bluuebunny/crossref_metadata_2025 huggingface dataset:
The emerging biology of muscle stem cells: Implications for cell‐based therapies
Authors: Bentzinger C. Florian , Wang Yu Xin , von Maltzahn Julia , Rudnicki Michael A.
Published: August 2012

Cell‐based therapies for degenerative diseases of the musculature remain on the verge of feasibility. Myogenic cells are relatively abundant, accessible, and typically harbor significant proliferative potential ex vivo. However, their use for therapeutic intervention is limited due to several critical aspects of their complex biology. Recent insights based on mouse models have advanced our understanding of the molecular mechanisms controlling the function of myogenic progenitors significantly. Moreover, the discovery of atypical myogenic cell types with the ability to cross the blood‐muscle barrier has opened exciting new therapeutic avenues. In this paper, we outline the major problems that are currently associated with the manipulation of myogenic cells and discuss promising strategies to overcome these obstacles.
Quantifying your body: A how‐to guide from a systems biology perspective
Authors: Smarr Larry
Published: August 2012

During the coming decade we will see an accelerated digital transformation of healthcare. Leading this change within the institutional medical community are both the move to digital medical records and the use of digital biomedical measurement devices. In addition to this institutional evolution, there is a non‐institutional, bottom‐up, unorganized, highly idiosyncratic movement by early adopters to “quantify” their own bodies. In this article, I share my decade‐long personal experience of tracking many blood and stool biomarkers, which provide insight into the health or disease of major subsystems of my body. These results are interpreted in the context of the genetics of my human DNA and that of the microbes in my gut. Even though I am a computer scientist and not a medical professional, by using commercially available tests and a systems biology integrative approach, I have become an early example of Leroy Hood's vision of the emergence of predictive, preventive, personalized, and participatory (P4) medicine. It is an individual's story illustrating how each of us can contribute to realizing this paradigm shift.
Simple methodology for the therapeutic drug monitoring of the tyrosine kinase inhibitors dasatinib and imatinib
Authors: Birch M. , Morgan P. E. , Handley S. , Ho A. , Ireland R. , Flanagan R. J.
Published: August 2012

A simple HPLC method has been developed to measure imatinib and N‐desmethylimatinib (norimatinib) in plasma or serum at concentrations attained during therapy. Adaptation of this method to LC‐MS/MS also allows dasatinib assay. A small sample volume (100 μL HPLC‐UV, 50 μL LC‐MS/MS) is required and analysis time is <5 min in each case. Detection was by UV (270 nm) or selective reaction monitoring (two transitions per analyte) tandem mass spectrometry. Assay calibration was linear (0.05–10 mg/L imatinib, 0.01–2.0 mg/L norimatinib and 1–200 µg/L dasatinib), with acceptable accuracy (86–114%) and precision (<14% RSD) for both methods. A comparison between whole blood and plasma confirmed that plasma is the preferred sample for imatinib and norimatinib assay. For dasatinib, although whole blood concentrations were slightly higher, plasma is still the preferred sample. Despite considerable variation in the (median, range) plasma imatinib and norimatinib concentrations in patient samples [1.66 (0.02–4.96) and 0.32 (0.01–0.99) mg/L, respectively, N = 104], plasma imatinib was >1 mg/L (suggested target for response) in all but one sample from patients achieving complete molecular response. As to dasatinib, the median (range) plasma dasatinib concentration was 13 (2‐143) µg/L (N = 33). More observations are needed to properly assess the potential role of therapeutic drug monitoring in guiding treatment with dasatinib. Copyright © 2012 John Wiley & Sons, Ltd.
LC‐MS/MS‐ESI method for simultaneous quantitation of metformin and repaglinidie in rat plasma and its application to pharmacokinetic study in rats
Authors: Sharma Kuldeep , Pawar Gopal , Yadam Swetha , Giri Sanjeev , Rajagopal Sriram , Mullangi Ramesh
Published: August 2012

A highly sensitive and specific LC‐MS/MS‐ESI method has been developed for simultaneous quantification of metformin (MFN) and repaglinide (RGN) in rat plasma (50 μL) using phenacetin as an internal standard (IS). Simple protein precipitation was used to extract MFN and RGN from rat plasma. The chromatographic resolution of MFN, RGN and IS was achieved with a mobile phase consisting of 0.2% formic acid in water–acetonitrile (1:1, v/v) with a time program flow gradient on a Chromolith RP‐18e column. The total chromatographic run time was 3.5 min and the elution of MFN, RGN and IS occurred at 1.64, 2.21 and 2.15 min, respectively. A linear response function was established for the range of concentrations 0.855–394 and 0.021–21.7 ng/mL for MFN and RGN, respectively. The intra‐ and inter‐day precision values for MFN and RGN met the acceptance as per FDA guidelines. MFN and RGN were stable in battery of stability studies viz., bench‐top, auto‐sampler and freeze–thaw cycles. The developed assay was applied to a pharmacokinetic study in rats. Copyright © 2012 John Wiley & Sons, Ltd.
Dose‐dependent effects of calorie restriction on gene expression, metabolism, and tumor progression are partially mediated by insulin‐like growth factor‐1
Authors: Nogueira Leticia M. , Lavigne Jackie A. , Chandramouli Gadisetti V. R. , Lui Huaitian , Barrett J. Carl , Hursting Stephen D.
Published: August 2012

