bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender differences in the knee adduction moment after anterior cruciate ligament reconstruction surgery
Authors: Webster Kate E , McClelland Jodie A , Palazzolo Simon E , Santamaria Luke J , Feller Julian A
Published: April 2011

Background

The external knee adduction moment during gait has previously been associated with knee pain and osteoarthritis (OA). Recently, the knee adduction moment has been shown to be increased following anterior cruciate ligament (ACL) reconstruction surgery and has been suggested as a potential mechanism for the progression of early onset knee OA in this population. No study has investigated the gender differences in gait biomechanics following ACL reconstruction.

Aim

To examine gender differences in gait biomechanics following ACL reconstruction surgery.

Methods

36 subjects (18 females, 18 males) who had previously undergone ACL reconstruction surgery (mean time since surgery 20 months) underwent gait analysis at a self-selected walking speed. Males and females were well matched for age, time since surgery and walking speed. Maximum flexion and adduction angles and moments were recorded during the stance phase of level walking and compared between the male and female groups.

Results

The knee adduction moment was 23% greater in the female compared with the male ACL group. No gender differences were seen in the sagittal plane. No differences were seen between the reconstructed and contralateral limb.

Conclusion

The higher knee adduction moment seen in females compared with males may suggest an increased risk for the development of OA in ACL-reconstructed females.
The angiome: a new concept in cancer biology
Authors: Blann A D , Ramcharan K S , Stonelake P S , Luesley D , Lip G Y H
Published: April 2011

Angiogenesis is a key process in cancer biology, and justifies focus on the endothelium. Separate studies have looked at different aspects of angiogenesis and vascular biology, primarily focusing on certain laboratory and imaging techniques that generally reflect one particular aspect of the assessment of the endothelium. These techniques include the secretion/release of molecules (such as growth factors) into the plasma, by the presence of mature and progenitor endothelial cells themselves in the circulation, but also by examination of peripheral blood flow and the local circulation of the tumour, and cells of the tumour itself. However, a limitation of this approach is that these methods, although themselves being useful, have often been viewed in isolation and thus can provide only a part of the vascular picture. The authors submit that this approach is weak, and introduce ‘the angiome’ as a term which fuses several different aspects of endothelial and tumour biology into a single concept. The authors suggest that the adoption of the concept of the angiome will bring improved insights into angiogenesis and thus cancer cell biology. In justifying this concept, the authors review the current understanding of endothelial biology and the methods of its assessment, and hypothesise that a more multifactorial approach to the angiome will be a crucial determinant of outcomes of and treatment strategies for diseases, in particular antiangiogenics for cancer therapy.
Hospital admissions for neurological and renal diseases among dentists and dental assistants occupationally exposed to mercury
Authors: Thygesen Lau Caspar , Flachs Esben Meulengracht , Hanehøj Kirsten , Kjuus Helge , Juel Knud
Published: April 2011

Objectives

For many years an amalgam containing metallic mercury, which has been associated with neurological and renal diseases, has been used in dentistry. In this nationwide study we compared hospital admissions due to neurological and renal diseases among dentists and dental assistants to admissions in controls.

Methods

This register-based cohort study included all Danish workers employed in dental clinics, general practitioners' clinics or lawyers' offices between 1964 and 2006. We compared dentists with general practitioners and lawyers, and dental assistants with medical secretaries, nurses and legal secretaries. We also compared dentists and dental assistants employed during periods with high occupational mercury exposure with dentists and dental assistants employed during periods with less mercury exposure. We followed all subjects in a nationwide register of hospital admissions. We analysed risk of neurological diseases, Parkinson's disease and renal diseases using a Cox regression model.

Results

The cohort consisted of 122 481 workers including 5371 dentists and 33 858 dental assistants. For neurological diseases, no association was observed for dental assistants, while for dentists an increasing risk for periods with less mercury exposure was observed. Among dental assistants, a negative association between employment length and risk of neurological disease was observed. Admissions for renal disease among dental assistants were increased during periods with less mercury exposure compared with controls. For dentists a non-significant increased risk was observed between employment length and renal disease risk.

Conclusions

Our nationwide study does not indicate that occupational exposure to mercury increases the risk of hospital admissions for neurological, Parkinson's or renal diseases.
Results of a national mass media campaign in India to warn against the dangers of smokeless tobacco consumption
Authors: Murukutla Nandita , Turk Tahir , Prasad C V S , Saradhi Ranjana , Kaur Jagdish , Gupta Shefali , Mullin Sandra , Ram Faujdar , Gupta Prakash C , Wakefield Melanie
Published: April 2011

Objective

Smokeless tobacco consumption in India is a significant source of morbidity and mortality. In order to educate smokeless tobacco users about the health harms of smokeless tobacco and to denormalise tobacco usage and encourage quitting, a national television and radio mass media campaign targeted at smokeless tobacco users was aired for 6 weeks during November and December 2009.

Methods

The campaign was evaluated with a nationally representative household survey of smokeless tobacco users (n=2898). The effect of campaign awareness was assessed with logistic regression analysis.

Results

The campaign affected smokeless tobacco users as intended: 63% of smokeless-only users and 72% of dual users (ie, those who consumed both smoking and smokeless forms) recalled the campaign advertisement, primarily through television delivery. The vast majority (over 70%) of those aware of the campaign said that it made them stop and think, was relevant to their lives and provided new information. 75% of smokeless-only users and 77% of dual users said that it made them feel concerned about their habit. Campaign awareness was associated with better knowledge, more negative attitudes towards smokeless tobacco and greater cessation-oriented intentions and behaviours among smokeless tobacco users.

