bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resveratrol and rapamycin: are they anti‐aging drugs?
Authors: Kaeberlein Matt 
Published: January 2010

AbstractStudies of the basic biology of aging have advanced to the point where anti‐aging interventions, identified from experiments in model organisms, are beginning to be tested in people. Resveratrol and rapamycin, two compounds that target conserved longevity pathways and may mimic some aspects of dietary restriction, represent the first such interventions. Both compounds have been reported to slow aging in yeast and invertebrate species, and rapamycin has also recently been found to increase life span in rodents. In addition, both compounds also show impressive effects in rodent models of age‐associated diseases. Clinical trials are underway to assess whether resveratrol is useful as an anti‐cancer treatment, and rapamycin is already approved for use in human patients. Compounds such as these, identified from longevity studies in model organisms, hold great promise as therapies to target multiple age‐related diseases by modulating the molecular causes of aging.
Muscle unloading potentiates the effects of acetyl‐L‐carnitine on the slow oxidative muscle phenotype
Authors: Cassano Pierluigi , Flück Martin , Giovanna Sciancalepore Anna , Pesce Vito , Calvani Menotti , Hoppeler Hans , Cantatore Palmiro , Gadaleta Maria Nicola 
Published: January 2010

AbstractThe effect of acetyl‐L‐carnitine (ALCAR) supplementation to 3‐month‐old rats in normal‐loading and unloading conditions has been here investigated by a combined morphological, biochemical and transcriptional approach to test whether ALCAR might cause a remodeling of the metabolic/contractile phenotype of soleus muscle. Morphological assessment demonstrated an increase of type I oxidative fiber content and cross‐sectional area in ALCAR‐treated animals both in normal‐loading and in unloading conditions. ALCAR prevented loss of mitochondrial mass in unloaded animals whereas no ALCAR‐dependent increase of mitochondrial mass occurred in normal‐loaded muscle. Validated microarray analysis delineated an ALCAR‐induced maintenance of a slow‐oxidative expression program only in unloaded soleus muscle. Indeed, the muscle adjustment of the expression profile of factors underlying mitochondrial oxidative metabolism, protein turnover, fiber type differentiation and an adaptation of voltage‐gated ion channel expression was distinguishable with respect to the loading status. This selectivity may suggest a key role of muscle loading status in the manifestation of ALCAR effects. The results extend to a broader level of biological informations the previous notion on ALCAR positive effect in rat soleus muscle during unloading and point to a role of ALCAR for the maintenance of its slow‐oxidative fiber character.
Solvation effects in calculated electrostatic association free energies for the C3d‐CR2 complex and comparison with experimental data
Authors: Cheung Alexander S. , Kieslich Chris A. , Yang Jianfeng , Morikis Dimitrios 
Published: January 2010

AbstractThe complement system is an integral part of the innate immune system that participates in the clearance of pathogens from the body. The association between complement protein fragment C3d and B or T cell‐receptor complement receptor (CR) 2 represents a crucial link between innate and adaptive immunities. The goal of this study is to predict association abilities of C3d and CR2 mutants by theoretically calculating electrostatic free energies of association and to assess the importance of solvation effects in the calculations. We demonstrate that calculated solvation free energy differences and Coulombic free energies of association are more sensitive than electrostatic free energies of association in solution and, thus, more accurate in predicting previously published experimental data for the association abilities (relative to the parent proteins) of specific C3d and CR2 mutants. We show that a proportional relationship exists between the predicted solvation free energy differences and the experimental data, while an inversely proportional relationship exists between the predicted Coulombic free energies of association and the experimental data. Our results yield new insights into the physicochemical properties underlying C3d‐CR2 association. We discuss the predictive validity of Coulombic, solvation, and solution electrostatic free energies of association and the generalization of our method for theoretical mutagenesis studies of other systems. This is a basic study, aimed toward improving our understanding of the theoretical basis of immune system regulation at the molecular level. Such insight can serve as the groundwork for the design of regulators with tailored properties, vaccines, and other biotechnology products. © 2010 Wiley Periodicals, Inc. Biopolymers 93:509–519, 2010.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Enhancement of farnesyl diphosphate pool as direct precursor of sesquiterpenes through metabolic engineering of the mevalonate pathway in Saccharomyces cerevisiae
Authors: Asadollahi Mohammad A. , Maury Jérôme , Schalk Michel , Clark Anthony , Nielsen Jens 
Published: January 2010

