bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surface Elastic Properties of Human Retinal Pigment Epithelium Melanosomes†
Authors: Guo Senli , Hong Lian , Akhremitchev Boris B. , Simon John D. 
Published: April 2008

AbstractAtomic force microscope (AFM) imaging and nanoindentation measurements in water were used to probe the mechanical properties of retinal pigment epithelium melanosomes isolated from 14‐year‐old and 76‐year‐old donors. Topographic imaging reveals surface roughness similar to previous measurements on dry melanosomes. Force‐indentation measurements show different types of responses that were catalogued into four different categories. In these measurements no permanent surface damage of melanosomes was observed as revealed by imaging before and after indentation measurements. The indentation measurements that exhibited nearly elastic responses were used to determine the Young’s modulus of melanosomes. The average Young’s modulus values are similar for 14‐year‐old and 76‐year‐old melanosomes with a somewhat narrower distribution for the 14‐year‐old sample. These elastic modulus values are considerably higher than the modulus of organelles with cytoplasm (<1 MPa) and approaching values of the modulus of protein crystals (∼100 MPa) indicating rather high packing density of biologic material in melanosomes. The width of the Young’s modulus distributions is considerable spanning from few megapascals to few tens of megapascals indicating large heterogeneity in the structure. A fraction of the force curves cannot be described by the homogeneous elastic sample model; these force curves are consistent with ∼10 nm structural heterogeneity in melanosomes. The approach‐withdraw hysteresis indicates a significant viscoelasticity, particularly in the samples from the 14‐year‐old sample. Adhesion of the AFM probe was detected on ∼3% and ∼20% of the surface of 14‐year‐old and 76‐year‐old samples, respectively. In light of previous studies on these same melanosomes using photoelectron emission microscopy, this adhesion is attributed to the presence of lipofuscin on the surface of the melanosomes. This suggestion indicates that part of the difference in photochemical properties between the old and young melanosomes originates from surface lipofuscin.
Quantitation of the Effect of Hydroxylamine on Rhodopsin Palmitylation†
Authors: Jackson Wesley , Ablonczy Zsolt , Crouch Rosalie K. 
Published: April 2008

AbstractRhodopsin (the photosensitive rod visual pigment) has been a model for photobiologic studies of the opsins as well as a structural model for G‐protein‐coupled receptors. The two palmitate groups attached to cysteines 322 and 323 are thought to serve as membrane anchors for the rhodopsin C‐terminus, but the absence of the palmitates does not alter membrane localization. However, removal of the palmitates affects rhodopsin function. Therefore, it is important to quantitate the stability of rhodopsin palmitates to hydroxylamine, which is a widely utilized reagent in biochemical preparations of the apoprotein. We have developed a mass spectrometric method to quantitate the resulting opsin palmitylation. Our data show that both of the bovine rhodopsin palmitates are labile to hydroxylamine, with significant depalmitylation occurring at concentrations of ≥100 mm, with an EC50 of 220 mm L−1. The palmitate at position 322 is the more stable to hydroxylamine. Samples prepared in the presence of >50 mm should therefore be considered to be at least partially depalmitylated and the results interpreted accordingly.
Identification of Six New Photoactive Yellow Proteins—Diversity and Structure–Function Relationships in a Bacterial Blue Light Photoreceptor†
Authors: Kumauchi Masato , Hara Miwa T. , Stalcup Page , Xie Aihua , Hoff Wouter D. 
Published: April 2008

