bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peptide inhibitors of the malaria surface protein, apical membrane antigen 1: Identification of key binding residues
Authors: Lee Erinna F. , Yao Shenggen , Sabo Jennifer K. , Fairlie W. Douglas , Stevenson Rachel A. , Harris Karen S. , Anders Robin F. , Foley Michael , Norton Raymond S. 
Published: January 2011

AbstractApical membrane antigen 1 (AMA1) is essential for malaria parasite invasion of erythrocytes and is therefore an attractive target for drug development. Peptides that bind AMA1 have been identified from random peptide libraries expressed on the surface of phage. Of these, R1, which binds to a hydrophobic ligand binding site on AMA1, was a particularly potent inhibitor of parasite invasion of erythrocytes in vitro. The solution structure of R1 contains a turn‐like conformation between residues 5–10. Here the importance of residues in this turn‐like structure for binding to AMA1 was examined by site‐directed mutagenesis and NMR spectroscopy. The peptide was expressed as a fusion protein following replacement of Met16 by Leu in order to accommodate cyanogen bromide cleavage. This modified peptide (R2) displayed the same affinity for AMA1 as R1, showing that the identity of the side chain at position 16 was not critical for binding. Substitution of Phe5, Pro7, Leu8, and Phe9 with alanine led to significant (7.5‐ to >350‐fold) decreases in affinity for AMA1. Comparison of backbone amide and CαH chemical shifts for these R2 analogues with corresponding values for R2 showed no significant changes, with the exception of R2(P7A), where slightly larger differences were observed, particularly for residues flanking position 7. The absence of significant changes in the secondary chemical shifts suggests that these mutations had little effect on the solution conformation of R2. The identification of a nonpolar region of these peptides containing residues essential for AMA1 binding establishes a basis for the design of anti‐malarial drugs based on R1 mimetics. © 2011 Wiley Periodicals, Inc. Biopolymers 95: 354–364, 2011.
Large scale chiral chromatography for the separation of an enantiomer to accelerate drug development
Authors: Hsu Leo C. , Kim Hyunjung , Yang Xiqin , Ross David 
Published: January 2011

AbstractThere are several approaches to produce enantiomerically pure drug substances, such as recrystallization, catalytic process (ligand and enzyme), indirect chromatographic resolution, and direct chromatographic resolution. However, the use of preparative chromatography with chiral stationary phases seems to be most effective for early phase projects, where the time and resources on the developments need to be minimized to get the drug candidates into the clinical studies. We showed that by following a well‐defined process, chiral chromatography can be easily scaled up from an analytical system to a pilot plant system. We also used the results from a multicolumn continuous chromatography (MCC) study to conclude that MCC can be a cost‐effective production method for chiral manufacturing. Chirality, 2011. © 2011 Wiley‐Liss, Inc.
Solvent‐free synthesis of chiral Schiff‐base ligands based on ferrocene under microwave irradiation and application to enantioselective nitroaldol (Henry) reaction
Authors: Öztürk Gülşen , Çolak Mehmet , Demirel Nadir 
Published: January 2011

AbstractChiral Schiff‐bases3a,3b,3c,3d,3e,3fbased on ferrocene were designed and synthesized using solvent‐free methods by mixing ferrocene carbaldehyde 1 with amino alcohols and amines2a,2b,2c,2d,2e,2funder microwave irradiation and classical method for the enantioselective nitroaldol (Henry) reaction. The Schiff‐bases were obtained in shorter reaction times and improved yield under microwave irradiation method over classical method. The highest enantioselectivity was observed in ligand3e(95% ee) when CH2Cl2was used as solvent. Chirality, 2011. © 2011 Wiley‐Liss, Inc.
Pharmacokinetics and magnetic resonance imaging of biodegradable macromolecular blood‐pool contrast agent PG–Gd in non‐human primates: a pilot study
Authors: Tian Mei , Wen Xiaoxia , Jackson Edward F. , Ng Chaan , Uthamanthil Rajesh , Liang Dong , Gelovani Juri G. , Li Chun 
Published: January 2011

