bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dendritic Cells Engineered to Express Defined Allo‐HLA Peptide Complexes Induce Antigen‐specific Cytotoxic T Cells Efficiently Killing Tumour Cells
Authors: Stronen E. , Abrahamsen I. W. , Gaudernack G. , Wälchli S. , Munthe E. , Buus S. , Johansen F.‐E. , Lund‐Johansen F. , Olweus J. 
Published: December 2008

AbstractMost tumour‐associated antigens (TAA) are non‐mutated self‐antigens. The peripheral T cell repertoire is devoid of high‐avidity TAA‐specific cytotoxic T lymphocytes (CTL) due to self‐tolerance. As tolerance is major histocompatibility complex‐restricted, T cells may be immunized against TAA presented by a non‐self human leucocyte antigen (HLA) molecule and transferred to cancer patients expressing that HLA molecule. Obtaining allo‐restricted CTL of high‐avidity and low cross‐reactivity has, however, proven difficult. Here, we show that dendritic cells transfected with mRNA encoding HLA‐A*0201, efficiently present externally loaded peptides from the antigen, Melan‐A/MART‐1 to T cells from HLA‐A*0201‐negative donors. CD8+ T cells binding HLA‐A*0201/MART‐1 pentamers were detected already after 12 days of co‐culture in 11/11 donors. The majority of cells from pentamer+ cell lines were CTL and efficiently killed HLA‐A*0201+ melanoma cells, whilst sparing HLA‐A*0201+ B‐cells. Allo‐restricted CTL specific for peptides from the leukaemia‐associated antigens CD33 and CD19 were obtained with comparable efficiency. Collectively, the results show that dendritic cells engineered to express defined allo‐HLA peptide complexes are highly efficient in generating CTL specifically reacting with tumour‐associated antigens.
ABCB1‐1Δ (MDR1‐1Δ) genotype is associated with adverse reactions in dogs treated with milbemycin oxime for generalized demodicosis
Authors: Barbet Joy L. , Snook Tara , Gay John M. , Mealey Katrina L. 
Published: December 2008

AbstractTwenty‐two dogs diagnosed with generalized demodicosis were treated with milbemycin oxime (MO) because of poor response to previous therapies or because the dog was a breed known to be susceptible to ivermectin toxicosis. Fifteen of the 22 dogs were herding breeds. Doses of MO ranged from 1.0 to 2.2 mg kg−1day−1per os. Cheek swab samples were obtained in order to determine each dog'sABCB1 genotype. Adverse drug reactions were recorded for each dog by the owners and/or veterinarians. TheABCB1‐1Δ genotype was significantly associated with the development of an adverse reaction (neurological toxicity) after treatment with MO. None of the 19 dogs with the wild‐type ABCB1 allele experienced adverse reactions, whereas two dogs homozygous for the ABCB1‐1Δ mutation developed ataxia. Assessing the ABCB1‐1Δ genotype prior to MO administration may prevent neurological toxicity in these patients.
TheABCB1‐1Δmutation is not responsible for subchronic neurotoxicity seen in dogs of non‐collie breeds following macrocyclic lactone treatment for generalized demodicosis
Authors: Bissonnette Stéphane , Paradis Manon , Daneau Isabelle , Silversides David W. 
Published: December 2008

AbstractP‐glycoprotein (P‐gp), encoded by the multiple drug resistance geneABCB1(also known asMDR1), is an integral component of the blood brain barrier crucial in limiting drug uptake into the central nervous system. Altered expression or function of P‐gp, as seen in dogs of the collie lineage homozygous for the nt228(del4) mutation of theABCB1gene (ABCB1‐1Δ), can result in potentially fatal neurotoxicosis, especially following administration of systemic macrocyclic lactones (SML). Occasionally, dogs from unrelated breeds develop subchronic signs of neurotoxicity when receiving SML to treat generalized demodicosis. It is possible that these dogs are heterozygous carriers of theABCB1‐1Δmutation, resulting in decreased P‐gp activity and central neurotoxicosis. Cheek swabs were collected from 28 dogs with generalized demodicosis that had shown subchronic signs of neurotoxicity following daily oral administration of ivermectin or other SML. Ten of these animals received concurrent systemic treatment with other confirmed or putative P‐gp substrates. After DNA extraction, the relevant portion of theABCB1gene was amplified by polymerase chain reaction, and sequenced. Twenty‐seven dogs were homozygous normal while one dog was heterozygous for theABCB1‐1Δmutation. Therefore, with the exception of one dog, the observed neurotoxicity could not be attributed to theABCB1‐1Δmutation. Possible explanations for the adverse reactions observed include pharmacological interactions (administration of SML with other P‐gp substrates or inhibitors), excessively high doses, polymorphisms in P‐gp expression, uncharacterized mutations in theABCB1gene or in another gene, or phenomena unrelated to the SML–P‐gp interaction.
Diversity of killer cell immunoglobulin‐like receptor genes in Indonesian populations of Java, Kalimantan, Timor and Irian Jaya
Authors: Velickovic M. , Velickovic Z. , Panigoro R. , Dunckley H. 
Published: December 2008