AbstractPhotoactive yellow proteins (PYP) are bacterial photoreceptors with a Per‐Arnt‐Sim (PAS) domain fold. We report the identification of six new PYPs, thus nearly doubling the size of this protein family. This extends the taxonomic diversity of PYP‐containing bacteria from photosynthetic to nonphotosynthetic bacteria, from aquatic to soil‐dwelling organisms, and from Proteobacteria to Salinibacter ruber from the phylum Bacteriodetes. The new PYPs greatly increase the sequence diversity of the PYP family, reducing the most prevalent pair‐wise identity from 45% to 25%. Sequence alignments and analysis indicate that all 14 PYPs share a common structure with 13 highly conserved residues that form the chromophore binding pocket. Nevertheless, the functional properties of the PYPs vary greatly—the absorbance maximum extends from 432 to 465 nm, the pKa of the chromophore varies from pH 2.8 to 10.2, and the lifetime of the presumed PYP signaling state ranges from 1 ms to 1 h. Thus, the PYP family offers an excellent opportunity to investigate how functional properties are tuned over a wide range, while maintaining the same overall protein structural fold. We discuss the implications of these results for structure–function relationships in the PYP family.
Escalating Antihypertensive Medications in End‐Stage Renal Disease Patients Does Not Improve Blood Pressure Control
Authors: Tapolyai Mihály , Karim Jariatul , Fakhruddin Atif 
Published: April 2008

The authors examined the efficacy of antihypertensive medication use in end‐stage renal disease (ESRD). They compared achieved blood pressures (BPs) in a cross‐sectional study of 106 ESRD patients whose medications had not been changed for at least 2 months. Group 1 (n=36) included patients who took 0 or 1 medication; group 2 (n=56), 2 or 3 medications; and group 3 (n=14), ≥4 medications. The population's mean age was 55.1 years, 87% were African American, and 57% were men weighing 76.9 kg who were on 229 minutes of hemodialysis with an edKt/V of 1.35; there was no difference between the 3 groups. The authors found a difference in the mean BPs: 139/72 mm Hg in group 1, 154/82 mm Hg in group 2, and 165/91 mm Hg in group 3 (P=.01 for systolic, P=.002 for diastolic), with a mean arterial pressure difference of 94.4, 106.4, and 115.4 mm Hg (P=.002). The authors conclude that in this group of primarily African American patients, the control of hypertension in ESRD is not achieved by escalating the number of antihypertensive medications.J Clin Hypertens (Greenwich). 2008;10:215–218.
Effects of Antenatal and Postnatal Environments on CD4 T-Cell Responses toMycobacterium bovisBCG in Healthy Infants in The Gambia
Authors: Miles David J. C. , van der Sande Marianne , Crozier Sarah , Ojuola Olubukola , Palmero Melba S. , Sanneh Mariama , Touray Ebrima S. , Rowland-Jones Sarah , Whittle Hilton , Ota Martin , Marchant Arnaud 
Published: April 2008

ABSTRACTTheMycobacterium bovisBCG vaccine has a poor record of efficacy in low-income tropical settings. Against this background, we evaluated the immune response of infants to mycobacterial antigens over the 2 years following BCG vaccination at birth by measuring the gamma interferon (IFN-γ), interleukin-2 (IL-2), and CD154 responses of CD4 T cells. Similar numbers of cells expressed IFN-γ in infants, 4- to 5-year-old children, and adults, while CD154 was not expressed at comparable levels until the second year of infancy. The IL-2 response remained relatively low in infants, children, and adults but correlated negatively with mother's body mass index and was highest among infants born to Mandinka mothers. Similarly, infants born in the wet season had a stronger CD154 response than those born in the dry season throughout the 2 years of the study. We conclude that the prenatal and perinatal environments have a lasting effect on the response of infants to the BCG vaccine.
Association of Mannose-Binding Lectin Gene Polymorphism but Not of Mannose-Binding Serine Protease 2 with Chronic Severe Aortic Regurgitation of Rheumatic Etiology
Authors: Ramasawmy Rajendranath , Spina Guilherme S. , Fae Kellen C. , Pereira Alexandre C. , Nisihara Renato , Messias Reason Iara Jose , Grinberg Max , Tarasoutchi Flavio , Kalil Jorge , Guilherme Luiza 
Published: April 2008