Conclusions

Social marketing campaigns that utilise mass media are feasible and efficacious interventions for tobacco control in India. Implications for future mass media tobacco control programming in India are discussed.
BFX: DIAGNOSING CONFLICTING REQUIREMENTS IN CONSTRAINT-BASED RECOMMENDATION
Authors: SCHUBERT MONIKA , FELFERNIG ALEXANDER
Published: April 2011

When interacting with constraint-based recommender applications, users describe their preferences with the goal of identifying the products that fit their wishes and needs. In such a scenario, users are repeatedly adapting and changing their requirements. As a consequence, situations occur where none of the products completely fulfils the given set of requirements and users need a support in terms of an indicator of minimal sets of requirements that need to be changed in order to be able to find a recommendation. The identification of such minimal sets relies heavily on the existence of (minimal) conflict sets. In this paper we introduce BFX (Boosted FastXplain), a conflict detection algorithm which exploits the basic structural properties of constraint-based recommendation problems. BFX shows a significantly better performance compared to existing conflict detection algorithms. In order to demonstrate the performance of BFX, we report the results of a comparative performance evaluation.
PARTICLE FILTERING FOR PEOPLE FOLLOWING BEHAVIOR USING LASER SCANS AND STEREO VISION
Authors: ANSUATEGUI ANDER , IBARGUREN AITOR , MARTÍNEZ-OTZETA JOSÉ MARÍA , TUBÍO CARLOS , LAZKANO ELENA
Published: April 2011

Mobile robots have a large application potential in everyday life. To build those applications some common and basic behaviors should be initially consolidated, including a people following behavior. In this paper a system able to follow a person based on information provided by a laser scan and a mono and stereo camera is presented. In order to accomplish this goal, a real-time particle filter system able to merge the information provided by the sensors (laser and 2D and 3D images) and calculate the position of the target is proposed, using probabilistic leg patterns, image features and optical flow to this end. The experiments carried out show promising results, allowing a real-time particle filtering based on two different information sources.
One-pot synthesis of 5-(8-ethoxycarbonyl-1-naphthyl)-10,15,20-triphenyl porphyrin (ENTPP) and spontaneous resolution upon crystallization
Authors: Yang Juanxia , Jiang Jiaxun , Fang Weiguang , Kai Xiaoxu , Hu Chuanjiang , Yang Yonggang
Published: April 2011

5-(8-ethoxycarbonyl-1-naphthyl)-10,15,20-triphenyl porphyrin (ENTPP) has been synthesized in a one-pot reaction, and the corresponding chiral crystalline samples have been obtained by spontaneous resolution. 1 H NMR spectrum suggests it is mononaphthyl substituted species and an ethyl group is over the porphyrin plane. The structure has been further confirmed by X-ray crystallography. ENTPP·C6H14 (C57H50N4O2 ): monoclinic, P21, a = 10.707(2) Å, b = 12.203(2) Å, c = 17.858(4) Å, β = 103.06(3)°, V = 2272.8(8) Å3, Z = 2. The 8-position substituent, ester group, lies above the porphyrin plane and leads to the conformational chirality. The entire structure is built up with homochiral molecules, which leads to a chiral crystal through packing in P21 space group. Circular dichroism (CD) spectra have exhibited remarkable absorptions in the Soret band region, which further confirms the homochirality of the crystalline samples.
Cu-S Nanocabbage Films with Tunable Optical Bandgap and Substantially Improved Stability by Pulse Electrodeposition
Authors: Dou Xincun , Li Hong , Mathews Nripan , Helena Wong Lydia , Ming Lam Yeng , Mhaisalkar Subodh
Published: April 2011

Cu-S nanocabbage films were synthesized on ITO substrate using pulse electrodeposition at elevated temperatures in aqueous solution. The bandgap of the films showed a dependence on reaction time and was found to increase linearly with reaction time. This increase was attributed to the change in phase and stoichiometry of the Cu-S nanocabbage films. The stability of Cu-S films is found to be improved substantially when deposited at higher temperature because the Cu atoms have sufficient energy to find the minimum energy site in the lattice.
Human myostatin negatively regulates human myoblast growth and differentiation
Authors: McFarlane Craig , Hui Gu Zi , Amanda Wong Zhi Wei , Lau Hiu Yeung , Lokireddy Sudarsanareddy , XiaoJia Ge , Mouly Vincent , Butler-Browne Gillian , Gluckman Peter D. , Sharma Mridula , Kambadur Ravi
Published: April 2011

