Luc J. H. J.
Published: November 2014

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease with prevalence of 0.2% in the population. More than 1000 mutations in more than 10 genes encoding for proteins of the cardiac sarcomere have been identified. Cardiac magnetic resonance imaging (CMR) is used to characterize left ventricular morphology with great precision in patients with HCM and it identifies unique structural abnormalities in patients with HCM. We present a case of a 56-year-old man who had positive family history of HCM who was a carrier of the genetic MYH-7 2770 G > C, exon 23 mutation. Transthoracic echocardiography showed thickening of the interventricular septum (16 mm) and in particular the basal septum. CMR confirmed the diagnosis of HCM in the anteroseptal myocardium with a thickness of 23 mm and also revealed large and deep myocardial crypts in the anterior wall. These myocardial crypts are rarely found in the so-called genotype positive and phenotype positive patients, as in our case. Also the crypts in this case are deeper and wider than those reported in other cases. So in conclusion, this case reveals an uncommon finding of a myocardial crypt at an unusual myocardial site with the unusual morphology in a patient with genotypic and phenotypic expression of hypertrophic cardiomyopathy.
An Efficient Sleepy Algorithm for Particle-Based Fluids
Authors: Nie Xiao , Chen Leiting , Xiang Tao
Published: November 2014

We present a novel Smoothed Particle Hydrodynamics (SPH) based algorithm for efficiently simulating compressible and weakly compressible particle fluids. Prior particle-based methods simulate all fluid particles; however, in many cases some particles appearing to be at rest can be safely ignored without notably affecting the fluid flow behavior. To identify these particles, a novel sleepy strategy is introduced. By utilizing this strategy, only a portion of the fluid particles requires computational resources; thus an obvious performance gain can be achieved. In addition, in order to resolve unphysical clumping issue due to tensile instability in SPH based methods, a new artificial repulsive force is provided. We demonstrate that our approach can be easily integrated with existing SPH based methods to improve the efficiency without sacrificing visual quality.
A New Pixels Flipping Method for Huge Watermarking Capacity of the Invoice Font Image
Authors: Li Li , Hou Qingzheng , Lu Jianfeng , Xu Qishuai , Dai Junping , Mao Xiaoyang , Chang Chin-Chen
Published: November 2014

Invoice printing just has two-color printing, so invoice font image can be seen as binary image. To embed watermarks into invoice image, the pixels need to be flipped. The more huge the watermark is, the more the pixels need to be flipped. We proposed a new pixels flipping method in invoice image for huge watermarking capacity. The pixels flipping method includes one novel interpolation method for binary image, one flippable pixels evaluation mechanism, and one denoising method based on gravity center and chaos degree. The proposed interpolation method ensures that the invoice image keeps features well after scaling. The flippable pixels evaluation mechanism ensures that the pixels keep better connectivity and smoothness and the pattern has highest structural similarity after flipping. The proposed denoising method makes invoice font image smoother and fiter for human vision. Experiments show that the proposed flipping method not only keeps the invoice font structure well but also improves watermarking capacity.
Human Lung Cancer Cell Line A-549 ATCC Is Differentially Affected by Supranutritional Organic and Inorganic Selenium
Authors: Flores Villavicencio Lérida Liss , Cruz-Jiménez Gustavo , Barbosa-Sabanero Gloria , Kornhauser-Araujo Carlos , Mendoza-Garrido M. Eugenia , de la Rosa Guadalupe , Sabanero-López Myrna
Published: November 2014

