bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD81 Is a Central Regulator of Cellular Events Required for Hepatitis C Virus Infection of Human Hepatocytes
Authors: Brazzoli Michela , Bianchi Alessia , Filippini Sara , Weiner Amy , Zhu Qing , Pizza Mariagrazia , Crotta Stefania 
Published: June 2008

ABSTRACT
Infection with hepatitis C virus (HCV) is still a major public health problem, and the events leading to hepatocyte infection are not yet fully understood. Combining confocal microscopy with biochemical analysis and studies of infection requirements using pharmacological inhibitors and small interfering RNAs, we show here that engagement of CD81 activates the Rho GTPase family members Rac, Rho, and Cdc42 and that the block of these signaling pathways drastically reduces HCV infectivity. Activation of Rho GTPases mediates actin-dependent relocalization of the HCV E2/CD81 complex to cell-cell contact areas where CD81 comes into contact with the tight-junction proteins occludin, ZO-1, and claudin-1, which was recently described as an HCV coreceptor. Finally, we show that CD81 engagement activates the Raf/MEK/ERK signaling cascade and that this pathway affects postentry events of the virus life cycle. In conclusion, we describe a range of cellular events that are manipulated by HCV to coordinate interactions with its multiple coreceptors and to establish productive infections and find that CD81 is a central regulator of these events.
Activation of Akt through gp130 Receptor Signaling Is Required for Kaposi's Sarcoma-Associated Herpesvirus-Induced Lymphatic Reprogramming of Endothelial Cells
Authors: Morris Valerie A. , Punjabi Almira S. , Lagunoff Michael 
Published: June 2008

ABSTRACTKaposi's sarcoma (KS) is the most common tumor of AIDS patients worldwide. KS-associated herpesvirus (KSHV) is the infectious cause of this highly vascularized skin tumor. The main cell type found within a KS lesion, the spindle cell, is latently infected with KSHV and has markers of both blood and lymphatic endothelial cells. During development, lymphatic endothelial cells differentiate from preexisting blood endothelial cells. Interestingly, KSHV infection of blood endothelial cells induces lymphatic endothelial cell differentiation. Here, we show that KSHV gene expression is necessary to maintain the expression of the lymphatic markers vascular endothelial growth factor receptor 3 (VEGFR-3) and podoplanin. KSHV infection activates many cell signaling pathways in endothelial cells and persistently activates STAT3 through the gp130 receptor, the common receptor of the interleukin 6 family of cytokines. We find that KSHV infection also activates the phosphatidylinositol 3-OH-kinase (PI3K)/Akt cell signaling pathway in latently infected endothelial cells and that gp130 receptor signaling is necessary for Akt activation. Using both pharmacological inhibitors and small interfering RNA knockdown, we show that the gp130 receptor-mediated activation of both the JAK2/STAT3 and PI3K/Akt cell signaling pathways is necessary for KSHV-induced lymphatic reprogramming of endothelial cells. The induction of the lymphatic endothelial cell-specific transcription factor Prox1 is also involved in KSHV-induced lymphatic reprogramming. The activation of gp130 receptor signaling is a novel mechanism for the differentiation of blood endothelial cells into lymphatic endothelial cells and may be relevant to the developmental or pathological differentiation of lymphatic endothelial cells as well as to KSHV pathogenesis.
Pathways of Cross-Species Transmission of Synthetically Reconstructed Zoonotic Severe Acute Respiratory Syndrome Coronavirus
Authors: Sheahan Timothy , Rockx Barry , Donaldson Eric , Corti Davide , Baric Ralph 
Published: June 2008