Myostatin, a member of the transforming growth factor-β superfamily, has been implicated in the potent negative regulation of myogenesis in murine models. However, little is known about the mechanism(s) through which human myostatin negatively regulates human skeletal muscle growth. Using human primary myoblasts and recombinant human myostatin protein, we show here that myostatin blocks human myoblast proliferation by regulating cell cycle progression through targeted upregulation of p21. We further show that myostatin regulates myogenic differentiation through the inhibition of key myogenic regulatory factors including MyoD, via canonical Smad signaling. In addition, we have for the first time demonstrated the capability of myostatin to regulate the Notch signaling pathway during inhibition of human myoblast differentiation. Treatment with myostatin results in the upregulation of Hes1, Hes5, and Hey1 expression during differentiation; moreover, when we interfere with Notch signaling, through treatment with the γ-secretase inhibitor L-685,458, we find enhanced myotube formation despite the presence of excess myostatin. Therefore, blockade of the Notch pathway relieves myostatin repression of differentiation, and myostatin upregulates Notch downstream target genes. Immunoprecipitation studies demonstrate that myostatin treatment of myoblasts results in enhanced association of Notch1-intracellular domain with Smad3, providing an additional mechanism through which myostatin targets and represses the activity of the myogenic regulatory factor MyoD. On the basis of these results, we suggest that myostatin function and mechanism of action are very well conserved between species, and that myostatin regulation of postnatal myogenesis involves interactions with numerous downstream signaling mediators, including the Notch pathway.
c-Src inactivation reduces renal epithelial cell-matrix adhesion, proliferation, and cyst formation
Authors: Elliott Justine , Zheleznova Nadezhda N. , Wilson Patricia D.
Published: April 2011

c-Src is a non-receptor tyrosine kinase whose activity is induced by phosphorylation at Y418 and translocation from the cytoplasm to the cell membrane. Increased activity of c-Src has been associated with cell proliferation, matrix adhesion, motility, and apoptosis in tumors. Immunohistochemistry suggested that activated (pY418)-Src activity is increased in cyst-lining autosomal dominant polycystic kidney disease (ADPKD) epithelial cells in human and mouse ADPKD. Western blot analysis showed that SKI-606 (Wyeth) is a specific inhibitor of pY418-Src without demonstrable effects on epidermal growth factor receptor or ErbB2 activity in renal epithelia. In vitro studies on mouse inner medullary collecting duct (mIMCD) cells and human ADPKD cyst-lining epithelial cells showed that SKI-606 inhibited epithelial cell proliferation over a 24-h time frame. In addition, SKI-606 treatment caused a striking statistically significant decrease in adhesion of mIMCD and human ADPKD to extracellular collagen matrix. Retained viability of unattached cells was consistent with a primary effect on epithelial cell anchorage dependence mediated by the loss of extracellular matrix (ECM)-attachment due to α2β1-integrin function. SKI-606-mediated attenuation of the human ADPKD hyperproliferative and hyper-ECM-adhesive epithelial cell phenotype in vitro was paralleled by retardation of the renal cystic phenotype of Pkd1 orthologous ADPKD heterozygous mice in vivo. This suggests that SKI-606 has dual effects on cystic epithelial cell proliferation and ECM adhesion and may have therapeutic potential for ADPKD patients.
Malonyl-CoA mediates leptin hypothalamic control of feeding independent of inhibition of CPT-1a
Authors: Gao Su , Keung Wendy , Serra Dolors , Wang Wei , Carrasco Patricia , Casals Nuria , Hegardt Fausto G. , Moran Timothy H. , Lopaschuk Gary D.
Published: April 2011

Hypothalamic fatty acid metabolism is involved in central nervous system controls of feeding and energy balance. Malonyl-CoA, an intermediate of fatty acid biosynthesis, is emerging as a significant player in these processes. Notably, hypothalamic malonyl-CoA has been implicated in leptin's feeding effect. Leptin treatment increases malonyl-CoA level in the hypothalamic arcuate nucleus (Arc), and this increase is required for leptin-induced decrease in food intake. However, the intracellular downstream mediators of malonyl-CoA's feeding effect have not been identified. A primary biochemical action of malonyl-CoA is the inhibition of the acyltransferase activity of carnitine palmitoyltransferase-1 (CPT-1). In the hypothalamus, the predominant isoform of CPT-1 that possesses the acyltransferase activity is CPT-1 liver type (CPT-1a). To address the role of CPT-1a in malonyl-CoA's anorectic action, we used a recombinant adenovirus expressing a mutant CPT-1a that is insensitive to malonyl-CoA inhibition. We show that Arc overexpression of the mutant CPT-1a blocked the malonyl-CoA-mediated inhibition of CPT-1 activity. However, the overexpression of this mutant did not affect the anorectic actions of leptin or central cerulenin for which an increase in Arc malonyl-CoA level is also required. Thus, CPT-1a does not appear to be involved in the malonyl-CoA's anorectic actions induced by leptin. Furthermore, long-chain fatty acyl-CoAs, substrates of CPT-1a, dissociate from malonyl-CoA's actions in the Arc under different feeding states. Together, our results suggest that Arc intracellular mechanisms of malonyl-CoA's anorectic actions induced by leptin are independent of CPT-1a. The data suggest that target(s), rather than CPT-1a, mediates malonyl-CoA action on feeding.
Sex differences in the modulation of vasomotor sympathetic outflow during static handgrip exercise in healthy young humans
Authors: Jarvis Sara S. , VanGundy Tiffany B. , Galbreath M. Melyn , Shibata Shigeki , Okazaki Kazunobu , Reelick Miriam F. , Levine Benjamin D. , Fu Qi
Published: April 2011