AbstractThe purpose of this study was to evaluate poly(L‐glutamic acid)‐benzyl‐DTPA–Gd (PG–Gd), a new biodegradable macromolecular magnetic resonance imaging contrast agent, for its pharmacokinetics and MRI enhancement in nonhuman primates. Studies were performed in rhesus monkeys at intravenous doses of 0.01, 0.02 and 0.08 mmol Gd/kg. T1‐weighted MR images were acquired at 1.5 T using fast spoiled gradient recalled echo and fast spin echo imaging protocols. The small‐molecule contrast agent Magnevist was used as a control. PG–Gd in the monkey showed a bi‐exponential disposition. The initial blood concentrations within 2 h of PG–Gd administration were much higher than those for Magnevist. The high blood concentration of PG–Gd was consistent with the MR imaging data, which showed prolonged circulation of PG–Gd in the blood pool. Enhancement of blood vessels and organs with a high blood perfusion (heart, liver, and kidney) was clearly visualized at 2 h after contrast injection at the three doses used. A greater than proportional increase of the area under the blood concentration–time curve was observed when the administered single dose was increased from 0.01 to 0.08 mmol/kg. By 2 days after PG–Gd injection, the contrast agent was mostly cleared from all major organs, including kidney. The mean residence time was 15 h at the 0.08 mmol/kg dose. A similar pharmacokinetic profile was observed in mice, with a mean residence time of 5.4 h and a volume of distribution at steady‐state of 85.5 ml/kg, indicating that the drug was mainly distributed in the blood compartment. Based on this pilot study, further investigations on the potential systemic toxicity of PG–Gd in both rodents and large animals are warranted before testing this agent in humans. Copyright © 2011 John Wiley & Sons, Ltd.
Cytomorphology of male breast lesions: Diagnostic pitfalls and clinical implications
Authors: Rosa Marilin , Masood Shahla 
Published: January 2011

AbstractBecause lesions of the male breast have been exceeded in number by those of the female breast, marginal attention was given to these lesions in the past. Fortunately, this has changed over the years leading to an increased awareness about male breast cancer. Although male breast cancer constitutes only about 1% of all diagnosed breast cancer cases, an increased mortality is seen in this patient population. This is probably caused by late diagnosis as a consequence of low level of concern about breast cancer among male patients.However, the vast majority of lesions of the male breast are benign, gynecomastia being the number one cause of unilateral or bilateral breast mass. Since it is important to avoid unnecessary surgical treatment without missing malignancy, accurate diagnostic tools are necessary in order to triage these patients. Fine‐needle aspiration biopsy has demonstrated excellent accuracy in the diagnosis and management of breast lesions in female patients. In addition, several authors have proven the value of this technique in the evaluation of lesions of the male breast. Fine‐needle aspiration biopsy permits accurate diagnosis in many lesions arising in the male breast. It also allows gathering cytological material that can be used for ancillary studies which enhances the diagnostic value of this technique. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.
Cytokeratin‐20 immunocytochemistry in voided urine cytology and its comparison with nuclear matrix protein‐22 and urine cytology in the detection of urothelial carcinoma
Authors: Srivastava Ruchi , Arora Vinod Kumar , Aggarwal Seema , Bhatia Arati , Singh Navjeevan , Agrawal Vivek 
Published: January 2011

AbstractThis study was done on 59 subjects (42 urinary bladder carcinoma patients and 17 non‐neoplastic controls). Urine cytology and bladder chek NMP22 test was done on all cases. CK20 immunostaining was performed on archived papanicolaou stained urine cytology smears in 34 cases (27 bladder carcinoma and 7 negative controls). Results of all three tests (cytology, NMP22, and CK20 immunostaining) were compared with histopathology to evaluate the accuracy of individual test. The combination of cytology and NMP22 was compared with combination of cytology and CK20 immunostaining for detection of bladder carcinoma. NMP22 had sensitivity of 92.9% and specificity of 70.6%, as compared with voided urine cytology (sensitivity of 76.2% and specificity of 76.5%) and CK20 immunostaining (sensitivity of 70.4% and specificity of 71.4%). Combination of cytology and NMP22 gave better results (sensitivity of 88.1% and specificity of 88.2%) than combination of cytology and CK20 immunostaining or any other test in isolation. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.
Forest ecohydrological research in the 21st century: what are the critical needs?
Authors: Vose James M. , Sun Ge , Ford Chelcy R. , Bredemeier Michael , Otsuki Kyoichi , Wei Xiaohua , Zhang Zhiqiang , Zhang Lu 
Published: January 2011

