bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial Cells Enhance Prostate Cancer Metastasis via IL-6→Androgen Receptor→TGF-β→MMP-9 Signals
Authors: Wang Xiaohai , Lee Soo Ok , Xia Shujie , Jiang Qi , Luo Jie , Li Lei , Yeh Shuyuan , Chang Chawnshang 
Published: March 2013

Abstract
Although the potential roles of endothelial cells in the microvascules of prostate cancer during angiogenesis have been documented, their direct impacts on the prostate cancer metastasis remain unclear. We found that the CD31-positive and CD34-positive endothelial cells are increased in prostate cancer compared with the normal tissues and that these endothelial cells were decreased upon castration, gradually recovered with time, and increased after prostate cancer progressed into the castration-resistant stage, suggesting a potential linkage of these endothelial cells with androgen deprivation therapy. The in vitro invasion assays showed that the coculture of endothelial cells with prostate cancer cells significantly enhanced the invasion ability of the prostate cancer cells. Mechanism dissection found that coculture of prostate cancer cells with endothelial cells led to increased interleukin (IL)-6 secretion from endothelial cells, which may result in downregulation of androgen receptor (AR) signaling in prostate cancer cells and then the activation of TGF-β/matrix metalloproteinase-9 (MMP-9) signaling. The consequences of the IL-6→AR→TGFβ→MMP-9 signaling pathway might then trigger the increased invasion of prostate cancer cells. Blocking the IL-6→AR→TGFβ→MMP-9 signaling pathway either by IL-6 antibody, AR-siRNA, or TGF-β1 inhibitor all interrupted the ability of endothelial cells to influence prostate cancer invasion. These results, for the first time, revealed the important roles of endothelial cells within the prostate cancer microenvironment to promote the prostate cancer metastasis and provide new potential targets of IL-6→AR→TGFβ→MMP-9 signals to battle the prostate cancer metastasis. Mol Cancer Ther; 12(6); 1026–37. ©2013 AACR.
Old genes and new genes: The evolution of the kallikrein locus
Authors: Lundwall Åke 
Published: March 2013

SummaryThe human kallikrein locus consists of KLK1, the gene of major tissue kallikrein, and 14 genes of kallikrein-related peptidases (KLKs) located in tandem on chromosome 19q13.3-13.4. In this review, based on information retrieved from the literature or extracted from genome databases, it is hypothesised that the kallikrein locus is unique to mammals. The majority of genes are highly conserved, as demonstrated by the identification of 11 KLK genes in the opossum, a metatherian species. In contrast, a sublocus, encompassing KLK1-4, has gone through major transformations that have generated new genes, which in most cases are closely related to KLK1. In the primate lineage, this process created KLK3, the gene of the prostate cancer marker, prostate-specific antigen (PSA), whereas in the murine lineage it gave rise to 13 genes unique to the mouse and nine unique to the rat. The KLK proteases are effector molecules that emerged early in mammalian evolution and their importance in skin homeostasis and male reproductive function is undisputed and there are also accumulating evidence for a role of KLK proteases in the development of the brain. It is speculated that the KLK gene family arose as part of the process that generated distinguishing mammalian features, like skin with hair and sweat glands, and specialised anatomical attributes of the brain and the reproductive tract.
Cardiac-Selective Expression of Extracellular Superoxide Dismutase After Systemic Injection of Adeno-Associated Virus 9 Protects the Heart Against Post–Myocardial Infarction Left Ventricular Remodeling
Authors: Konkalmatt Prasad R. , Beyers Ronald J. , O’Connor Daniel M. , Xu Yaqin , Seaman Marc E. , French Brent A. 
Published: March 2013

Background—
Cardiac magnetic resonance imaging has not been used previously to document the attenuation of left ventricular (LV) remodeling after systemic gene delivery. We hypothesized that targeted expression of extracellular superoxide dismutase (EcSOD) via the cardiac troponin-T promoter would protect the mouse heart against both myocardial infarction (MI) and subsequent LV remodeling.