Sex differences in sympathetic neural control during static exercise in humans are few and the findings are inconsistent. We hypothesized women would have an attenuated vasomotor sympathetic response to static exercise, which would be further reduced during the high sex hormone [midluteal (ML)] vs. the low hormone phase [early follicular (EF)]. We measured heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) in 11 women and 10 men during a cold pressor test (CPT) and static handgrip to fatigue with 2 min of postexercise circulatory arrest (PECA). HR increased during handgrip, reached its peak at fatigue, and was comparable between sexes. BP increased during handgrip and PECA where men had larger increases from baseline. Mean ± SD MSNA burst frequency (BF) during handgrip and PECA was lower in women (EF, P < 0.05), as was ΔMSNA-BF smaller (main effect, both P < 0.01). ΔTotal activity was higher in men at fatigue (EF: 632 ± 418 vs. ML: 598 ± 342 vs. men: 1,025 ± 416 a.u./min, P < 0.001 for EF and ML vs. men) and during PECA (EF: 354 ± 321 vs. ML: 341 ± 199 vs. men: 599 ± 327 a.u./min, P < 0.05 for EF and ML vs. men). During CPT, HR and MSNA responses were similar between sexes and hormone phases, confirming that central integration and the sympathetic efferent pathway was comparable between the sexes and across hormone phases. Women demonstrated a blunted metaboreflex, unaffected by sex hormones, which may be due to differences in muscle mass or fiber type and, therefore, metabolic stimulation of group IV afferents.
Simvastatin enhances aquaporin-2 surface expression and urinary concentration in vasopressin-deficient Brattleboro rats through modulation of Rho GTPase
Authors: Li Wei , Zhang Yan , Bouley Richard , Chen Ying , Matsuzaki Toshiyuki , Nunes Paula , Hasler Udo , Brown Dennis , Lu Hua A. Jenny
Published: April 2011

Statins are 3-hydroxyl-3-methyglutaryl-CoA reductase inhibitors that are commonly used to inhibit cholesterol biosynthesis. Emerging data have suggested that they also have “pleotropic effects,” including modulating actin cytoskeleton reorganization. Here, we report an effect of simvastatin on the trafficking of aquaporin-2 (AQP2). Specifically, simvastatin induced the membrane accumulation of AQP2 in cell cultures and kidneys in situ. The effect of simvastatin was independent of protein kinase A activation and phosphorylation at AQP2-Ser256, a critical event involved in vasopressin (VP)-regulated AQP2 trafficking. Further investigation showed that simvastatin inhibited endocytosis in parallel with downregulation of RhoA activity. Overexpression of active RhoA attenuated simvastatin's effect, suggesting the involvement of this small GTPase in simvastatin-mediated AQP2 trafficking. Finally, the effect of simvastatin on urinary concentration was investigated in VP-deficient Brattleboro rats. Simvastatin acutely (3–6 h) increased urinary concentration and decreased urine output in these animals. In summary, simvastatin regulates AQP2 trafficking in vitro and urinary concentration in vivo via events involving downregulation of Rho GTPase activity and inhibition of endocytosis. Our study provides an alternative mechanism to regulate AQP2 trafficking, bypassing the VP-vasopressin receptor signaling pathway.
Chronic nicotine exposure exacerbates acute renal ischemic injury
Authors: Arany Istvan , Grifoni Samira , Clark Jeb S. , Csongradi Eva , Maric Christine , Juncos Luis A.
Published: April 2011

Recent epidemiological reports showed that smoking has a negative impact on renal function and elevates the renal risk not only in the renal patient but perhaps also in the healthy population. Studies suggested that nicotine, a major tobacco alkaloid, links smoking to renal dysfunction. While several studies showed that smoking/chronic nicotine exposure exacerbates the progression of chronic renal diseases, its impact on acute kidney injury is virtually unknown. Here, we studied the effects of chronic nicotine exposure on acute renal ischemic injury. We found that chronic nicotine exposure increased the extent of renal injury induced by warm ischemia-reperfusion as evidenced by morphological changes, increase in plasma creatinine level, and kidney injury molecule-1 expression. We also found that chronic nicotine exposure elevated markers of oxidative stress such as nitrotyrosine as well as malondialdehyde. Interestingly, chronic nicotine exposure alone increased oxidative stress and injury in the kidney without morphological alterations. Chronic nicotine treatment not only increased reactive oxygen species (ROS) production and injury but also exacerbated oxidative stress-induced ROS generation through NADPH oxidase and mitochondria in cultured renal proximal tubule cells. The resultant oxidative stress provoked injury through JNK-mediated activation of the activator protein (AP)-1 transcription factor in vitro. This mechanism might exist in vivo as phosphorylation of JNK and its downstream target c-jun, a component of the AP-1 transcription factor, is elevated in the ischemic kidneys exposed to chronic nicotine. Our results imply that smoking may sensitize the kidney to ischemic insults and perhaps facilitates progression of acute kidney injury to chronic kidney injury.
Heme oxygenase-1 induction contributes to renoprotection by G-CSF during rhabdomyolysis-associated acute kidney injury
Authors: Wei Qingqing , Hill William D. , Su Yunchao , Huang Shuang , Dong Zheng
Published: April 2011