ABSTRACTN-Acetylglucosamine (GlcNAc) is the major immunoepitope of group A streptococcal cell wall carbohydrates. Antistreptococcal antibodies cross-reactive with anti-GlcNAc and laminin are present in sera of patients with rheumatic fever. The cross-reactivity of these antibodies with human heart valvular endothelium and the underlying basement membrane has been suggested to be a possible cause of immune-mediated valve lesion. Mannose-binding lectin (MBL) encoded by theMBL2gene, a soluble pathogen recognition receptor, has high affinity for GlcNAc. We postulated that mutations in exon 1 of theMBL2 gene associated with a deficient serum level of MBL may contribute to chronic severe aortic regurgitation (AR) of rheumatic etiology. We studied 90 patients with severe chronic AR of rheumatic etiology and 281 healthy controls (HC) for the variants of theMBL2gene at codons 52, 54, and 57 by using a PCR-restriction fragment length polymorphism-based method. We observed a significant difference in the prevalence of defectiveMBL2alleles between patients with chronic severe AR and HC. Sixteen percent of patients with chronic severe AR were homozygotes or compound heterozygotes for defective MBL alleles in contrast to 5% for HC (P= 0.0022; odds ratio, 3.5 [95% confidence interval, 1.6 to 7.7]). No association was detected with the variant of theMASP2gene. Our study suggests that MBL deficiency may contribute to the development of chronic severe AR of rheumatic etiology.
Caspofungin Disk Diffusion Breakpoints and Quality Control
Authors: Brown Steven D. , Traczewski Maria M. 
Published: April 2008

ABSTRACT

Interpretive disk diffusion breakpoints for caspofungin are proposed by evaluating 762 isolates of
Candida
spp., representing 10 different species obtained as part of the caspofungin clinical trials. Standardized broth microdilution reference tests were compared to the zone diameters observed with 5-μg caspofungin disks produced by two different disk manufacturers. Disk diffusion breakpoints of ≥11 mm for susceptible are proposed. Compared to results from MIC testing, these zone diameters produced error rates that were ≤0.3% for all categories. In addition, an eight-laboratory disk diffusion quality control (QC) study was performed, and QC ranges are proposed for the four QC strains recommended by the CLSI.
The LEM Domain Proteins Emerin and LAP2α Are Dispensable for Human Immunodeficiency Virus Type 1 and Murine Leukemia Virus Infections
Authors: Mulky Alok , Cohen Tatiana V. , Kozlov Serguei V. , Korbei Barbara , Foisner Roland , Stewart Colin L. , KewalRamani Vineet N. 
Published: April 2008

ABSTRACT
The human nuclear envelope proteins emerin and lamina-associated polypeptide 2α (LAP2α) have been proposed to aid in the early replication steps of human immunodeficiency virus type 1 (HIV-1) and murine leukemia virus (MLV). However, whether these factors are essential for HIV-1 or MLV infection has been questioned. Prior studies in which conflicting results were obtained were highly dependent on RNA interference-mediated gene silencing. To shed light on these contradictory results, we examined whether HIV-1 or MLV could infect primary cells from mice deficient for emerin, LAP2α, or both emerin and LAP2α. We observed HIV-1 and MLV infectivity in mouse embryonic fibroblasts (MEFs) from emerin knockout, LAP2α knockout, or emerin and LAP2α double knockout mice to be comparable in infectivity to wild-type littermate-derived MEFs, indicating that both emerin and LAP2α were dispensable for HIV-1 and MLV infection of dividing, primary mouse cells. Because emerin has been suggested to be important for infection of human macrophages by HIV-1, we also examined HIV-1 transduction of macrophages from wild-type mice or knockout mice, but again we did not observe a difference in susceptibility. These findings prompted us to reexamine the role of human emerin in supporting HIV-1 and MLV infection. Notably, both viruses efficiently infected human cells expressing high levels of dominant-negative emerin. We thus conclude that emerin and LAP2α are not required for the early replication of HIV-1 and MLV in mouse or human cells.
Mutagenesis of the Active-Site Cysteine in the Ubiquitin-Specific Protease Contained in Large Tegument Protein pUL36 of Pseudorabies Virus Impairs Viral Replication In Vitro and Neuroinvasion In Vivo
Authors: Böttcher Sindy , Maresch Christina , Granzow Harald , Klupp Barbara G. , Teifke Jens P. , Mettenleiter Thomas C. 
Published: April 2008

