bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Inbreeding on Male Courtship Behaviour and Coloration in Guppies
Authors: Mariette Mylene , Kelley Jennifer L , Brooks Robert , Evans Jonathan P 
Published: June 2006

AbstractDespite an extensive literature on inbreeding depression in a variety of traits, relatively little is known about the effects of inbreeding on patterns of sexual behaviour. In this study, we use the guppy Poecilia reticulata to investigate the influence of parental relatedness (full‐sib. vs. unrelated matings) on sexual behaviour and colour pattern variation in adult male offspring. Our results revealed that one generation of full‐sibling mating resulted in a strong decline in male sexual motivation (courtship intensity and following behaviour) and mating success (number of successful copulations and insemination success – as estimated by the frequency of post‐copulatory jerks after mating), but we detected no significant influence of inbreeding on colour pattern variation. Our finding that sexual ornamentation (colour) did not show similar inbreeding depression to courtship behaviour may be due to differences in the genetic basis of these traits. Our findings indicate that courtship can be a sensitive indicator of genetic stress and add to an emerging picture that sexually selected traits can be severely affected by inbreeding depression.
Female polyandry under male harassment: the case of the common toad (Bufo bufo)
Authors: Sztatecsny M. , Jehle R. , Burke T. , Hödl W. 
Published: June 2006

AbstractSeveral recent studies have demonstrated the occurrence of multiple paternity in anuran amphibians, implying that it is more common than previously thought. However, an adaptive explanation for polyandry in anurans is still lacking. The common toad Bufo bufo is an explosively breeding species that releases its eggs in strings. The operational sex ratio (OSR) is male biased, causing strong scramble competition among males; females can even drown through harassment during multiple amplexi. We used microsatellite markers to determine patterns of paternity in natural B. bufo populations and experimentally mated individuals (females exposed to either two or six males). Thirty per cent of field‐collected and 22% of experimentally produced egg strings were sired by at least two males; all others were sired by a single father. Multiple paternities arose only from multiple amplexi, and we found no indication of fertilization from non‐amplexing males, for example through free‐swimming sperm. Our results suggest that polyandry in B. bufo is likely to occur most often at high population densities, and under the most male‐biased OSRs. Moreover, polyandry might be interpreted as being the consequence of females spawning when amplexed by a few males, to avoid the risk of drowning by amplexus with multiple males.
Obligatory Requirement for Antibody in Recovery from a Primary Poxvirus Infection
Authors: Chaudhri Geeta , Panchanathan Vijay , Bluethmann Horst , Karupiah Gunasegaran 
Published: June 2006

ABSTRACTTo understand the correlates of protective immunity against primary variola virus infection in humans, we have used the well-characterized mousepox model. This is an excellent surrogate small-animal model for smallpox in which the disease is caused by infection with the closely related orthopoxvirus, ectromelia virus. Similarities between the two infections include virus replication and transmission, aspects of pathology, and development of pock lesions. Previous studies using ectromelia virus have established critical roles for cytokines and effector functions of CD8 T cells in the control of acute stages of poxvirus infection. Here, we have used mice deficient in B cells to demonstrate that B-cell function is also obligatory for complete virus clearance and recovery of the host. In the absence of B cells, virus persists and the host succumbs to infection, despite the generation of CD8 T-cell responses. Intriguingly, transfer of naive B cells or ectromelia virus-immune serum to B-cell-deficient mice with established infection allowed these animals to clear virus and fully recover. In contrast, transfer of ectromelia virus-immune CD8 T cells was ineffective. Our data show that mice deficient in CD8 T-cell function die early in infection, whereas those deficient in B cells or antibody production die much later, indicating that B-cell function becomes critical after the effector phase of the CD8 T-cell response to infection subsides. Strikingly, our results show that antibody prevents virus from seeding the skin and forming pock lesions, which are important for virus transmission between hosts.
Cyclooxygenase 2 Induced by Kaposi's Sarcoma-Associated Herpesvirus Early during In Vitro Infection of Target Cells Plays a Role in the Maintenance of Latent Viral Gene Expression
Authors: Sharma-Walia Neelam , Raghu Hari , Sadagopan Sathish , Sivakumar Ramu , Veettil Mohanan Valiya , Naranatt Pramod P. , Smith Marilyn M. , Chandran Bala 
Published: June 2006