The prevalence of obesity, an established risk and progression factor for breast and many other cancer types, remains very high in the United States and throughout the world. Calorie restriction (CR), a reduced‐calorie dietary regimen typically involving a 20–40% reduction in calorie consumption, prevents or reverses obesity, and inhibits mammary and other types of cancer in multiple tumor model systems. Unfortunately, the mechanisms underlying the tumor inhibitory effects of CR are poorly understood, and a better understanding of these mechanisms may lead to new intervention targets and strategies for preventing or controlling cancer. We have previously shown that the anticancer effects of CR are associated with decreased systemic levels of insulin‐like growth factor‐1 (IGF‐1), the primary source of which is liver. We have also reported that CR strongly suppresses tumor development and growth in multiple mammary cancer models. To identify CR‐responsive genes and pathways, and to further characterize the role of IGF‐1 as a mediator of the anticancer effects of CR, we assessed hepatic and mammary gland gene expression, hormone levels and growth of orthotopically transplanted mammary tumors in control and CR mice with and without exogenous IGF‐1. C57BL/6 mice were fed either control AIN‐76A diet ad libitum (AL), subjected to 20%, 30%, or 40% CR plus placebo timed‐release pellets, or subjected to 30% or 40% CR plus timed‐release pellets delivering murine IGF‐1 (mIGF‐1, 20 μg/day). Compared with AL‐fed controls, body weights were decreased 14.3% in the 20% CR group, 18.5% in the 30% CR group, and 38% in the 40% CR group; IGF‐1 infusion had no effect on body weight. Hepatic transcriptome analyses indicated that compared with 20% CR, 30% CR significantly modulated more than twice the number of genes and 40% CR more than seven times the number of genes. Many of the genes specific to the 40% CR regimen were hepatic stress‐related and/or DNA damage‐related genes. Exogenous IGF‐1 rescued the hepatic expression of several metabolic genes and pathways affected by CR. Exogenous IGF‐1 also rescued the expression of several metabolism‐ and cancer‐related genes affected by CR in the mammary gland. Furthermore, exogenous IGF‐1 partially reversed the mammary tumor inhibitory effects of 30% CR. We conclude that several genes and pathways, particularly those associated with macronutrient and steroid hormone metabolism, are associated with the anticancer effects of CR, and that reduced IGF‐1 levels can account, at least in part, for many of the effects of CR on gene expression and mammary tumor burden.
Intravascular ultrasound complements the diagnostic capability of carbon dioxide digital subtraction angiography for patients with allergies to iodinated contrast medium
Authors: Kusuyama Takanori , Iida Hidetaka , Mitsui Hideya
Published: August 2012

Carbon dioxide digital subtraction angiography (CO2 DSA) is a useful and safe alternative for patients with renal dysfunction or allergies to iodinated contrast medium. However, CO2 DSA image quality is worse than that of angiography with iodinated contrast medium, primarily because of movement during imaging and stent struts. In angioplasty of arteries of the lower extremities, CO2 DSA cannot be used to sufficiently evaluate target lesions and determine the most efficient intervention. However, in the current case report, we describe a patient with severe allergies to iodinated contrast medium (Stevens–Johnson syndrome), because of which we were unable to use any iodinated contrast medium when conducting angioplasty. Therefore, we used intravascular ultrasound (IVUS), which facilitated the complete observation of the target lesion after stent implantation without requiring iodinated contrast medium. In this case, IVUS was used to complement the diagnostic capabilities of CO2 DSA. © 2012 Wiley Periodicals, Inc.
Impact of target vessel on long‐term survival after percutaneous coronary intervention for chronic total occlusions
Authors: Claessen Bimmer E. , Dangas George D. , Godino Cosmo , Henriques José P.S. , Leon Martin B. , Park Seung‐Jung , Stone Gregg W. , Moses Jeffrey W. , Colombo Antonio , Mehran Roxana ,   Multinational CTO Registry
Published: August 2012

Background

This study sought to investigate whether there is a differential prognostic effect of successful percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) according to the target vessel the CTO is located in.

Methods

Between 1998 and 2007, a total of 1,791 patients underwent PCI of a CTO at three tertiary care centers in the US, Italy, and South Korea. Patients with CTOs in multiple target vessels or the left main stem were excluded (n = 57). Of the remaining 1,734 patients, 609 had a CTO in the left anterior descending (LAD, 35.1%), 391 in the left circumflex (LCX, 22.5%), and 734 in the right coronary artery (RCA, 42.3%). Five‐year mortality and the need for coronary artery bypass grafting (CABG) were compared between patients with successful vs. unsuccessful PCI stratified by target vessel.

Results

Procedural success was obtained in 71.1% of LAD patients, 69.1% of LCX patients, and 65.1% of RCA patients (P = 0.06). The mean follow‐up duration was 1,178 days. Kaplan–Meier estimates of long‐term mortality were 6.7% vs. 11.0% (P = 0.03), 5.5% vs. 13.9% (P < 0.01), and 6.6% vs. 4.1% (P = 0.80) in successful vs. unsuccessful LAD, LCX, and RCA patients, respectively. After multivariate analysis, successful CTO PCI remained associated with lower mortality in the LAD (HR 0.41, P = 0.02) and LCX groups (HR 0.32, P < 0.01). The need for CABG was lower after successful CTO PCI in all three groups (LAD 4.6% vs. 16.0%, P < 0.01; LCX 2.9% vs. 18.2%, P < 0.01, RCA 2.3% vs. 8.4%, P < 0.01).

