bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Immunodominant Peptide Presentation Strategy: a Featured HLA-A*2402-Restricted Cytotoxic T-Lymphocyte Epitope Stabilized by Intrachain Hydrogen Bonds from Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein
Authors: Liu Jun , Wu Peng , Gao Feng , Qi Jianxun , Kawana-Tachikawa Ai , Xie Jing , Vavricka Christopher J. , Iwamoto Aikichi , Li Taisheng , Gao George F. 
Published: September 2010

ABSTRACTAntigenic peptides recognized by virus-specific cytotoxic T lymphocytes (CTLs) are presented by major histocompatibility complex (MHC; or human leukocyte antigen [HLA] in humans) molecules, and the peptide selection and presentation strategy of the host has been studied to guide our understanding of cellular immunity and vaccine development. Here, a severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid (N) protein-derived CTL epitope, N1 (QFKDNVILL), restricted by HLA-A*2402 was identified by a series ofin vitrostudies, including a computer-assisted algorithm for prediction, stabilization of the peptide by co-refolding with HLA-A*2402 heavy chain and β2-microglobulin (β2m), and T2-A24 cell binding. Consequently, the antigenicity of the peptide was confirmed by enzyme-linked immunospot (ELISPOT), proliferation assays, and HLA-peptide complex tetramer staining using peripheral blood mononuclear cells (PBMCs) from donors who had recovered from SARS donors. Furthermore, the crystal structure of HLA-A*2402 complexed with peptide N1 was determined, and the featured peptide was characterized with two unexpected intrachain hydrogen bonds which augment the central residues to bulge out of the binding groove. This may contribute to the T-cell receptor (TCR) interaction, showing a host immunodominant peptide presentation strategy. Meanwhile, a rapid and efficient strategy is presented for the determination of naturally presented CTL epitopes in the context of given HLA alleles of interest from long immunogenic overlapping peptides.
Reduction of Immune Activation with Chloroquine Therapy during Chronic HIV Infection
Authors: Murray Shannon M. , Down Carrie M. , Boulware David R. , Stauffer William M. , Cavert Winston P. , Schacker Timothy W. , Brenchley Jason M. , Douek Daniel C. 
Published: September 2010

ABSTRACT

Increased levels of activated T cells are a hallmark of the chronic stage of human immunodeficiency virus (HIV) infection and are highly correlated with HIV disease progression. We evaluated chloroquine (CQ) as a potential therapy to reduce immune activation during HIV infection. We found that the frequency of CD38
+
HLA-DR
+
CD8 T cells, as well as Ki-67 expression in CD8 and CD4 T cells, was significantly reduced during CQ treatment. Our data indicate that treatment with CQ reduces systemic T-cell immune activation and, thus, that its use may be beneficial for certain groups of HIV-infected individuals.
Species-Specific Regions of Occludin Required by Hepatitis C Virus for Cell Entry
Authors: Michta Maria L. , Hopcraft Sharon E. , Narbus Christopher M. , Kratovac Zerina , Israelow Benjamin , Sourisseau Marion , Evans Matthew J. 
Published: September 2010

ABSTRACT
Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. As HCV infects only human and chimpanzee cells, antiviral therapy and vaccine development have been hampered by the lack of a convenient small-animal model. In this study we further investigate how the species tropism of HCV is modulated at the level of cell entry. It has been previously determined that the tight junction protein occludin (OCLN) is essential for HCV host cell entry and that human OCLN is more efficient than the mouse ortholog at mediating HCV cell entry. To further investigate the relationship between OCLN sequence and HCV species tropism, we compared OCLN proteins from a range of species for their ability to mediate infection of naturally OCLN-deficient 786-O cells with lentiviral pseudoparticles bearing the HCV glycoproteins. While primate sequences function equivalently to human OCLN, canine, hamster, and rat OCLN had intermediate activities, and guinea pig OCLN was completely nonfunctional. Through analysis of chimeras between these OCLN proteins and alanine scanning mutagenesis of the extracellular domains of OCLN, we identified the second half of the second extracellular loop (EC2) and specific amino acids within this domain to be critical for modulating the HCV cell entry factor activity of this protein. Furthermore, this critical region of EC2 is flanked by two conserved cysteine residues that are essential for HCV cell entry, suggesting that a subdomain of EC2 may be defined by a disulfide bond.
A Proteasome Inhibitor, Bortezomib, Inhibits Breast Cancer Growth and Reduces Osteolysis by Downregulating Metastatic Genes
Authors: Jones Marci D. , Liu Julie C. , Barthel Thomas K. , Hussain Sadiq , Lovria Erik , Cheng Dengfeng , Schoonmaker Jesse A. , Mulay Sudhanshu , Ayers David C. , Bouxsein Mary L. , Stein Gary S. , Mukherjee Siddhartha , Lian Jane B. 
Published: September 2010

