bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cloning of novel kinectin splice variants with alternative C‐termini: Structure, distribution and evolution of mouse kinectin
Authors: LEUNG EUPHEMIA , PRINT CRISTIN G , PARRY DAVID AD , CLOSHY DAVID N , LOCKHART PETER J , SKINNER STEPHEN JM , BATCHELOR DAVID C , KRISSANSEN GEOFFREY W 
Published: June 2007

SummaryThe analysis of cDNA clones encoding novel variant forms of mouse kinectin, an endoplasmic reticulum (ER)‐bound receptor for the motor protein kinesin, is reported. Kinesin and cytoplasmic dynein are involved in mediating the anterograde and retrograde movements of intracellular vesicles along the microtubule network. The amino acid sequence deduced from kinectin cDNA isolated from mouse spleen cell and testis libraries revealed a long signal peptide or transmembrane sequence, and a 328 amino acid residue globular N‐terminal domain adjacent to a much larger 858–999‐residue C‐terminal coiled‐coil rod domain. The C‐terminal domain was composed of 18 coiled‐coil regions formed from multiple contiguous heptad repeats which undergo alternative splicing as evidenced by the presence of at least five small (23‐33 amino acid residue) insertion sequences scattered throughout. The inserts are present in any one of a number of combinations, generating an array of novel kinectin variants. Insert 5 contains a termination codon, producing a C‐terminus that is highly homologous to that of human kinectin. Three out of five mouse kinectin clones lack insert 5, generating a novel eleven amino acid C‐terminus encoded by sequence that extends past the insertion site. The existence of alternative C‐termini may have functional relevance given that the C‐termini are exposed for interaction with kinesin, whereas the globular N‐terminus is embedded in the ER membrane. Alternative C‐termini represent candidate modifications that could determine specificity of binding to kinesin or cytoplasmic dynein, and the switching of directionality of movement. The cDNA hybridized to 4.5 kb transcripts expressed in ail mouse cell lines and tissues examined, which provides the first indication that the kinectins are very widely distributed. Mouse kinectin is 42% similar over a 203 amino acid region to the chicken extracellular cardiac morphogen ES/130, whose canine homologue containing an inserted sequence of 10 amino acids repeated 54 times in tandem, is a ribosome receptor expressed on the ER. Mouse kinectin shares 64 and 83% identity, respectively, with its M, 160 000 chicken and human kinectin homologues. There is a two‐fold molar excess of kinectin over kinesin in unextracted vesicles, suggesting that kinectin might be a dimer. The electrostatic properties of the coited‐coil region of mouse kinectin. together with the relative frequencies of residues in particular positions within the heptad repeats support this notion.
Breast cancer immunotherapy: Current status and future prospects
Authors: APOSTOLOPOULOS VASSO , McKENZIE IAN FC , PIETERSZ GEOFFREY A 
Published: June 2007

SummaryThe development of an immunotherapeutic approach to cancer is the concern for many immunologists, but despite the impressive progress over the past decade, such as the identification of tumour antigens and antigenic peptides as potential targets, there are still many obstacles in eliciting an effective immune response to eradicate cancer. Mucins have attracted interest as potential targets for immunotherapy in the development of vaccines for cancers expressing Mucin 1 (MUC1; e.g. breast, pancreas, ovary etc.). All of the identified targets for cancer, including MUC1, are normal proteins; however MUC1 expressed on tumours can be considered as tumour specific due to their overexpression, altered glycosylation and its ubiquitous distribution on the cell surface rather than at the secretory pole in adenocarcinomas. These observations have led to the development of several different approaches to immunize against breast cancer using synthetic carbohydrates or peptides conjugated to carriers and given together with a variety of adjuvants to elicit the appropriate immune response. Mannan, a polymannose carbohydrate isolated from the cell wall of yeast, is an appropriate and effective protein carrier for eliciting a cellular (T1‐type) or humoral (T2‐type) immune response depending on the mode of conjugation (oxidized or reduced). In addition, mannan holds promise and opens many avenues as a carrier for vaccine development for other antigens. Several clinical trials are in progress to evaluate the immunogenicity of MUC1 and its suitability as to use for immunotherapy/vaccine for breast cancer.
Tumour necrosis factor and lymphotoxin: Molecular aspects and role in tissue‐specific autoimmunity
Authors: KORNER HEINRICH , SEDGWICK JONATHON D 
Published: June 2007