Conclusion

The results from this large contemporary cohort of patients suggest that successful PCI of a CTO in the LAD and the LCX, but not the RCA, is associated with improved long‐term survival. © 2013 Wiley Periodicals, Inc.
Distal anastomotic lesions after coronary artery bypass surgery: Incidence, pathogenesis, and treatment approach
Authors: Badr Salem , Dvir Danny , Waksman Ron
Published: August 2012

Distal anastomotic lesions are the most common reason for venous and arterial graft failure. Redo coronary artery bypass surgery carries a higher risk for mortality and non‐fatal myocardial infarction. Many operators therefore consider percutaneous coronary intervention as a good alternative for relieving angina symptoms in this subset of patients with anastomotic lesions. However, the best percutaneous method for treating these lesions is still controversial. Here we review reported data on the incidence, pathogenesis, and treatment of distal anastomotic lesions in both venous and arterial bypass grafts. © 2012 Wiley Periodicals, Inc.
Emergent use of retrograde left ventricular support in patients after transcatheter aortic valve replacement
Authors: Martinez Claudia A. , Singh Vikas , Heldman Alan W. , O'Neill William W.
Published: August 2012

Transcatheter aortic valve replacement (TAVR) is currently a therapeutic alternative to open aortic valve replacement for high‐risk patients with severe symptomatic aortic valve stenosis. The procedure is associated with some life‐threatening complications including circulatory collapse which may require temporary hemodynamic support. We describe our experience with the use of the Impella 2.5 system to provide emergent left ventricular support in cases of hemodynamic collapse after TAVR with the Edwards SAPIEN prosthesis.© 2012 Wiley Periodicals, Inc.
Residual mitral valve regurgitation after percutaneous mitral valve repair with the mitraclip® system is a risk factor for adverse one‐year outcome
Authors: Paranskaya Liliya , D'Ancona Giuseppe , Bozdag‐Turan Ilkay , Akin Ibrahim , Kische Stephan , Turan Gökmen R. , Rehders Tim , Ortak Jasmin , Nienaber Christoph A. , Ince Hüseyin
Published: August 2012

Objectives

We undertook this study to investigate the mid‐term clinical results after MitraClip® implantation and the impact of post‐repair mitral valve (MV) function and anatomy on survival and outcome composite endpoint in high‐risk patients.

Background

Percutaneous MV repair is a potential treatment option for high‐risk patients with severe mitral regurgitation (MR).

Methods

MitraClip® was implanted in patients with symptomatic MR rejected to conventional surgery. Differences between patients that survived at follow‐up and patients deceased were tested. A stepwise Cox multivariate analysis was performed to identify independent predictors for composite endpoint of mortality, cardiac re‐hospitalization, re‐intervention, and major cerebro‐vascular and cardiac events.

Results

A total of 85 consecutive patients [78 ± 6 years, 48 (56.5%) men] with severe MR were included. There was no operative mortality while in‐hospital mortality was 3.5% (n = 3) and 30‐day mortality 4.7% (n = 4). Follow‐up was 211 ± 173 days. Survival and composite endpoint‐free survival at one year were 71% and 55%. Multivariate analysis revealed that residual MR immediately after MitraClip® placement (OR 7.4; 95% CI 2.3–23.7) and preoperative MV gradient (OR 2.7; 95% CI 1.5–5.0) were predictors for composite endpoint. Chronic obstructive pulmonary disease (OR 8.3; 95% CI 1.9–37.1) was an additional predictor for composite endpoint.

Conclusion

MitraClip® is a valid tool with favorable outcomes in high‐risk patients. The degree of residual MR seems to impact on follow‐up composite endpoint outcome. An optimal correction of MR after MitraClip placement could be advocated to optimize the benefits of the procedure and minimize the risk of adverse outcomes. © 2012 Wiley Periodicals, Inc.
Transcatheter aortic valve implantation through a diseased left common carotid artery: Combined approach with endarterectomy and left carotid‐subclavian bypass
Authors: Magalhães Marco A. , Souza Januário M. , Grube Eberhard
Published: August 2012

We report a case of transcatheter aortic valve implantation (TAVI) with the self‐expanding Medtronic CoreValve bioprosthesis (Medtronic, Minneapolis, MI) through a diseased left common carotid (LCC) artery. This 81‐year‐old male patient presented with heart failure due to a severe degenerative aortic valve stenosis. Comorbidities included diabetes, hypertension, and dyslipidemia as well as peripheral and coronary artery disease, resulting in a logistic EuroScore II of 25.9%. Consequently, he was rejected to undergo surgery and a transcatheter approach was planned. Due to severe peripheral vascular disease with iliofemoral lesions, significant calcifications and unfavourable angulations of the innominate artery as well as prior bypass surgery precluding a direct aortic and subclavian approach, none of the established access sites were suitable. Therefore, we considered a left carotid access, which had to be combined with a surgical endarterectomy for treatment of a significant common carotid bifurcation stenosis and left subclavian‐LCC permanent tunnel bypass graft. The procedure was successful without cardiac, cerebrovascular, or access complications. This case illustrates a true heart team approach, establishing a unique access for TAVI for patients without regular access options. © 2012 Wiley Periodicals, Inc.
Resolute® and xience V® polymer‐based drug‐eluting stents compared in an atherosclerotic rabbit double injury model
Authors: Van Dyck Christophe J. , Hoymans Vicky Y. , Bult Hidde , Fransen Erik , Haine Steven , Bosmans Johan M. , Timmermans Jean‐Pierre , Vrints Christiaan J.
Published: August 2012