Methods and Results—

Using reporter genes, we first compared the specificity, time course, magnitude, and distribution of gene expression from adeno-associated virus (AAV) 1, 2, 6, 8, and 9 after intravenous injection. The troponin-T promoter restricted gene expression largely to the heart for all AAV serotypes tested. AAV1, 6, 8, and 9 provided early-onset gene expression that approached steady-state levels within 2 weeks. Gene expression was highest with AAV9, which required only 3.15×10
11
viral genomes per mouse to achieve an 84% transduction rate. AAV9-mediated, cardiac-selective gene expression elevated EcSOD enzyme activity in heart by 5.6-fold (
P
=0.015), which helped protect the heart against both acute MI and subsequent LV remodeling. In acute MI, infarct size in EcSOD-treated mice was reduced by 40% compared with controls (
P
=0.035). In addition, we found that cardiac-selective expression of EcSOD increased myocardial capillary fractional area and decreased neutrophil infiltration after MI. In a separate study of LV remodeling, after a 60-minute coronary occlusion, cardiac magnetic resonance imaging revealed that LV volumes at days 7 and 28 post-MI were significantly lower in the EcSOD group compared with controls.

Conclusions—
Cardiac-selective expression of EcSOD from the cardiac troponin-T promoter after systemic administration of AAV9 provides significant protection against both acute MI and LV remodeling.
The role of serotonin in cognitive function: evidence from recent studies and implications for understanding depression
Authors: Cowen Philip , Sherwood Ann C 
Published: March 2013

Background: Symptoms of cognitive impairment such as poor concentration, memory loss and difficulty with decision making are prevalent in patients with depression, but currently are not specific targets for treatment. However, patients can continue to demonstrate cognitive impairments even when apparently clinically recovered. Drugs that potentiate serotonin (5-HT) function, such as selective serotonin reuptake inhibitors (SSRIs), are the mainstay of treatment for depression. Nevertheless, our understanding of the effects of SSRIs and other conventional antidepressant therapy on cognitive function in healthy humans and depressed patients remains limited. Objective: The purpose of this article is to provide a concise overview for clinicians on the impact of pharmacological manipulation of 5-HT on cognitive function in healthy humans with additional reference to animal models where human data are lacking, particularly regarding specific 5-HT receptor subtype modulation. Findings: The most consistent observation following manipulation of serotonin levels in humans is that low extracellular 5-HT levels are associated with impaired memory consolidation. Preclinical data show that agonism and antagonism at specific 5-HT receptors can exert effects in animal models of cognition. Conclusions: Larger, consistently designed studies are needed to understand the roles of 5-HT in cognition in healthy and depressed individuals. Efforts to target specific 5-HT receptors to improve cognitive outcomes are warranted.
From ClinicalTrials.gov trial registry to an analysis-ready database of clinical trial results
Authors: Cepeda M Soledad , Lobanov Victor , Berlin Jesse A 
Published: March 2013

Background The ClinicalTrials.gov web site provides a convenient interface to look up study results, but it does not allow downloading data in a format that can be readily used for quantitative analyses. Purpose To develop a system that automatically downloads study results from ClinicalTrials.gov and provides an interface to retrieve study results in a spreadsheet format ready for analysis. Methods Sherlock® identifies studies by intervention, population, or outcome of interest and in seconds creates an analytic database of study results ready for analyses. The outcome classification algorithms used in Sherlock were validated against a classification by an expert. Conclusions Having a database ready for analysis that can be updated automatically, dramatically extends the utility of the ClinicalTrials.gov trial registry. It increases the speed of comparative research, reduces the need for manual extraction of data, and permits answering a vast array of questions.
Impact of isolated germline JAK2V617I mutation on human hematopoiesis
Authors: Mead Adam J. , Chowdhury Onima , Pecquet Christian , Dusa Alexandra , Woll Petter , Atkinson Deborah , Burns Adam , Score Joannah , Rugless Michelle , Clifford Ruth , Moule Simon , Bienz Nicola , Vyas Paresh , Cross Nick , Gale Rosemary E. , Henderson Shirley , Constantinescu Stefan N. , Schuh Anna , Jacobsen Sten Eirik W. 
Published: March 2013

Key Points
Germline JAK2V617I mutation as a sole genetic event does not suppress hematopoietic stem cells. JAK2V617I induces weaker constitutive activation than JAK2V617F but considerable cytokine hyperresponsiveness.
Tat engagement of p38 MAP kinase and IRF7 pathways leads to activation of interferon-stimulated genes in antigen-presenting cells
Authors: Kim Nayoung , Kukkonen Sami , Martinez-Viedma Maria Del Pilar , Gupta Sumeet , Aldovini Anna 
Published: March 2013