ABSTRACT

Herpesviruses specify a ubiquitin-specific protease activity located within their largest tegument protein. Although its biological role is still largely unclear, mutation within the active site abolished deubiquitinating (DUB) activity and decreased virus replication in vitro and in vivo. To further elucidate the role of DUB activity for herpesvirus replication, the conserved active-site cysteine at amino acid position 26 within pUL36 of
Pseudorabies virus
(PrV) (
Suid herpesvirus 1
), a neurotropic alphaherpesvirus, was mutated to serine. Whereas one-step growth kinetics of the resulting mutant virus PrV-UL36(C
26
S) were moderately reduced, plaque size was decreased to 62% of that of the wild-type virus. Ultrastructural analysis revealed large accumulations of unenveloped nucleocapsids in the cytoplasm, but incorporation of the tegument protein pUL37 was not abolished. After intranasal infection with PrV-UL36(C
26
S) mice showed survival times two times longer than those of mice infected with wild-type or rescued virus. Thus, the DUB activity is important for PrV replication in vitro and for neuroinvasion in mice.
Enhanced Pathogenesis of an Attenuated Herpes Simplex Virus for Mice Lacking Stat1
Authors: Pasieka Tracy Jo , Lu Betty , Leib David A. 
Published: April 2008

ABSTRACT

Mice lacking the Stat1 interferon signaling gene were infected with herpes simplex virus type 1 (HSV-1) or an attenuated recombinant lacking virion host shutoff (Δ
vhs
). Δ
vhs
virus
-
infected Stat1
−/−
mice showed levels of replication equivalent to that of the wild-type virus-infected control mice but reduced relative to wild-type virus-infected Stat1
−/−
mice. Stat1 deficiency relieves the immunomodulatory deficiency of Δ
vhs
virus, but not its inherent growth defect. Also Vhs is dispensable for reactivation.
Systematic Study of the Functions for the Residues around the Nucleotide Pocket in Simian Virus 40 AAA+ Hexameric Helicase
Authors: Greenleaf William B. , Shen Jingping , Gai Dahai , Chen Xiaojiang S. 
Published: April 2008

ABSTRACT

The high-resolution structural data for simian virus 40 large-T-antigen helicase revealed a set of nine residues bound to ATP/ADP directly or indirectly. The functional role of each of these residues in ATP hydrolysis and also the helicase function of this AAA+ (
A
TPases
a
ssociated with various cellular
a
ctivities) molecular motor are unclear. Here, we report our mutational analysis of each of these residues to examine their functionality in oligomerization, DNA binding, ATP hydrolysis, and double-stranded DNA (dsDNA) unwinding. All mutants were capable of oligomerization in the presence of ATP and could bind single-stranded DNA and dsDNA. ATP hydrolysis was substantially reduced for proteins with mutations of residues making direct contact with the γ-phosphate of ATP or the apical water molecule. A potentially noncanonical “arginine finger” residue, K418, is critical for ATP hydrolysis and helicase function, suggesting a new type of arginine finger role by a lysine in the stabilization of the transition state during ATP hydrolysis. Interestingly, our mutational data suggest that the positive- and negative-charge interactions in the uniquely observed residue pairs, R498/D499 and R540/D502, in large-T-antigen helicase are critically involved in the transfer of energy of ATP binding/hydrolysis to DNA unwinding.
Site 1 Protease Is Required for Proteolytic Processing of the Glycoproteins of the South American Hemorrhagic Fever Viruses Junin, Machupo, and Guanarito
Authors: Rojek Jillian M. , Lee Andrew M. , Nguyen NgocThao , Spiropoulou Christina F. , Kunz Stefan 
Published: April 2008