Aim

To evaluate differences in strut coverage, inflammation and endothelialization between two second‐generation polymer‐based drug‐eluting stents (DES) in an atherosclerotic rabbit double‐injury iliac artery model at 28 days follow‐up. Methods and results: Rabbits with induced atheroma received bilateral iliac artery stents: everolimus‐eluting stent (Xience V EES; Abbott Vascular), zotarolimus‐eluting stent (Resolute ZES; Medtronic CardioVascular), or bare‐metal stent (BMS; MultiLink Vision; Abbott Vascular). After 28 days, total neointimal coverage examined by scanning electron microscopy was >98% for all three stent types. Neointimal thickness above stent struts was decreased by 50% in Xience V EES (0.06 ± 0.01 mm; P = 0.00001) compared with BMS (0.15 ± 0.03 mm) and Resolute ZES (0.12 ± 0.04 mm). Luminal area was largest for Xience V EES (3.79 ± 0.33 mm2; P = 0.0003 for Xience V EES vs. BMS), followed by Resolute ZES (3.46 ± 0.45 mm2; P = 0.083 for Resolute ZES vs. BMS) and BMS (3.07 ± 0.53 mm2). Percentage area stenosis was smallest for Xience V EES (17.23 ± 3.64%; P = 0.00001), while BMS (30.25 ± 7.48%) and Resolute ZES (30.79 ± 7.15%) did not differ. Endothelial monolayer regrowth was significantly lower in Resolute ZES (65 ± 13%) versus BMS (79 ± 11%; P = 0.004). There was no difference between Xience V EES (74 ± 10%) and BMS. Xience V EES was further associated with a lower number of inflammatory cells surrounding the stent struts (7 ± 2 per strut) in comparison to Resolute ZES (15 ± 6; P = 0.0001) and BMS (17 ± 9; P = 0.0005).

Conclusion

In this atherosclerotic rabbit model, Xience V EES suppressed neointimal thickening better, with normal endothelial regrowth as compared with BMS, and less strut‐induced inflammation. © 2012 Wiley Periodicals, Inc.
Resuspension of Abiotic Particles from Ceramic Membranes
Authors: Quadt T. , Schmidt E.
Published: August 2012

Adhesion forces are an important factor when dealing with particle resuspension. A direct measurement of these forces is not possible in industrial membrane filtration processes. However, more knowledge about the acting adhesion forces would be very helpful to use membrane filtration in an economically more efficient way. This article introduces basic experiments that should lead to an indirect, time‐resolved measurement of adhesion forces acting during the process of membrane surface regeneration. The aim is to optimize the existing regeneration process and to find new solutions for membrane regeneration.
Anterior PAR proteins function during cytokinesis and maintain DYN‐1 at the cleavage furrow in Caenorhabditis elegans
Authors: Pittman Kelly J. , Skop Ahna R.
Published: August 2012

PAR proteins are key regulators of cellular polarity and have links to the endocytic machinery and the actin cytoskeleton. Our data suggest a unique role for PAR proteins in cytokinesis. We have found that at the onset of cytokinesis, anterior PAR‐6 and posterior PAR‐2 proteins are redistributed to the furrow membrane in a temporal and spatial manner. PAR‐6 and PAR‐2 localize to the furrow membrane during ingression but PAR‐2‐GFP is distinct in that it is excluded from the extreme tip of the furrow. Once the midbody has formed, PAR‐2‐GFP becomes restricted to the midbody region (the midbody plus the membrane flanking it). Depletion of both anterior PAR proteins, PAR‐3 and PAR‐6, led to an increase in multinucleate embryos, suggesting that the anterior PAR proteins are necessary during cytokinesis and that PAR‐3 and PAR‐6 function in cytokinesis may be partially redundant. Lastly, anterior PAR proteins play a role in the maintenance of DYN‐1 in the cleavage furrow. Our data indicate that the PAR proteins are involved in the events that occur during cytokinesis and may play a role in promoting the membrane trafficking and remodeling events that occur during this time. © 2012 Wiley Periodicals, Inc
Centralspindlin and chromosomal passenger complex behavior during normal and Rappaport furrow specification in echinoderm embryos
Authors: Argiros Haroula , Henson Lauren , Holguin Christiana , Foe Victoria , Shuster Charles Bradley
Published: August 2012

The chromosomal passenger (CPC) and Centralspindlin complexes are essential for organizing the anaphase central spindle and providing cues that position the cytokinetic furrow between daughter nuclei. However, echinoderm zygotes are also capable of forming “Rappaport furrows” between asters positioned back‐to‐back without intervening chromosomes. To understand how these complexes contribute to normal and Rappaport furrow formation, we studied the localization patterns of Survivin and mitotic‐kinesin‐like‐protein1 (MKLP1), members respectively of the CPC and the Centralspindlin complex, and the effect of CPC inhibition on cleavage in mono‐ and binucleate echinoderm zygotes. In zygotes, Survivin initially localized to metaphase chromosomes, upon anaphase onset relocalized to the central spindle and then, together with MKLP1 spread towards the equatorial cortex in an Aurora‐dependent manner. Inhibition of Aurora kinase activity resulted in disruption of central spindle organization and furrow regression, although astral microtubule elongation and furrow initiation were normal. In binucleate cells containing two parallel spindles MKLP1 and Survivin localized to the plane of the former metaphase plate, but were not observed in the secondary cleavage plane formed between unrelated spindle poles, except when chromosomes were abnormally present there. However, the secondary furrow was sensitive to Aurora inhibition, indicating that Aurora kinase may still contribute to furrow ingression without chromosomes nearby. Our results provide insights that reconcile classic micromanipulation studies with current molecular understanding of furrow specification in animal cells. © 2012 Wiley Periodicals, Inc
Symmetric cell division of the mouse zygote requires an actin network
Authors: Chew Ting Gang , Lorthongpanich Chanchao , Ang Wei Xia , Knowles Barbara B. , Solter Davor
Published: August 2012

