bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxia promotes dissemination of multiple myeloma through acquisition of epithelial to mesenchymal transition-like features
Authors: Azab Abdel Kareem , Hu Jinsong , Quang Phong , Azab Feda , Pitsillides Costas , Awwad Rana , Thompson Brian , Maiso Patricia , Sun Jessica D. , Hart Charles P. , Roccaro Aldo M. , Sacco Antonio , Ngo Hai T. , Lin Charles P. , Kung Andrew L. , Carrasco Ruben D. , Vanderkerken Karin , Ghobrial Irene M.
Published: March 2012

The spread of multiple myeloma (MM) involves (re)circulation into the peripheral blood and (re)entrance or homing of MM cells into new sites of the BM. Hypoxia in solid tumors was shown to promote metastasis through activation of proteins involved in the epithelial-mesenchymal transition (EMT) process. We hypothesized that MM-associated hypoxic conditions activate EMT-related proteins and promote metastasis of MM cells. In the present study, we have shown that hypoxia activates EMT-related machinery in MM cells, decreases the expression of E-cadherin, and, consequently, decreases the adhesion of MM cells to the BM and enhances egress of MM cells to the circulation. In parallel, hypoxia increased the expression of CXCR4, consequently increasing the migration and homing of circulating MM cells to new BM niches. Further studies to manipulate hypoxia to regulate tumor dissemination as a therapeutic strategy are warranted.
Approximate Euler-Lagrange quadratic mappings
Authors: Kim Hark-Mahn , Lee Juri , Son Eunyoung
Published: March 2012

For any fixed integer k with k ≠ 0, 1, we prove the Hyers-Ulam stability of an Euler-Lagrange-type quadratic functional equation

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+
k
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in normed spaces and in non-Archimedean normed spaces.
Association analysis of photoperiodic flowering time genes in west and central African sorghum [Sorghum bicolor (L.) Moench]
Authors: Bhosale Sankalp U , Stich Benjamin , Rattunde H Frederick W , Weltzien Eva , Haussmann Bettina IG , Hash C Thomas , Ramu Punna , Cuevas Hugo E , Paterson Andrew H , Melchinger Albrecht E , Parzies Heiko K
Published: March 2012

Background

Photoperiod-sensitive flowering is a key adaptive trait for sorghum (Sorghum bicolor) in West and Central Africa. In this study we performed an association analysis to investigate the effect of polymorphisms within the genes putatively related to variation in flowering time on photoperiod-sensitive flowering in sorghum. For this purpose a genetically characterized panel of 219 sorghum accessions from West and Central Africa was evaluated for their photoperiod response index (PRI) based on two sowing dates under field conditions.

Results

Sorghum accessions used in our study were genotyped for single nucleotide polymorphisms (SNPs) in six genes putatively involved in the photoperiodic control of flowering time. Applying a mixed model approach and previously-determined population structure parameters to these candidate genes, we found significant associations between several SNPs with PRI for the genesCRYPTOCHROME 1(CRY1-b1) andGIGANTEA(GI).

Conclusions

The negative values of Tajima's D, found for the genes of our study, suggested that purifying selection has acted on genes involved in photoperiodic control of flowering time in sorghum. The SNP markers of our study that showed significant associations with PRI can be used to create functional markers to serve as important tools for marker-assisted selection of photoperiod-sensitive cultivars in sorghum.
Ezrin phosphorylation on tyrosine 477 regulates invasion and metastasis of breast cancer cells
Authors: Mak Hannah , Naba Alexandra , Varma Sonal , Schick Colleen , Day Andrew , SenGupta Sandip K , Arpin Monique , Elliott Bruce E
Published: March 2012

Background

The membrane cytoskeletal crosslinker, ezrin, a member of the ERM family of proteins, is frequently over-expressed in human breast cancers, and is required for motility and invasion of epithelial cells. Our group previously showed that ezrin acts co-operatively with the non-receptor tyrosine kinase, Src, in deregulation of cell-cell contacts and scattering of epithelial cells. In particular, ezrin phosphorylation on Y477 by Src is specific to ezrin within the ERM family, and is required for HGF-induced scattering of epithelial cells. We therefore sought to examine the role of Y477 phosphorylation in ezrin on tumor progression.

Methods

Using a highly metastatic mouse mammary carcinoma cell line (AC2M2), we tested the effect of over-expressing a non-phosphorylatable form of ezrin (Y477F) on invasive colony growth in 3-dimensional Matrigel cultures, and on local invasion and metastasis in an orthotopic engraftment model.

Results

AC2M2 cells over-expressing Y477F ezrin exhibited delayed migration in vitro, and cohesive round colonies in 3-dimensional Matrigel cultures, compared to control cells that formed invasive colonies with branching chains of cells and numerous actin-rich protrusions. Moreover, over-expression of Y477F ezrin inhibits local tumor invasion in vivo. Whereas orthotopically injected wild type AC2M2 tumor cells were found to infiltrate into the abdominal wall and visceral organs within three weeks, tumors expressing Y477F ezrin remained circumscribed, with little invasion into the surrounding stroma and abdominal wall. Additionally, Y477F ezrin reduces the number of lung metastatic lesions.