ABSTRACT

The cellular proprotein convertase
s
ite
1 p
rotease (S1P) has been implicated in the proteolytic processing of the glycoproteins (GPs) of Old World arenaviruses. Here we report that S1P is also involved in the processing of the GPs of the genetically more-distant South American hemorrhagic fever viruses Guanarito, Machupo, and Junin. Efficient cleavage of Guanarito virus GP, whose protease recognition sites deviate from the reported S1P consensus sequence, indicates a broader specificity of S1P than anticipated. Lack of GP processing of Junin virus dramatically reduced production of infectious virus and prevented cell-to-cell propagation. Infection of S1P-deficient cells resulted in viral persistence over several weeks without the emergence of escape variants able to use other cellular proteases for GP processing.
A Subgenomic Segment of Theiler's Murine Encephalomyelitis Virus RNA Causes Demyelination
Authors: Baida Gleb , Popko Brian , Wollmann Robert L. , Stavrou Spyridon , Lin Wensheng , Tretiakova Maria , Krausz Thomas N. , Roos Raymond P. 
Published: April 2008

ABSTRACTThe DA strain of Theiler's murine encephalomyelitis virus (TMEV) causes a persistent central nervous system (CNS) infection of mice with a restricted virus gene expression and induces an inflammatory demyelinating disease that is thought to be immune mediated and a model of multiple sclerosis (MS). The relative contribution of virus vis-à-vis the immune system in the pathogenesis of DA-induced white matter disease remains unclear, as is also true in MS. To clarify the pathogenesis of DA-induced demyelination, we used Cre/loxP technology to generate a transgenic mouse that has tamoxifen (Tm)-inducible expression of a subgenomic segment of DA RNA in oligodendrocytes and Schwann cells. Tm-treated young transgenic mice developed progressive weakness leading to death, with abnormalities of oligodendrocytes and Schwann cells and demyelination, but without inflammation, demonstrating that DA virus can play a direct pathogenic role in demyelination. Tm treatment of mice at a later age resulted in milder disease, with evidence of peripheral nerve remyelination and focal fur depigmentation; surviving weak mice had persistent expression of the recombined transgene in the CNS, suggesting that the DA subgenomic segment can cause cellular dysfunction but not death, possibly similar to the situation seen during DA virus persistence. These studies demonstrate that DA RNA or a DA protein(s) is toxic to myelin-synthesizing cells. This Cre/loxP transgenic system allows for spatially and temporally controlled expression of the viral transgene and is valuable for clarifying nonimmune (and immune) mechanisms of demyelination induced by TMEV as well as other viruses.
Small Intestine CD4
+
T Cells Are Profoundly Depleted during Acute Simian-Human Immunodeficiency Virus Infection, Regardless of Viral Pathogenicity
Authors: Fukazawa Yoshinori , Miyake Ariko , Ibuki Kentaro , Inaba Katsuhisa , Saito Naoki , Motohara Makiko , Horiuchi Reii , Himeno Ai , Matsuda Kenta , Matsuyama Megumi , Takahashi Hidemi , Hayami Masanori , Igarashi Tatsuhiko , Miura Tomoyuki 
Published: April 2008

ABSTRACT

To analyze the relationship between acute virus-induced injury and the subsequent disease phenotype, we compared the virus replication and CD4
+
T-cell profiles for monkeys infected with isogenic highly pathogenic (KS661) and moderately pathogenic (#64) simian-human immunodeficiency viruses (SHIVs). Intrarectal infusion of SHIV-KS661 resulted in rapid, systemic, and massive virus replication, while SHIV-#64 replicated more slowly and reached lower titers. Whereas KS661 systemically depleted CD4
+
T cells, #64 caused significant CD4
+
T-cell depletion only in the small intestine. We conclude that SHIV, regardless of pathogenicity, can cause injury to the small intestine and leads to CD4
+
T-cell depletion in infected animals during acute infection.
Influence of age on masonry bond strength and mortar microstructureThis article is one of a selection of papers published in this Special Issue on Masonry.
Authors: Sugo Heber , Page Adrian W. , Lawrence Stephen 
Published: April 2008