Abstract
Purpose: The incidence of bone metastasis in advanced breast cancer (BrCa) exceeds 70%. Bortezomib, a proteasome inhibitor used for the treatment of multiple myeloma, also promotes bone formation. We tested the hypothesis that proteasome inhibitors can ameliorate BrCa osteolytic disease.
Experimental Design: To address the potentially beneficial effect of bortezomib in reducing tumor growth in the skeleton and counteracting bone osteolysis, human MDA-MB-231 BrCa cells were injected into the tibia of mice to model bone tumor growth for in vivo assessment of treatment regimens before and after tumor growth.
Results: Controls exhibited tumor growth, destroying trabecular and cortical bone and invading muscle. Bortezomib treatment initiated following inoculation of tumor cells strikingly reduced tumor growth, restricted tumor cells mainly to the marrow cavity, and almost completely inhibited osteolysis in the bone microenvironment over a 3- to 4-week period as shown by [18F]fluorodeoxyglucose positron emission tomography, micro–computed tomography scanning, radiography, and histology. Thus, proteasome inhibition is effective in killing tumor cells within the bone. Pretreatment with bortezomib for 3 weeks before inoculation of tumor cells was also effective in reducing osteolysis. Our in vitro and in vivo studies indicate that mechanisms by which bortezomib inhibits tumor growth and reduces osteolysis result from inhibited cell proliferation, necrosis, and decreased expression of factors that promote BrCa tumor progression in bone.
Conclusion: These findings provide a basis for a novel strategy to treat patients with BrCa osteolytic lesions, and represent an approach for protecting the entire skeleton from metastatic bone disease. Clin Cancer Res; 16(20); 4978–89. ©2010 AACR.
Exploratory Analysis of Early Toxicity of Sunitinib in Advanced Hepatocellular Carcinoma Patients: Kinetics and Potential Biomarker Value
Authors: Zhu Andrew X. , Duda Dan G. , Ancukiewicz Marek , di Tomaso Emmanuelle , Clark Jeffrey W. , Miksad Rebecca , Fuchs Charles S. , Ryan David P. , Jain Rakesh K. 
Published: September 2010

Abstract
Purpose: Sunitinib—a multitargeted tyrosine kinase inhibitor—can modulate circulating inflammatory factors in cancer patients that may be relevant for hepatocellular carcinoma (HCC) progression. However, a recent phase III study of sunitinib in HCC was halted due to its toxicity. Here, we studied the early kinetics of adverse events after sunitinib, and explored their association with circulating proteins and clinical outcome in advanced HCC in a single-arm phase II study.
Experimental Design: Toxicity was evaluated every two weeks during the first cycle of therapy. Biomarker changes from baseline were tested after adjusting for multiple comparisons. Correlation between toxicities and overall survival (OS) or time-to-tumor progression (TTP) was evaluated in a Cox model using log-transformed levels or change in biomarkers, after stratifying by stage and adjusting for baseline level.
Results: Myeloid and lymphoid blood cell counts decreased by 20% to 50% after sunitinib treatment (P &lt; 0.05 for all). The extent of the early decrease in neutrophils and monocytes, and the development of nonhematologic toxicities (i.e., skin toxicities), were significantly associated with both OS and TTP (P &lt; 0.05). Changes in circulating cells significantly associated with specific changes in plasma biomarkers (i.e., changes in platelets with changes in VEGF-C and soluble-VEGFR3; changes in neutrophils with changes in IL-8, TNF-α, and soluble-VEGFR2).
Conclusions: The adverse effects of sunitinib, particularly on the hematopoietic system, may be rapid and appear directly related to its activity in HCC. This exploratory study suggests that early hematopoietic toxicities may potentially predict outcome in advanced HCC after sunitinib treatment. Clin Cancer Res; 17(4); 918–27. ©2010 AACR.
Short term changes in sex ratio and density alter coercive male mating tactics
Authors: Cureton II James , Deaton Raelynn , Martin Rachel 
Published: September 2010

