bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDK2 Regulates HIV-1 Transcription by Phosphorylation of CDK9 on Serine 90
Authors: Breuer Denitra , Kotelkin Alexander , Ammosova Tatiana , Kumari Namita , Ivanov Andrey , Ilatovskiy Andrey V , Beullens Monique , Roane Philip R , Bollen Mathieu , Petukhov Michael G , Kashanchi Fatah , Nekhai Sergei 
Published: November 2012

Abstract

Background
HIV-1 transcription is activated by the viral Tat protein that recruits host positive transcription elongation factor-b (P-TEFb) containing CDK9/cyclin T1 to the HIV-1 promoter. P-TEFb in the cells exists as a lower molecular weight CDK9/cyclin T1 dimer and a high molecular weight complex of 7SK RNA, CDK9/cyclin T1, HEXIM1 dimer and several additional proteins. Our previous studies implicated CDK2 in HIV-1 transcription regulation. We also found that inhibition of CDK2 by iron chelators leads to the inhibition of CDK9 activity, suggesting a functional link between CDK2 and CDK9. Here, we investigate whether CDK2 phosphorylates CDK9 and regulates its activity.

Results
The siRNA-mediated knockdown of CDK2 inhibited CDK9 kinase activity and reduced CDK9 phosphorylation. Stable shRNA-mediated CDK2 knockdown inhibited HIV-1 transcription, but also increased the overall level of 7SK RNA. CDK9 contains a motif (90SPYNR94) that is consensus CDK2 phosphorylation site. CDK9 was phosphorylated on Ser90 by CDK2 in vitro. In cultured cells, CDK9 phosphorylation was reduced when Ser90 was mutated to an Ala. Phosphorylation of CDK9 on Ser90 was also detected with phospho-specific antibodies and it was reduced after the knockdown of CDK2. CDK9 expression decreased in the large complex for the CDK9-S90A mutant and was correlated with a reduced activity and an inhibition of HIV-1 transcription. In contrast, the CDK9-S90D mutant showed a slight decrease in CDK9 expression in both the large and small complexes but induced Tat-dependent HIV-1 transcription. Molecular modeling showed that Ser 90 of CDK9 is located on a flexible loop exposed to solvent, suggesting its availability for phosphorylation.

Conclusion
Our data indicate that CDK2 phosphorylates CDK9 on Ser 90 and thereby contributes to HIV-1 transcription. The phosphorylation of Ser90 by CDK2 represents a novel mechanism of HIV-1 regulated transcription and provides a new strategy for activation of latent HIV-1 provirus.
RabGDI controls axonal midline crossing by regulating Robo1 surface expression
Authors: Philipp Melanie , Niederkofler Vera , Debrunner Marc , Alther Tobias , Kunz Beat , Stoeckli Esther T 
Published: November 2012

Abstract

Background
Axons navigate to their future synaptic targets with the help of choice points, intermediate targets that express axon guidance cues. Once they reach a choice point, axons need to switch their response from attraction to repulsion in order to move on with the next stage of their journey. The mechanisms underlying the change in axonal responsiveness are poorly understood. Commissural axons become sensitive to the repulsive activity of Slits when they cross the ventral midline of the CNS. Responsiveness to Slits depends on surface expression of Robo receptors. In Drosophila, Commissureless (Comm) plays a crucial regulatory role in midline crossing by keeping Robo levels low on precommissural axons. Interestingly, to date no vertebrate homolog of comm has been identified. Robo3/Rig1 has been shown to control Slit sensitivity before the midline, but without affecting Robo1 surface expression.

Results
We had identified RabGDI, a gene linked to human mental retardation and an essential component of the vesicle fusion machinery, in a screen for differentially expressed floor-plate genes. Downregulation of RabGDI by in ovo RNAi caused commissural axons to stall in the floor plate, phenocopying the effect observed after downregulation of Robo1. Conversely, premature expression of RabGDI prevented commissural axons from entering the floor plate. Furthermore, RabGDI triggered Robo1 surface expression in cultured commissural neurons. Taken together, our results identify RabGDI as a component of the switching mechanism that is required for commissural axons to change their response from attraction to repulsion at the intermediate target.