ABSTRACT

Infection of human dermal microvascular endothelial (HMVEC-d) cells and human foreskin fibroblast (HFF) cells in vitro by Kaposi's sarcoma-associated herpesvirus (KSHV) provides an excellent in vitro model system to study viral latency. KSHV infection is characterized by the induction of preexisting host signal cascades; sustained expression of the latency-associated open reading frame 73 (ORF73) (LANA-1), ORF72, and K13 genes; transient expression of a limited number of lytic genes, including the lytic cycle switch ORF50 (replication and transcription activator) gene; and reprogramming of host transcriptional machinery regulating a variety of cellular processes, including several proinflammatory responses. The cyclooxygenase 2 (COX-2) gene was one of the host cell genes that was highly up-regulated at 2 and 4 h postinfection (p.i.) of HMVEC-d and HFF cells (P. P. Naranatt, H. H. Krishnan, S. R. Svojanovsky, C. Bloomer, S. Mathur, and B. Chandran, Cancer Res. 64:72-84, 2004). Since COX-2 is an important mediator of inflammatory and angiogenic responses, here, using real-time PCR, Western blot, and immunofluorescence assays, we characterized the COX-2 stimulation and its role in KSHV infection. KSHV induced a robust COX-2 expression, which reached a maximum at 2 h p.i. in HMVEC-d cells and at 8 h p.i. in HFF cells, and significantly higher levels were continuously detected for up to 72 h p.i. Constitutive COX-1 protein levels were not modulated by KSHV infection. Moderate levels of COX-2 were also induced by UV-irradiated KSHV and by envelope glycoproteins gB and gpK8.1A; however, viral gene expression appears to be essential for the increased COX-2 induction. High levels of prostaglandin E
2
(PGE
2
), a COX-2 product, were released in the culture supernatant medium of infected cells. PGE
2
synthase, catalyzing the biosynthesis of PGE
2
, also increased upon infection and inhibition of COX-2 by NS-398, and indomethacin drastically reduced the levels of PGE
2
and PGE
2
synthase. COX-2 inhibition did not affect KSHV binding, internalization of virus, or the trafficking to the infected cell nuclei. However, latent ORF73 gene expression and ORF73 promoter activity were significantly reduced by COX-2 inhibitors, and this inhibition was relieved by exogenous supplementation with PGE
2
. In contrast, lytic ORF50 gene expression and ORF50 promoter activity were unaffected. These studies demonstrate that COX-2 and PGE
2
play roles in facilitating latent viral gene expression and the establishment and maintenance of latency and suggest that KSHV has evolved to utilize the inflammatory responses induced during infection of endothelial cells for the maintenance of viral latent gene expression.
Intracellular Activated Notch1 Is Critical for Proliferation of Kaposi's Sarcoma-Associated Herpesvirus-Associated B-Lymphoma Cell Lines In Vitro
Authors: Lan Ke , Choudhuri Tathagata , Murakami Masanao , Kuppers Daniel A. , Robertson Erle S. 
Published: June 2006

ABSTRACTKaposi's sarcoma-associated herpesvirus (KSHV) is a human tumor virus expressing latent antigens critical for pathogenesis. The mechanism by which KSHV mediates oncogenesis has not been fully elucidated. Notch signaling is an evolutionarily conserved pathway controlling diverse events related to development, proliferation, and tissue homeostasis. Deregulation of Notch signaling has also been shown to be highly correlated with oncogenesis. Here we show that the activated intracellular domain of Notch1 (ICN) is aberrantly accumulated in latently KSHV-infected pleural effusion lymphoma cells and results in increased proliferation. Specifically, growth of the infected cells was dramatically inhibited at the G1phase by treatment with a γ-secretase inhibitor which specifically blocks the production of ICN. Increased ICN also up-regulated the cyclin D1 cell cycle regulator. Taken together, these studies define an important mechanism directly linking latent KSHV infection to induction of oncogenesis through dysregulation of the conserved Notch signaling pathway.
Poxvirus CD8+T-Cell Determinants and Cross-Reactivity in BALB/c Mice
Authors: Tscharke David C. , Woo Wai-Ping , Sakala Isaac G. , Sidney John , Sette Alessandro , Moss Denis J. , Bennink Jack R. , Karupiah Gunasegaran , Yewdell Jonathan W. 
Published: June 2006