Conclusions

Our study implicates a role of Y477 ezrin, which is phosphorylated by Src, in regulating local invasion and metastasis of breast carcinoma cells, and provides a clinically relevant model for assessing the Src/ezrin pathway as a potential prognostic/predictive marker or treatment target for invasive human breast cancer.
Chewing areca nut increases the risk of coronary artery disease in taiwanese men: a case-control study
Authors: Tsai Wei-Chung , Wu Ming-Tsang , Wang Guei-Jane , Lee Kun-Tai , Lee Chien-Hung , Lu Ye-Hsu , Yen Hsueh-Wei , Chu Chih-Sheng , Chen Yi-Ting , Lin Tsung-Hsien , Su Ho-Ming , Hsu Po-Chao , Cheng Kai-Hung , Duh Tsai-Hui , Ko Ying-Chin , Sheu Sheng-Hsiung , Lai Wen-Ter
Published: March 2012

Background

Areca nut chewing has been reported to be associated with obesity, metabolic syndrome, hypertension, and cardiovascular mortality in previous studies. The aim of this study was to examine whether chewing areca nut increases the risk of coronary artery disease (CAD) in Taiwanese men.

Methods

This study is a hospital-based case-control study. The case patients were male patients diagnosed in Taiwan between 1996 and 2009 as having a positive Treadmill exercise test or a positive finding on the Thallium-201 single-photon emission computed tomography myocardial perfusion imaging. The case patients were further evaluated by coronary angiography to confirm their CAD. Obstructive CAD was defined as a ≥ 50% decrease in the luminal diameter of one major coronary artery. The patients who did not fulfill the above criteria of obstructive CAD were excluded.

The potential controls were males who visited the same hospital for health check-ups and had a normal electrocardiogram but no history of ischemic heart disease or CAD during the time period that the case patients were diagnosed. The eligible controls were randomly selected and frequency-matched with the case patients based on age. Multiple logistic regression analyses were used to estimate the odds ratio of areca nut chewing and the risk of obstructive CAD.

Results

A total of 293 obstructive CAD patients and 720 healthy controls, all men, were analyzed. Subjects who chewed areca nut had a 3.5-fold increased risk (95% CI = 2.0-6.2) of having obstructive CAD than those without, after adjusting for other significant covariates. The dose-response relationship of chewing areca nut and the risk of obstructive CAD was also noted. After adjusting for other covariates, the 2-way additive interactions for obstructive CAD risk were also significant between areca nut use and cigarette smoking, hypertension and dyslipidemia.

Conclusions

Long-term areca nut chewing was an independent risk factor of obstructive CAD in Taiwanese men. Interactive effects between chewing areca nut and cigarette smoking, hypertension, and dyslipidemia were also observed for CAD risk. Further exploration of their underlying mechanisms is necessary.
Hyperinsulinemia correlates with low levels of plasma B-type natriuretic peptide in Japanese men irrespective of fat distribution
Authors: Nakatsuji Hideaki , Kishida Ken , Funahashi Tohru , Nakagawa Tohru , Shimomura Iichiro
Published: March 2012

Background

B-type natriuretic peptide (BNP), a member of the natriuretic peptide family, is a cardiac-derived secretory hormone with natriuretic, diuretic, and vasorelaxant activities. Intraabdominal fat accumulation is associated with atherosclerotic cardiovascular diseases and cardiac dysfunction. Circulating BNP levels are relatively low (within the normal limits) in obesity and the metabolic syndrome. However, the relationship between plasma BNP levels and visceral fat accumulation in general population has not been reported. The present study analyzed the relationships between plasma BNP levels and various clinical variables, including insulin, visceral and subcutaneous fat area (VFA and SFA, respectively), in normal Japanese men.

Methods

The study (Victor-J study) subjects were consecutive 500 Japanese male workers, who underwent a health checkup and were measured VFA and SFA by computed tomography.

Results

Age-adjusted simple linear regression analysis showed that log-BNP correlated positively with HDL-cholesterol, and negatively with VFA, log-immunoreactive insulin (IRI), log-triglyceride, and LDL-cholesterol, but not body mass index or SFA. Stepwise multiple regression analysis identified log-IRI and HDL-cholesterol as significant determinants of log-BNP. Subjects with IRI ≥5.5 μIU/mL had lower plasma BNP levels than those with IRI < 5.5 μIU/mL, irrespective of obesity (body mass index, cutoff value 25 kg/m2), visceral fat accumulation (VFA, cutoff value 100 cm2) and subcutaneous fat accumulation (SFA, cutoff value 128 cm2).

Conclusions

Our study showed that hyperinsulinemia correlated with low levels of plasma BNP in general men, irrespective of fat distribution.

Trial registration

UMIN 000004318.
Magnetic nanoparticle density mapping from the magnetically induced displacement data: a simulation study
Authors: Hossain ABM Aowlad , Cho MH , Lee SY
Published: March 2012

Background

Magnetic nanoparticles are gaining great roles in biomedical applications as targeted drug delivery agents or targeted imaging contrast agents. In the magnetic nanoparticle applications, quantification of the nanoparticle density deposited in a specified region is of great importance for evaluating the delivery of the drugs or the contrast agents to the targeted tissues. We introduce a method for estimating the nanoparticle density from the displacement of tissues caused by the external magnetic field.