Conclusion
RabGDI takes over the functional role of fly Comm by regulating the surface expression of Robo1 on commissural axons in vertebrates. This in turn allows commissural axons to switch from attraction to repulsion at the midline of the spinal cord.
Vitreoretinal surgery for bilateral macular holes after laser-assisted in situ keratomileusis for the correction of myopia: a case report
Authors: García-Fernández Miriam , Castro-Navarro Joaquín , Bajo-Fuente Antonio 
Published: November 2012

Abstract

Introduction
Laser-assisted in situ keratomileusis surgery may induce postoperative changes in the vitreomacular interface due to the mechanical stretch of the vitreous produced by the suction ring and the shock waves generated by the excimer laser and, subsequently, may provoke macular hole formation.

Case presentation
A 53-year-old Spanish woman who had undergone a laser-assisted in situ keratomileusis for the correction of myopia in her right and left eye (10 years ago) was referred to our department with a complaint of decreased visual acuity in both eyes. A fundoscopy and optical coherence tomography examination revealed a bilateral full-thickness macular hole. A 23-gauge sutureless pars plana vitrectomy was performed in both eyes, and 1 month after surgery her visual acuity improved and the hole closed.

Conclusion
The development of a bilateral full-thickness macular hole after laser-assisted in situ keratomileusis has been reported once. This case study enhances our understanding of the vitreoretinal pathology induced by laser-assisted in situ keratomileusis, showing the importance of a rigorous follow-up, because complications may occur even a decade later. In this case study we must also consider the contribution of the underlying myopia to the development of the bilateral macular holes.
Inhibition of the ecto-beta subunit of F1F0-ATPase inhibits proliferation and induces apoptosis in acute myeloid leukemia cell lines
Authors: Wen-Li Zhao , Jian Wang , Yan-Fang Tao , Xing Feng , Yan-Hong Li , Xue-Ming Zhu , Min Zhang , Jian Ni , Jian Pan 
Published: November 2012

Abstract

Background
Leukemia, a heterogeneous clonal disorder of hematopoietic progenitor cells, presents a world-wide health problem, especially in childhood. F1F0 ATPase, an inner mitochondrial enzyme, is expressed on the plasma membrane of tumor cells, and its inhibition induces both anti-angiogenic and anti-tumorigenic activity.

Methods
Monoclonal Antibody (McAb) against ATPase was produced by polyethylene glycol-mediated fusions and screened by ELISA. Proliferation, cell cycle and apoptosis of cells were analyzed when the surface ATPase of cells was blockaded with McAb.

Results
We detected cell-membrane expression of the F1F0 ATPase β subunit on 0.1% to 56% of the 11 cell lines derived from leukemia, including acute myeloid leukemia (AML). We produced a monoclonal antibody, McAb7E10, which recognizes both the native and recombinant ATPase β subunit, with a dissociation constant (KD) of 3.26E–10. We demonstrate that McAb7E10 binds to ATPase at the cell surface, where it is able to inhibit ATP synthesis. McAb7E10 significantly inhibited proliferation of AML cell lines in vitro: the relative inhibitory rates of 50 μg/mL McAb7E10 treated MV4-11and HL-60 cells were 69.6% and 81.9% respectively. Cell cycle analysis indicated that McAb7E10 significantly induced apoptosis in MV4-11 and HL-60 cells: the relative rates of apoptosis in 5, 10 and 50ug/mL McAb7E10 treated MV4-11 cells was 3.6 ± 0.83%, 8.4 ± 1.69% and 17.3 ± 2.56% compared to 1.5% ± 0.85% in mouse IgG treated cells (p < 0.01). The relative rate of apoptosis in 5, 10 and 50ug/mL McAb7E10 treated HL-60 cells was 5.5 ± 2.37%, 11.3 ± 3.62% and 19.9 ± 3.31% compared to 1.56% ± 0.97% in mouse IgG treated cells (p < 0.01). Annexin V staining demonstrated that the relative apoptotic rates in 50 μg/mL McAb7E10 treated MV4-11 and HL-60 cells were 50.5% ± 7.04% and 32.9% ± 4.52%, respectively, significantly higher than IgG control antibody treated cells were 21.9% ± 3.11% and 15.3% ± 3.95%, p < 0.01.