SummaryTumour necrosis factor (TNF) is a highly potent, proinflammatory cytokine with broad‐ranging functions from the regulation of endothelial cell adhesion molecules to facilitate entry of leucocytes into tissues, to direct induction of cellular cytotoxicity. This diversity of function potentially attributable to TNF in the genesis of inflammatory disorders place TNF as a primary candidate for clinical targeting and considerable success in this regard has been achieved, particularly in rheumatoid arthritis (RA). In this article we provide a short overview of TNF and its homologue lymphotoxin (LT) α and β. Particular emphasis is placed on recent discoveries regarding the cell surface expression of these cytokines and the role of TNF/LT in experimental autoimmune encephalomyelitis (EAE), an animal model of the human demyelinating disease, multiple sclerosis (MS).
NK cell proliferation and inflammation
Authors: WARREN HILARY S 
Published: June 2007

SummaryConsiderable progress has been made in recent years in understanding the biology of NK cells. NK cells are no longer ‘null cells’, but express an array of functionally important molecules with which they mediate and regulate their cytolytic activity and the cytokines they secrete. Activation and proliferation of NK cells is influenced by cytokines produced by activated monocytes (IL‐15, IL‐12, 1L‐10) and activated T cells (IL–2). This paper reviews the phenotype and effector functions of NK cells, their tissue distribution, and evidence that NK cells proliferate in vivo as part of productive or pathologic consequences of immunity.
Characterization of IgG Fc receptors on CD34 antigen‐expressing cell lines (KG‐1 and KG‐la)
Authors: WU ZHANHE , MARKOVIC BOBAN , CHESTERMAN COLIN N , CHONG BENG H 
Published: June 2007

SummaryAlthough Fcγ receptors (FcγR) on mature blood cells have been extensively studied, there are only limited data on FcγR expression in the early haematopoietic progenitor cells. In this study, we used the stem cell antigen (CD34)‐expressing cell line (KG‐1) and its less differentiated subline (KG‐1a) as a model for the study of FcγR in the early haematopoietic progenitors. Flow cytometry and immunoprecipitation studies on KG‐1 and KG‐1 a cells with anti‐FcγR mAb showed that FcγRII is the only FcγR expressed on the cell surface. Analysis of the steady‐state levels of FcγR mRNA in KG‐1 and KG‐la cells using a quantitative in situ hybridization assay revealed the presence of only FcγRII mRNA. On further analysis FcγRIIA mRNA but no FcγRIIB or FcγRIIC transcripts were found in these cells: FcγRIIA transcripts with and without the transmem‐brane exon were present in approximately equal amounts. These findings are surprisingly similar to those observed previously with FcγR in platelets and megakaryocytic cells but different from those found with FcγR in cells of other lineages. These data suggest that the FcγR transcript distribution pattern observed in the early haematopoietic progenitors (KG‐l cells) is retained in later stages of haematopoietic differentiation only in cells of megakaryocytic lineage.
Primary cytotoxicity of SEB‐activated human PBMC and separated CD8+ and CD4+ T lymphocytes elicited by two different stimulation protocols
Authors: SEPRÉNYI GYÖRGY , ABE JUN , KOHSAKA TAKAO 
Published: June 2007