Methods

We can exert magnetic force to the magnetic nanoparticles residing in a living subject by applying magnetic gradient field to them. The nanoparticles under the external magnetic field then exert force to the nearby tissues causing displacement of the tissues. The displacement field induced by the nanoparticles under the external magnetic field is governed by the Navier's equation. We use an approximation method to get the inverse solution of the Navier's equation which represents the magnetic nanoparticle density map when the magnetic nanoparticles are mechanically coupled with the surrounding tissues. To produce the external magnetic field inside a living subject, we propose a coil configuration, the Helmholtz and Maxwell coil pair, that is capable of generating uniform magnetic gradient field. We have estimated the coil currents that can induce measurable displacement in soft tissues through finite element method (FEM) analysis.

Results

From the displacement data obtained from FEM analysis of a soft-tissue-mimicking phantom, we have calculated nanoparticle density maps. We obtained the magnetic nanoparticle density maps by approximating the Navier's equation to the Laplacian of the displacement field. The calculated density maps match well to the original density maps, but with some halo artifacts around the high density area. To induce measurable displacement in the living tissues with the proposed coil configuration, we need to apply the coil currents as big as 104A.

Conclusions

We can obtain magnetic nanoparticle maps from the magnetically induced displacement data by approximating the Navier's equation under the assumption of uniform-gradient of the external magnetic field. However, developing a coil driving system with the capacity of up to 104A should be a great technical challenge.
Preliminary clinical study of left ventricular myocardial strain in patients with non-ischemic dilated cardiomyopathy by three-dimensional speckle tracking imaging
Authors: Duan Fengxia , Xie Mingxing , Wang Xinfang , Li Yuman , He Lin , Jiang Lan , Fu Qian
Published: March 2012

Background

Non-ischemic dilated cardiomyopathy (DCM) is the most common cardiomyopathy worldwide, with significant mortality. Correct evaluation of the patient's myocardial function has important clinical significance in the diagnosis, therapeutic effect assessment and prognosis in non-ischemic DCM patients. This study evaluated the feasibility of three-dimensional speckle tracking imaging (3D-STE) for assessment of the left ventricular myocardial strain in patients with non-ischemic dilated cardiomyopathy (DCM).

Methods

Apical full-volume images were acquired from 65 patients with non-ischemic DCM (DCM group) and 59 age-matched normal controls (NC group), respectively. The following parameters were measured by 3D-STE: the peak systolic radial strain (RS), circumferential strain (CS), longitudinal strain (LS) of each segment. Then all the parameters were compared between the two groups.

Results

The peak systolic strain in different planes had certain regularities in normal groups, radial strain (RS) was the largest in the mid region, the smallest in the apical region, while circumferential strain (CS) and longitudinal strain (LS) increased from the basal to the apical region. In contrast, the regularity could not be applied to the DCM group. RS, CS, LS were significantly decreased in DCM group as compared with NC group (P < 0.001 for all). The interobserver, intraobserver and test-retest reliability were acceptable.

Conclusions

3D-STE is a reliable tool for evaluation of left ventricular myocardial strain in patients with non-ischemic DCM, with huge advantage in clinical application.
Prostaglandin-induced cervical remodelling in humans in the first trimester is associated with increased expression of specific tight junction, but not gap junction proteins
Authors: Ghulé Vidita V , Gray Colin , Galimberti Andrea , Anumba Dilly OC
Published: March 2012

Background

Prostaglandins (PG) are widely employed to induce cervical remodelling (CR) in pregnancy. However, the underlying molecular mechanisms are not fully elucidated. Tight junctions (TJ) and gap junctions (GJ) regulate paracellular and intercellular solute transport respectively but their role in the process of CR remains unexplored. We hypothesized that the synthetic prostaglandin E1 analogue Misoprostol (M), widely used in clinical practice to induce CR, may alter TJ and GJ expression as part of the changes in the extracellular matrix (ECM) associated with remodelling. We investigated the effects of Misoprostol exposure on the expression of cervical TJ (claudins 1, 2, 4, 5, 7 and occludin) and GJ (connexins 43, 30 and 26) in the 1st trimester.

Methods

Cervical biopsies were obtained from pregnant women and comparisons of TJ and GJ protein expression (by western blotting) and immunolocalisation (laser scanning confocal microscopy) made between those who were administered vaginal Misoprostol (n = 10) and those who were not (n = 5).

Results

We found that Misoprostol-treated tissue (M+) had higher expression of Claudins 1,2,4,7 and occludin (p < 0.05) than untreated (M-) tissue. Expression levels of Claudins 1, 2 and 4 were positively correlated to interval from Misoprostol treatment to biopsy, whilst occludin was negatively correlated. Misoprostol-treated cervical tissue demonstrated more endothelial claudin-5 and occludin, whilst expression of GJs were unchanged.

Conclusion

Our observations suggest, for the first time, that increased expression of tight junction proteins may be one of the mechanisms by which Misoprostol induces CR in humans. Further studies are needed to explore if TJ proteins may be therapeutic targets to alter timing of CR in clinical practice.
Who fans the flames of Alzheimer's disease brains? Misfolded tau on the crossroad of neurodegenerative and inflammatory pathways
Authors: Zilka Norbert , Kazmerova Zuzana , Jadhav Santosh , Neradil Peter , Madari Aladar , Obetkova Dominika , Bugos Ondrej , Novak Michal
Published: March 2012