AbstractKiller cell immunoglobulin‐like receptors (KIRs) regulate the activity of natural killer and T cells through interactions with specific human leucocyte antigen class I molecules on target cells. Population studies performed over the last several years have established that KIR gene frequencies (GFs) and genotype content vary considerably among different ethnic groups, indicating the extent of KIR diversity, some of which have also shown the effect of the presence or absence of specific KIR genes in human disease. We have determined the frequencies of 16 KIR genes and pseudogenes and genotypes in 193 Indonesian individuals from Java, East Timor, Irian Jaya (western half of the island of New Guinea) and Kalimantan provinces of Indonesian Borneo. All 16 KIR genes were observed in all four populations. Variation in GFs between populations was observed, except for KIR2DL4, KIR3DL2, KIR3DL3, KIR2DP1 and KIR3DP1 genes, which were present in every individual tested. When comparing KIR GFs between populations, both principal component analysis and a phylogenetic tree showed close clustering of the Kalimantan and Javanese populations, while Irianese populations were clearly separated from the other three populations. Our results indicate a high level of KIR polymorphism in Indonesian populations that probably reflects the large geographical spread of the Indonesian archipelago and the complex evolutionary history and population migration in this region.
HLA‐A, ‐B, ‐C, and ‐DRB1 allele and haplotype frequencies distinguish Eastern European Americans from the general European American population
Authors: Mack S. J. , Tu B. , Lazaro A. , Yang R. , Lancaster A. K. , Cao K. , Ng J. , Hurley C. K. 
Published: December 2008

AbstractSequence‐based typing was used to identify human leukocyte antigen (HLA)‐A, ‐B, ‐C, and ‐DRB1 alleles from 558 consecutively recruited US volunteers with Eastern European ancestry for an unrelated hematopoietic stem cell registry. Four of 31 HLA‐A alleles, 29 HLA‐C alleles, 59 HLA‐B alleles, and 42 HLA‐DRB1 alleles identified (A*0325, B*440204, Cw*0332, and *0732N) are novel. The HLA‐A*02010101g allele was observed at a frequency of 0.28. Two‐, three‐, and four‐locus haplotypes were estimated using the expectation‐maximization algorithm. The highest frequency extended haplotypes (A*010101g–Cw*070101g–B*0801g–DRB1*0301 and A*03010101g–Cw*0702–B*0702–DRB1*1501) were observed at frequencies of 0.04 and 0.03, respectively. Linkage disequilibrium values () of the constituent two‐locus haplotypes were highly significant for both extended haplotypes (Pvalues were less than 8 × 10−10) but were consistently higher for the more frequent haplotype. Balancing selection was inferred to be acting on all the four loci, with the strongest evidence of balancing selection observed for the HLA‐C locus. Comparisons of the A–C–B haplotypes and DRB1 frequencies in this population with those for African, European, and western Asian populations showed high degrees of identity with Czech, Polish, and Slovenian populations and significant differences from the general European American population.
Ethnic variability in human leukocyte antigen‐E haplotypes
Authors: Antoun A. , Jobson S. , Cook M. , Moss P. , Briggs D. 
Published: December 2008