The effects of organic and inorganic forms of selenium (Se) on human cells have been extensively studied for nutritional concentrations; however, to date, little is known about the potential toxicity at supranutritional levels. In the present study we determined the effects of sodium selenite (SSe) and selenomethionine (SeMet) on cell growth and intracellular structures in lung cancer cells exposed at Se concentrations between 0 and 3 mM. Our results showed that SSe affected cell growth more rapidly than SeMet (24 h and 48 h, resp.). After 24 h of cells exposure to 0.5, 1.5, and 3 mM SSe, cell growth was reduced by 10, 50, and 60%, as compared to controls. After 48 h, nuclear fragmentation was evident in cells exposed to SSe, suggesting an induction to cell death. In contrast, SeMet did not affect cell proliferation, and the cells were phenotypically similar to controls. Microtubules and microfilaments structures were also affected by both Se compounds, again SSe being more toxic than SeMet. To our knowledge, this is the first report on the differential effects of organic and inorganic Se in supranutritional levels in lung cancer cells.
Effect of Process Parameters of CNT Containing Friction Powder on Flexural Properties and Friction Performance of Organic Brake Friction Materials
Authors: Lee Kuo-Jung , Hsu Mao-Hsiang , Cheng Huy-Zu
Published: November 2014

This research is to investigate the influences of carbon nanotube (CNT) containing friction powder prepared through different process parameters on flexural properties and friction performance of organic brake friction materials. Experimental results indicate significant influence on flexural property and friction performance of organic brake friction materials when the modified CNT/friction powders are adopted. Particularly for the specimens adopted the modified CNT/friction powders prepared through 2.0 M concentration of catalyst and 30% C2H2 show the highest flexural strength, better ductility and toughness, most stable friction coefficient, and lowest weight loss. However, too many amorphous carbon clusters and CNTs aggregation derived from higher concentration of catalyst and ratio of C2H2/N2 would cause poor formation of specimens and reduction of reinforcement effectiveness.
Akt1 and Akt3 Exert Opposing Roles in the Regulation of Vascular Tumor Growth
Authors: Phung Thuy L. , Du Wa , Xue Qi , Ayyaswamy Sriram , Gerald Damien , Antonello Zeus , Nhek Sokha , Perruzzi Carole A. , Acevedo Isabel , Ramanna-Valmiki Rajesh , Rodriguez-Waitkus Paul , Enayati Ladan , Hochman Marcelo L. , Lev Dina , Geeganage Sandaruwan , Benjamin Laura E.
Published: November 2014

Vascular tumors are endothelial cell neoplasms whose mechanisms of tumorigenesis are poorly understood. Moreover, current therapies, particularly those for malignant lesions, have little beneficial effect on clinical outcomes. In this study, we show that endothelial activation of the Akt1 kinase is sufficient to drive de novo tumor formation. Mechanistic investigations uncovered opposing functions for different Akt isoforms in this regulation, where Akt1 promotes and Akt3 inhibits vascular tumor growth. Akt3 exerted negative effects on tumor endothelial cell growth and migration by inhibiting activation of the translation regulatory kinase S6-Kinase (S6K) through modulation of Rictor expression. S6K in turn acted through a negative feedback loop to restrain Akt3 expression. Conversely, S6K signaling was increased in vascular tumor cells where Akt3 was silenced, and the growth of these tumor cells was inhibited by a novel S6K inhibitor. Overall, our findings offer a preclinical proof of concept for the therapeutic utility of treating vascular tumors, such as angiosarcomas, with S6K inhibitors. Cancer Res; 75(1); 40–50. ©2014 AACR.
SYK Is a Candidate Kinase Target for the Treatment of Advanced Prostate Cancer
Authors: Ghotra Veerander P.S. , He Shuning , van der Horst Geertje , Nijhoff Steffen , de Bont Hans , Lekkerkerker Annemarie , Janssen Richard , Jenster Guido , van Leenders Geert J.L.H. , Hoogland A. Marije M. , Verhoef Esther I. , Baranski Zuzanna , Xiong Jiangling , van de Water Bob , van der Pluijm Gabri , Snaar-Jagalska B. Ewa , Danen Erik H.J.
Published: November 2014