Neurodegeneration, induced by misfolded tau protein, and neuroinflammation, driven by glial cells, represent the salient features of Alzheimer's disease (AD) and related human tauopathies. While tau neurodegeneration significantly correlates with disease progression, brain inflammation seems to be an important factor in regulating the resistance or susceptibility to AD neurodegeneration. Previously, it has been shown that there is a reciprocal relationship between the local inflammatory response and neurofibrillary lesions. Numerous independent studies have reported that inflammatory responses may contribute to the development of tau pathology and thus accelerate the course of disease. It has been shown that various cytokines can significantly affect the functional and structural properties of intracellular tau. Notwithstanding, anti-inflammatory approaches have not unequivocally demonstrated that inhibition of the brain immune response can lead to reduction of neurofibrillary lesions. On the other hand, our recent data show that misfolded tau could represent a trigger for microglial activation, suggesting the dual role of misfolded tau in the Alzheimer's disease inflammatory cascade. On the basis of current knowledge, we can conclude that misfolded tau is located at the crossroad of the neurodegenerative and neuroinflammatory pathways. Thus disease-modified tau represents an important target for potential therapeutic strategies for patients with Alzheimer's disease.
MR-Radix: a multi-relational data mining algorithm
Authors: Valêncio Carlos Roberto , Oyama Fernando Takeshi , Scarpelini Neto Paulo , Colombini Angelo Cesar , Cansian Adriano Mauro , de Souza Rogéria Cristiane Gratão , Corrêa Pedro Luiz Pizzigatti
Published: March 2012

Background

Once multi-relational approach has emerged as an alternative for analyzing structured data such as relational databases, since they allow applying data mining in multiple tables directly, thus avoiding expensive joining operations and semantic losses, this work proposes an algorithm with multi-relational approach.

Methods

Aiming to compare traditional approach performance and multi-relational for mining association rules, this paper discusses an empirical study between PatriciaMine - an traditional algorithm - and its corresponding multi-relational proposed, MR-Radix.

Results

This work showed advantages of the multi-relational approach in performance over several tables, which avoids the high cost for joining operations from multiple tables and semantic losses. The performance provided by the algorithm MR-Radix shows faster than PatriciaMine, despite handling complex multi-relational patterns. The utilized memory indicates a more conservative growth curve for MR-Radix than PatriciaMine, which shows the increase in demand of frequent items in MR-Radix does not result in a significant growth of utilized memory like in PatriciaMine.

Conclusion

The comparative study between PatriciaMine and MR-Radix confirmed efficacy of the multi-relational approach in data mining process both in terms of execution time and in relation to memory usage. Besides that, the multi-relational proposed algorithm, unlike other algorithms of this approach, is efficient for use in large relational databases.
Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks
Authors: Newman Aaron M , Gallo Natasha B , Hancox Lisa S , Miller Norma J , Radeke Carolyn M , Maloney Michelle A , Cooper James B , Hageman Gregory S , Anderson Don H , Johnson Lincoln V , Radeke Monte J
Published: March 2012

Background

Age-related macular degeneration (AMD) is a leading cause of blindness that affects the central region of the retinal pigmented epithelium (RPE), choroid, and neural retina. Initially characterized by an accumulation of sub-RPE deposits, AMD leads to progressive retinal degeneration, and in advanced cases, irreversible vision loss. Although genetic analysis, animal models, and cell culture systems have yielded important insights into AMD, the molecular pathways underlying AMD's onset and progression remain poorly delineated. We sought to better understand the molecular underpinnings of this devastating disease by performing the first comparative transcriptome analysis of AMD and normal human donor eyes.

Methods

RPE-choroid and retina tissue samples were obtained from a common cohort of 31 normal, 26 AMD, and 11 potential pre-AMD human donor eyes. Transcriptome profiles were generated for macular and extramacular regions, and statistical and bioinformatic methods were employed to identify disease-associated gene signatures and functionally enriched protein association networks. Selected genes of high significance were validated using an independent donor cohort.

Results

We identified over 50 annotated genes enriched in cell-mediated immune responses that are globally over-expressed in RPE-choroid AMD phenotypes. Using a machine learning model and a second donor cohort, we show that the top 20 global genes are predictive of AMD clinical diagnosis. We also discovered functionally enriched gene sets in the RPE-choroid that delineate the advanced AMD phenotypes, neovascular AMD and geographic atrophy. Moreover, we identified a graded increase of transcript levels in the retina related to wound response, complement cascade, and neurogenesis that strongly correlates with decreased levels of phototransduction transcripts and increased AMD severity. Based on our findings, we assembled protein-protein interactomes that highlight functional networks likely to be involved in AMD pathogenesis.

Conclusions

We discovered new global biomarkers and gene expression signatures of AMD. These results are consistent with a model whereby cell-based inflammatory responses represent a central feature of AMD etiology, and depending on genetics, environment, or stochastic factors, may give rise to the advanced AMD phenotypes characterized by angiogenesis and/or cell death. Genes regulating these immunological activities, along with numerous other genes identified here, represent promising new targets for AMD-directed therapeutics and diagnostics.