The effect of age on bond strength and mortar microstructure was investigated as part of an ongoing masonry bond strength research program at The University of Newcastle. Previous work has shown that both strength losses and strength gains occur with age. The potential loss of bond strength with time has structural implications as the design of masonry using the Australian masonry standard AS 3700–2001 is based on the 7 d bond strength. In this investigation, a single mortar-and-unit combination (dry pressed clay and 1:1:6 mortar) cured under ambient laboratory conditions was studied. Bond strength was determined at ages ranging from 3 to 365 d using a small-scale uniaxial tension test. Maximum bond strength was observed to occur at 180 d with strength minima occurring at 90 and 365 d. Scanning electron microscopy and X-ray diffraction techniques were used to further identify the mortar constituents and hydration levels. Changes in the density of the paste microstructure were observed up to 28 d, which correlated with the initial increase in bond strength. No other microstructural change to account for the strength variations between 28 and 365 d could be observed using these techniques.
A New Hybrid Iterative Algorithm for Fixed-Point Problems, Variational Inequality Problems, and Mixed Equilibrium Problems
Authors: Yao Yonghong , Liou Yeong-Cheng , Yao Jen-Chih 
Published: April 2008

AbstractWe introduce a new hybrid iterative algorithm for finding a common element of the set of fixed points of an infinite family of nonexpansive mappings, the set of solutions of the variational inequality of a monotone mapping, and the set of solutions of a mixed equilibrium problem. This study, proves a strong convergence theorem by the proposed hybrid iterative algorithm which solves fixed-point problems, variational inequality problems, and mixed equilibrium problems.
Down-Regulation of Class II Phosphoinositide 3-Kinase α Expression below a Critical Threshold Induces Apoptotic Cell Death
Authors: Elis Winfried , Triantafellow Ellen , Wolters Natalie M. , Sian Katie R. , Caponigro Giordano , Borawski Jason , Gaither L. Alex , Murphy Leon O. , Finan Peter M. , MacKeigan Jeffrey P. 
Published: April 2008

Abstract
Members of the phosphoinositide 3-kinase (PI3K) family collectively control multiple cellular responses, including proliferation, growth, chemotaxis, and survival. These diverse effects can partly be attributed to the broad range of downstream effectors being regulated by the products of these lipid kinases, the 3′-phosphoinositides. However, an additional layer of complexity is introduced by the existence of multiple PI3K enzyme isoforms. Much has been learned over the last years on the roles of the classes I and III PI3K members in cellular signaling, but little is known about the isoform-specific tasks done by the class II PI3Ks (C2α, β, and γ). In this study, we used quantitative reverse transcription–PCR and RNA interference in mammalian cells to gain further insight into the function of these lesser studied PI3K enzymes. We find that PI3K-C2α, but not PI3K-C2β, has an important role in controlling cell survival and by using a panel of RNA interference reagents, we were able to determine a critical threshold of PI3K-C2α mRNA levels, below which the apoptotic program is switched on, via the intrinsic cell death pathway. In addition, knockdown of PI3K-C2α to levels that by themselves do not induce apoptosis sensitize cells to the anticancer agent Taxol (paclitaxel). Lastly, we report that lowering the levels of PI3K-C2α in a number of cancer cell lines reduces their proliferation and cell viability, arguing that PI3K inhibitors targeting not only the class Iα isoform but also class IIα may contribute to an effective anticancer strategy. (Mol Cancer Res 2008;6(4):614–23)