AbstractThe mevalonate pathway in the yeast Saccharomyces cerevisiae was deregulated in order to enhance the intracellular pool of farnesyl diphosphate (FPP), the direct precursor for the biosynthesis of sesquiterpenes. Over‐expression of the catalytic domain of HMG1, both from the genome and plasmid, resulted in higher production of cubebol, a plant originating sesquiterpene, and increased squalene accumulation. Down‐regulation of ERG9 by replacing its native promoter with the regulatable MET3 promoter, enhanced cubebol titers but simultaneous over‐expression of tHMG1 and repression of ERG9 did not further improve cubebol production. Furtheremore, the concentrations of squalene and ergosterol were measured in the engineered strains. Unexpectedly, significant accumulation of squalene and restoring the ergosterol biosynthesis were observed in the ERG9 repressed strains transformed with the plasmids harboring cubebol synthase gene. This could be explained by a toxicity effect of cubebol, possibly resulting in higher transcription levels for the genes under control of MET3 promoter, which could lead to accumulation of squalene and ergosterol. Biotechnol. Bioeng. 2010; 106: 86–96. © 2010 Wiley Periodicals, Inc.
Microarray and proteomics expression profiling identifies several candidates, including the valosin‐containing protein (VCP), involved in regulating high cellular growth rate in production CHO cell lines
Authors: Doolan Padraig , Meleady Paula , Barron Niall , Henry Michael , Gallagher Ross , Gammell Patrick , Melville Mark , Sinacore Martin , McCarthy Kevin , Leonard Mark , Charlebois Timothy , Clynes Martin 
Published: January 2010

AbstractA high rate of cell growth (µ) leading to rapid accumulation of viable biomass is a desirable phenotype during scale up operations and the early stages of production cultures. In order to identify genes and proteins that contribute to higher growth rates in Chinese hamster ovary (CHO) cells, a combined approach using microarray and proteomic expression profiling analysis was carried out on two matched pairs of CHO production cell lines that displayed either fast or slow growth rates. Statistical analysis of the microarray and proteomic data separately resulted in the identification of 118 gene transcripts and 58 proteins that were differentially expressed between the fast‐ and slow‐growing cells. Overlap comparison of both datasets identified a priority list of 21 candidates associated with a high growth rate phenotype in CHO. Functional analysis (by siRNA) of five of these candidates identified the valosin‐containing protein (VCP) as having a substantial impact on CHO cell growth and viability. Knockdown of HSPB1 and ENO1 also had an effect on cell growth (negative and positive, respectively). Further functional validation in CHO using both gene knockdown (siRNA) and overexpression (cDNA) confirmed that altered VCP expression impacted CHO cell proliferation, indicating that VCP and other genes and proteins identified here may play an important role in the regulation of CHO cell growth during log phase culture and are potential candidates for CHO cell line engineering strategies. Biotechnol. Bioeng. 2010; 106: 42–56. © 2010 Wiley Periodicals, Inc.
Structure and Antibacterial Activity of Brominated Diterpenes from the Red Alga Sphaerococcus coronopifolius
Authors: Smyrniotopoulos Vangelis , Vagias Constantinos , Rahman Mukhlesur M. , Gibbons Simon , Roussis Vassilios 
Published: January 2010

AbstractFour new tetracyclic brominated diterpenes, 1–4, were isolated from the organic extract of Sphaerococcus coronopifolius, collected from the rocky coasts of Corfu Island. The structures of the new natural products, as well as their relative configurations, were elucidated on the basis of extensive spectral analyses, including 2D‐NMR experiments. The isolated metabolites were evaluated for their antibacterial activity against a panel of bacteria including multidrug‐resistant (MDR) and methicillin‐resistant Staphylococcus aureus (MRSA) with MIC values in the range of 16–128 μg/ml.
Terpene Conjugates of the Nigella sativa Seed‐Oil Constituent Thymoquinone with Enhanced Efficacy in Cancer Cells
Authors: Effenberger Katharina , Breyer Sandra , Schobert Rainer 
Published: January 2010