AbstractShort term fluctuations in operational sex ratio (OSR) and density can strongly influence male mating, often exacerbating conflict between males and females. Livebearing fishes of the genus Gambusia are ideal for investigating sexual conflict because males of all sizes mate coercively. In this study, we tested how short-term fluctuations in OSR and density influence coercive male mating behaviours. Specifically, we tested the prediction that as OSR becomes more female biased, males will mate with all available females. In contrast, as OSR becomes more male biased, male aggression will inhibit mating frequency. As predicted, males mated with more females as the number of available females increased. Moreover, males were less aggressive as the proportion of females increased and more aggressive as the number of males increased. This resulted in an inverse relationship between mating and aggression with OSR and density. Coercive males attempt to maximize their reproductive success by mating with all available females, which supports classic theory on the impact of OSR and density on reproductive activity.
Female mimicry and an enhanced sexually selected trait: what does it take to fool a male?
Authors: Morris Molly , Darrah Abby , Rios-Cardenas Oscar 
Published: September 2010

AbstractFemale mimicry is commonly considered in the context of alternative mating tactics as mimics can avoid male–male competition to gain increased access to females. We describe a case where one of the benefits to being a female mimic could be the increase in size of a sexually selected trait that should eventually decrease the mimics' ability to fool males. In the swordtail fish Xiphophorus nezahualcoyotl, a small percentage of males have a permanent pigment pattern known as 'false brood spot' (FBS), express a horizontal bar pigment pattern common for females, and yet have longer swords (a sexually selected trait) for their body size. FBS males did not use more 'coercive' behaviours in the field, and females do not appear to distinguish between males based on whether or not they have FBS in the laboratory. However, in the field males with FBS were chased less by other males, spent significantly more time feeding, and those that expressed the horizontal bar had greater access to females. We suggest that FBS males with swords can still fool other males into thinking they are females because the true brood spot remains informative as long as the frequency of FBS males (mimics) remains low.
Mechanisms determining relationships between feeding group size and foraging success in food patch use by Japanese macaques (Macaca fuscata)
Authors: Kazahari Nobuko , Agetsuma Naoki 
Published: September 2010

AbstractWe evaluated the effects of social monitoring and feeding competition on foraging success in relation to the feeding group size of wild Japanese macaques (Macaca fuscata). Social monitoring is visual scanning by group members that assists them in following their own group. Individuals in smaller feeding groups may frequently use social monitoring while foraging, because they have an increased risk of losing their group. Therefore, social monitoring could be a cost for group-foraging animals. We made four predictions: (1) individuals in smaller feeding groups tend to abandon food patches to follow group members; (2) social monitoring frequency is higher in smaller feeding groups; (3) feeding rate decreases with increased social monitoring frequency; and (4) feeding rate initially increases with feeding group size because decreased social monitoring outweighs increased feeding competition, but after the feeding group reaches a certain size, feeding rate declines with increasing feeding group size due to the high costs of feeding competition. These predictions were supported by our results. Thus, the relationship between feeding group size and feeding rate can show three patterns (positive, neutral and negative) in response to the balance between the costs of social monitoring and feeding competition.
The Genesis and Manuscripts of Beer Sheva by Bella and Beer Perlhefter
Authors: Riemer Nathanael 
Published: September 2010