AbstractModern ecohydrologic science will be critical for providing the best information to policy makers and society to address water resource challenges in the 21st century. Implicitly, ecohydrology involves understanding both the functional interactions among vegetation, soils, and hydrologic processes at multiple scales and the linkages among upland, riparian, and aquatic components. In this paper, we review historical and contemporary ecohydrologic science, focusing on watershed structure and function and the threats to watershed structure and function. Climate change, land use change, and invasive species are among the most critical contemporary issues that affect water quantity and quality, and a mechanistic understanding of watershed ecosystem structure and function is required to understand their impacts on water quantity and quality. Economic and social values of ecosystem services such as water supply from forested watersheds must be quantified in future research, as land use decisions that impact ecohydrologic function are driven by the interplay among economic, social, political, and biological constraints. Future forest ecohydrological research should focus on: (1) understanding watershed responses to climate change and variability, (2) understanding watershed responses to losses of native species or additions of non‐native species, (3) developing integrated models that capitalize on long‐term data, (4) linking ecohydrologic processes across scales, and (5) managing forested watersheds to adapt to climate change. We stress that this new ecohydrology research must also be integrated with socio‐economic disciplines. Published in 2011. This article is a US Government work and is in the public domain in the USA.
Assessment of heritable genetic effects using new genetic tools and sentinels in an era of personalized medicine
Authors: Elespuru Rosalie K. 
Published: January 2011

AbstractThe challenge of estimating human health effects from damage to the germ line may be met in the genomic era. Understanding the genetic, as opposed to postconception developmental basis of birth defects is critical to their use in monitoring heritable genetic damage. The causes of common birth defects are analyzed here: mendelian genetic, multigenic, developmental, inherited, or combinational. Only a small fraction of these (noninherited, mendelian genetic) are likely to be informative relative to germ cell mutagenesis, and these won't be discernible against the general background of birth defects. Targeted genetic testing as part of personalized medicine could be integrated into a strategy for assessing germ cell alterations in populations. Thus, “sentinel mutations,” as originally proposed by Mulvihill and Ceizel, need not be restricted to X‐linked or dominant mutations or conditions visible at birth. Several new sentinels related to personalized medicine are proposed, based on health impact (likelihood of monitoring), frequency, and genetic target suitability (responsiveness to diverse mutational mechanisms). Candidates could include CYP genes (related to metabolism of xenobiotics) important in optimizing drug doses and avoiding adverse reactions. High frequency LDLR mutations (related to familial high cholesterol) predict myocardial infarction in ∼50% of individuals. The more common recessive genetic diseases (cystic fibrosis, phenylketonuria, and others) monitored in newborn screening programs could be informative given parental analysis. New opportunities for genetic analyses need to be coupled with epidemiological studies on environmental exposures. These could focus on adverse outcomes related to tobacco, the mostubiquitous and potent environmental mutagen. Environ. Mol. Mutagen., 2011. Published 2011 Wiley‐Liss, Inc.
Expression of N‐methyl D‐aspartate receptor subunits in amoeboid microglia mediates production of nitric oxide via NF‐κB signaling pathway and oligodendrocyte cell death in hypoxic postnatal rats
Authors: Murugan Madhuvika , Sivakumar Viswanathan , Lu Jia , Ling Eng‐Ang , Kaur Charanjit 
Published: January 2011