Granulocyte colony-stimulating factor (G-CSF) is renoprotective during acute kidney injury (AKI) induced by ischemia and cisplatin nephrotoxicity; however, the underlying mechanism is not entirely clear. Rhabdomyolysis is another important clinical cause of AKI, due to the release of nephrotoxins (e.g., heme) from disrupted muscles. The current study has determined the effects of G-CSF on rhabdomyolysis-associated AKI using in vivo and in vitro models. In C57BL/6 mice, intramuscular injection of glycerol induced AKI, which was partially prevented by G-CSF pretreatment. Consistently, glycerol-induced renal tissue damage was ameliorated by G-CSF. In addition, animal survival following the glycerol injection was improved from ∼30 to ∼70% by G-CSF. In cultured renal tubular cells, hemin-induced apoptosis was also suppressed by G-CSF. Interestingly, G-CSF induced heme oxygenase-1 (HO-1, a critical enzyme for heme/hemin degradation and detoxification) in both cultured tubular cells and mouse kidneys. Blockade of HO-1 with protoporphyrin IX zinc(II) (ZnPP) could largely diminish the protective effects of G-CSF. Together, these results demonstrated the renoprotective effects of G-CSF in rhabdomyolysis-associated AKI. Notably, G-CSF may directly protect against tubular cell injury under the disease condition by inducing HO-1.
Selective impact of MeCP2 and associated histone deacetylases on the dynamics of evoked excitatory neurotransmission
Authors: Nelson Erika D. , Bal Manjot , Kavalali Ege T. , Monteggia Lisa M.
Published: April 2011

An imbalance between the strengths of excitatory and inhibitory synaptic inputs has been proposed as the cellular basis of autism and related neurodevelopmental disorders. Previous studies examining spontaneous levels of excitatory and inhibitory neurotransmission in the forebrain regions of methyl-CpG-binding protein 2 ( Mecp2) mutant mice, models of the autism spectrum disorder Rett syndrome, have identified a decrease in excitatory drive, in some cases coupled with an increase in inhibitory synaptic strength, as a major source of this imbalance. Here, we reevaluated this question by examining the short-term dynamics of evoked neurotransmission between hippocampal neurons cultured from MeCP2 knockout mice and found a marked increase in evoked excitatory neurotransmission that is consistent with an increase in presynaptic release probability. This increase in evoked excitatory drive was not matched with alterations in evoked inhibitory neurotransmission. Moreover, we observed similar excitatory drive specific changes after the loss of key histone deacetylases (histone deacetylase 1 and 2) that form a complex with MeCP2 and mediate transcriptional regulation. These findings suggest a distinct role for MeCP2 and its cofactors in the regulation of evoked excitatory neurotransmission compared with their essential role in basal synaptic activity.
Postactivation depression and recovery of reflex transmission during repetitive electrical stimulation of the human tibial nerve
Authors: Clair Joanna M. , Anderson-Reid Jamie M. , Graham Caitlin M. , Collins David F.
Published: April 2011

H-reflexes are progressively depressed, relative to the first response, at stimulation frequencies above 0.1 Hz (postactivation depression; PAD). Presently, we investigated whether H-reflexes “recover” from this depression throughout 10-s trains of stimulation delivered at physiologically relevant frequencies (5–20 Hz) during functionally relevant tasks (sitting and standing) and contraction amplitudes [relaxed to 20% maximum voluntary contraction (MVC)]. When participants held a 10% MVC, reflex amplitudes did not change during 5-Hz stimulation. During stimulation at 10 Hz, reflexes were initially depressed by 43% but recovered completely by the end of the stimulation period. During 20-Hz stimulation, reflexes were depressed to 10% and recovered to 36% of the first response, respectively. This “postactivation depression and recovery” (PAD&R) of reflex amplitude was not different between sitting and standing. In contrast, PAD&R were strongly influenced by contraction amplitude. Reflexes were depressed to 10% of the first response during the relaxed condition (10-Hz stimulation) and showed no depression during a 20% MVC contraction. A partial recovery of reflex amplitude occurred when participants were relaxed and during contractions of 1–5% MVC. Surprisingly, reflexes could recover completely by the third pulse within a stimulation train when participants held a contraction between 5 and 10% MVC during stimulation at 10 Hz, a finding that challenges classical ideas regarding PAD mechanisms. Our results support the idea that there is an ongoing interplay between depression and facilitation when motoneurons receive trains of afferent input. This interplay depends strongly on the frequency of the afferent input and the magnitude of the background contraction but is relatively insensitive to changes in task.
FoxM1 in Tumorigenicity of the Neuroblastoma Cells and Renewal of the Neural Progenitors
Authors: Wang Zebin , Park Hyun Jung , Carr Janai R. , Chen Yi-ju , Zheng Yu , li Jing , Tyner Angela L. , Costa Robert H. , Bagchi Srilata , Raychaudhuri Pradip
Published: April 2011

Malignant neuroblastomas contain stem-like cells. These tumors also overexpress the Forkhead box transcription factor FoxM1. In this study, we investigated the roles of FoxM1 in the tumorigenicity of neuroblastoma. We showed that depletion of FoxM1 inhibits anchorage-independent growth and tumorigenicity in mouse xenografts. Moreover, knockdown of FoxM1 induces differentiation in neuroblastoma cells, suggesting that FoxM1 plays a role in the maintenance of the undifferentiated progenitor population. We showed that inhibition of FoxM1 in malignant neuroblastoma cells leads to the downregulation of the pluripotency genes sex determining region Y box 2 (Sox2) and Bmi1. We provided evidence that FoxM1 directly activates expression of Sox2 in neuroblastoma cells. By using a conditional deletion system and neurosphere cultures, we showed that FoxM1 is important for expression of Sox2 and Bmi1 in the mouse neural stem/progenitor cells and is critical for its self-renewal. Together, our observations suggested that FoxM1 plays an important role in the tumorigenicity of the aggressive neuroblastoma cells through maintenance of the undifferentiated state. Cancer Res; 71(12); 4292–302. ©2011 AACR.
Characterization of Eu- and Heterochromatin of Citrus with a Focus on the Condensation Behavior of 45S rDNA Chromatin
Authors: Marques A. , Fuchs J. , Ma L. , Heckmann S. , Guerra M. , Houben A.
Published: April 2011