The article focuses on investigating the extant manuscripts entitled Beer Sheva, written in Yiddish by the Prague rabbi Beer Shmuel Issachar (ca. 1650–ca. 1713) and his wife Bella (Beile) Perlhefter (ca. 1650–1710) on the threshold of the turn to the eighteenth century. The work is dedicated to the seven deceased children of the married couple as a book of remembrance and solace.
The article presents the known versions of the manuscript in their external form, utilizing procedures in paleography and textual criticism. There are a total of nine extant versions of Beer Sheva in various states of preservation, and varying in their completeness, in various libraries around the world. I then provide an overview of the genesis of the work in three phases of editing and the copies made. The number of copies is unusually large for such an extensive Yiddish work.
Between Jesus and the Besht
Authors: Gal-Ed Efrat 
Published: September 2010

Two particular groups of poems from Itzik Manger’s largely unpublished early work (1921–1929), those about Jesus and those about the Baal Shem Tov, form a poetical polarity in his work; at the same time they act as complementary forces in the psychological unfolding of Manger’s creative process.
As an itinerant poet travelling on Romanian back roads, Manger encountered many wayside crosses with scenes of crucifixion, and found in the image of Jesus a tragic companion, who embodied homelessness, helplessness, and human pain. From 1921 to 1928 this companion mirrors in Manger’s work the shadows of the poet’s soul and also engages his fascination; in the figure of Christ Manger was able to name the unbearable in his own life, experimenting in that process with symbolist and expressionist forms and models.
In 1927, Manger discovered his deep connection to the Besht. Childhood memories of travelling with his grandfather in the Carpathian Mountains reinforced the connection. Mesmerized by the figure of the Besht, Manger then developed in a new group of poems a healing counter-world to the one depicted in the Christ poems, a world that is tangibly inhabited by the sacred.
Manger thus moved from Golgotha into the open space between Kosev (Kosov) and Kitev (Kuty), and in so doing created poems with a new sonority, poignantly evocative of Yiddish folk songs. The Christ figure disappears once Manger becomes aware of this poetic and psychological fault line in himself, though Christian motifs remain part of his poetic vocabulary.
Effect of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant in human cranial arteries
Authors: Edvinsson Lars , Chan Kayi Y , Eftekhari Sajedeh , Nilsson Elisabeth , de Vries René , Säveland Hans , Dirven Clemens MF , Danser AH Jan , MaassenVanDenBrink Antoinette 
Published: September 2010

Introduction: Calcitonin gene-related peptide (CGRP) is a neuronal messenger in intracranial sensory nerves and is considered to play a significant role in migraine pathophysiology.Materials and methods: We investigated the effect of the CGRP receptor antagonist, telcagepant, on CGRP-induced cranial vasodilatation in human isolated cerebral and middle meningeal arteries. We also studied the expression of the CGRP receptor components in cranial arteries with immunocytochemistry. Concentration response curves to αCGRP were performed in human isolated cerebral and middle meningeal arteries in the absence or presence of telcagepant. Arterial slices were stained for RAMP1, CLR and actin in a double immunofluorescence staining.Results: In both arteries, we found that: (i) telcagepant was devoid of any contractile or relaxant effects per se; (ii) pretreatment with telcagepant antagonised the αCGRP-induced relaxation in a competitive manner; and (iii) immunohistochemistry revealed expression and co-localisation of CLR and RAMP1 in the smooth muscle cells in the media layer of both arteries.Conclusions: Our findings provide morphological and functional data on the presence of CGRP receptors in cerebral and meningeal arteries, which illustrates a possible site of action of telcagepant in the treatment of migraine.
The characterization of conserved binding motifs and potential target genes for M. tuberculosis MtrAB reveals a link between the two-component system and the drug resistance of M. smegmatis
Authors: Li Yuqing , Zeng Jumei , Zhang Hua , He Zheng-Guo 
Published: September 2010

Abstract

Background
The two-component systems of Mycobacterium tuberculosis are apparently required for its growth and resistance in hostile host environments. In such environments, MtrAB has been reported to regulate the expression of the M. tuberculosis replication initiator gene, dnaA. However, the dnaA promoter binding sites and many potential target genes for MtrA have yet to be precisely characterized.