AbstractThymoquinone (TQ; 1) is a weak anticancer constituent of black seed oil. Derivatives bearing terpene‐terminated 6‐alkyl residues were tested in cells of human HL‐60 leukemia, 518A2 melanoma, multidrug‐resistant KB‐V1/Vbl cervix, and MCF‐7/Topo breast carcinomas, as well as in non‐malignant human foreskin fibroblasts. Derivatives with a short four‐atom spacer between quinone and cyclic monoterpene moieties were more antiproliferative than analogues with longer spacers. 6‐(Menthoxybutyryl)thymoquinone (3a) exhibited single‐digit micromolar IC50 (72 h) values in all four cell lines. It was seven times more active than TQ (1) in 518A2 melanoma cells and four times in KB‐V1/Vbl cervix carcinoma cells, while only half as toxic in the fibroblasts. Compound 3a was also not a substrate for the P‐gp and BCRP drug transporters of the resistant cancer cells. The caryophyllyl and germacryl conjugates 3e and 3f specifically inhibited the growth of the resistant MCF‐7 breast carcinoma cells. Conjugation of TQ with the triterpene betulinic acid via the OH group as in 3g led to a loss in activity, while conjugation via the carboxylic acid afforded compound 4 with nanomolar IC50 (72 h) activity against HL‐60 cells. All anticancer‐active derivatives of TQ (1) induced apoptosis associated with DNA laddering, a decrease in mitochondrial membrane potential and a slight increase in reactive oxygen species.
Diagnostic accuracy and limitations of fine‐needle aspiration cytology of bone and soft tissue lesions
Authors: Khalbuss Walid E. , Teot Lisa A. , Monaco Sara E. 
Published: January 2010

AbstractBACKGROUND:Fine‐needle aspiration (FNA) cytology is increasingly being used as a diagnostic modality for soft tissue and bone lesions. These diagnoses can be challenging because of a variety of factors, including interpretation and sampling issues. This study investigates the diagnostic utility of FNA biopsy, in addition to the diagnostic pitfalls, in soft tissue and bone cytopathology.METHODS:We retrospectively reviewed the soft tissue and bone FNAs over a 4‐year period (2004‐2008), along with available ancillary studies, pathological follow‐up, and clinical data. The cases with a cytologic‐histologic discrepancy were then reviewed.RESULTS:A total of 1114 soft tissue and bone FNAs were identified. Of the 1114 aspirates, 525 (47%) were positive for malignant cells, 505 (45.5%) were benign aspirates (including 189 benign lesions/neoplasms), 37 (3.5%) were inadequate, 34 (3%) had atypical cells, and 13 (1%) were suspicious for malignancy. Of the 586 cases (53%) with follow‐up, including 445 cases with histological follow‐up and 141 with ancillary studies, the overall sensitivity was 96%, the specificity was 98%, the positive predictive value was 99%, and the negative predictive value was 92%. A total of 15 false negatives and 3 false positives were identified with errors because of sampling (9 cases), interpretation (7 cases), and screening (2 cases).CONCLUSIONS:This large series demonstrates that there can be a high sensitivity and specificity in diagnosing bone and soft tissue lesions by FNA. Our data supports prior studies in the literature in showing that FNA cytology can be a valuable method for diagnosing these lesions. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.
Receptive‐field properties of V1 and V2 neurons in mice and macaque monkeys
Authors: Van den Bergh Gert , Zhang Bin , Arckens Lutgarde , Chino Yuzo M. 
Published: January 2010

AbstractWe report the results of extracellular single‐unit recording experiments where we quantitatively analyzed the receptive‐field (RF) properties of neurons in V1 and an adjacent extrastriate visual area (V2L) of anesthetized mice with emphasis on the RF center‐surround organization. We compared the results with the RF center‐surround organization of V1 and V2 neurons in macaque monkeys. If species differences in spatial scale are taken into consideration, mouse V1 and V2L neurons had remarkably fine stimulus selectivity, and the majority of response properties in V2L were not different from those in V1. The RF center‐surround organization of mouse V1 neurons was qualitatively similar to that for macaque monkeys (i.e., the RF center is surrounded by extended suppressive regions). However, unlike in monkey V2, a significant proportion of cortical neurons, largely complex cells in V2L, did not exhibit quantifiable RF surround suppression. Simple cells had smaller RF centers than complex cells, and the prevalence and strength of surround suppression were greater in simple cells than in complex cells. These findings, particularly on the RF center‐surround organization of visual cortical neurons, give new insights into the principles governing cortical circuits in the mouse visual cortex and should provide further impetus for the use of mice in studies on the genetic and molecular basis of RF development and synaptic plasticity. J. Comp. Neurol. 518:2051–2070, 2010. © 2010 Wiley‐Liss, Inc.
Topography of ganglion cells and photoreceptors in the sheep retina
Authors: Shinozaki Aya , Hosaka Yoshinao , Imagawa Tomohiro , Uehara Masato 
Published: January 2010