Summary.The primary cytotoxicity of Staphylococcal enterotoxin B (SEB)‐stimulated PBMC and separated CD8+ and CD4+ T cells against Burkitt's lymphoma target cells has been characterized by applying two stimulation protocols. In the bulk protocol, the PBMC were stimulated with 100 ng/mL SEB for 3 days before separation to CD4+ and CD8+ T subsets. In the direct protocol, the separated CD4+ and CD8+ T cells were stimulated with 100 ng SEB preabsorbed to mitomycin C (MMC)‐treated APC. Comparison of the results of the two different protocols revealed the following differences: (i) PBMC in the direct protocol provided greater cytolytic activity than in the bulk protocol; and (ii) the CD4+ T cells acquired cytotoxicity only in the direct protocol. Unexpectedly, the superantigen‐dependent cellular cytotoxicity (SDCC) of SEB‐stimulated cells was not dominant compared with the basal cytotoxicity. The classical NK target, K‐562 was also sensitive to SEB‐augmented cytotoxicity. The parallel stimulation with IL‐2 and SEB caused a similar extent of cytotoxicity enhancement against both types of target cells. However, the cyclosporin A (CSA) inhibited only the SEB‐induced cytotoxicity. The results suggest that SEB‐induced PBMC acquire mainly a LAK‐like cytotoxicity, as a consequence of newly produced lymphokines. This observation might propose a different approach in pathological studies.
Cloning of the mucosal addressin MAdCAM‐1 from human brain: Identification of novel alternatively spliced transcripts
Authors: LEUNG E , GREENE J , NI J , RAYMOND LG , LEHNERT K , LANGLEY R , KRISSANSEN GW 
Published: June 2007

Summary.The mucosal addressin cell adhesion molecule‐1 (MAdCAM‐1). expressed selectively on high endothelial venules (HEV) and lamina propria venules, directs lymphocyte traffic by binding the lymphocyte Peyer's patch adhesion molecule‐1 (LPAM‐1, α4β7). Full‐length DNA encoding human MAdCAM‐1 was obtained by combining sequences from an expressed sequence tag (EST) identified in an early stage human brain cDNA library, a polymerase chain reaction‐derived clone, and a MAdCAM‐1 genomic clone. The deduced amino acid sequence revealed an 18 amino acid signal peptide, two N‐terminal immunoglobulin (Ig)‐like domains conserved (59–65%) in sequence with those of the mouse homologue, an 86 amino acid mucin‐like region rich in serine‐threonine residues, a 20 amino acid transmembrane domain and a 43 amino acid charged cytoplasmic domain. No counterpart to the third IgA‐like domain of mouse MAdCAM‐1 was present; however, the serine‐threonine‐rich mucin domain was extended as two distinguishable major and minor mucin regions unrelated to the mouse mucin domain. The major domain is formed from six tandem repeats of an eight amino acid sequence having the MUC‐2‐related consensus DTTSPEP/SP. Human MAdCAM‐1 mRNA transcripts were restricted to small intestine, colon, spleen, pancreas and brain. Alternatively spliced MAdCAM‐1 variants were identified that lack parts of the second Ig domain and all or part of the major mucin domain, indicating that the function of this vascular addressin is regulated by extensive modifications to its multi‐domain structure.
Masters of deception: A review of herpesvirus immune evasion strategies
Authors: DAVIS‐POYNTER NICHOLAS J , FARRELL HELEN E 
Published: June 2007

Summary.Herpesviruses have acquired a variety of different mechanisms to avoid the damaging effects of host immunity. Frequently, these viruses subvert normal immune regulatory functions utilized by the host. The focus of this review is upon herpesvirus genes encoding known or potential immunomodulatory proteins. Areas covered include inhibition of complement and antibody function, herpesvirus‐encoded homologues of cytokines and chemokine receptors, and potential disruption of cellular recognition of virally infected targets.
Evasion of apoptosis by DNA viruses
Authors: CUFF SIMONE , RUBY JANET 
Published: June 2007