To characterize the properties of eu- and heterochromatic regions in Citrus species, the chromosomal distribution of different histone H3 marks, DNA methylation sites (5mC) and 45S ribosomal DNA sites were determined for C. clementina, C. paradisi, C. sinensis, and for the hybrid Ortanique C. reticulata × C. sinensis. Our data show that in the relatively small genomes of investigated Citrus species (genome size ranges from 378–400 Mbp) the euchromatin is characterized by histone H3 lysine 4 mono-, di- and trimethylation (H3K4me1/ 2/3) and histone H3 lysine 9 trimethylation (H3K9me3). In contrast, histone H3 lysine 9 mono- and dimethylation (H3K9me1/2), histone H3 lysine 27 mono-, di- and trimethylation (H3K27me1/2/3) as well as 5-methylcytosine (5mC) were enriched at certain heterochromatin fractions. Whereas H3K9me1/2 and H3K27me1 were preferentially enriched at the chromomycin A3-bright (CMA+) heterochromatin, H3K27me2/3 showed a higher accumulation at the DAPI brightly-stained heterochromatin. 5mC signals were associated with most of the CMA+ areas as well as with the DAPI strongly-stained heterochromatin fraction. Therefore, extensive methylation of DNA as well as of H3K9me1/2 and H3K27me1/2/3, and depletion of H3K4me1/2/3 and H3K9me3 appear to be specific features of heterochromatin in Citrus. Transcriptionally active decondensed 45S rDNA sites were found DNA hypomethylated, while the silenced condensed sites were strongly 5mC methylated. Although the number of chromosomal 45S rDNA sites differed between the species, the number of transcriptionally active rDNA sites remains constant.
The Interdependence of Tonal and Durational Cues in the Perception of Rhythmic Groups
Authors: Cumming Ruth E.
Published: April 2011

This experiment investigated whether rising fundamental frequency (f0) and increased duration are interdependent perceptual cues to rhythmic groups in speech, and whether this depends on listeners’ native language. In a twoalternative forced- choice decision task, listeners had to indicate whether they perceived a 3 + 2 or 2 + 3 grouping in 5- syllable- long series of various digits and letters, in which f0 and duration were manipulated in the second and/or third syllable. The listeners were native speakers of Swiss German, Swiss French, or French. These languages differ from each other in terms of prosodic properties involving f0 and duration. The results demonstrate that rising f0 and increased duration are interdependent cues to rhythmic groups, since the two cues were significantly more effective than one when heard simultaneously, but significantly less effective than one when heard in conflicting positions around the rhythmic- group boundary location. Moreover, listeners’ native language influenced whether f0 or duration was the more effective cue. These findings are important not only for their insight into the perception of prosodic groups in speech, but also because they have implications for current research on speech rhythm.
Chromosome Painting in Two Genera of South American Monkeys: Species Identification, Conservation, and Management
Authors: Stanyon R. , Garofalo F. , Steinberg E.R. , Capozzi O. , Di Marco S. , Nieves M. , Archidiacono N. , Mudry M.D.
Published: April 2011

Cytogenetic studies showed that a number of New World primate taxa, particularly the genera Alouatta, Aotus, and Callicebus, have highly derived karyotypes. Cytogenetics in these primates, at every level of analysis, has contributed to the recognition of species and revealed that their number was certainly underestimated by researchers relying solely on traditional morphological data. Further attention was drawn to Alouatta and Aotus because they are characterized by translocations of the Y chromosome to autosomes, generating multiple sex chromosome systems. Here we present a report on the hybridization of human chromosome-specific paints on metaphases from 4 individuals originally assigned to Alouatta caraya and 1 individual of Aotuslemurinus. This is only the third karyotype studied with chromosome painting out of more than 10 known karyomorphs in Aotus. The banded chromosomes matched those of karyotype II as defined by Ma et al. [1976a], and we were able to more precisely assign the origin of the sample to A. l. griseimembra. Our results on the Argentinean Alouatta caraya samples were generally comparable to the banding and hybridization pattern of previous studies of A. caraya including the presence of an X1X1X2X2/X1X2Y1Y2 sex chromosome system. The karyotype of the Brazilian Alouatta sample labeled as A. caraya differs from the 3 Argentinean samples by at least 10 chromosome rearrangements. The diploid number, G banding, and hybridization pattern of this female cell line was almost identical to previous painting results on Alouatta guariba guariba. Therefore we must conclude that this cell line is actually from an A. guariba guariba individual. The contribution of cytogenetic tools in identifying species or in this case assigning individuals or cell lines to their precise taxonomic allocation is stressed. Gathering further molecular cytogenetic data on New World primates should be conservation and management priorities.
Netrin-1 Overexpression in Oxygen-Induced Retinopathy Correlates with Breakdown of the Blood-Retina Barrier and Retinal Neovascularization
Authors: Tian Xiao-Feng , Xia Xiao-Bo , Xiong Si-Qi , Jiang Jian , Liu Dan , Liu Jiao-Lian
Published: April 2011