AbstractHuman leukocyte antigen‐E (HLA‐E) is an important nonclassical major histocompatibility complex (MHC) class I (Ib) molecule that acts as the ligand for NKG2A/B/C receptors expressed on natural killer (NK) cells and T cells. Unlike the classical class I molecules, HLA‐E is highly conserved in evolution and the biological significance of polymorphism is therefore unclear. Our aim was to investigate the polymorphism in HLA‐E gene in three ethnic groups in the UK and to obtain population data relating to any variations observed at this locus. We developed a polymerase chain reaction–sequence‐specific primer (PCR‐SSP) method for identifying HLA‐E single nucleotide polymorphisms (SNPs) in genomic DNA. This was used to investigate the genotype distribution and allele frequency of nine published SNPs in the coding region of HLA‐E in 223 Euro‐Caucasoid, 60 Afro‐Caribbean and 52 Asian healthy individuals. Genotype frequencies were in Hardy–Weinberg equilibrium. No polymorphism was observed for seven previously reported SNPs and these should not be considered polymorphic. However, positions 1114 and 1446 were confirmed as polymorphic and different genotype frequencies were identified at nucleotide position 1114 between the three studied ethnic groups. We present these data together with the intragene haplotype frequencies in these populations. To our knowledge, this is the first description of population frequencies of nine different SNPs in HLA‐E in three main large ethnic groups. The data generated from this study will be of importance in the context of describing the effect of HLA‐E polymorphism in clinical settings such as transplantation and autoimmune diseases.
Social context predicts recognition systems in ant queens
Authors: DREIER S. , D’ETTORRE P. 
Published: December 2008

AbstractRecognition of group‐members is a key feature of sociality. Ants use chemical communication to discriminate nestmates from intruders, enhancing kin cooperation and preventing parasitism. The recognition code is embedded in their cuticular chemical profile, which typically varies between colonies. We predicted that ants might be capable of accurate recognition in unusual situations when few individuals interact repeatedly, as new colonies started by two to three queens. Individual recognition would be favoured by selection when queens establish dominance hierarchies, because repeated fights for dominance are costly; but it would not evolve in absence of hierarchies. We previously showed that Pachycondyla co‐founding queens, which form dominance hierarchies, have accurate individual recognition based on chemical cues. Here, we used the ant Lasius niger to test the null hypothesis that individual recognition does not occur when co‐founding queens do not establish dominance hierarchies. Indeed, L. niger queens show a similar level of aggression towards both co‐foundresses and intruders, indicating that they are unable of individual recognition, contrary to Pachycondyla. Additionally, the variation in chemical profiles of Lasius and Pachycondyla queens is comparable, thus informational constraints are unlikely to apply. We conclude that selection pressure from the social context is of crucial significance for the sophistication of recognition systems.
Diet and social conditions during sexual maturation have unpredictable influences on female life history trade‐offs
Authors: BARRETT E. L. B. , MOORE A. J. , MOORE P. J. 
Published: December 2008

AbstractThe trade‐off between gametes and soma is central to life history evolution. Oosorption has been proposed as a mechanism by which females can redirect nutrients invested in oocytes into survival when conditions for reproduction are poor. Although positive correlations between oocyte degradation and lifespan have been documented in oviparous insects, the adaptive significance of this process in species with more complex reproductive biology has not been explored. Further, environmental condition is a multivariate state, and combinations of environmental stresses may interact in unpredictable ways. Previous work on the ovoviviparous cockroach, Nauphoeta cinerea, revealed that females manipulated to mate late relative to sexual maturation experience age‐related loss in fecundity because of loss of viable oocytes via apoptosis. This loss in fecundity is correlated with a reduction in female mate choice. Food deprivation while mating is delayed further increases levels of oocyte apoptosis, but the relationship between starvation‐induced apoptosis and life history are unknown. To investigate this, virgin females were either fed or starved from eclosion until provided with a mate at a time known to be suboptimal for fertility. Following mating, females were fed for the duration of their lifespan. We measured lifetime reproductive performance. Contrary to predictions, under conditions of delayed mating opportunity, starved females had greater fecundity, gave birth to more high‐quality offspring and had increased longevity compared with that of fed females. We suggest that understanding proximal mechanisms underlying life history trade‐offs, including the function of oocyte apoptosis, and how these mechanisms respond to varied environmental conditions is critical.
Selection efficiency and effective population size in Drosophila species
Authors: PETIT N. , BARBADILLA A. 
Published: December 2008

AbstractA corollary of the nearly neutral theory of molecular evolution is that the efficiency of natural selection depends on effective population size. In this study, we evaluated the differences in levels of synonymous polymorphism among Drosophila species and showed that these differences can be explained by differences in effective population size. The differences can have implications for the molecular evolution of the Drosophila species, as is suggested by our results showing that the levels of codon bias and the proportion of adaptive substitutions are both higher in species with higher levels of synonymous polymorphism. Moreover, species with lower synonymous polymorphism have higher levels of nonsynonymous polymorphism and larger content of repetitive sequences in their genomes, suggesting a diminished efficiency of selection in species with smaller effective population size.
Production of Antiserum to Recombinant Coat Protein for Detecting Lily mottle virus in Yunnan, China
Authors: Kong Baohua , Yu Jialin , Chen Hairu , Li Dawei , Han Chenggui , Wang Jihua 
Published: December 2008