Positioning of the cleavage plane is regulated to ensure proper animal development. Most animal cells rely on the astral microtubules to position the mitotic spindle, which in turn specifies the cleavage plane. The mouse zygote lacks discernible astral microtubules but still divides symmetrically. Here, we demonstrate a cloud‐like accumulation of F‐actin surrounds the spindle in zygotes and when this actin network is disassembled, the spindle assumes an off‐center position, and the resulting zygote divides asymmetrically into two unequal size blastomeres. Interestingly, when the spindle is micromanipulated to the subcortical region, the zygote without the actin network is unable to reposition the spindle and cleavage plane at the cell center. This study reveals that an actin network maintains the central spindle position in anastral mitosis, and ensures the first embryonic mitosis is symmetrical. © 2012 Wiley Periodicals, Inc
Randomly biased walks on subcritical trees
Authors: Ben Arous Gérard , Hammond Alan
Published: August 2012

As a model of trapping by biased motion in random structure, we study the time taken for a biased random walk to return to the root of a subcritical Galton‐Watson tree. We do so for trees in which these biases are randomly chosen, independently for distinct edges, according to a law that satisfies a logarithmic nonlattice condition. The mean return time of the walk is in essence given by the total conductance of the tree. We determine the asymptotic decay of this total conductance, finding it to have a pure power‐law decay. In the case of the conductance associated to a single vertex at maximal depth in the tree, this asymptotic decay may be analyzed by the classical defective renewal theorem, due to the nonlattice edge‐bias assumption. However, the derivation of the decay for total conductance requires computing an additional constant multiple outside the power law that allows for the contribution of all vertices close to the base of the tree. This computation entails a detailed study of a convenient decomposition of the tree under conditioning on the tree having high total conductance. As such, our principal conclusion may be viewed as a development of renewal theory in the context of random environments.

For randomly biased random walks on a supercritical Galton‐Watson tree with positive extinction probability, our main results may be regarded as a description of the slowdown mechanism caused by the presence of subcritical trees adjacent to the backbone that may act as traps that detain the walker. Indeed, this conclusion is exploited in a sequel by the second author to obtain a stable limiting law for walker displacement in such a tree. © 2012 Wiley Periodicals, Inc.
Birth timing and the mother–infant relationship predict variation in infant behavior and physiology
Authors: Vandeleest Jessica J. , Mendoza Sally P. , Capitanio John P.
Published: August 2012

The current study explored whether birth timing, known to influence the mother–infant relationship, also affected infant physiology up to 9 months later and infant behavior at weaning. Infant blood samples were collected at 5.75 and 8.75 months of age to assess functioning of the hypothalamic–pituitary–adrenal axis as well as the antibody response to a Cholera vaccination. Path analysis indicated infants born late in the birth season had less Relaxed relationships with their mothers. A less‐Relaxed relationship was associated with greater infant Positive Engagement and Distress, which were negatively correlated, suggesting infants may have different strategies of coping with this type of relationship. Low Relaxed scores were also associated with higher infant cortisol concentrations at 5.75 months, which was associated with a reduced immune response to a vaccination 3 months later. Together these results indicate that the influence of birth timing on the mother–infant relationship may have consequences for infant development. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 829–837, 2013.
Craniofacial abnormalities result from knock down of nonsyndromic clefting gene, crispld2, in zebrafish
Authors: Yuan Qiuping , Chiquet Brett T. , DeVault Laura , Warman Matthew L. , Nakamura Yukio , Swindell Eric C. , Hecht Jacqueline T.
Published: August 2012

Nonsyndromic cleft lip and palate (NSCLP), a common birth defect, affects 4,000 newborns in the US each year. Previously, we described an association between CRISPLD2 and NSCLP and showed Crispld2 expression in the murine palate. These results suggested that a perturbation in CRISPLD2 activity affects craniofacial development. Here, we describe crispld2 expression and the phenotypic consequence of its loss of function in zebrafish. crispld2 was expressed at all stages of zebrafish morphogenesis examined and localized to the rostral end by 1‐day postfertilization. Morpholino knockdown of crispld2 resulted in significant jaw and palatal abnormalities in a dose‐dependent manner. Loss of crispld2 caused aberrant patterning of neural crest cells (NCC) suggesting that crispld2 is necessary for normal NCC formation. Altogether, we show that crispld2 plays a significant role in the development of the zebrafish craniofacies and alteration of normal protein levels disturbs palate and jaw formation. These data provide support for a role of CRISPLD2 in NSCLP. genesis 50:871–881, 2012. © 2012 Wiley Periodicals, Inc.
Trideuteriomethoxylation of Aryl and Heteroaryl Halides
Authors: Dash Pragyanditi , Janni Manojkumar , Peruncheralathan S.
Published: August 2012

Direct access to trideuteriomethoxylated aromatic and heteroaromatic compounds has been developed. Various aryl and heteroaryl halides underwent d3‐methoxylation under mild reaction conditions by using a catalyst system composed of the commercially available monodentate phosphane ligand tBuXPhos and Pd(OAc)2. Inexpensive CD3OD served as an efficient trideuteriomethoxylating agent.
Man‐Tailored Biomimetic Sensor of Molecularly Imprinted Materials for the Potentiometric Measurement of Rivastigmine in Tablets and Biological Fluids and Employing the Taguchi Optimization Methodology to Optimize the MIP‐Based Membranes
Authors: Arvand Majid , Fallahi Parisa
Published: August 2012