ABSTRACTMouse models of orthopoxvirus disease provide great promise for probing basic questions regarding host responses to this group of pathogens, which includes the causative agents of monkeypox and smallpox. However, some essential tools for their study that are taken for granted with other mouse models are not available for these viruses. Here we map and characterize the initial CD8+T-cell determinants for poxviruses inH-2d-haplotype mice. CD8+T cells recognizing these three determinants make up around 40% of the total responses to vaccinia virus during and after resolution of infection. We then use these determinants to test if predicted conservation across orthopoxvirus species matches experimental observation and find an unexpectedly cross-reactive variant peptide encoded by ectromelia (mousepox) virus.
Suppression of the Interferon-Mediated Innate Immune Response by Pseudorabies Virus
Authors: Brukman Alla , Enquist L. W. 
Published: June 2006

ABSTRACT
Pseudorabies virus (PRV) is an alphaherpesvirus related to the human pathogens herpes simplex virus type 1 (HSV-1) and varicella-zoster virus. PRV is capable of infecting and killing a wide variety of mammals. How it avoids innate immune defenses in so many hosts is not understood. While the anti-interferon (IFN) strategies of HSV-1 have been studied, little is known about how PRV evades the IFN-mediated immune response. In this study, we determined if wild-type PRV infection can overcome the establishment of a beta interferon (IFN-β)-induced antiviral state in primary rat fibroblasts. Using microarray technology, we found that the expression of a subset of genes normally induced by IFN-β in these cells was not induced when the cells were simultaneously infected with a wild-type PRV strain. Expression of transcripts associated with major histocompatibility complex class I antigen presentation and NK cell activation was reduced, while transcripts associated with inflammation either were unaffected or were induced by viral infection. This suppression of IFN-stimulated gene expression occurred because IFN signal transduction, in particular the phosphorylation of STAT1, became less effective in PRV-infected cells. At least one virion-associated protein is involved in inhibition of STAT1 tyrosine phosphorylation. This ability to disarm the IFN-β response offers an explanation for the uniform lethality of virulent PRV infection of nonnatural hosts.
A Highly Restricted T-Cell Receptor Dominates the CD8+T-Cell Response to Parvovirus B19 Infection in HLA-A*2402-Positive Individuals
Authors: Kasprowicz V. , Isa A. , Jeffery K. , Broliden K. , Tolfvenstam T. , Klenerman P. , Bowness P. 
Published: June 2006

ABSTRACTSix of seven HLA-A*2402-positive individuals with acute parvovirus B19 infections made vigorous CD8-positive cytotoxic T-cell (CTL) responses to the viral epitope FYTPLADQF. All responders showed highly focused T-cell receptor (TCR) usage, using almost exclusively BV5.1. The BV5.1 TCR dominated the acute response, was maintained over time, and was also used by a remotely infected individual. Nine CTL clones and two oligoclonal lines obtained from three unrelated individuals used BV5.1, BJ2.1, and a conserved TCR CDR3 of nine amino acids. This commonly recognized epitope is likely important in long-term protective immunity and should be included in vaccine design.
Semi-quantitative scoring of potentially predictive markers for endocrine treatment of breast cancer: a comparison between whole sections and tissue microarrays
Authors: Henriksen Katrine L , Rasmussen Birgitte B , Lykkesfeldt Anne E , Møller Susann , Ejlertsen Bent , Mouridsen Henning T 
Published: June 2006

Aim:To assess whether immunohistochemically stained tissue microarrays (TMA) of 2 mm cores from paraffin embedded tumour tissue may replace whole sections in semi-quantitative evaluation of selected potential markers for endocrine treatment.Methods:Whole sections and 2 mm cores on TMA were used for immunohistochemical staining of potential markers for endocrine treatment. The Allred scoring system was used for the markers with nuclear localisation: the oestrogen receptor, the progesterone receptor, p27 and the oestrogen receptor co-regulator amplified in breast cancer 1 (AIB1). The Allred scoring system was also used for the non-nuclear markers Bcl-2, pS2 and cyclooxygenase 2 (COX-2); the membrane receptors HER-2, insulin-like growth factor I receptor (IGF-IR) and epidermal growth factor receptor were quantified according to the guidelines for the Herceptest.Results:The data and statistical analyses showed that the semi-quantitative evaluation of oestrogen receptor, progesterone receptor, AIB1, COX-2, HER-2 and IGF-IR on TMA blocks was comparable with analysis on whole sections.Conclusions:This study shows that semi-quantitative scoring of 2 mm cores on TMA is feasible for several potential markers for endocrine therapy. Considering the small size of many breast tumours, the speed and cost-effectiveness of immunohistochemistry on TMA compared with whole sections, and the importance of the expression level of the proteins, semi-quantitative scoring on TMA has great potential in both retrospective and prospective studies aiming at improving the prediction of response to endocrine treatment.
Overexpression of cellular inhibitor of apoptosis protein 2 is an early event in the progression of pancreatic cancer
Authors: Esposito Irene , Kleeff Jörg , Abiatari Ivane , Shi Xined , Giese Nathalia , Bergmann Frank , Roth Wilfried , Friess Helmut , Schirmacher Peter 
Published: June 2006