Key PointsTat acts as an inflammatory cytokine and as an antiviral factor via interaction with MAP2K6, MAP2K3, and IRF7 promoters in APCs. These interactions are the molecular events that link HIV to p38 MAPK activation, which is a mediator of HIV-associated pathology and immune activation.
Construction of a plant-transformation-competent BIBAC library and genome sequence analysis of polyploid Upland cotton (Gossypium hirsutumL.)
Authors: Lee Mi-Kyung , Zhang Yang , Zhang Meiping , Goebel Mark , Kim Hee Jin , Triplett Barbara A , Stelly David M , Zhang Hong-Bin 
Published: March 2013

Abstract

Background
Cotton, one of the world’s leading crops, is important to the world’s textile and energy industries, and is a model species for studies of plant polyploidization, cellulose biosynthesis and cell wall biogenesis. Here, we report the construction of a plant-transformation-competent binary bacterial artificial chromosome (BIBAC) library and comparative genome sequence analysis of polyploid Upland cotton (Gossypium hirsutum L.) with one of its diploid putative progenitor species, G. raimondii Ulbr.

Results
We constructed the cotton BIBAC library in a vector competent for high-molecular-weight DNA transformation in different plant species through either Agrobacterium or particle bombardment. The library contains 76,800 clones with an average insert size of 135 kb, providing an approximate 99% probability of obtaining at least one positive clone from the library using a single-copy probe. The quality and utility of the library were verified by identifying BIBACs containing genes important for fiber development, fiber cellulose biosynthesis, seed fatty acid metabolism, cotton-nematode interaction, and bacterial blight resistance. In order to gain an insight into the Upland cotton genome and its relationship with G. raimondii, we sequenced nearly 10,000 BIBAC ends (BESs) randomly selected from the library, generating approximately one BES for every 250 kb along the Upland cotton genome. The retroelement Gypsy/DIRS1 family predominates in the Upland cotton genome, accounting for over 77% of all transposable elements. From the BESs, we identified 1,269 simple sequence repeats (SSRs), of which 1,006 were new, thus providing additional markers for cotton genome research. Surprisingly, comparative sequence analysis showed that Upland cotton is much more diverged from G. raimondii at the genomic sequence level than expected. There seems to be no significant difference between the relationships of the Upland cotton D- and A-subgenomes with the G. raimondii genome, even though G. raimondii contains a D genome (D5).

Conclusions
The library represents the first BIBAC library in cotton and related species, thus providing tools useful for integrative physical mapping, large-scale genome sequencing and large-scale functional analysis of the Upland cotton genome. Comparative sequence analysis provides insights into the Upland cotton genome, and a possible mechanism underlying the divergence and evolution of polyploid Upland cotton from its diploid putative progenitor species, G. raimondii.
Demonstration of protein-fragment complementation assay using purified firefly luciferase fragments
Authors: Ohmuro-Matsuyama Yuki , Chung Chan-I , Ueda Hiroshi 
Published: March 2013

Abstract

Background
Human interactome is predicted to contain 150,000 to 300,000 protein-protein interactions, (PPIs). Protein-fragment complementation assay (PCA) is one of the most widely used methods to detect PPI, as well as Förster resonance energy transfer (FRET). To date, successful applications of firefly luciferase (Fluc)-based PCA have been reported in vivo, in cultured cells and in cell-free lysate, owing to its high sensitivity, high signal-to-background (S/B) ratio, and reversible response. Here we show the assay also works with purified proteins with unexpectedly rapid kinetics.

Results
Split Fluc fragments both fused with a rapamycin-dependently interacting protein pair were made and expressed in E. coli system, and purified to homogeneity. When the proteins were used for PCA to detect rapamycin-dependent PPI, they enabled a rapid detection (~1 s) of PPI with high S/B ratio. When Fn7-8 domains (7 nm in length) that was shown to abrogate GFP mutant-based FRET was inserted between split Fluc and FKBP12 as a rigid linker, it still showed some response, suggesting less limitation in interacting partner’s size. Finally, the stability of the probe was investigated. Preincubation of the probes at 37 degreeC up to 1 h showed marked decrease of the luminescent signal to 1.5%, showing the limited stability of this system.