Please see related commentary: http://www.biomedcentral.com/1741-7015/10/21/abstract
Ultrashallow depth imaging of a channel stratigraphy with first-arrival traveltime inversion and prestack depth migration: A case history from Bull Creek, Oklahoma
Authors: Fesseha Woldearegay Ammanuel , Jaiswal Priyank , Simms Alexander R. , Alexander Hanna , Bement Leland C. , Carter Brian J.
Published: March 2012

Depth imaging in ultrashallow ([Formula: see text]) environments presents twofold challenge: (1) coda available for depth migration is very limited; and (2) conventional time processing with limited coda generally fails to estimate reliable velocity models for depth migration. We studied the combining of first-arrival traveltime inversion and prestack depth migration (PSDM) for depth imaging of ultrashallow paleochannel stratigraphy associated with the Bull Creek drainage system, Oklahoma. Restricted by a limited number of geophones (24) we acquired data for inversion and migration through two coincident profiles. The first profile for inversion has a wider survey-aperture (115-m maximum shot-receiver spacing) and consequently sparse CMP spacing (2.5 m), whereas the second profile for PSDM has denser CMP spacing (1 m) and consequently a narrower survey aperture (46-m maximum shot-receiver spacing). We also found that the velocity model from traveltime inversion of the wider-aperture data set is more preferable for depth-migration than the velocity model from time processing of the denser data set. The preferred depth image showed three episodes of incision whose chronological order is resolved through radio-carbon dating of terrace sediments. Results suggested that even with limited geophones, depth imaging of ultrashallow targets can be achieved by combining first-arrival traveltime inversion and PSDM through coincident wide- and narrow-aperture acquisitions.
Nodal Signaling Regulates the Entry into Meiosis in Fetal Germ Cells
Authors: Souquet Benoit , Tourpin Sophie , Messiaen Sébastien , Moison Delphine , Habert René , Livera Gabriel
Published: March 2012

The mechanisms regulating the entry into meiosis in mammalian germ cells remain incompletely understood. We investigated the involvement of the TGF-β family members in fetal germ cell meiosis initiation. Nodal, a member of the TGF-β family, and its target genes are precociously expressed in embryonic gonads and show sexual dimorphism in favor of the developing testis. Nodal receptor genes, Acvr2a and Acvr2b, Alk4, and Tdgf1/Cripto, were identified in male germ cells. Nodal itself, Tdgf1, and Lefty1 and Lefty2 are targets of Nodal signaling and were all found specifically expressed in male germ cells. To elucidate the role of this signaling pathway, activin-like kinases that mediate TGF-β/Nodal/activin signaling were inhibited in 11.5 d postconception testis in organotypic culture. Activin-like kinases inhibition disrupted normal male germ cell development and induced germ cell entry into meiosis such as that observed in female germ cells at the equivalent stage. Interestingly Stra8, the gatekeeper of the mitotic/meiotic switch, was induced independently of any change of either Cyp26b1 or Fgf9 expression, the two genes currently identified as testicular meiotic inhibitors. On the other hand, recombinant Nodal significantly dampened Stra8 expression and germ cell meiosis in cultured 11.5 d postconception ovaries. Our results allowed us to propose for the first time an autocrine role of Nodal during the development of germ cells and indicate that members of the TGB-β family may reinforce the male fate and prevent meiosis in embryonic germ cells.
Ionotropic Glutamate Receptors in Hypothalamic Paraventricular and Supraoptic Nuclei Mediate Vasopressin and Oxytocin Release in Unanesthetized Rats
Authors: Busnardo Cristiane , Crestani Carlos C. , Resstel Leonardo B. M. , Tavares Rodrigo F. , Antunes-Rodrigues José , Corrêa Fernando M. A.
Published: March 2012

We report changes in plasma arginine vasopressin (AVP) and oxytocin (OT) concentrations evoked by the microinjection of l-glutamate (l-glu) into the hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN) of unanesthetized rats, as well as which local mechanisms are involved in their mediation. l-Glu microinjection (10 nmol/100 nl) into the SON increased the circulating levels of both AVP and OT. The AVP increases were blocked by local pretreatment with the selective non-N-methyl-d-aspartate (NMDA) receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) (2 nmol/100 nl), but it was not affected by pretreatment with the NMDA-receptor antagonist LY235959 (2 nmol/100 nl). The OT response to l-glu microinjection into the SON was blocked by local pretreatment with either NBQX or LY235959. Furthermore, the administration of either the non-NMDA receptor agonist (±)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA) (5 nmol/100 nl) or NMDA receptor agonist NMDA (5 nmol/100 nl) into the SON had no effect on OT baseline plasma levels, but when both agonists were microinjected together these levels were increased. l-Glu microinjection into the PVN did not change circulating levels of either AVP or OT. However, after local pretreatment with LY235959, the l-glu microinjection increased plasma levels of the hormones. The l-glu microinjection into the PVN after the local treatment with NBQX did not affect the circulating AVP and OT levels. Therefore, results suggest the AVP release from the SON is mediated by activation of non-NMDA glutamate receptors, whereas the OT release from this nucleus is mediated by an interaction of NMDA and non-NMDA receptors. The present study also suggests an inhibitory role for NMDA receptors in the PVN on the release of AVP and OT.
Wild-Type Tumor Repressor Protein 53 (TRP53) Promotes Ovarian Cancer Cell Survival
Authors: Mullany Lisa K. , Liu Zhilin , King Erin R. , Wong Kwong-Kwok , Richards JoAnne S.
Published: March 2012