Aim:To determine the role of two antiapoptotic proteins of the inhibitor of apoptosis protein family, cellular inhibitor of apoptosis protein 1 (cIAP1) and cellular inhibitor of apoptosis protein 2 (cIAP2), in human pancreatic carcinogenesis.Methods:mRNA levels were measured in pancreatic tissues and pancreatic cancer cell lines by quantitative reverse transcriptase PCR. Protein expression was assessed in pancreatic cancer cell lines by immunoblotting and in pancreatic tissues by immunohistochemistry, and correlated with pathological and survival data.Results:cIAP1 expression was constantly high in non-neoplastic pancreatic tissues, in pancreatic intraepithelial neoplasia (PanIN) lesions, as well as in a subset of primary and metastatic pancreatic ductal adenocarcinomas (PDAC), and a preferential cytoplasmatic localisation was observed in the tumour tissues. cIAP1 expression was rare in a cohort of cystic tumours. cIAP2 mRNA levels were significantly higher (2.4 fold) in PDAC than in normal tissues. cIAP2 protein was overexpressed in PDAC, and was detectable in low- and high-grade PanIN lesions. Moreover, cIAP2 was often expressed in pancreatic cystic tumours. cIAP1 and cIAP2 mRNA and protein were detected in all the examined cell lines. Survival analysis revealed a shorter survival in patients with cIAP1/cIAP2-positive tumours.Conclusions:cIAP1 might contribute to the regulation of the apoptotic process in the normal and in the neoplastic pancreas, depending on its subcellular localisation. Overexpression of cIAP2 is a common and early event in the progression of pancreatic cancer, and could therefore potentially influence the important pathophysiological aspects of PDAC, such as anoikis or chemoresistance.
Melanoma-Reactive T Cells in the Bone Marrow of Melanoma Patients: Association with Disease Stage and Disease Duration
Authors: Müller-Berghaus Jan , Ehlert Katrin , Ugurel Selma , Umansky Viktor , Bucur Mariana , Schirrmacher Volker , Beckhove Philipp , Schadendorf Dirk 
Published: June 2006

AbstractUsing IFN-γ enzyme-linked immunospot, we investigated reactivity of T cells from bone marrow and peripheral blood to melanoma lysate-pulsed autologous dendritic cells in 40 melanoma patients. Melanoma-reactive T cells were present in the bone marrow of seven patients and in peripheral blood of four patients. In the bone marrow, melanoma-reactive T cells were present in 6 of 21 stage IV patients and in 1 of 10 stage III patients, whereas none were detected in stage I to II patients (0 of 9). The occurrence of tumor-reactive bone marrow T cells in melanoma patients was associated with advanced disease stage, disease duration and tumor load, and independent of treatment. These findings provide new insights into the generation of T-cell responses in melanoma patients. (Cancer Res 2006; 66(12): 5997-6001)
Haploinsufficiency of RAD51B Causes Centrosome Fragmentation and Aneuploidy in Human Cells
Authors: Date Osamu , Katsura Mari , Ishida Mari , Yoshihara Takashi , Kinomura Aiko , Sueda Taijiro , Miyagawa Kiyoshi 
Published: June 2006