Summary.Apoptosis is a form of cell death distinct from necrosis which plays an important role in processes such as homoeostasis and the elimination of damaged cells. It can be triggered by a variety of stimuli including DNA damage and cytotoxic T lymphocyte activity,1 both of which may be induced in the course of a viral infection. Initially, induction of apoptosis may occur through pathways which have also been shown to be activated on disturbance of the cell cycle or damage to cellular DNA.2 At later time points during the course of infection, apoptosis can also be triggered by cytokines and immune effector cells.1 Apoptosis of the host cell before the completion of the viral replication cycle may limit the number of progeny and the spread of infection. The importance of apoptosis as an antiviral defence is illustrated by the presence of multiple pathways for apoptosis induction and inhibition in both the host and virus. In this review, the inhibition of apoptosis is described in adenovirus and poxvirus infection. These examples illustrate two of the divergent paths by which viruses may avoid the apoptotic response.
Regulation of host cell function by glycosylphosphatidylinositols of the parasitic protozoa
Authors: SCHOFIELD LOUIS , TACHADO SOUVENIR D 
Published: June 2007

Summary.Antigenic variation, antigenic drift, molecular mimicry, intracellular localization and sequestration in privileged sites are important mechanisms of immune evasion by infectious organisms. Added to this however is the phenomenon by which pathogens deliberately regulate host cell function by the production of glycolipids with agonistic or antagonistic signal transduction capacity. Such pro‐active glycolipids are often pathogenicity factors, but they also serve as immunomodulators and immunosuppressants, and these activities may serve as mechanisms of immune evasion. Here we review glycosylphosphatidylinositols and related structures, a novel class of glycolipid common to eukaryotic parasites and their hosts, which recent studies suggest may play a role in immune evasion and immunosuppression by regulating host cell function via the activation or suppression of endogenous host signalling pathways.
Freshwater fishes of the Altiplano
Authors: Vila Irma , Pardo Rodrigo , Scott Sergio 
Published: June 2007

Fisheries of the Altiplano, dating from 1500 to 2000 BC, are active in the Andean inter-montane plateau that extends from Ancash, Perú, to Antofagasta, Chile, at altitudes above 3600 m. The ancient and remote nature of these systems has merited the inclusion of many areas as National Parks and RAMSAR sites.
Among 58 native fish species, 45 belong to the killifish complex Orestias and the rest to the catfish complex Trichomycterus. The main fishery resources consist of “ispi”, Orestias ispi, with 32 175 (64.5%) metric tons and “karachi”, Orestias of the group agassii, with 455 metric tons (0.9%). The introduced fishes “silversides”, Odontesthes bonariensis, and “trouts”, Oncorhynchus mykiss, contribute 16 900 metric tons (33.9%) and 324 metric tons (0.7%) respectively.
Hydro-acoustic evaluations show a permanent diminution of the endemic Orestias. Lake species such as O. pentlandii “boga” and O. cuvieri “humanto” were important for their biogeographic relationships and were highly endemic. Native fishes are nowadays threatened by the salmonids, Oncorhynchus mykiss, Salvelinus namaycush, Salvelinus fontinalis and Salmo trutta, introduced since 1939. Later, the silverside Odontesthes bonariensis was introduced during 1955–1956.
Resistance to Botrytis cinerea in sitiens, an Abscisic Acid-Deficient Tomato Mutant, Involves Timely Production of Hydrogen Peroxide and Cell Wall Modifications in the Epidermis
Authors: Asselbergh Bob , Curvers Katrien , França Soraya C. , Audenaert Kris , Vuylsteke Marnik , Van Breusegem Frank , Höfte Monica 
Published: June 2007