Loss of Pten in the KrasG12D;Amhr2-Cre mutant mice leads to the transformation of ovarian surface epithelial (OSE) cells and rapid development of low-grade, invasive serous adenocarcinomas. Tumors occur with 100% penetrance and express elevated levels of wild-type tumor repressor protein 53 (TRP53). To test the functions of TRP53 in the Pten;Kras (Trp53+) mice, we disrupted the Trp53 gene yielding Pten;Kras(Trp53−) mice. By comparing morphology and gene expression profiles in the Trp53+ and Trp53− OSE cells from these mice, we document that wild-type TRP53 acts as a major promoter of OSE cell survival and differentiation: cells lacking Trp53 are transformed yet are less adherent, migratory, and invasive and exhibit a gene expression profile more like normal OSE cells. These results provide a new paradigm: wild-type TRP53 does not preferentially induce apoptotic or senescent related genes in the Pten;Kras(Trp53+) cancer cells but rather increases genes regulating DNA repair, cell cycle progression, and proliferation and decreases putative tumor suppressor genes. However, if TRP53 activity is forced higher by exposure to nutlin-3a (a mouse double minute-2 antagonist), TRP53 suppresses DNA repair genes and induces the expression of genes that control cell cycle arrest and apoptosis. Thus, in the Pten;Kras(Trp53+) mutant mouse OSE cells and likely in human TP53+ low-grade ovarian cancer cells, wild-type TRP53 controls global molecular changes that are dependent on its activation status. These results suggest that activation of TP53 may provide a promising new therapy for managing low-grade ovarian cancer and other cancers in humans in which wild-type TP53 is expressed.
Limited variation in visual sensitivity among bowerbird species suggests that there is no link between spectral tuning and variation in display colouration
Authors: Coyle Brian J. , Hart Nathan S. , Carleton Karen L. , Borgia Gerald
Published: March 2012

Variation in visual spectral tuning has evolved in concert with signal colour in some taxa, but there is limited evidence of this pattern in birds. To further investigate this possibility, we compared spectral sensitivity among bowerbird species that occupy different visual habitats and are highly diverged in plumage and decoration colour displays, which are important in mate choice and possibly reproductive isolation. Microspectrophotometry of violet-, short-, medium- and long-wavelength-sensitive cones revealed no significant interspecific variation in visual pigment peak spectral absorbance values that ranged between 404–410, 454, 503–511 and 558–568 nm, respectively. Mean cut-off wavelength values for C-, Y-, R- and P-type coloured oil droplets were 418–441, 508–523, 558–573 and 412–503 nm, respectively, with values at longer wavelengths in ventral compared with dorsal retina cones. Low ocular media mid-wavelength transmission values (340–352 nm) suggest that bowerbirds may represent a transitional stage in the evolution from the ancestral violet-sensitive- to the derived ultraviolet-sensitive-type short-wavelength-sensitive-1-based visual system found in younger passerine lineages. Sequence data obtained for rod opsin and four cone opsin genes were identical at key tuning sites, except for an interspecific leucine-52-alanine polymorphism in the short-wavelength-sensitive 2 opsin. There was no obvious relationship between relative proportions of cone classes and either visual habitat or display colour. Overall, we detected little interspecific variation in bowerbird spectral sensitivity and no association between sensitivity and display diversity, which is consistent with the general trend among avian taxa.
Structural characterisation of theN-glycan moiety of the barnacle settlement-inducing protein complex (SIPC)
Authors: Pagett Helen E. , Abrahams Jodie L. , Bones Jonathan , O’Donoghue Niaobh , Marles-Wright Jon , Lewis Richard J. , Harris J. Robin , Caldwell Gary S. , Rudd Pauline M. , Clare Anthony S.
Published: March 2012

Many barnacle species are gregarious and their cypris larvae display a remarkable ability to explore surfaces before committing to permanent attachment. The chemical cue to gregarious settlement behaviour – the settlement-inducing protein complex (SIPC) – is an α2-macroglobulin-like glycoprotein. This cuticular protein may also be involved in cyprid reversible adhesion if its presence is confirmed in footprints of adhesive deposited during exploratory behaviour, which increase the attractiveness of surfaces and signal other cyprids to settle. The full-length open-reading frame of the SIPC gene encodes a protein of 1547 amino acids with seven potential N-glycosylation sites. In this study on Balanus amphitrite, glycan profiling of the SIPC via hydrophilic interaction liquid chromatography with fluorescence detection (HILIC-fluorescence) provided evidence of predominantly high mannose glycans (M2–9), with the occurrence of monofucosylated oligomannose glycans (F(6)M2–4) in lower proportions. The high mannose glycosylation found supports previous observations of an interaction with mannose-binding lectins and exogenous mannose increasing settlement in B. amphitrite cypris larvae. Transmission electron microscopy of the deglycosylated SIPC revealed a multi-lobed globular protein with a diameter of ∼8 nm. Obtaining a complete structural characterisation of the SIPC remains a goal that has the potential to inspire solutions to the age-old problem of barnacle fouling.
Adaptation strategies to seasonal changes in environmental conditions of a domesticated horse breed, the Shetland pony (Equus ferus caballus)
Authors: Brinkmann Lea , Gerken Martina , Riek Alexander
Published: March 2012