Purposes: Recent research has shown netrin-1 to promote neovascularization. We evaluate the expression of netrin-1 during retinal neovascularization in a murine model of oxygen-induced retinopathy. Methods: C57BL/6J mice were exposed to 75 ± 5% oxygen for 5 days and returned to room air to induce retinal neovascularization. Retinal neovascularization was observed by fluorescence angiography and was quantified by counting the endothelial nuclei protruding into the vitreous cavity after hematoxylin-eosin staining. RT-PCR and Western blot analyses were used to determine retinal netrin-1 mRNA and protein levels at postnatal days (PN) 13, 15 and 17. Results: In fluorescence angiograms, irregular neovascularization and fluorescein leakage were observed surrounding the unperfused areas in the hypoxic group. The hypoxic group had, on average, 50.70 ± 4.56 neovascular nuclei protruding into the vitreous body, while similar nuclei were absent in the control group. Compared to the normoxic group, there were significant increases in both retinal netrin-1 mRNA and protein levels in the hypoxic group at PN13, PN15 and PN17. Conclusion: The netrin-1 level increases in murine retina under hypoxia and may be key in inducing retinal neovascularization.
Conserved although Very Different Karyotypes in Gliridae and Sciuridae and Their Contribution to Chromosomal Signatures in Glires
Authors: Sannier J. , Gerbault-Seureau M. , Dutrillaux B. , Richard F.A.
Published: April 2011

Rodents represent the largest order of living mammals. It comprises 5 sub-orders, among which Sciuromorpha (Sciuridae, Gliridae and Aplodontiidae) are assumed to occupy a basal position in rodent evolution. Banded karyotypes of some representatives of the Sciuridae family have been compared to each other, and comparisons with man were performed using chromosome paintings. Sciuridae karyotypes have conserved several eutherian ancestral syntenies. Like Sciuridae, Gliridae possess some chromosomes easily comparable with those of Primates. Comparisons of Gliridae and Sciuridae chromosomes with those of the presumed eutherian ancestor provide information about their chromosomal evolution and their position among Rodentia. Although both Sciuridae and Gliridae karyotypes are relatively conserved, they display many differences, indicating their early divergence. The reconstruction of their chromosomal evolution allowed us to propose the composition of their presumed ancestral karyotypes, with 2n = 48 and 2n = 38 for Gliridae and Sciuridae, respectively. Since rodent emergence, a single rearrangement is common to these 2 families. It formed a chromosome with fragments homologous to human chromosomes 4-8p-4-12-22, not detected in other rodents, and thus characteristic for the Sciuromorpha. This allowed us to reassess the chromosomal signatures of Rodentia. Finally, we show that the speed of chromosomal evolution in Gliridae is intermediate between that of Sciuridae (low) and Muridae (high).
Status of the Cattle Genome Map
Authors: Larkin D.M.
Published: April 2011

During the last 30 years, the cattle genome map has been expanded from 4 genes linked on chromosome X to over 22,000 genes identified in the cattle genome sequence assembly. This progress has been achieved due to numerous projects on linkage and physical mapping of the cattle genome driven by its agricultural and scientific significance. Indeed, the high-resolution mapping and functional analysis of the genome led to the discovery of major quantitative trait loci (QTL) regions and several quantitative trait nucleotides (QTNs), as well as some disease genes in the cow population. In addition, a comparison of the cattle genome to the genomes of other mammals has revealed its unique features gained during the speciation and adaptation. With the development of non-expensive sequencing techniques, the analysis of the cattle genome will shift towards the identification of differences between breeds or individuals within breeds that account for the unique features of each breed. This approach holds promise for the development of effective tools for the marker assistant selection and disease diagnostics in cattle.
Noninvasive Evaluation of Retinal Leakage Using Optical Coherence Tomography
Authors: Bernardes Rui , Santos Torcato , Serranho Pedro , Lobo Conceição , Cunha-Vaz José
Published: April 2011

Purpose: To demonstrate the association between changes in the blood-retinal barrier (BRB) identified by fluorescein leakage and those in the optical properties of the human retina determined by optical coherence tomography (OCT) and show how these changes can be quantified and their location identified within the retina. Methods: Two imaging techniques were applied: the retinal leakage analyzer, to map BRB function into intact or disrupted regions, and OCT, to measure refractive index changes along the light path within the human ocular fundus. Results: A total of 140 comparisons were made, 77 between areas of regions receiving the same classification (intact or disrupted BRB) and 63 between areas of regions receiving distinct classifications, from 4 pathological cases: 2 eyes with nonproliferative diabetic retinopathy and 2 eyes with wet age-related macular degeneration. In all cases, the distribution of OCT data between regions of intact and regions of disrupted BRB, identified by the retinal leakage analyzer, was quantified and was statistically significantly different (p < 0.001). In addition, it was found that the differences could be localized in the retina to specific structural sequences. Conclusions: Using a novel method to analyze OCT data, we showed that it may be possible to quantify differences in the extracellular compartment in eyes with retinal disease and alterations of the BRB. Based on quantitative techniques, our findings demonstrate the presence of indirect information on the BRB status within noninvasive OCT data.
Association of Apolipoprotein J Polymorphism 1598delT with Coronary Artery Disease and Lipoprotein Levels
Authors: Pan Ju-Pin , Wei Shu-Liang Peter , Chiang Shu-Chiung , Lee-Chen Guey-Jen
Published: April 2011