ABSTRACT
Zoonotic severe acute respiratory syndrome coronavirus (SARS-CoV) likely evolved to infect humans by a series of transmission events between humans and animals in markets in China. Virus sequence data suggest that the palm civet served as an amplification host in which civet and human interaction fostered the evolution of the epidemic SARS Urbani strain. The prototypic civet strain of SARS-CoV, SZ16, was isolated from a palm civet but has not been successfully cultured in vitro. To propagate a chimeric recombinant SARS-CoV bearing an SZ16 spike (S) glycoprotein (icSZ16-S), we constructed cell lines expressing the civet ortholog (DBT-cACE2) of the SARS-CoV receptor (hACE2). Zoonotic SARS-CoV was completely dependent on ACE2 for entry. Urbani grew with similar kinetics in both the DBT-cACE2 and the DBT-hACE2 cells, while icSZ16-S only grew in DBT-cACE2 cells. The SZ16-S mutant viruses adapted to human airway epithelial cells and displayed enhanced affinity for hACE2 but exhibited severe growth defects in the DBT-cACE2 cells, suggesting that the evolutionary pathway that promoted efficient hACE2 interactions simultaneously abolished efficient cACE2 interactions. Structural modeling predicted two distinct biochemical interaction networks by which zoonotic receptor binding domain architecture can productively engage hACE2, but only the Urbani mutational repertoire promoted efficient usage of both hACE2 and cACE2 binding interfaces. Since dual species tropism was preserved in Urbani, it is likely that the virus evolved a high affinity for cACE2/hACE2 receptors through adaptation via repeated passages between human and civet hosts. Furthermore, zoonotic SARS-CoV was variably neutralized by antibodies that were effective against the epidemic strain, highlighting their utility for evaluating passive immunization efficacy.
Neurovirulence of Polytropic Murine Retrovirus Is Influenced by Two Separate Regions on Opposite Sides of the Envelope Protein Receptor Binding Domain
Authors: Peterson Karin E. , Pourciau Susan , Du Min , LaCasse Rachel , Pathmajeyan Melissa , Poulsen David , Agbandje-McKenna Mavis , Wehrly Kathy , Chesebro Bruce 
Published: June 2008

ABSTRACT
Changes in the envelope proteins of retroviruses can alter the ability of these viruses to infect the central nervous system (CNS) and induce neurological disease. In the present study, nine envelope residues were found to influence neurovirulence of the Friend murine polytropic retrovirus Fr98. When projected on a three-dimensional model, these residues were clustered in two spatially separated groups, one in variable region B of the receptor binding site and the other on the opposite side of the envelope. Further studies indicated a role for these residues in virus replication in the CNS, although the residues did not affect viral entry.
Capsid Proteins from Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus SIV
mac
Can Coassemble into Mature Cores of Infectious Viruses
Authors: Chen Jianbo , Pathak Vinay K. , Peng Weiqun , Hu Wei-Shau 
Published: June 2008

ABSTRACT

We have recently shown that the Gag polyproteins from human immunodeficiency virus type 1 (HIV-1) and HIV-2 can coassemble and functionally complement each other. During virion maturation, the Gag polyproteins undergo proteolytic cleavage to release mature proteins including capsid (CA), which refolds and forms the outer shell of a cone-shaped mature core. Less than one-half of the CA proteins present within the HIV-1 virion are required to form the mature core. Therefore, it is unclear whether the mature core in virions containing both HIV-1 and HIV-2 Gag consists of CA proteins from a single virus or from both viruses. To determine whether CA proteins from two different viruses can coassemble into mature cores of infectious viruses, we exploited the specificity of the tripartite motif 5α protein from the rhesus monkey (rhTRIM5α) for cores containing HIV-1 CA (hCA) but not the simian immunodeficiency virus SIV
mac
CA protein (sCA). If hCA and sCA cannot coassemble into the same core when equal amounts of sCA and hCA are coexpressed, the infectivities of such virus preparations in cells should be inhibited less than twofold by rhTRIM5α. However, if hCA and sCA can coassemble into the same core structure to form a mixed core, rhTRIM5α would be able to recognize such cores and significantly restrict virus infectivity. We examined the restriction phenotypes of viruses containing both hCA and sCA. Our results indicate that hCA and sCA can coassemble into the same mature core to produce infectious virus. To our knowledge, this is the first demonstration of functional coassembly of heterologous CA protein into the retroviral core.
Year-class strength and growth rates after metamorphosis of Japanese sardine (Sardinops melanostictus) in the western North Pacific Ocean during 1996–2003
Authors: Takahashi Motomitsu , Nishida Hiroshi , Yatsu Akihiko , Watanabe Yoshiro 
Published: June 2008