Improved targeted therapies are needed to combat metastatic prostate cancer. Here, we report the identification of the spleen kinase SYK as a mediator of metastatic dissemination in zebrafish and mouse xenograft models of human prostate cancer. Although SYK has not been implicated previously in this disease, we found that its expression is upregulated in human prostate cancers and associated with malignant progression. RNAi-mediated silencing prevented invasive outgrowth in vitro and bone colonization in vivo, effects that were reversed by wild-type but not kinase-dead SYK expression. In the absence of SYK expression, cell surface levels of the progression-associated adhesion receptors integrin α2β1 and CD44 were diminished. RNAi-mediated silencing of α2β1 phenocopied SYK depletion in vitro and in vivo, suggesting an effector role for α2β1 in this setting. Notably, pharmacologic inhibitors of SYK kinase currently in phase I–II trials for other indications interfered similarly with the invasive growth and dissemination of prostate cancer cells. Our findings offer a mechanistic rationale to reposition SYK kinase inhibitors for evaluation in patients with metastatic prostate cancer. Cancer Res; 75(1); 230–40. ©2014 AACR.
Molecular Pathways: Translational and Therapeutic Implications of the Notch Signaling Pathway in Cancer
Authors: Previs Rebecca A. , Coleman Robert L. , Harris Adrian L. , Sood Anil K.
Published: November 2014

Over 100 years have passed since the first observation of the notched wing phenotype in Drosophila melanogaster, and significant progress has been made to characterize the role of the Notch receptor, its ligands, downstream targets, and cross-talk with other signaling pathways. The canonical Notch pathway with four Notch receptors (Notch1-4) and five ligands (DLL1, 3-4, Jagged 1-2) is an evolutionarily conserved cell signaling pathway that plays critical roles in cell-fate determination, differentiation, development, tissue patterning, cell proliferation, and death. In cancer, these roles have a critical impact on tumor behavior and response to therapy. Because the role of Notch remains tissue and context dependent, alterations within this pathway may lead to tumor suppressive or oncogenic phenotypes. Although no FDA-approved therapies currently exist for the Notch pathway, multiple therapeutics (e.g., demcizumab, tarextumab, GSI MK-0752, R04929097, and PF63084014) have been developed to target different aspects of this pathway for both hematologic and solid malignancies. Understanding the context-specific effects of the Notch pathway will be important for individualized therapies targeting this pathway. Clin Cancer Res; 21(5); 955–61. ©2014 AACR.
Neural Tube Defects: The Experience of the Registry of Congenital Malformations of Alsace, France, 1995-2009
Authors: Timbolschi Dana , Schaefer Elise , Monga Bondo , Fattori Delphine , Dott Béatrice , Favre Romain , Kohler Monique , Nisand Israël , Viville Brigitte , Astruc Dominique , Kehrli Pierre , Gasser Bernard , Lindner Véronique , Marcellin Luc , Flori Elisabeth , Girard-Lemaire Françoise , Dollfus Hélène , Doray Bérénice
Published: November 2014

Context and Objective: Considering the lack of accurate and up-to-date information available about neural tube defects (NTDs) in France, the purpose of this study was to review clinical and epidemiological data of NTDs and to evaluate the current efficiency of prenatal diagnosis in Alsace (northeastern France). Methods: A population-based retrospective study was performed from data of the Registry of Congenital Malformations of Alsace between 1995 and 2009. Data were analyzed as a whole and according to the anatomical type of the malformation (anencephaly, cephalocele and spina bifida). Statistical analyses were carried out using the Statistical Package for the Social Sciences. Results: 272 NTDs were recorded divided in 113 cases of anencephaly (42%), 35 cases of cephalocele (13%) and 124 cases of spina bifida (45%). The total prevalence at birth of 14/10,000 (95% CI 13-16) was stable throughout the reporting period. A chromosome abnormality was identified in 27 cases (12% of all karyotyped cases). NTDs were prenatally diagnosed by ultrasound in 88% of the cases. The mean age upon prenatal diagnosis slightly declined during the 15-year period, significantly for spina bifida only. The global rate of terminations of pregnancy following prenatal diagnosis was 97% (230/238). Conclusion: This work constitutes a unique population-based study providing accurate and specific up-to-date data from a unique center over a longer period (1995-2009). The most important information concerns the high and stable prevalence, which calls into question the efficiency of the primary prevention by folic acid supplementation and the efficiency of prenatal diagnosis.