Conclusions
These findings indicate that ectopic expression of ATPase β subunit may be a tumor-associated antigen in hematological malignancies. The F1F0 ATPase β subunit provides a potential target for immunotherapy in AML and hematological malignancies.
Hemolymph osmotic, ionic status, and branchial Na+/K+-ATPase activity under varying environmental conditions in the intertidal grapsid crab, Gaetice depressusd
Authors: Nanba Takeshi , Takahashi Hideya , Abe Tsukasa , Godo Waichirou , Ogoshi Maho , Sakamoto Hirotaka , Tsutsui Naoaki , Sakamoto Tatsuya 
Published: November 2012

Abstract
Osmo- and ionoregulatory abilities were examined in the intertidal grapsid crab, Gaetice depressus, transferred from normal seawater (30 ppt) to low (10 ppt) or high (50 ppt) salinities for 2 and 10 days, in addition to animals kept out of water for 2 days. The results of the hemolymph osmotic and ionic status indicate that G. depressus is able to adapt for more than 10 days in these salinities and for 2 days under terrestrial conditions. Especially, the free Ca2+ concentration was relatively maintained compared with concentrations of monovalent ions and osmolality values in 10 and 50 ppt, partly using the complexed calcium (total minus free calcium) as an internal reserve in the hemolymph. In 10 ppt, complexed calcium disappeared from the hemolymph after 10 days, indicating that all the hemolymph calcium was ionized. In 50 ppt, free Ca2+ was regulated to lower levels than concentrations in the medium, while total calcium increased to higher levels after 2 days. Examination of Na+/K+-ATPase activity, which has been implicated in ion transport in many crustaceans, revealed that induction of high Na+/K+-ATPase activity varies among the posterior gills in response to salinities. Ten-ppt salinity induces activity in two of the posterior gills (gill numbers 6 and 7, eight in total), albeit with differing degrees of response. In contrast, 50-ppt salinity stimulates the activity primarily in gill number 8, suggesting that this gill may be associated specifically with ion excretion in G. depressus. As a euryhaline amphibious crab, this abundant species around Japan will serve as a model to study the osmotic/ionic regulatory mechanisms which operate in crustaceans.
Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation
Authors: Luissint Anny-Claude , Artus Cédric , Glacial Fabienne , Ganeshamoorthy Kayathiri , Couraud Pierre-Olivier 
Published: November 2012

AbstractThe Blood–brain barrier (BBB), present at the level of the endothelium of cerebral blood vessels, selectively restricts the blood-to-brain paracellular diffusion of compounds; it is mandatory for cerebral homeostasis and proper neuronal function. The barrier properties of these specialized endothelial cells notably depend on tight junctions (TJs) between adjacent cells: TJs are dynamic structures consisting of a number of transmembrane and membrane-associated cytoplasmic proteins, which are assembled in a multimolecular complex and acting as a platform for intracellular signaling. Although the structural composition of these complexes has been well described in the recent years, our knowledge about their functional regulation still remains fragmentary. Importantly, pericytes, embedded in the vascular basement membrane, and perivascular microglial cells, astrocytes and neurons contribute to the regulation of endothelial TJs and BBB function, altogether constituting the so-called neurovascular unit.The present review summarizes our current understanding of the structure and functional regulation of endothelial TJs at the BBB. Accumulating evidence points to a correlation between BBB dysfunction, alteration of TJ complexes and progression of a variety of CNS diseases, such as stroke, multiple sclerosis and brain tumors, as well as neurodegenerative diseases like Parkinson’s and Alzheimer’s diseases. Understanding how TJ integrity is controlled may thus help improve drug delivery across the BBB and the design of therapeutic strategies for neurological disorders.
Quantitative hormone therapy follow-up in an ER+/ERαKD mouse tumor model using FDG and [11C]-methionine PET imaging
Authors: Paquette Michel , Tremblay Sébastien , Bénard Francois , Lecomte Roger 
Published: November 2012