Growth trajectories during larval to early juvenile stages in Japanese sardine ( Sardinops melanostictus ) were backcalculated based on the widths of otolith daily increments from 1996 to 2003 in the nursery grounds, Kuroshio–Oyashio transitional waters. Planktonic larvae hatched near Kuroshio have been transported northeastward from the Kuroshio waters to the transitional waters. We show that the somatic growth rates sharply increased after metamorphosis to the early juvenile stage, whereas previously, others showed that growth rate decreases during the larval stage. Otolith growth rates were more variable during the juvenile stage than the larval stage. Interannual variations in the otolith growth rate after metamorphosis explained more than 80% of variation in abundances of recruits (ca. 8–10 months old) in the Pacific coastal waters, whereas no correlation was found between the growth rate during the early larval stage and abundance. Our result was consistent with the hypothesis of growth rate-dependent recruitment success in the Kuroshio–Oyashio transitional waters.
Transport and growth of larval cisco (Coregonus artedi) in the Keweenaw Current region of Lake Superior
Authors: Oyadomari Jason K. , Auer Nancy A. 
Published: June 2008

Larval cisco ( Coregonus artedi ) were sampled from Lake Superior off the western coast of the Keweenaw Peninsula (Michigan, USA) to determine if the Keweenaw Current influences their distribution and growth. Bongo net tows were conducted during April–June 2000 from four transects extending from 0.1 to 17 km offshore. For most sampling dates, cisco tended to be slightly more abundant, larger, and older at inshore locations. Later-hatched larvae appeared at the western-most transects first, during which time earlier-hatched larvae disappeared from the study area. This pattern followed what would be expected if larvae were being transported eastward by the prevailing Keweenaw Current. Estimated growth rates were 84% higher for later-hatched compared with earlier-hatched larvae and 25% lower for offshore larvae from the eastern-most transects compared with elsewhere. Accordingly, surface water temperatures partly explained spatial and temporal variations in growth rate. These results indicate that cisco larvae in Lake Superior may be transported great distances from major spawning sites by longshore currents and that the temperature regime of nursery areas may largely control their growth.
Utilizing magnetic resonance imaging (MRI) to assess the effects of angling-induced barotrauma on rockfish (Sebastes)
Authors: Rogers Bonnie L. , Lowe Christopher G. , Fernández-Juricic Esteban , Frank Lawrence R. 
Published: June 2008

The physical consequences of barotrauma on the economically important rockfish ( Sebastes ) were evaluated with a novel method using T2-weighted magnetic resonance imaging (MRI) in combination with image segmentation and analysis. For this pilot study, two fishes were captured on hook-and-line from 100 m, euthanized, and scanned in a 3 Tesla human MRI scanner. Analyses were made on each fish, one exhibiting swim bladder overinflation and exophthalmia and the other showing low to moderate swim bladder overinflation. Air space volumes in the body were quantified using image segmentation techniques that allow definition of individual anatomical regions in the three-dimensional MRIs. The individual exhibiting the most severe signs of barotrauma revealed the first observation of a gas-filled orbital space behind the eyes, which was not observable by gross dissection. Severe exophthalmia resulted in extreme stretching of the optic nerves, which was clearly validated with dissections and not seen in the other individual. Expanding gas from swim bladder overinflation must leak from the swim bladder, rupture the peritoneum, and enter the cranium. This MRI method of evaluating rockfish following rapid decompression is useful for quantifying the magnitude of internal barotrauma associated with decompression and complementing studies on the effects of capture and discard mortality of rockfishes.
Intratumoral Estrogens and Estrogen Receptors in Human Non–Small Cell Lung Carcinoma
Authors: Niikawa Hiromichi , Suzuki Takashi , Miki Yasuhiro , Suzuki Satoshi , Nagasaki Shuji , Akahira Junichi , Honma Seijiro , Evans Dean B. , Hayashi Shin-ichi , Kondo Takashi , Sasano Hironobu 
Published: June 2008