AbstractThe present study was focused on identifying the expression of N‐methyl D‐aspartate receptor (NMDAR) subunits on activated microglia and to determine their role in the pathogenesis of periventricular white matter damage (PWMD) in neonatal rats following hypoxia. One day old wistar rats were subjected to hypoxia (5% O2; 95% N2) and the mRNA and protein expression of NMDAR subunits (NR1, NR2A‐D, and NR3A) in the periventricular white matter (PWM) was determined at different time points (3,24 h, 3, 7, and 14 days) following hypoxic exposure. Immunoexpression of NR1 and NR2A‐D was localized in amoeboid microglial cells (AMC) suggesting the presence of functional NMDARs in them. The expression of NMDAR in primary microglial cultures was ascertained by RT‐PCR analysis and double immunofluorescence studies. The functionality of the microglial NMDAR in cultured microglial cells was examined by monitoring calcium movements in cells with fura‐2. In primary microglial cultures, hypoxia induced the nuclear translocation of NF‐κB which was suppressed by administration of MK801, an NMDAR antagonist. MK801 also down regulated the hypoxia‐induced expression of tumor necrosis factor‐α, interleukin‐1β, inducible nitric oxide synthase (iNOS), and nitric oxide (NO) production by microglia which may be mediated by the NF‐κB signaling pathway. NO produced by microglia is known to cause death of oligodendrocytes in the developing PWM. In this connection, pharmacological agents such as MK801, BAY (NF‐κB inhibitor), and 1400w (iNOS inhibitor) proved to be beneficial since they reduced the hypoxia‐induced iNOS expression, NO production, and a corresponding reduction in the death of oligodendrocytes following hypoxia. © 2011 Wiley‐Liss, Inc.
Transcriptional regulation of peripheral glial cell differentiation in the embryonic nervous system of drosophila
Authors: Schmidt Imke , Franzdóttir Sigrídur Rut , Edenfeld Gundula , Rodrigues Floriano , Zierau Ariane , Klämbt Christian 
Published: January 2011

AbstractThe Drosophila nervous system is ideally suited to study glial cell development and function, because it harbors only relatively few glial cells, and nervous system development is very well conserved during evolution. In the past, enhancer trap studies provided tools allowing to study glial cells with a single‐cell resolution and, moreover, disclosed a surprising molecular heterogeneity among the different glial cells. The peripheral nervous system in the embryo comprises only 12 glial cells in one hemisegment and thus offers a unique opportunity to decipher the mechanisms directing glial development. Here, we focus on transcriptional regulators that have been reported to function during gliogenesis. To uncover additional regulators, we have conducted a genetic screen and report the identification of two additional transcriptional regulators involved in the control of peripheral glial migration: nejire and tango. © 2011 Wiley‐Liss, Inc.
Following nerve injury neuregulin‐1 drives microglial proliferation and neuropathic pain via the MEK/ERK pathway
Authors: Calvo Margarita , Zhu Ning , Grist John , Ma Zhenzhong , Loeb Jeffrey A. , Bennett David L. H. 
Published: January 2011

AbstractFollowing peripheral nerve injury microglia accumulate within the spinal cord and adopt a proinflammatory phenotype a process which contributes to the development of neuropathic pain. We have recently shown that neuregulin‐1, a growth factor released following nerve injury, activates erbB 2, 3, and 4 receptors on microglia and stimulates proliferation, survival and chemotaxis of these cells. Here we studied the intracellular signaling pathways downstream of neuregulin‐1‐erbB activation in microglial cells. We found that neuregulin‐1 in vitro induced phosphorylation of ERK1/2 and Akt without activating p38MAPK. Using specific kinase inhibitors we found that the mitogenic effect of neuregulin‐1 on microglia was dependant on MEK/ERK1/2 pathway, the chemotactic effect was dependant on PI3K/Akt signaling and survival was dependant on both pathways. Intrathecal treatment with neuregulin‐1 was associated with microgliosis and development of mechanical and cold pain related hypersensitivity which was dependant on ERK1/2 phosphorylation in microglia. Spinal nerve ligation results in a robust microgliosis and sustained ERK1/2 phosphorylation within these cells. This pathway is downstream of neuregulin‐1/erbB signaling since its blockade resulted in a significant reduction in microglial ERK1/2 phosphorylation. Inhibition of the MEK/ERK1/2 pathway resulted in decreased spinal microgliosis and in reduced mechanical and cold hypersensitivity after peripheral nerve damage. We conclude that neuregulin‐1 released after nerve injury activates microglial erbB receptors which consequently stimulates the MEK/ERK1/2 pathway that drives microglial proliferation and contributes to the development of neuropathic pain. © 2011 Wiley‐Liss, Inc.
A systematic review of the effects of physical activity on physical functioning, quality of life and depression in older people with dementia
Authors: Potter Rachel , Ellard David , Rees Karen , Thorogood Margaret 
Published: January 2011