Abstract

Background
The estrogen receptor α (ERα) is known to play an important role in the modulation of tumor response to hormone therapy. In this work, the effect of different hormone therapies on tumors having different ERα expression levels was followed up in vivo in a mouse model by PET imaging using 2-deoxy-2-[18F]fluoro-d-glucose (FDG) and [11C]-methionine ([11C]-MET). A new model of MC7-L1 ERα-knockdown (ERαKD) tumor cell lines was designed as a negative estrogen receptor control to follow up the effects of changes in ERα expression on the early metabolic tumor response to different hormone therapies.

Methods
MC7-L1 (ER+) and MC7-L1 ERα-knockdown cell lines were implanted subcutaneously in Balb/c mice and allowed to grow up to 4 mm in diameter. Animals were separated into 4 groups (n = 4 or 5) and treated with a pure antiestrogen (fulvestrant), an aromatase inhibitor (letrozole), a selective estrogen receptor modulator (tamoxifen), or not treated (control). Tumor metabolic activity was assessed by PET imaging with FDG and [11C]-MET at days 0 (before treatment), 7, and 14 after the treatment. Tumor uptake of each radiotracer in %ID/g was measured for each tumor at each time point and compared to tumor growth. Quantitative PCR (qPCR) was performed to verify the expression of breast cancer-related genes (ERα, ErbB2, progesterone receptor (PR), and BRCA1) in each tumor cell lines.

Results
While both ER+ and ERαKD tumors had similar uptake of both radiotracers without treatment, higher uptake values were generally seen in ERαKD tumors after 7 and 14 days of treatment, indicating that ERαKD tumors behave in a similar fashion as hormone-unresponsive tumors. Furthermore, the ERα-specific downregulation induced a slight PR expression decrease and overexpression of BRCA1 and ErbB2.

Conclusion
The results indicate that the proposed ER+/ERαKD tumor-bearing mouse model is suitable to test pure antiestrogen and aromatase inhibitor therapies in vivo in a preclinical setting and could help to elucidate the impact of ERα levels on tumor response to hormone therapy.
Life-event specificity: bipolar disorder compared with unipolar depression
Authors: Hosang Georgina M. , Korszun Ania , Jones Lisa , Jones Ian , McGuffin Peter , Farmer Anne E. 
Published: November 2012

BackgroundLittle is known about the impact of different types of stressful events (for example divorcev.bereavement) on unipolar depression compared with bipolar disorder. Inconsistencies exist concerning the association between independent events (beyond an individual's control, such as bereavement) and bipolar disorder.AimsTo examine the role of specific, independent and dependent events in mood disorders.MethodLife-event information was collected from 512 people with bipolar disorder, 1448 people with unipolar depression and over 600 controls.ResultsVarious events were associated with unipolar depression and bipolar disorder, but some event specificity was detected. For example, financial crisis was more strongly related to bipolar disorder rather than unipolar depression. Independent events were only related to unipolar depression and not bipolar disorder.ConclusionsThe events that were linked to bipolar disorder and unipolar depression were similar. Independent events were not associated with bipolar episodes, suggesting that life stress may be a consequence of, rather than a trigger for, bipolar episodes.
Prospective Histomorphometric and DXA Evaluation of Bone Remodeling in Imatinib-Treated CML Patients: Evidence for Site-Specific Skeletal Effects
Authors: Vandyke Kate , Fitter Stephen , Drew Jenny , Fukumoto Seiji , Schultz Christopher G. , Sims Natalie A. , Yeung David T. , Hughes Timothy P. , Zannettino Andrew C. W. 
Published: November 2012