Abstract
Plant defense mechanisms against necrotrophic pathogens, such as Botrytis cinerea, are considered to be complex and to differ from those that are effective against biotrophs. In the abscisic acid-deficient sitiens tomato (Solanum lycopersicum) mutant, which is highly resistant to B. cinerea, accumulation of hydrogen peroxide (H2O2) was earlier and stronger than in the susceptible wild type at the site of infection. In sitiens, H2O2 accumulation was observed from 4 h postinoculation (hpi), specifically in the leaf epidermal cell walls, where it caused modification by protein cross-linking and incorporation of phenolic compounds. In wild-type tomato plants, H2O2 started to accumulate 24 hpi in the mesophyll layer and was associated with spreading cell death. Transcript-profiling analysis using TOM1 microarrays revealed that defense-related transcript accumulation prior to infection was higher in sitiens than in wild type. Moreover, further elevation of sitiens defense gene expression was stronger than in wild type 8 hpi both in number of genes and in their expression levels and confirmed a role for cell wall modification in the resistant reaction. Although, in general, plant defense-related reactive oxygen species formation facilitates necrotrophic colonization, these data indicate that timely hyperinduction of H2O2-dependent defenses in the epidermal cell wall can effectively block early development of B. cinerea.
SDIR1 Is a RING Finger E3 Ligase That Positively Regulates Stress-Responsive Abscisic Acid Signaling inArabidopsis
Authors: Zhang Yiyue , Yang Chengwei , Li Yin , Zheng Nuoyan , Chen Hao , Zhao Qingzhen , Gao Ting , Guo Huishan , Xie Qi 
Published: June 2007

AbstractUbiquitination plays important roles in plant hormone signal transduction. We show that the RING finger E3 ligase, Arabidopsis thaliana SALT- AND DROUGHT-INDUCED RING FINGER1 (SDIR1), is involved in abscisic acid (ABA)-related stress signal transduction. SDIR1 is expressed in all tissues of Arabidopsis and is upregulated by drought and salt stress, but not by ABA. Plants expressing the ProSDIR1–β-glucuronidase (GUS) reporter construct confirmed strong induction of GUS expression in stomatal guard cells and leaf mesophyll cells under drought stress. The green fluorescent protein–SDIR1 fusion protein is colocalized with intracellular membranes. We demonstrate that SDIR1 is an E3 ubiquitin ligase and that the RING finger conservation region is required for its activity. Overexpression of SDIR1 leads to ABA hypersensitivity and ABA-associated phenotypes, such as salt hypersensitivity in germination, enhanced ABA-induced stomatal closing, and enhanced drought tolerance. The expression levels of a number of key ABA and stress marker genes are altered both in SDIR1 overexpression and sdir1-1 mutant plants. Cross-complementation experiments showed that the ABA-INSENSITIVE5 (ABI5), ABRE BINDING FACTOR3 (ABF3), and ABF4 genes can rescue the ABA-insensitive phenotype of the sdir1-1 mutant, whereas SDIR1 could not rescue the abi5-1 mutant. This suggests that SDIR1 acts upstream of those basic leucine zipper family genes. Our results indicate that SDIR1 is a positive regulator of ABA signaling.
Mouse strain differences in inflammatory responses of colonic mucosa induced by dextran sulfate sodium cause differential susceptibility to PhIP‐induced large bowel carcinogenesis
Authors: Nakanishi Masako , Tazawa Hiroshi , Tsuchiya Naoto , Sugimura Takashi , Tanaka Takuji , Nakagama Hitoshi 
Published: June 2007