AbstractBackgroundDepression is common in older people with dementia. Physical activity is effective in reducing depression in adults but there is limited evidence about its effectiveness in people with dementia.Design and MethodsA systematic review and partial meta‐analysis of physical activity interventions in people with dementia is reported. We searched eight databases for English language papers and reference lists of relevant papers. Included studies reported a physical activity intervention lasting at least 12 weeks in which participants were older and had a diagnosis of dementia. Studies compared the intervention with a non‐active or a no‐intervention control and reported at least one outcome related to physical function, quality of life or depression. At least two authors independently assessed each paper for inclusion and for study quality and extracted data.ResultsWe included 13 randomised controlled trials with 896 participants. Three of six trials that reported walking as an outcome found an improvement, as did four of the five trials reporting timed get up and go tests. Only one of the four trials that reported depression as an outcome found a positive effect. Both trials that reported quality of life found an improvement.ConclusionsThere is some evidence that physical activity interventions improve physical function in older people with dementia. Evidence for an effect on depression and quality of life is limited. Copyright © 2011 John Wiley & Sons, Ltd.
Epigenetic regulation of miR‐34b and miR‐129 expression in gastric cancer
Authors: Tsai Kuo‐Wang , Wu Chew‐Wun , Hu Ling‐Yueh , Li Sung‐Chou , Liao Yu‐Lun , Lai Chun‐Hung , Kao Hsiao‐Wei , Fang Wen‐Liang , Huang Kuo‐Hung , Chan Wen‐Ching , Lin Wen‐Chang 
Published: January 2011

AbstractMicroRNAs (miRNAs) are small noncoding RNAs that play fundamental roles in diverse biological and pathological processes by targeting the expression of specific genes. Here, we identified 38 methylation‐associated miRNAs, the expression of which could be epigenetically restored by cotreatment with 5‐aza‐2′‐deoxycytidine and trichostatin A. Among these 38 miRNAs, we further analyzed miR‐34b, miR‐127‐3p, miR‐129‐3p and miR‐409 because CpG islands are predicted adjacent to them. The methylation‐silenced expression of these miRNAs could be reactivated in gastric cancer cells by treatment with demethylating drugs in a time‐dependent manner. Analysis of the methylation status of these miRNAs showed that the upstream CpG‐rich regions of mir‐34b and mir‐129‐2 are frequently methylated in gastric cancer tissues compared to adjacent normal tissues, and their methylation status correlated inversely with their expression patterns. The expression of miR‐34b and miR‐129‐3p was downregulated by DNA hypermethylation in primary gastric cancers, and the low expression was associated with poor clinicopathological features. In summary, our study shows that tumor‐specific methylation silences miR‐34b and miR‐129 in gastric cancer cells.
Activated hepatic stellate cells promote hepatocellular carcinoma development in immunocompetent mice
Authors: Zhao Wenxiu , Zhang Lei , Yin Zhenyu , Su Weixue , Ren Guangli , Zhou Changsheng , You Junyong , Fan Jia , Wang Xiaomin 
Published: January 2011

AbstractActivated hepatic stellate cells (HSCs) play a central role in the hepatic fibrosis and cirrhosis. Recently, HSCs were reported to have strong immune modulatory activities. However, the role of HSCs in hepatocellular carcinoma (HCC) remains unclear. In this study, we showed that HSCs could promote HCC growth both in vitro and in vivo. We examined the HSC‐mediated inhibition of T‐cell proliferation and the ability of conditioned medium from activated HSCs to promote the growth of murine HCC cell lines in vitro. We also assessed the immune suppression by HSCs during the development of HCC in immunocompetent mice. Cotransplantation of HSCs promoted HCC growth and progression by enhancing tumor angiogenesis and tumor cell proliferation and by creating an immunosuppressed microenvironment. Cotransplanted HSCs inhibited the lymphocyte infiltration in tumors and the spleens of mice bearing tumors, induced apoptosis of infiltrating mononuclear cells, and enhanced the expression of B7H1 and CD4+CD25+ Treg cells. The immune modulation by HSCs seemed to be systemic. In conclusion, our data provide new information to support an integral role for HSCs in promoting HCC progression in part via their immune regulatory activities, and suggest that HSCs may serve as a therapeutic target in HCC.