AbstractContext:Imatinib is a tyrosine kinase inhibitor that has been successfully used to treat Philadelphia chromosome-positive chronic myeloid leukemia (CML) and Kit+ gastrointestinal stromal tumors. We have previously shown that imatinib therapy is associated with an increase in trabecular bone volume.Objective:In the present study, we performed a prospective analysis of bone indices in imatinib-treated CML patients to determine the mechanism responsible for this altered bone remodeling.Design, Patients, and Intervention:This study assessed the effects of high-dose (600 mg/d) imatinib on bone parameters in newly diagnosed chronic-phase Philadelphia chromosome-positive CML patients (n = 11) enrolled in the TIDEL II study. At baseline and after 6, 12, and 24 months of treatment, serum markers of bone remodeling were quantitated, dual-energy x-ray absorptiometry analysis of bone mineral density (BMD) was carried out, and a bone biopsy was collected for histological and micro-computed tomography analysis.Results:Our studies show that the increase in trabecular bone volume and trabecular thickness after imatinib treatment was associated with a significant decrease in osteoclast numbers, accompanied by a significant decrease in serum levels of a marker of osteoclast activity. In contrast, osteoblast numbers were not altered by up to 24 months of imatinib treatment. Notably, we also found that imatinib caused a site-specific decrease in BMD at the femoral neck.Conclusions:These data suggest that imatinib therapy dysregulates bone remodeling, causing a generalized decrease in osteoclast number and activity that is not counterbalanced by a decrease in osteoblast activity, leading to increased trabecular bone volume. Further long-term investigations are required to determine the causes and consequences of the site-specific decrease in BMD at the femoral neck.
Synthesis, Crystal Structure, and Electrochemical Properties of (Li,Na)xMn1−yTiyO2 (0 &lt; y &lt; 0.49) with O3-type Layered Structure
Authors: Ishida Naoya , Hayakawa Hiroshi , Shibuya Hideka , Imaizumi Junichi , Akimoto Junji 
Published: November 2012

Abstract
O3-type (Li,Na)xMn1−yTiyO2 (0 &lt; y &lt; 0.49) materials were first prepared from Na0.7Mn1−yTiyO2 via Na/Li ion exchange. The substitution of Ti for Mn was confirmed by using XRD and STEM-EDX mapping. The solubility limit of Ti for Mn was estimated to be less than 0.49. The electrochemical measurements between 4.5 and 2.4 V showed that the initial discharge capacity increased from 163 to 191 mA h g−1 with decreasing Ti contents, while the capacity retention rate increased with Ti contents.
Wavelength Dependence of IR Laser for Dual-laser Shattering of a Water Microdroplet
Authors: Sugiyama Akinori , Nakajima Atsushi 
Published: November 2012

Abstract
For the single- and dual-laser shattering of water microdroplets, the wavelength dependence of an infrared (IR) laser was experimentally examined in the range 2.25–3.75 µm using ion current measurements coupled with time-resolved imaging. Compared to a single IR laser, simultaneous illumination by dual IR lasers effectively compresses the spatial distribution of small fragments around the absorption maximum for the OH-stretching vibration of liquid water (λ = 2.75–3.25 µm). The effect can be explained by the small penetration depth of the IR laser toward water microdroplets.
Synthesis of an Amphiphilic Macromonomer Bearing a Terminal Fluorene Moiety and Its Application to the Preparation of Fluorescent Polymer Particles
Authors: Motoyanagi Jin , Nagura Katsutoshi , Sawada Kohei , Miki Sadao , Minoda Masahiko 
Published: November 2012