Abstract
The Rad51-like proteins, Rad51B, Rad51C, Rad51D, XRCC2, and XRCC3, have been shown to form two distinct complexes and seem to assist Rad51 in the early stages of homologous recombination. Although these proteins share sequence similarity with Rad51, they do not show functional redundancy. Among them, Rad51B is unique in that the gene maps to the human chromosome 14q23-24, the region frequently involved in balanced chromosome translocations in benign tumors particularly in uterine leiomyomas. Despite accumulating descriptive evidence of altered Rad51B function in these tumors, the biological significance of this aberration is still unknown. To assess the significance of reduced Rad51B function, we deleted the gene in the human colon cancer cell line HCT116 by gene targeting. Here, we show that haploinsufficiency of RAD51B causes mild hypersensitivity to DNA-damaging agents, a mild reduction in sister chromatid exchange, impaired Rad51 focus formation, and an increase in chromosome aberrations. Remarkably, haploinsufficiency of RAD51B leads to centrosome fragmentation and aneuploidy. In addition, an ∼50% reduction in RAD51B mRNA levels by RNA interference also leads to centrosome fragmentation in the human fibrosarcoma cell line HT1080. These findings suggest that the proper biallelic expression of RAD51B is required for the maintenance of chromosome integrity in human cells. (Cancer Res 2006; 66(12): 6018-24)
Osteopontin Is an Oncogenic Vav1– but not Wild-type Vav1–Responsive Gene: Implications for Fibroblast Transformation
Authors: Schapira Vered , Lazer Galit , Katzav Shulamit 
Published: June 2006

AbstractMammalian wild-type Vav1 (wtVav1) encodes a specific GDP/GTP nucleotide exchange factor that is exclusively expressed in the hematopoietic system. Despite numerous studies, the mechanism underlying transformation of fibroblasts by oncogenic Vav1 (oncVav1) is not well defined. We identified osteopontin, a marker for tumor aggressiveness, as an oncVav1-inducible gene. Osteopontin is highly expressed in oncVav1-transformed NIH3T3 cells (NIH/oncVav1) but is barely detected in NIH3T3 expressing wtVav1 (NIH/wtVav1) even following epidermal growth factor stimulation, which normally induces osteopontin. Depleting oncVav1 in NIH/oncVav1 using small interfering RNA led to a considerable decrease in osteopontin, whereas reducing osteopontin expression did not affect oncVav1 expression, suggesting that oncVav1 operates upstream of osteopontin. Vav1-depleted NIH/oncVav1 cells, but not osteopontin-depleted NIH/oncVav1 cells, exhibited impaired extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase phosphorylation. Inhibition of ERK phosphorylation in NIH/oncVav1 cells led to a decrease in osteopontin expression, implying that the elevated osteopontin expression in these cells is dependent on ERK phosphorylation. Vav1-depleted or osteopontin-depleted NIH/oncVav1 cells lost their tumorigenic properties as judged by the soft agar and invasion assays, although loss of osteopontin expression had a less dramatic effect. Suppression of Vav1 expression in NIH/oncVav1 cells led to reversion to “normal” morphology, whereas when only osteopontin expression was diminished cells retained their transformed morphology. This work strongly supports a role for oncVav1 as a master oncogene and provides clues to the molecular mechanism underlying oncVav1 transformation. (Cancer Res 2006; 66(12): 6183-91)
Characterization of Endogenous Human Promyelocytic Leukemia Isoforms
Authors: Condemine Wilfried , Takahashi Yuki , Zhu Jun , Puvion-Dutilleul Francine , Guegan Sarah , Janin Anne , de Thé Hugues 
Published: June 2006

Abstract
Promyelocytic leukemia (PML) has been implicated in a variety of functions, including control of TP53 function and modulation of cellular senescence. Sumolated PML is the organizer of mature PML bodies, recruiting a variety of proteins onto these nuclear domains. The PML gene is predicted to encode a variety of protein isoforms. Overexpression of only one of them, PML-IV, promotes senescence in human diploid fibroblasts, whereas PML-III was proposed to specifically interact with the centrosome. We show that all PML isoform proteins are expressed in cell lines or primary cells. Unexpectedly, we found that PML-III, PML-IV, and PML-V are quantitatively minor isoforms compared with PML-I/II and could not confirm the centrosomal targeting of PML-III. Stable expression of each isoform, in a pml-null background, yields distinct subcellular localization patterns, suggesting that, like in other RBCC/TRIM proteins, the COOH-terminal domains of PML are involved in interactions with specific cellular components. Only the isoform-specific sequences of PML-I and PML-V are highly conserved between man and mouse. That PML-I contains all conserved exons and is more abundantly expressed than PML-IV suggests that it is a critical contributor to PML function(s). (Cancer Res 2006; 66(12): 6192-8)