Recent results suggest that the wild ancestor of the horse, the Przewalski horse, exhibits signs of a hypometabolism. However, there are speculations that domestic animals lost the ability to reduce energy expenditure during food shortage and adverse environmental conditions. Therefore, we investigated physiological and behavioural strategies employed by a robust domesticated horse breed, the Shetland pony, over the course of a year under temperate conditions by measuring ambient temperature (Ta), subcutaneous temperature (Ts), locomotor activity (LA), lying time, resting heart rate, body mass and body condition score. Ten animals were kept on pasture in summer and in open stables in winter; further, in winter the animals were allocated into one control and one feed-restricted group of five animals each to simulate natural seasonal food shortage. The annual course of the mean daily Ts of all horses showed distinct fluctuations from a mean of 35.6±0.5°C, with higher variations in summer than in winter. Diurnal amplitudes in Ts were highest (P<0.001) in April (12.6°C) and lowest in January (4.0°C), with a nadir around dawn and a peak around mid-day. The feed-restricted group had a significantly lower daily Ts compared with the control group on cold winter days, with Ta values below 0°C. Mean annual heart rate and LA followed Ta closely. Heart rate of the feed-restricted animals significantly decreased from a mean of 52.8±8.1 beats min–1 in summer to 29±3.9 beats min–1 in winter and differed from the control group (P<0.001). Mean daily LA was lowest at the end of winter (7000 activity impulses day–1) and highest in summer (25,000 activity impulses day–1). Our results show that Shetland ponies exhibit signs of a winter hypometabolism indicated by reduced heart rate and Ts. Thus, domesticated horses seem to have maintained the capacity for seasonal adaptation to environmental conditions by seasonal fluctuations in their metabolic rate.
Cutaneous water loss and covalently bound lipids of the stratum corneum in nestling house sparrows (Passer domesticus L.) from desert and mesic habitats
Authors: Clement Michelle E. , Muñoz-Garcia Agustí , Williams Joseph B.
Published: March 2012

Lipids of the stratum corneum (SC), the outer layer of the epidermis of birds and mammals, provide a barrier to water vapor diffusion through the skin. The SC of birds consists of flat dead cells, called corneocytes, and two lipid compartments: an intercellular matrix and a monolayer of covalently bound lipids (CBLs) attached to the outer surface of the corneocytes. We previously found two classes of sphingolipids, ceramides and cerebrosides, covalently bound to corneocytes in the SC of house sparrows (Passer domesticus L.); these lipids were associated with cutaneous water loss (CWL). In this study, we collected adult and nestling house sparrows from Ohio and nestlings from Saudi Arabia, acclimated them to either high or low humidity, and measured their rates of CWL. We also measured CWL for natural populations of nestlings from Ohio and Saudi Arabia, beginning when chicks were 2 days old until they fledged. We then evaluated the composition of the CBLs of the SC of sparrows using thin layer chromatography. We found that adult house sparrows had a greater diversity of CBLs in their SC than previously described. During ontogeny, nestling sparrows increased the amount of CBLs and developed their CBLs differently, depending on their habitat. Acclimating nestlings to different humidity regimes did not alter the ontogeny of the CBLs, suggesting that these lipids represent a fundamental component of SC organization that does not respond to short-term environmental change.
A buckling region in locust hindlegs contains resilin and absorbs energy when jumping or kicking goes wrong
Authors: Bayley T. G. , Sutton G. P. , Burrows M.
Published: March 2012

If a hindleg of a locust slips during jumping, or misses its target during kicking, energy generated by the two extensor tibiae muscles is no longer expended in raising the body or striking a target. How, then, is the energy in a jump (4100–4800 μJ) or kick (1700 μJ) dissipated? A specialised buckling region found in the proximal hind-tibia where the bending moment is high, but not present in the other legs, buckled and allowed the distal part of the tibia to extend. In jumps when a hindleg slipped, it bent by a mean of 23±14 deg at a velocity of 13.4±9.5 deg ms–1; in kicks that failed to contact a target it bent by 32±16 deg at a velocity of 32.9±9.5 deg ms–1. It also buckled 8.5±4.0 deg at a rate of 0.063±0.005 deg ms–1 when the tibia was prevented from flexing fully about the femur in preparation for both these movements. By experimentally buckling this region through 40 deg at velocities of 0.001–0.65 deg ms–1, we showed that one hindleg could store about 870 μJ on bending, of which 210 μJ was dissipated back to the leg on release. A band of blue fluorescence was revealed at the buckling region under UV illumination that had the two key signatures of the elastic protein resilin. A group of campaniform sensilla 300 μm proximal to the buckling region responded to imposed buckling movements. The features of the buckling region show that it can act as a shock absorber as proposed previously when jumping and kicking movements go wrong.
Ethnic and social disparity in glycaemic control in type 2 diabetes; cohort study in general practice 2004–9
Authors: D James Gareth , Baker Peter , Badrick Ellena , Mathur Rohini , Hull Sally , Robson John
Published: March 2012

Objective

To determine whether ethnic group differences in glycated haemoglobin (HbA1c) changed over a 5-year period in people on medication for type 2 diabetes.

Design

Open cohort in 2004–9.

Setting

Electronic records of 100 of the 101 general practices in two inner London boroughs.

Participants

People aged 35 to 74 years on medication for type 2 diabetes.

Main outcome measures

Mean HbA1c and proportion with HbA1c controlled to ≤7.5%.

Results

In this cohort of 24,111 people, 22% were White, 58% South Asian and 17% Black African/Caribbean. From 2004 to 2009 mean HbA1c improved from 8.2% to 7.8% for White, from 8.5% to 8.0% for Black African/Caribbean and from 8.5% to 8.0% for South Asian people. The proportion with HbA1c controlled to 7.5% or less, increased from 44% to 56% in White, 38% to 53% in Black African/Caribbean and 34% to 48% in South Asian people. Ethnic group and social deprivation were independently associated with HbA1c. South Asian and Black African/Caribbean people were treated more intensively than White people.