This work proposes a novel biomimetic sensor for the potentiometric transduction of rivastigmine based on molecularly imprinted polymer (MIP). Using the Taguchi method, this study analyzed the optimum conditions for preparing the MIP‐based membranes. The rank order of each controllable factor was also determined. MIP‐based membranes exhibited a Nernstian response (30.7±1.1 mV decade−1) in a concentration range from 1.0×10−5 to 1.0×10−2 mol L−1 with a LOD of 6.3×10−6 mol L−1. The sensor was successfully applied to the determination of rivastigmine concentrations in human serum, plasma, urine, rat brain and tablets.
Disposable Electrochemical Magnetoimmunosensor for the Determination of Troponin T Cardiac Marker
Authors: de Ávila Berta Esteban‐Fernández , Escamilla‐Gómez Vanessa , Campuzano Susana , Pedrero María , Pingarrón José M.
Published: August 2012

The preparation and performance of a disposable amperometric magnetoimmunosensor for the specific detection and quantification of human cardiac Troponin T is reported. The immunosensor design involves binding of streptavidin‐ magnetic beads to a specific biotinylated capture antibody and detection with a HRP‐labeled antibody. The resulting modified‐MBs are magnetically captured on the surface of a disposable gold screen‐printed electrode and the amperometric response obtained at −0.10 V upon addition of 3,3′,5,5′‐tetramethylbenzidine and H2O2 is used to monitor the affinity reaction. This methodology achieves a detection limit of 0.017 ng mL−1, a good selectivity and has been successfully tested with serum samples.
A HEALTH PRODUCTION MODEL WITH ENDOGENOUS RETIREMENT
Authors: Galama Titus , Kapteyn Arie , Fonseca Raquel , Michaud Pierre‐Carl
Published: August 2012

We formulate a stylized structural model of health, wealth accumulation and retirement decisions building on the human capital framework of health and derive analytic solutions for the time paths of consumption, health, health investment, savings and retirement. We argue that the literature has been unnecessarily restrictive in assuming that health is always at the ‘optimal’ health level. Exploring the properties of corner solutions, we find that advances in population health decrease the retirement age, whereas at the same time, individuals retire when their health has deteriorated. This potentially explains why retirees point to deteriorating health as an important reason for early retirement, whereas retirement ages have continued to fall in the developed world, despite continued improvements in population health and mortality. In our model, workers with higher human capital invest more in health and, because they stay healthier, retire later than those with lower human capital whose health deteriorates faster. Copyright © 2012 John Wiley & Sons, Ltd.
Effects of a red tide on the structure of estuarine fish assemblages in northeastern Brazil
Authors: Amorim Reis‐Filho José , da Silva Eduardo M. , de Anchieta Cintra da Costa Nunes José , Barros Francisco
Published: August 2012

The present study evaluated changes in an estuarine fish community caused by blooms of the dinoflagellate Akashiwo sanguinea. Samples were collected before, during and after the red tide using seine nets and surface and bottom nets in three areas near the affected area. The area was around the mouth of the Paraguaçu River. A total of 144 samples were collected, containing 1,989 individuals, with a total weight of 51.4 kg, belonging to 42 species in 29 families. During the red tide, fish density, richness and biomass decreased significantly. Atherinella brasiliensis and Sphoeroides greeleyi were the most abundant species during the red tide, indicating some possible resistance to the effects of the red tide. One month after the red tide, there was a rapid recovery of the density, biomass and richness of fish, and Cetengraulis edentulus was the most captured species. An important result of the present study is the finding that the dynamics of small populations of fish are often influenced by fortuitous events, and stochasticity may dominate. The establishment of a continuous and adequate monitoring program in the area may contribute to understanding the effects of red tides on fish population dynamics. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Seasonal dynamics and composition of cladoceran and copepod assemblages in ponds of a Hungarian cutaway peatland
Authors: Vad Csaba Ferenc , Horváth Zsófia , Kiss Keve Tihamér , Ács Éva , Török Júlia Katalin , Forró László
Published: August 2012

Seasonal dynamics of cladoceran and copepod zooplankton were studied over a one‐year period in five permanent ponds of a cutaway peatland, situated in the Danube−Tisza Interfluve, Central Hungary. 17 cladoceran, 11 cyclopoid copepod and 6 harpacticoid copepod species were identified and most of them were typical of small lowland ponds. Nevertheless, some taxa like Cyclops insignis, Ceriodaphnia setosa and Macrocyclops distinctus are considered to be rare in Hungary. The microcrustacean assemblages exhibited apparent seasonal succession with typical seasonal species. There appears to be at least two main successional patterns in the five ponds. After general cyclopoid copepod dominance in winter (Cyclops strenuus and Cyclops insignis), at sites with higher proportion of open water and submerged vegetation, spring was characterized by the dominance of the large cladoceran Daphnia curvirostris, which declined during summer, when microcrustacean assemblages composed mainly of smaller, littoral cladocerans. At these sites, species richness and diversity reached their maximum in autumn. In the case of duckweed covered ponds, succession led to less diverse autumn assemblages with fewer species, dominated by Simocephalus exspinosus. Our results draw the attention to the importance of long‐term investigations and the often neglected winter sampling in the accurate evaluation of species richness (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Hypoxia‐induced downregulation of XIAP in trophoblasts mediates apoptosis via interaction with IMUP‐2: Implications for placental development during pre‐eclampsia
Authors: Jeon Su Yeon , Lee Hyun‐Jung , Na Kyu‐Hwan , Cha Dong‐Hyun , Kim Jin Kyeoung , Park Jong‐Wan , Yoon Tae Ki , Kim Gi Jin
Published: August 2012