Conclusion
Fluc PCA using purified components will enable a rapid and handy detection of PPIs with high S/B ratio, avoiding the effects of concomitant components. Although the system might not be suitable for large-scale screening due to its limited stability, it can detect an interaction over larger distance than by FRET. This would be the first demonstration of Fluc PCA in vitro, which has a distinct advantage over other PPI assays. Our system enables detection of direct PPIs without risk of perturbation by PPI mediators in the complex cellular milieu.
Optimized gold nanoshell ensembles for biomedical applications
Authors: Sikdar Debabrata , Rukhlenko Ivan D , Cheng Wenlong , Premaratne Malin 
Published: March 2013

Abstract
We theoretically study the properties of the optimal size distribution in the ensemble of hollow gold nanoshells (HGNs) that exhibits the best performance at in vivo biomedical applications. For the first time, to the best of our knowledge, we analyze the dependence of the optimal geometric means of the nanoshells’ thicknesses and core radii on the excitation wavelength and the type of human tissue, while assuming lognormal fit to the size distribution in a real HGN ensemble. Regardless of the tissue type, short-wavelength, near-infrared lasers are found to be the most effective in both absorption- and scattering-based applications. We derive approximate analytical expressions enabling one to readily estimate the parameters of optimal distribution for which an HGN ensemble exhibits the maximum efficiency of absorption or scattering inside a human tissue irradiated by a near-infrared laser.
Design of a multi-walled carbon nanotube field emitter with micro vacuum gauge
Authors: Dong Ki-Young , Lee Yang Doo , Kang Byung Hyun , Choi Jinnil , Ju Byeong-Kwon 
Published: March 2013

Abstract
The variation of vacuum level inside a field emission device when electron is emitted from multi-walled carbon nanotubes (MWCNTs) by electric field was measured where MWCNT gauge packaged with a vacuum device was used to measure the degree of a vacuum until the end of the vacuum device life. It was found that the electrical properties of MWCNTs altered with the degree of a vacuum. We fabricated MWCNT gauge which were printed and pasted by the screen printer. In this paper, we report the successful detection of the ionization of gases in vacuum state.
Silica nanoparticles as a tool for fluorescence collection efficiency enhancement
Authors: Krajnik Bartosz , Gajda-Rączka Magdalena , Piątkowski Dawid , Nyga Piotr , Jankiewicz Bartłomiej , Hofmann Eckhard , Mackowski Sebastian 
Published: March 2013

AbstractIn this work we demonstrate enhancement of the fluorescence collection efficiency for chlorophyll-containing photosynthetic complexes deposited on SiO2 spherical nanoparticles. Microscopic images of fluorescence emission reveal ring-like emission patterns associated with chlorophyll-containing complexes coupled to electromagnetic modes within the silica nanoparticles. The interaction leaves no effect upon the emission spectra of the complexes, and the transient behavior of the fluorescence also remains unchanged, which indicates no influence of the silica nanoparticles on the radiative properties of the fluorophores. We interpret this enhancement as a result of efficient scattering of electromagnetic field by the dielectric nanoparticles that increases collection efficiency of fluorescence emission.
Characterising the biology of novel lytic bacteriophages infecting multidrug resistant Klebsiella pneumoniae
Authors: Kęsik-Szeloch Agata , Drulis-Kawa Zuzanna , Weber-Dąbrowska Beata , Kassner Jerzy , Majkowska-Skrobek Grażyna , Augustyniak Daria , Łusiak-Szelachowska Marzanna , Żaczek Maciej , Górski Andrzej , Kropinski Andrew M 
Published: March 2013