AbstractRetinal topographies of some cell types and distribution of the tapetum lucidum in the sheep's eye were investigated in this study. The tapetum was observed macroscopically in the fundus. The topographical distributions of retinal ganglion cells (RGCs), cones, and rods were simultaneously analyzed in retinal whole mounts stained with cresyl violet. Short‐wavelength‐sensitive (S) cones were immunocytochemically identified in retinal whole mounts. The tapetum was located dorsal to the optic disc, with the nasal part elongated horizontally and the temporal part expanded dorsally. RGCs were distributed densely in the area centralis, horizontal visual streak, and anakatabatic area. The highest density in the area centralis was approximately 18,000 RGCs/mm2. Cones showed high density in the horizontal area crossing the optic disc and dorsotemporal area, whereas rods showed high density in the horizontal area, which was greater in height than the horizontal area of high cone density. S cones showed high density in the dorsotemporal retina. The rod/cone ratios were high horizontally in the dorsal retina to the optic disc, with a mean value of 11:1. The cone/RGC and rod/RGC ratios were lower in the horizontal and dorsotemporal retina, and the rod/cone/RGC ratio was lowest in the area centralis (9:1:1). The retinal topographies and distribution of the tapetum were specialized in the horizontal and dorsotemporal fundus. This suggests that sheep have better visual acuity in horizontal and anteroinferior visual fields and that this specialization is related to the visual ecology of sheep. J. Comp. Neurol. 518:2305–2315, 2010. © 2010 Wiley‐Liss, Inc.
Comparative study of Pax2 expression in glial cells in the retina and optic nerve of birds and mammals
Authors: Stanke Jennifer , Moose Holly E. , El‐Hodiri Heithem M. , Fischer Andy J. 
Published: January 2010

AbstractLittle is known about the expression of Pax2 in mature retina or optic nerve. Here we probed for the expression of Pax2 in late stages of embryonic development and in mature chick retina. We find two distinct Pax2 isoforms expressed by cells within the retina and optic nerve. Surprisingly, Müller glia in central regions of the retina express Pax2, and levels of expression are decreased with increasing distance from the nerve head. In Müller glia, the expression levels of Pax2 are increased by acute retinal damage or treatment with growth factors. At the optic nerve, Pax2 is expressed by peripapillary glia, at the junction of the neural retina and optic nerve head and by glia within the optic nerve. In addition, we assayed for Pax2 expression in glial cells in mammalian retinas. In mammalian retinas, unlike the case in chick retina, the Müller glia do not express Pax2. Pax2‐expressing cells are found in the optic nerve and astrocytes within the mouse retina. By comparison, Pax2‐positive cells are not found within the guinea pig retina; Pax2‐expressing glia are confined to the optic nerve. In dog and monkey (Macaca fascicularis), Pax2 is expressed by astrocytes that are scattered across inner retinal layers and by numerous glia within the optic nerve. Interestingly, Pax2‐positive glial cells are found at the peripheral edge of the dog retina, but only in older animals. We conclude that the expression of Pax2 in the vertebrate eye is restricted to retinal astrocytes, peripapillary glia, and glia within the optic nerve. J. Comp. Neurol. 518:2316–2333, 2010. © 2010 Wiley‐Liss, Inc.
Electronic volume, aldehyde dehydrogenase, and stem cell marker expression in cells from human peripheral blood apheresis samples
Authors: Sharma Siddharth , Shariatmadar Sherry , Krishan Awtar 
Published: January 2010