Conclusion

HbA1c control improved for all ethnic groups between 2004–9. However, South Asian and Black African/Caribbean people had persistently worse control despite more intensive treatment and significantly more improvement than White people. Higher social deprivation was independently associated with worse control.
Caring for reproductive-aged women with spinal cord injuries: a case report
Authors: Ward Jill , Walker Christopher
Published: March 2012

In 2008 there were an estimated 259,000 people living in the USA with spinal cord injuries (SCI). The majority of these people are in their reproductive years, and over 19% are estimated to be women. Advances in medical management have allowed many women to live successfully with congenital defects or injuries resulting in SCI that even a few years ago would have been fatal. Although many of these women may be classified as ‘disabled’, fertility is not usually affected in SCI and many of these women desire children of their own. It is important to counsel these women regarding the range of issues related to pregnancy. These include conception issues, parenting with a disability, emotional concerns of the family, nutrition and exercise in pregnancy, risks in pregnancy, labour and delivery, postpartum care, and breastfeeding. For health-care providers it is important to know and understand your patient’s disability and be able to provide the best patient-centred quality care, understanding that each patient's circumstance may be unlike any other patient.
The Influence of Body Size Descriptors on the Estimation of Kidney Function in Normal Weight, Overweight, Obese, and Morbidly Obese Adults
Authors: Park Eun Jung , Pai Manjunath P , Dong Ting , Zhang Jialu , Ko Chia-Wen , Lawrence John , Crentsil Victor , Zhang Lei , Xu Nancy N
Published: March 2012

Background:

Dosing adjustments for patients with impaired kidney function are often based on estimated creatinine clearance (eCrCI) because measuring kidney (unction is not always possible for dose adjustment. However, there is no consensus on the body size descriptor that should be used in the estimation equations.

Objective:

To compare the use of alternative body size descriptors (ABSDs) on the performance of kidney function estimation equations compared with measured CrCI (mCrCI).

Methods:

We combined 2 data sources with mCrCI: a Food and Drug Administration clinical trial database that includes subjects with body mass index (BMI) less than 40 kg/m2 and published data from those 40 kg/m2 or more. The 3 parent equations (Cockcroft-Gault [CG], Modification of Diet in Renal Disease [MDRD], Chronic Kidney Disease-Epidemiology Collaboration [CKDEPI]), and 14 ABSD-modilied equations were compared with mCrCI for accuracy, bias, agreement, goodness of (it (R2). and prediction error. These equations were also compared across mCrCI and BMI strata.

Results:

Subjects (n = 590) were aged 19–80 years; 33.9% were female and BMI ranged from 17.2 to 95.6 kg/m2. Compared with mCrCI, the use of total weight in the CG equation yielded low accuracy (12.5%) and significant bias (–107 mL/min) in the morbidly obese group. In contrast, the use of lean body weights (BMI ≥40 kg/m2) and total ± adjusted weights (BMI <40 kg/m2) with the CG equation yielded higher accuracy, greater than or equal to 60.7% across all BMI strata, and was unbiased. Transforming the MDRD or CKDEPI equations with body surface area improved accuracy only at mCrCI of 30–80 mL/min and increased the overall prediction error.

Conclusions:

No kidney function equation was consistently accurate and unbiased across weight, mCrCI. and estimate ranges. The accuracy and over-estimation bias of the CG equation in obese subjects was improved through the selective use of total, adjusted, and lean body weight by BMI strata.
Intravesicular Cidofovir for the Treatment of Polyomavirus-Associated Hemorrhagic Cystitis
Authors: Mackey Melissa C
Published: March 2012

Objective:

To review the literature regarding the use of intravesicular cidofovir in the treatment of polyomavirus-associated hemorrhagic cystitis.

Data Sources:

Searches of PubMed were conducted, with key search terms including intravesicular cidofovir, polyomavirus, BK virus, JC virus, and hemorrhagic cystitis. Limits were set to include human subjects.

Study Selection and Data Extraction:

All articles identified were evaluated, and one was excluded due to being published only in the German language. All case studies/case series were included if patients received at least 1 dose of intravesicular cidofovir for treatment of cystitis.

Data Synthesis:

Polyomavirus-associated hemorrhagic cystitis is more common in immunocompromised patients, particularly those who have undergone stem cell transplantation. Early-onset cystitis is often due to chemotherapy agents, while cystitis that develops 10–14 days into therapy is often associated with infection with Polyomavirus, such as BK virus. There is no standard of therapy for polyomavirus-associated cystitis other than hyperhydration and continuous bladder irrigation, and many different therapeutic agents have been used in this setting, with mixed results. One such agent, intravenous cidofovir, provides clinical improvement but carries a risk of renal failure. Intravesicular cidofovir has been reported in case reports/series to provide positive symptomatic improvement; however, it has not been universally found to decrease urine viral load.

Conclusions:

At this time, it appears that intravesicular cidofovir may be used as an option to provide symptomatic relief in patients with polyomavirus-associated hemorrhagic cystitis. However, it is not definitively known whether its use significantly decreases urine virus load in these patients. Larger clinical trials need to be conducted to fully understand the role of intravesicular cidofovir in this setting.