The regulation of trophoblast apoptosis is essential for normal placentation, and increased placental trophoblast cell apoptosis is the cause of pathologies such as intrauterine growth retardation (IUGR) and pre‐eclampsia. X‐linked inhibitor of apoptosis (XIAP) is expressed in trophoblasts, but little is known about the role of XIAP in placental development. In the present study, the function of XIAP in the placenta and in HTR‐8/SVneo trophoblasts under hypoxic conditions was examined. In addition, the correlation between XIAP and immortalization‐upregulated protein‐2 (IMUP‐2) was demonstrated in HTR‐8/SVneo trophoblasts under hypoxia, based on a previous study showing that increased IMUP‐2 induces trophoblast apoptosis and pre‐eclampsia. XIAP was downregulated in pre‐eclamptic placentas (P < 0.05). In HTR‐8/SVneo trophoblasts, XIAP expression was decreased and the expression of apoptosis‐related genes was increased in response to hypoxia. Ectopic expression of hypoxia inducible factor (HIF)‐1α in HRT‐8 SV/neo cells induced the nuclear translocation of XIAP and alterations of XIAP protein stability. Furthermore, hypoxia induced nuclear translocated XIAP co‐localized with upregulated IMUP‐2 in trophoblast nuclei, and the interaction between XIAP and IMUP‐2 induced apoptosis in HRT‐8 SV/neo cells. The present results suggest that hypoxia‐induced down‐regulation of XIAP mediates apoptosis in trophoblasts through interaction with increased IMUP‐2, and that this mechanism underlies the pathogenesis of pre‐eclampsia. J. Cell. Biochem. 114: 89–98, 2012. © 2012 Wiley Periodicals, Inc.
Multiphoton tomography visualizes collagen fibers in the tumor microenvironment that maintain cancer‐cell anchorage and shape
Authors: Uchugonova Aisada , Zhao Ming , Weinigel Martin , Zhang Yong , Bouvet Michael , Hoffman Robert M. , König Karsten
Published: August 2012

Second harmonic generation (SHG) multiphoton imaging can visualize fibrillar collagen in tissues. SHG has previously shown that fibrillar collagen is altered in various types of cancer. In the present study, in vivo high resolution SHG multi‐photon tomography in living mice was used to study the relationship between cancer cells and intratumor collagen fibrils. Using green fluorescent protein (GFP) to visualize cancer cells and SHG to image collagen, we demonstrated that collagen fibrils provide a scaffold for cancer cells to align themselves and acquire optimal shape. These results suggest a new paradigm for a stromal element of tumors: their role in maintaining anchorage and shape of cancer cells that may enable them to proliferate. J. Cell. Biochem. 114: 99–102, 2012. © 2012 Wiley Periodicals, Inc.
D2 dopamine receptor antagonist raclopride induces non‐canonical autophagy in cardiac myocytes
Authors: Yan Hao , Li Wen‐lin , Xu Jian‐jun , Zhu Shu‐qiang , Long Xiang , Che Jian‐peng
Published: August 2012

Cell death by autophagy is an important means of maintaining cellular homeostasis in adult cardiac myocytes. Autophagy was previously shown to exert a cardioprotective effect, suggesting that modulation of autophagy pathways is a potential therapeutic strategy in the treatment of heart disease. Although dopamine is known to induce autophagy in neuroblastoma cells, the underlying mechanism and the types of dopamine receptors involved in this process remain unclear. In this study, we used various dopamine receptor antagonists and agonists to identify the specific dopamine receptor that mediates induction of autophagy. We evaluated autophagy induction by the expression of autophagy markers in neonatal rat ventricular cardiac myocytes. We evaluated intracellular calcium levels using Fluo‐3/AM and demonstrated autophagy‐induced morphological changes in cardiac myocytes using electron microscopy. We also examined the pathway for dopamine‐induced autophagy using RNAi‐mediated gene knockdown. Raclopride, the well‐documented D2 receptor antagonist, significantly upregulated autophagy in cardiac myocytes via an mTOR‐independent pathway. There was no difference in intracellular calcium levels between raclopride‐treated cells and untreated cells. siRNA‐mediated knockdown of Rab9 resulted in decreased expression of autophagy markers in raclopride‐treated cells. Interestingly, siRNA‐mediated knockdown of Atg7 resulted in a significant increase in Rab9 levels in raclopride‐treated cells, suggesting that blocking the classical autophagy pathway results in activation of an alternative pathway. Our study suggests that (1) the D2 dopamine receptor plays a role in autophagy and (2) raclopride mediated a non‐canonical autophagy pathway in cardiac myocytes via Rab9. J. Cell. Biochem. 114: 103–110, 2012. © 2012 Wiley Periodicals, Inc.
Characterization of human NLZ1/ZNF703 identifies conserved domains essential for proper subcellular localization and transcriptional repression
Authors: Pereira‐Castro Isabel , Costa Ângela M. Sousa , Oliveira Maria José , Barbosa Inês , Rocha Ana Sofia , Azevedo Luisa , da Costa Luís Teixeira
Published: August 2012

NET family members have recently emerged as important players in the development of multiple structures, from the trachea of fly larvae to the vertebrate eye and human breast cancers. However, their mechanisms of action are still poorly understood, and we lack a detailed characterization of their functional domains, as well as gene expression patterns—particularly in adult mammals. Here, we present a characterization of human NLZ1/ZNF703 (NocA‐like zinc finger 1/Zinc finger 703), one of the two human NET family member genes. We show that the gene is ubiquitously expressed in adult human and mouse tissues, that three mRNA species with the same coding sequence are generated by alternative polyadenylation, and that the encoded protein contains six evolutionarily conserved domains, three of which are specific to NET proteins. Finally, we present functional evidence that these domains are necessary for proper subcellular distribution of and transcription repression by the NLZ1 protein, but not for its interaction with Groucho family co‐repressors. J. Cell. Biochem. 114: 120–133, 2012. © 2012 Wiley Periodicals, Inc.
Differentiation potential and GFP labeling of sheep bone marrow‐derived mesenchymal stem cells
Authors: Czernik Marta , Fidanza Antonella , Sardi Martina , Galli Cesare , Brunetti Dario , Malatesta Daniela , Della Salda Leonardo , Matsukawa Kazutsugu , Ptak Grazyna E. , Loi Pasqualino
Published: August 2012