Abstract
A new amphiphilic macromonomer MA-PMEEVE-FmPH bearing a methacryloyl group at the α-terminus and a fluorene moiety at the ω-terminus was synthesized by living cationic polymerization and reductive amination, and its application to the preparation of monodisperse polymer particles was studied. It was found that the macromonomer afforded colloidal spheres covered with fluorene moieties, causing it to exhibit fluorescence.
Nickel-catalyzed Cycloaddition of α,β-Unsaturated Oximes with Alkynes: Synthesis of Highly Substituted Pyridine Derivatives
Authors: Yoshida Yuji , Kurahashi Takuya , Matsubara Seijiro 
Published: November 2012

Abstract
A nickel-catalyzed cycloaddition of α,β-unsaturated oximes with alkynes to afford 2,3,4,6-tetrasubstituted pyridine derivatives has been developed. The reaction involves oxidative addition of the N–O bond of α,β-unsaturated oximes to Ni(0) and subsequent alkyne insertion to an N–Ni bond, followed by intramolecular cyclization. It was also found that β,γ-unsaturated oximes participate in the nickel-catalyzed reaction with alkynes to furnish pyridine derivatives.
Rose Bengal Immobilized on Wool as an Efficiently “Green” Sensitizer for Photooxygenation Reactions
Authors: Yan Zhang , Wei Wang , Xun He , Anguo Sang 
Published: November 2012

Abstract
A new type of supported photosensitizer derived from renewable wool and Rose Bengal is described. The novel sensitizer could efficiently promote the photooxygenation of furan derivatives to the corresponding 5-hydroxy-2-(5H)-furanone in excellent yields, via singlet oxygen, using visible light as the energy source. The sensitizer could be easily recovered from the reaction mixture by a simple filtration. It is discovered that the recovered sensitizer can be reused four times.
Synthesis of Unsymmetrical Diarylethynes by Pd(0)/Cu(I)-cocatalyzed Sila-Sonogashira–Hagihara Coupling Reactions of Alkynylsilanes with Aryl Tosylates or Mesylates
Authors: Nishihara Yasushi , Ogawa Daisuke , Noyori Shintaro , Iwasaki Masayuki 
Published: November 2012

Abstract
Palladium/copper-cocatalyzed cross-coupling reactions of alkynylsilanes with aryl tosylates or mesylates afforded the corresponding unsymmetrical diarylethynes in moderate to good yields. The optimized reaction conditions to afford higher yields of cross-coupled products were found to be 5 mol % of [PdCl2(bpy)], 15 mol % of BrettPhos, and 10 mol % of CuICl in DMF as a solvent.
Effect of Temperature on DNA Chromatographic Separation in Free Solution
Authors: Li Ruonan , Liu Lei , Wang Yu , Wang Xiayan 
Published: November 2012

Abstract
Narrow-bore open capillaries without stationary-phase coatings were used for DNA chromatographic separation in free solution. The retention behaviors of various sizes of DNA fragments were investigated using 1 × TE buffer as the eluent at various temperatures. It was shown that the temperature was an important parameter affecting the speed of DNA separation, with little loss of resolution in narrow-bore open-capillary chromatography.
Rapid and High-capacity Adsorption of Glucose Oxidase on Amine-functionalized Mesoporous Silica SBA-15 Platelets
Authors: Ding Yi , Yin Guangfu , Liao Xiaoming , Huang Zhongbin , Chen Xianchun , Yao Yadong 
Published: November 2012

Abstract
We have synthesized platelet-like SBA-15 particles and functionalized their surfaces with amine groups for use as adsorbent materials in glucose oxidase (GOD) adsorption. The amine-functionalized SBA-15 exhibits very rapid (&lt;20 min to reach equilibrium) and high-capacity (up to 680 mg g−1) adsorption of GOD. It is found that electrostatic interaction is the dominant driving force for GOD adsorption on these mesoporous materials.