Objectives: To investigate a polymorphism of the apolipoprotein J (APOJ) gene in relation to coronary artery disease (CAD) and lipid variables in a Chinese male population of genetically unrelated individuals. Methods: In this study, we recruited 126 control male subjects and 237 CAD male patients. CAD was defined as a fixed stenotic lesion with luminal narrowing ≧50% in at least one of the major or minor coronary arteries. In cases with documented myocardial infarction, only those rated as fully recovered for more than 3 months were enrolled. Patients with acute or chronic infectious diseases and those with malignancies were excluded. All subjects with a fasting serum triglyceride level higher than 300 mg/dl were likewise excluded. Results: We identified a single nucleotide polymorphism, 1598delT, and showed its association with CAD. Subjects with the I/I genotype showed a significantly higher CAD risk compared to those with the D/D genotype (OR 2.34, 95% CI 1.11–4.94, p = 0.026). Patients with the I/I genotype also had abnormal levels of high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol associated with CAD. Conclusions: Our data indicated that the APOJ single nucleotide polymorphism (1598delT) is associated with risk factors for CAD in a Chinese population.
Is There a Specific Pattern of Attention Deficit in Mild Cognitive Impairment with Subcortical Vascular Features? Evidence from the Attention Network Test
Authors: Fernández Pedro J. , Campoy Guillermo , García Santos Jose M. , Antequera Martirio M. , García-Sevilla Julia , Castillo Alejandro , Antúnez Carmen , Fuentes Luis J.
Published: April 2011

Background: Mild cognitive impairment (MCI) is an intermediate state between normal aging and early dementia. Some MCI patients show white matter hyperintensities in magnetic resonance imaging, revealing subcortical vascular damage (SVD). This study aimed to evaluate potential attention deficits not previously described in these patients. Specifically, we evaluated attention network functioning in MCI on the basis of Posner’s cognitive neuroscience model, which considers attention as a set of networks: alerting, orienting and executive control. Methods: Three groups of participants were tested: 19 MCI patients with SVD (svMCI), 15 MCI patients free from SVD (nvMCI) and 19 healthy controls (HC). We used a task in which the three attention networks and their interactions can be assessed simultaneously, the Attention Network Test (ANT). Results: The svMCI group showed smaller orienting effect compared with the nvMCI and HC groups. In contrast to the HC and nvMCI groups, svMCI patients did not show improvement in the executive network from the valid visual cue. Conclusions: svMCI patients show a deficit in orienting attention networks. This deficit could be related to an effect of SVD on the cholinergic system because acetylcholine is implicated in the modulation of covert orienting responses of attention.
Multidimensional Assessment of Awareness in Early-Stage Dementia: A Cluster Analytic Approach
Authors: Clare Linda , Whitaker Christopher J. , Nelis Sharon M. , Martyr Anthony , Markova Ivana S. , Roth Ilona , Woods Robert T. , Morris Robin G.
Published: April 2011

Background/Aims: Research on awareness in dementia has yielded variable and inconsistent associations between awareness and other factors. This study examined awareness using a multidimensional approach and applied cluster analytic techniques to identify associations between the level of awareness and other variables. Methods: Participants were 101 individuals with early-stage dementia (PwD) and their carers. Explicit awareness was assessed at 3 levels: performance monitoring in relation to memory, evaluative judgement in relation to memory, everyday activities and socio-emotional functioning, and metacognitive reflection in relation to the experience and impact of the condition. Implicit awareness was assessed with an emotional Stroop task. Results: Different measures of explicit awareness scores were related only to a limited extent. Cluster analysis yielded 3 groups with differing degrees of explicit awareness. These groups showed no differences in implicit awareness. Lower explicit awareness was associated with greater age, lower MMSE scores, poorer recall and naming scores, lower anxiety and greater carer stress. Conclusion: Multidimensional assessment offers a more robust approach to classifying PwD according to level of awareness and hence to examining correlates and predictors of awareness.
Acute Kidney Injury following Cardiac Surgery: Role of Perioperative Blood Pressure Control
Authors: Weir Matthew R. , Aronson Solomon , Avery Edwin G. , Pollack, Jr. Charles V.
Published: April 2011

Background/Aims: Patients who develop acute kidney injury (AKI) after cardiac surgery continue to have a high mortality rate. Although factors that predispose to postoperative renal dysfunction have been identified, this knowledge has not been associated with a substantial reduction in the incidence of this serious adverse event. Methods: This review uses the existing literature to explore the relationship between AKI and perioperative blood pressure (BP) control in cardiac surgery patients. The results of recent novel analyses are introduced, and the implications of these studies for the management of cardiac surgery patients in the perioperative period are discussed. Results: Preexisting isolated systolic hypertension and wide pulse pressure increase the risk of postoperative renal dysfunction in the cardiac surgery population. New data suggest that BP lability (i.e., BP excursions outside an acceptable physiologic range) during cardiac surgery may also be an important predictor of subsequent renal dysfunction. Conclusion: Recently published data suggest that perioperative BP lability influences both the risk of postoperative renal dysfunction and 30-day mortality. Future studies will determine whether the use of agents that allow improved BP control within a desirable range will reduce the incidence of postoperative AKI in cardiac surgery patients.