Abstract
Purpose: The possible involvement of gender-dependent factors has been suggested in human non-small cell lung carcinomas (NSCLC), but their precise roles remain largely unclear. Therefore, we examined intratumoral estradiol concentrations in NSCLC to examine local actions of estrogens in NSCLC.
Experimental Design: Fifty-nine frozen specimens of NSCLC were available for liquid chromatography/electrospray tandem mass spectrometry to study intratumoral estradiol concentrations. In addition, A549 NSCLC cells stably expressing estrogen receptor (ER) α (A549 + ERα) or ERβ (A549 + ERβ) were used in vitro studies.
Results: Forty-three (73%) of 59 NSCLC showed higher concentration of estradiol in carcinoma tissues than the corresponding nonneoplastic lung tissues from the same patient, and intratumoral estradiol concentrations were significantly (P = 0.0002 and 2.2-fold) higher than the corresponding nonneoplastic lungs. The intratumoral concentration of estradiol was positively correlated with aromatase expression, tumor size, and Ki-67 status in ERα- or ERβ-positive cases. In in vitro studies, estradiol significantly increased cell proliferation of A549 + ERα or A549 + ERβ, which was significantly suppressed by selective ER modulators, tamoxifen or raloxifene. Both A549 + ERα and A549 + ERβ cells expressed aromatase. The cell proliferation level in these cells was significantly increased under treatment with testosterone, and it was inhibited by addition of the aromatase inhibitor letrozole.
Conclusions: These results suggest that estradiol is locally produced in NSCLC mainly by aromatase and plays an important role in the growth of ERα- or ERβ-positive NSCLC. Therefore, use of selective ER modulators and/or aromatase inhibitors may be clinically effective in NSCLC that are positive for both ER and aromatase.
Expression of t-DARPP Mediates Trastuzumab Resistance in Breast Cancer Cells
Authors: Belkhiri Abbes , Dar Altaf A. , Peng Dun Fa , Razvi Mohammad H. , Rinehart Cammie , Arteaga Carlos L. , El-Rifai Wael 
Published: June 2008

Abstract
Purpose: We have investigated the role of t-DARPP in trastuzumab resistance in ERBB2-amplified and overexpressed breast cancer cell lines.
Experimental Design: We have used the HR-5 and HR-6 trastuzumab-resistant cells that were established from tumors that recurred in the presence of trastuzumab therapy following xenografts of BT-474 cells in nude mice. In addition, SKBR-3 cells, engineered for stable expression of t-DARPP, and HCC-1569 cells, which have constitutive expression of t-DARPP and are de novo resistant to trastuzumab, were used.
Results: We reported ≥15-fold up-regulation of mRNA and protein levels of t-DARPP in HR-5 and HR-6 cells compared with their progenitor BT-474 trastuzumab-sensitive cells. The t-DARPP expression was not regulated by changes in its promoter DNA methylation levels. The SKBR-3 cells stably expressing t-DARPP developed resistance to trastuzumab compared with their parental cells and empty vector controls (P &lt; 0.01). The trastuzumab-resistant cell lines showed a significant increase in pAKT (Ser473) and BCL2 protein levels. The small interfering RNA knockdown of t-DARPP in all trastuzumab-resistant cells led to a significant reduction in ERBB2, pAKT (Ser473), and BCL2 protein levels with a significant decrease in cell viability (P ≤ 0.001) and an increase in cleaved caspase-3 levels, indicating the progression of these cells toward apoptosis. The t-DARPP protein was associated with both heat shock protein 90 and ERBB2 forming a potential protein complex. This association may play a role in regulating ERBB2 protein in trastuzumab-resistant cells.
Conclusion: We conclude that t-DARPP is a novel molecular target that can mediate the therapeutic resistance to trastuzumab in breast cancer cells.
The Derivation of kordiakos: A New Proposal
Authors: Rainbow Jesse John 
Published: June 2008

AbstractThe medical term kordiakos (m. Git. 7:1) is derived not from the anatomical situs of disease, but from the harmful action of a pathogenic demon who acts upon the "heart" to effect a husband's legal incompetence. This is consistent with the Talmud's own definition of kordiakos as the name of a spirit. The Talmud's interest in tales of Solomon's mastery of the demons (b. Git. 67b-71b) is due to the derivation of kordiakos from the verb καρδιóω in Song 4:9 (LXX), which readers understood to describe the enchantment whereby Solomon was led to his own moral collapse (1 Kgs 11:1-10).
Christ King: A Charismatic Appeal for an Ecological Lifestyle
Authors: Suurmond Jean-Jacques 
Published: June 2008