Mesenchymal stem cells (MSCs) are an important cell population in the bone marrow microenvironment. MSCs have the capacity to differentiate in vitro into several mesenchymal tissues including bone, cartilage, fat, tendon, muscle, and marrow stroma. This study was designed to isolate, expand, and characterize the differentiation ability of sheep bone marrow‐derived MSCs and to demonstrate the possibility to permanently express a reporter gene. Bone marrow was collected from the iliac crest and mononuclear cells were separated by density gradient centrifugation. Sheep MSCs cell lines were stable characterized as CD44+ and CD34− and then transfected with a green fluorescent protein (GFP) reporter gene. The GFP expression was maintained in about half (46.6%) of cloned blastocysts produced by nuclear transfer of GFP+ sheep MSCs, suggesting the possibility to establish multipotent embryonic cells' lines carrying the fluorescent tag for comparative studies on the differentiation capacity of adult stem cells (MSCs) versus embryonic stem cells. We found that sheep MSCs under appropriate culture conditions could be induced to differentiate into adipocytes, chondrocytes, and osteoblast lineages. Our results confirm the plasticity of sheep MSCs and establish the foundation for the development of a pre‐clinical sheep model to test the efficiency and safety of cell replacement therapy. J. Cell. Biochem. 114: 134–143, 2012. © 2012 Wiley Periodicals, Inc.
The release of glutamate from cortical neurons regulated by BDNF via the TrkB/Src/PLC‐γ1 pathway
Authors: Zhang Zitao , Fan Jin , Ren Yongxin , Zhou Wei , Yin Guoyong
Published: August 2012

The brain‐derived neurotrophic factor (BDNF) participates in the regulation of cortical neurons by influencing the release of glutamate. However, the specific mechanisms are unclear. Hence, we isolated and cultured the cortical neurons of Sprague Dawley rats. Specific inhibitors of TrkB, Src, PLC‐γ1, Akt, and MEK1/2 (i.e., K252a, PP2, U73122, LY294002, and PD98059, respectively) were used to treat cortical neurons and to detect the glutamate release from cortical neurons stimulated with BDNF. BDNF significantly increased glutamate release, and simultaneously enhanced phosphorylation levels of TrkB, Src, PLC‐γ, Akt, and Erk1/2. For BDNF‐stimulated cortical neurons, K252a inhibited glutamate release and inhibited the phosphorylation levels of TrkB, Src, PLC‐γ, Erk1/2, and Akt (P < 0.05). PP2 reduced the glutamate release from BDNF‐stimulated cortical neurons (P < 0.05) and inhibited the phosphorylation levels of TrkB and PLC‐γ1 (P < 0.05). However, PP2 had no effect on the phosphorylation levels of Erk1/2 or Akt (P > 0.05). U73122 inhibited the glutamate release from BDNF‐stimulated cortical neurons, but had no influence on the phosphorylation levels of TrkB, Src, Erk1/2, or Akt (P > 0.05). LY294002 and PD98059 did not affect the BDNF‐stimulated glutamate release and did not inhibit the phosphorylation levels of TrkB, Src, or PLC‐γ1. In summary, BDNF stimulated the glutamate release from cortical neurons via the TrkB/Src/PLC‐γ1 signaling pathway. J. Cell. Biochem. 114: 144–151, 2012. © 2012 Wiley Periodicals, Inc.
Galangin inhibits tumor growth and metastasis of B16F10 melanoma
Authors: Zhang Wenjing , Tang Bo , Huang Qilai , Hua Zichun
Published: August 2012

Galangin, an active flavonoid extracted from the root of the Alpinia officinarum Hance, showed a cytotoxic effect on several cancer cell lines in vitro. However, there is no information available concerning its antimetastatic effect. Focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase, is involved in many aspects of cellular processes such as proliferation, adhesion, and invasion. Studies have shown that FAK is a promising target for therapeutic intervention in melanoma. In the present study, proliferation of B16F10 cells was suppressed when exposed to various doses of galangin. Inhibition on proliferation by galangin was also detected by clonogenic survival assay. The capabilities of cell adhesion, cell spreading, and cell motility were impaired by galangin, reinforced by F‐actin rearrangement. Molecular data showed that both FAK mRNA level and protein level were reduced dose‐dependently. Additionally, galangin reduced phosphorylation of FAK (Tyr397) protein. Transient transfection reporter assays showed that galangin suppressed the transcription of FAK gene, indicating FAK expression is a candidate target of galangin. The antimetastatic function of galangin is further supported by the fact that it could inhibit the formation of tumor colonies in the lung tissue on C57BL/6J mouse lung metastatic model using B16F10 melanoma cells. Immunochemical analyses showed that galangin decreased FAK expression in vivo. These data add to our new understanding that galangin can inhibit B16F10 melanoma metastasis both in vivo and in vitro, and that FAK is a valid therapeutic target against melanoma. J. Cell. Biochem. 114: 152–161, 2012. © 2012 Wiley Periodicals, Inc.