Results
In this study, a 7 bp sequence motif in the dnaA promoter region was identified for MtrA binding using DNaseI footprinting assays and surface plasmon resonance (SPR) analysis. Approximately 420 target genes potentially regulated by MtrA, including the isoniazid inducible gene iniB, were further characterized from M. tuberculosis and M. smegmatis genomes. When assayed using quantitative real-time PCR (qRT-PCR), many of the target genes demonstrated significant expression changes when the antisense mRNA of the mtrA gene was expressed in M. smegmatis. The recombinant mycobacteria grew in length and were more sensitive to two anti-tuberculosis drugs, isoniazid and streptomycin.

Conclusions
These findings yield critical information about the regulatory mechanisms of the MtrAB two-component system and its role in the drug resistance of M. smegmatis.
Effects on mitochondrial transcription of manipulating mTERF protein levels in cultured human HEK293 cells
Authors: Hyvärinen Anne K , Kumanto Mona K , Marjavaara Sanna K , Jacobs Howard T 
Published: September 2010

Abstract

Background
Based on its activities in vitro, the mammalian mitochondrial transcription termination factor mTERF has been proposed to regulate mitochondrial transcription by favouring termination at its high-affinity binding immediately downstream of the rDNA segment of mitochondrial DNA, and initiation selectively at the PH1 site of the heavy-strand promoter. This defines an rDNA transcription unit distinct from the 'global' heavy-strand transcription unit initiating at PH2. However, evidence that the relative activities of the two heavy-strand transcription units are modulated by mTERF in vivo is thus far lacking.

Results
To test this hypothesis, we engineered human HEK293-derived cells for over-expression or knockdown of mTERF, and measured the steady-state levels of transcripts belonging to different transcription units, namely tRNALeu(UUR) and ND1 mRNA for the PH2 transcription unit, and tRNAPhe plus 12S and 16S rRNA for the PH1 transcription unit. The relative levels of 16S rRNA and ND1 mRNA were the same under all conditions tested, although mTERF knockdown resulted in increased levels of transcripts of 12S rRNA. The amount of tRNAPhe relative to tRNALeu(UUR) was unaffected by mTERF over-expression, altered only slightly by mTERF knockdown, and was unchanged during recovery from ethidium bromide-induced depletion of mitochondrial RNA. mTERF overexpression or knockdown produced a substantial shift (3-5-fold) in the relative abundance of antisense transcripts either side of its high-affinity binding site.

Conclusions
mTERF protein levels materially affect the amount of readthrough transcription on the antisense strand of mtDNA, whilst the effects on sense-strand transcripts are complex, and suggest the influence of compensatory mechanisms.
Non-dominant hand movement facilitates the frontal N30 somatosensory evoked potential
Authors: Legon Wynn , Dionne Jennifer K , Meehan Sean K , Staines W Richard 
Published: September 2010

Abstract

Background
Previous literature has shown that the frontal N30 is increased during movement of the hand contralateral to median nerve stimulation. This finding was a result of non-dominant left hand movement in right-handed participants. It is unclear however if the effect depends upon non-dominant hand movement or if this is a generalized phenomenon across the upper-limbs. This study tests the effect of dominant and non-dominant hand movement upon contralateral frontal and parietal somatosensory evoked potentials (SEPs) and further tests if this relationship persists in left hand dominant participants. Median nerve SEPs were elicited from the wrist contralateral to movement in both right hand and left hand dominant participants alternating the movement hand in separate blocks. Participants were required to volitionally squeeze (~ 20% of a maximal voluntary contraction) a pressure-sensitive bulb every ~3 seconds with the hand contralateral to median nerve stimulation. SEPs were continuously collected during the task and individual traces were grouped into time bins relative to movement according to the timing of components of the Bereitschaftspotential. SEPs were then averaged and quantified from both FCZ and CP3/4 scalp electrode sites during both the squeeze task and at rest.

Results
The N30 is facilitated during non-dominant hand movement in both right and left hand dominant individuals. There was no effect for dominant hand movement in either group.

Conclusions
N30 amplitude increase may be a result of altered sensory gating from motor areas known to be specifically active during non-dominant hand movement.