AbstractBackgroundMembers of the genusKlebsiellaare among the leading microbial pathogens associated with nosocomial infection. The increased incidence of antimicrobial resistance in these species has propelled the need for alternate/combination therapeutic regimens to aid clinical treatment. Bacteriophage therapy forms one of these alternate strategies.MethodsElectron microscopy, burst size, host range, sensitivity of phage particles to temperature, chloroform, pH, and restriction digestion of phage DNA were used to characterizeKlebsiellaphages.Results and conclusionsOf the 32 isolated phages eight belonged to the familyMyoviridae, eight to theSiphoviridaewhilst the remaining 16 belonged to thePodoviridae. The host range of these phages was characterised against 254 clinicalEnterobacteriaceaestrains including multidrug resistantKlebsiellaisolates producing extended-spectrum beta-lactamases (ESBLs). Based on their lytic potential, six of the phages were further characterised for burst size, physicochemical properties and sensitivity to restriction endonuclease digestion. In addition, five were fully sequenced. Multiple phage-encoded host resistance mechanisms were identified. TheSiphoviridaephage genomes (KP16 and KP36) contained low numbers of host restriction sites similar to the strategy found in T7-like phages (KP32). In addition, phage KP36 encoded its own DNA adenine methyltransferase. The φKMV-like KP34 phage was sensitive to all endonucleases used in this study. Dam methylation of KP34 DNA was detected although this was in the absence of an identifiable phage encoded methyltransferase. TheMyoviridaephages KP15 and KP27 both carried Dam and Dcm methyltransferase genes and other anti-restriction mechanisms elucidated in previous studies. No other anti-restriction mechanisms were found, e.g. atypical nucleotides (hmC or glucosyl hmC), althoughMyoviridaephage KP27 encodes an unknown anti-restriction mechanism that needs further investigation.
Role of Voltage Gated Ca2+ Channels in Rat Visceral Hypersensitivity Change Induced by 2, 4, 6-Trinitrobenzene Sulfonic Acid
Authors: Qian Aihua , Song Dandan , Li Yong , Liu Xinqiu , Tang Dong , Yao Weiyan , Yuan Yaozong 
Published: March 2013

Background Visceral pain is common symptom involved in many gastrointestinal disorders such as inflammatory bowel disease. The underlying molecular mechanisms remain elusive. We investigated the molecular mechanisms and the role for voltage gated calcium channel (VGCC) in the pathogenesis in a rat model of 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) induced visceral inflammatory hypersensitivity. Results Using Agilent cDNA arrays, we found 172 genes changed significantly in dorsal root ganglia (DRG) of TNBS treated rats. Among these changed genes, Cav1.2 and Cav2.3 were significantly up-regulated. Then the RT-PCR and Western blot further confirmed the up-regulation of Cav1.2 and Cav2.3. The whole cell patch clamp recording of acutely dissociated colonic specific DRG neurons showed that the peak IBa density was significantly increased in colonic neurons of TNBS treated rats compared with control rats (−127.82 ± 20.82 pA/pF Vs −91.67 ± 19.02 pA/pF, n = 9, *P < 0.05). To distinguish the different type of calcium currents with the corresponding selective channel blockers, we found that L-type (−38.56 ± 3.97 pA/pF Vs −25.75 ± 3.35 pA/pF, n = 9, * P < 0.05) and R-type (−13.31 ± 1.36 pA/pF Vs −8.60 ± 1.25 pA/pF, n = 9, * P < 0.05) calcium current density were significantly increased in colonic DRG neurons of TNBS treated rats compared with control rats. In addition, pharmacological blockade with L-type antagonist (nimodipine) and R-type antagonist (SNX-482) with intrathecal injection attenuates visceral pain in TNBS induced inflammatory visceral hypersensitivity. Conclusion Cav1.2 and Cav2.3 in colonic primary sensory neurons play an important role in visceral inflammatory hyperalgesia, which maybe the potential therapeutic targets.
Delayed ventricular septal rupture complicating acute inferior wall myocardial infarction
Authors: Cho Jae Hyung , Sattiraju Srinivasan , Mehta Sanjay , Missov Emil 
Published: March 2013

Abstract

Background
Ventricular septal rupture is a potentially fatal complication of acute myocardial infarction. Its incidence has declined with modern reperfusion therapy. In the era of percutaneous coronary interventions, it occurs a median of 18–24 hours after myocardial infarction and is most commonly associated with anterior myocardial infarction. We present a case of delayed ventricular septal rupture complicating acute inferior wall myocardial infarction.

Case presentation
A 53-year-old Caucasian male presented with epigastric pain for three days and electrocardiographic evidence for an acute inferior wall myocardial infarction. Coronary angiography revealed a total occlusion of the proximal right coronary artery. Reperfusion was achieved by balloon angioplasty followed by placement of a bare metal stent. On hospital day six, the patient developed acute respiratory distress, a new loud pansystolic murmur, and hemodynamic instability. Echocardiography revealed the presence of a large defect in the inferobasal interventricular septum with significant left-to-right shunt consistent with ventricular septal rupture. The patient underwent emergent surgical repair with a bovine pericardial patch.

Conclusion
Ventricular septal rupture after myocardial infarction should be suspected in the presence of new physical findings and hemodynamic compromise regardless of revascularization therapy.