AbstractAs yet, neither Pentecostalism nor the charismatic renewal has produced a consistent theology involving the whole of life. In this article, I hope to show how the spiritual gifts (charisms), poured out on the Church, entail the challenge to manifest the universal reign of Christ. By anticipating the end of creation in which God will become "all in all," his eschatological reign promotes already in the present an ecological unity in diversity.
An Intercomparison of Model Simulations and VPR Estimates of the Vertical Structure of Warm Stratiform Rainfall during TWP-ICE
Authors: Prat Olivier P. , Barros Ana P. , Williams Christopher R. 
Published: June 2008

Abstract
A model of rain shaft microphysics that solves the stochastic advection–coalescence–breakup equation in an atmospheric column was used to simulate the evolution of a stratiform rainfall event during the Tropical Warm Pool-International Cloud Experiment (TWP-ICE) in Darwin, Australia. For the first time, a dynamic simulation of the evolution of the drop spectra within a one-dimensional rain shaft is performed using realistic boundary conditions retrieved from real rain events. Droplet size distribution (DSD) retrieved from vertically pointing radar (VPR) measurements are sequentially imposed at the top of the rain shaft as boundary conditions to emulate a realistic rain event. Time series of model profiles of integral parameters such as reflectivity, rain rate, and liquid water content were subsequently compared with estimates retrieved from vertically pointing radars and Joss–Waldvogel disdrometer (JWD) observations. Results obtained are within the VPR retrieval uncertainty estimates. Besides evaluating the model’s ability to capture the dynamical evolution of the DSD within the rain shaft, a case study was conducted to assess the potential use of the model as a physically based interpolator to improve radar retrieval at low levels in the atmosphere. Numerical results showed that relative improvements on the order of 90% in the estimation of rain rate and liquid water content can be achieved close to the ground where the VPR estimates are less reliable. These findings raise important questions with regard to the importance of bin resolution and the lack of sensitivity for small raindrop size (&lt;0.03 cm) in the interpretation of JWD data, and the implications of using disdrometer data to calibrate radar algorithms.
Diagnostic Analysis of Tidal Winds and the Eliassen–Palm Flux Divergence in the Mesosphere and Lower Thermosphere from TIMED/SABER Temperatures
Authors: Zhu Xun , Yee Jeng-Hwa , Talaat E. R. , Mlynczak M. , Russell J. M. 
Published: June 2008

Abstract
For migrating tides or fast-moving planetary waves, polarization relations derived from the linear wave equations are required to accurately derive the wind components from the temperature field. A common problem in diagnosing winds from the measured temperature is the error amplification associated with apparent singularities in the wave polarization relations. The authors have developed a spectral module that accurately derives tidal winds from the measured tidal temperature field and effectively eliminates the error amplification near the apparent singularities. The algorithm is used to perform a diagnostic analysis of tidal winds and the Eliassen–Palm (EP) flux divergence in the mesosphere and lower thermosphere (MLT) based on the zonal mean and tidal temperature fields derived from 6 yr of temperature measurements made by the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument onboard the Thermosphere–Ionosphere–Mesosphere Energetics and Dynamics (TIMED) satellite. The derived zonal mean wind and diurnal tidal amplitude reveal new insights into the mesospheric biennial oscillation (MBO) that exists in the MLT at both equatorial and midlatitude regions. The equatorial MBO in the zonal mean wind is present in the entire mesosphere from 50 to 90 km. The equatorial MBO in the temperature amplitude of the diurnal tide occurs near the mesopause region between 80 and 90 km and is largely coincident with the downward phase propagation of the equatorial MBO in the zonal mean wind, indicating a possible mechanism of wave–mean flow interaction between the two. On the other hand, the newly discovered midlatitude MBOs in zonal mean wind and the meridional wind in diurnal tide occur at different altitudes, suggesting possibly a remote forcing–response relationship. The acceleration or deceleration of the zonal mean wind due to EP flux divergence that is contributed by the migrating tides peaks at midlatitudes with a typical value of 10–20 m s−1 day−1 around 95 km.