In mice, 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) induces a high incidence of malignant lymphoma and leukemia, but exhibits little, if any, carcinogenic activity in the large intestine after long‐term exposure. However, recent studies have revealed that colonic adenocarcinomas can be efficiently and rapidly induced by combined treatment with PhIP and dextran sulfate sodium (DSS), a potent inducer of colitis. In the present study, the authors investigated the effects of inflammation on PhIP‐induced carcinogenesis using two mouse strains, C57BL/6J and MSM/Ms, showing distinct temporal profiles of inflammatory responses to DSS. A long‐term carcinogenesis experiment conducted with a single i.g. administration of PhIP (200 mg/kg body weight), followed by DSS treatment in drinking water for 4–6 days, revealed an increase in tumor incidence in C57BL/6J mice in accordance with the DSS intake. In contrast, neoplastic lesions were rarely observed in the MSM/Ms strain. From the short‐term exposure to DSS for 4 days, C57BL/6J mice demonstrated severe chronic colitis, accompanied by hyperplastic cryptal epithelium and extensive cellular infiltration. Splenomegaly and swelling of mesenteric lymph nodes were also evident for over 1 month as chronic symptoms of systemic immunological disturbance. However, no inflammatory lesions were detected in MSM/Ms mice. The present results provide strong evidence that prolonged chronic inflammatory responses induced by DSS are directly responsible for the observed enhancement of PhIP‐induced large bowel carcinogenicity. (Cancer Sci 2007; 98: 1157–1163)
Detection of mitochondrial DNA from domestic cattle in bison on Santa Catalina Island
Authors: Vogel A. B. , Tenggardjaja K. , Edmands S. , Halbert N. D. , Derr J. N. , Hedgecock D. 
Published: June 2007

SummaryIn 1924, 14 American bison (Bison bison) were introduced to Santa Catalina Island, California and sporadically supplemented thereafter with additional animals. To reduce the herd and its impact on native vegetation, over 2000 animals have been exported during the past four decades. Today, the herd is estimated to contain around 250 individuals. Genetic analysis was performed on 98 animals removed from the island in 2004. Forty‐four samples (45%) had domestic cattle mitochondrial DNA (mtDNA), 12 (12%) had previously reported bison haplotypes and 42 (43%) had a new haplotype differing by one base pair from a previously reported bison haplotype. A complement of five restriction enzymes was found to be useful in identifying bison with domestic cattle mtDNA.
Airway cell and cytokine changes in early asthma deterioration after inhaled corticosteroid reduction
Authors: Khor Y. H. , Feltis B. N. , Reid D. W. , Ward C. , Johns D. P. , Wood‐Baker R. , Walters E. H. 
Published: June 2007

SummaryBackground
Back‐titration of inhaled corticosteroid (ICS) dose in well‐controlled asthma patients is emphasized in clinical guidelines, but there are few published data on the airway cell and cytokine changes in relation to ICS reduction. In our study, 20 mild‐to‐moderate persistent (inspite of low‐moderate dose ICS treatment) asthmatic subjects prospectively rendered largely asymptomatic by high‐dose ICS were assessed again by clinical, physiological, and airway inflammatory indices after 4–8 weeks of reduced ICS treatment. We aimed at assessing the underlying pathological changes in relation to clinical deterioration.Methods
Patients recorded daily symptom scores and peak expiratory flows (PEF). Spirometry and airways hyperreactivity (AHR) were measured and bronchoscopy was performed with assessment of airway biopsies (mast cells, eosinophils, neutrophils, and T lymphoctyes), bronchoalveolar lavage (BAL) IL‐5 and eotaxin levels and cellular profiles at the end of high‐dose ICS therapy and again after ICS dose reduction. Baseline data were compared with symptomatic steroid‐free asthmatics (n=42) and non‐asthmatic controls (n=28).Results
After ICS reduction, subjects experienced a variable but overall significant increase in symptoms and reductions in PEF and forced expiratory volume in 1 s. There were no corresponding changes in AHR or airways eosinophilia. The most relevant pathogenic changes were increased CD4+/CD8+ T cell ratio, and decreased sICAM‐1 and CD18 macrophage staining (potentially indicating ligand binding). However, there was no relationship between the spectrum of clinical deterioration and the changes in cellular profiles or BAL cytokines.Conclusions
These data suggest that clinical markers remain the most sensitive measures of early deterioration in asthma during back‐titration of ICS, occurring at a time when AHR and conventional indices of asthmatic airway inflammation appear unchanged. These findings have major relevance to management and to how back‐titration of ICS therapy is monitored.