AbstractBackground:Over‐expression of aldehyde dehydrogenase and other stem cell markers is characteristic of cells with tumorigenic potential in NOD/SCID mice. Most of these studies have focused on metastatic cells in bone marrow and on solid tumors. There are no studies on correlation of marker expression with ALDH1 expression in cells from human peripheral blood apheresis (HPC‐A) samples.Methods:HPC‐A samples from 44 patients were incubated with Aldefluor® with or without the presence of aldehyde dehydrogenase inhibitor DEAB. Cells with high aldehyde dehydrogenase expression (ALDH1bright) were analyzed for stem/progenitor markers CD34, CD90, CD117, and CD133. Electronic volume measured by Coulter principal in a Quanta flow analyzer was correlated with ALDH1 and marker expression.Results:In ALDH1bright/SSClow cells, 0.13% of the cells had CD34+ expression and three distinct populations were seen. Expression of CD90 was dim and the frequency of ALDH1bright/SSClow/CD90dim cells amongst the nonlineage depleted samples was 0.04%. CD117dim‐bright expression was seen in 0.17% of the samples. Three distinct populations of cells with CD133 expression were seen in ALDH1bright/SSClow nonlineage depleted cells with a frequency of 0.28%. The ALDH1bright/CD90dim cells had the smallest mean electronic volume of 264.9 μm3 when compared with cells with CD34bright expression (270.2 μm3) and ALDH1dim/CD90dim cells (223 μm3).Conclusions:ALDH1bright/SSClow cells show heterogeneity in expression of the four stem cell markers studied. The CD90 cells in both the ALDH1bright and ALDH1dim populations had the smallest mean electronic volume when compared with similar cells with CD117 expression. © 2010 Clinical Cytometry Society
Diagnosis of sternomastoid tumor of infancy by fine‐needle aspiration cytology
Authors: Kumar Bipin , Pradhan Anju 
Published: January 2010

AbstractSternomastoid tumor of infancy, also known as fibromatosis colli or muscular torticollis, is a benign fibroblastic lesion of the sternocleidomastoid muscle presenting as a firm, fusiform, nontender neck mass of 1–3 cm in greatest dimension in the perinatal period. Various modalities are used for the diagnosis including radiographic studies, fine‐needle aspiration cytology (FNAC), and open biopsy. We report eight cases of sternomastoid tumor of infancy diagnosed by FNAC. The objective of the study is to present the role of FNAC in the diagnosis of sternomastoid tumor with its cytomorphological features. FNA was done by using 23‐guage needle and 10 ml disposable plastic syringe. The wet smears were fixed in 95% ethanol and processed for Papanicolaou stain. The dried smears were stained with May–Grünwald–Giemsa stain. The smears were studied for cytomorphologic features. The age of the patients ranged between 2 and 10 weeks. Male: Female ratio was 1.6:1. Six of eight had history of prolonged labor, two had history of breech presentation, and three had history of forceps assisted vaginal delivery. Cytologic findings included singly scattered and loose clusters of benign fibroblasts with moderate amount of unipolar to bipolar cytoplasm and plumped, ovoid nuclei. Many multinucleated giant cells consistent with atrophic muscle fibers were also seen. FNAC is a reliable, safe, and cost‐effective method and can provide a rapid and reliable diagnosis of sternomastoid tumor of infancy. Diagn. Cytopathol. 2011;39:13–17. © 2010 Wiley‐Liss, Inc.
Improving the diagnostic accuracy of thyroid follicular neoplasms: Cytological features in fine‐needle aspiration cytology
Authors: Maruta Junko , Hashimoto Hironobu , Suehisa Yuri , Yamashita Hiroto , Noguchi Shiro , Aratake Yatsuki , Ohno Eiji , Kobayashi Tadao K. 
Published: January 2010

AbstractCytological diagnosis in follicular neoplasms of the thyroid has to surmount some difficulties. Capsular/vascular invasions or metastasis are the histological criteria for follicular carcinoma (FC), and, on fine‐needle aspiration (FNA) samples, marked cytological atypias are only observed in moderately to poorly differentiated FC, while they may be completely lacking in well differentiated angio‐ or capsulo‐invasive FC. To clarify the cytological features and to improve the accuracy and reliability of aspiration cytology, 892 follicular adenomas and 82 FCs were reviewed. A macrofollicular pattern or large sheet pattern of follicular cells with thin colloid in the background were found to be indicators of follicular adenoma. Crowding or irregular arrangement of follicular cells were found to indicate microfollicular lesions but could not discriminate between benign and malignant conditions. High nucleo‐cytoplasmic ratio, nuclear atypia, and coarse granular or dense chromatin were more important criteria for malignancy than nuclear grooves or intranuclear cytoplasmic inclusions. The cytomorphologic features of the follicular neoplasms of the thyroid are described, and the difficulties encountered in the cytodiagnosis of follicular lesions are discussed at length. Diagn. Cytopathol. 2011;39:28–34. © 2010 Wiley‐Liss, Inc.