Abstract Lily mottle virus (LMoV), Potyvirus genus, is very difficult to purify for the preparation of diagnostic antisera. The coat protein (CP) gene of LMoV was amplified by RT‐PCR from infected plants and cloned into the prokaryotic pET‐30a vector to generate the recombinant plasmid pET‐CP. The resulting carboxy‐terminal His‐tagged CP was over‐expressed in Escherichia coli BL 21 cells by Isopropyl‐β‐d‐thiogalactoside (IPTG) induction and purified over Ni‐NTA affinity columns. The purified CP was used to elicit a polyclonal antiserum in rabbits. The antiserum had a titre of 1 : 128 in double diffusion tests, and specifically recognized LMoV in Western blots, Enzyme‐Linked Immunosorbent Assays and Immuno‐Electron Microscopy. The CP antiserum was also used to evaluate LMoV infection of lily bulbs used for commercial production in Yunnan, China. Substantial levels of infection were found in both imported and native bulbs, and provide the basis to implement flexible, rapid and large‐scale virus indexing of lily plants for use in propagation and to meet virus‐free quarantine regulations.
Molecular markers for detection, surveillance and prognostication of bladder cancer
Authors: Vrooman Olaf PJ , Witjes J Alfred 
Published: December 2008

AbstractMany markers for the detection of bladder cancers have been tested and almost all urinary markers reported are better than cytology with regard to sensitivity, but they score lower in specificity. Currently molecular and genetic changes play an important role in the discovery of new molecular markers for detection, prognostication and surveillance. The purpose of this review is to highlight the most important urinary molecular biomarker developments that have been studied and reported recently. In the current review we have summarized the most recent and relevant published reports on molecular urinary markers. The results of this review show that the first generation of urinary markers did not add much to urinary cytology. The current generation of markers is better, but additional clinical trials are needed. Our knowledge of molecular pathways in bladder cancer is growing and new methods of marker development emerge, but the perfect marker is still to be found. Currently, there are not clinically usable molecular markers that can guide us in diagnosis or surveillance, nor guide us in lowering the frequency of urethrocystoscopy in bladder cancer.
A case of late onset leukoencephalopathy with cerebral calcifications and cysts in a 59‐year‐old woman
Authors: Kaffenberger T. , Valko P. O. , Von Meyenburg J. , Baráth K. , Hewer E. , Heppner F. L. , Jagella C. E. , Horst A. , Siccoli M. M. 
Published: December 2008

Background:  Leukoencephalopathy with cerebral calcifications and cysts (LCC) is a recently described, very rare entity, clinically characterized by progressive neurological deficits such as cognitive decline, epileptic seizures, pyramidal, extrapyramidal and cerebellar symptoms/signs. With the exception of two patients with adult onset, in all previously described cases symptoms onset occurred between early infancy and adolescence.Results:  We report a case of late onset LCC in a 59‐year‐old woman presenting with urinary and fecal incontinence and behavioural changes, then rapid progression with hemianopia, hemiparesis, ataxia and cognitive decline. Extensive work‐up was performed, including brain magnetic resonance imaging, magnetic resonance spectroscopy, cyst fluid analysis and brain biopsy, confirming the final diagnosis of LCC.Conclusion:  Our case supports the existence of a late onset adult form of LCC.
Spinal cord sarcoidosis: report of seven cases
Authors: Varron L. , Broussolle C. , Candessanche J.‐P. , Marignier R. , Rousset H. , Ninet J. , Sève P. 
Published: December 2008

Background:  Spinal cord involvement in sarcoidosis is rare, occurring in <1% of patients with sarcoidosis.Methods:  We report seven cases of spinal cord sarcoidosis, seen in two French hospitals over a 13‐year period. Presentation of disease, methods of diagnosis and response to treatment, with quantification according to the reduction of the modified Rankin scale (MRS), were noted.Results:  Six patients presented insidious paresthesias or weakness and one a sudden paraplegia. Average MRS at diagnosis was to 2. Spine MRI showed one or several intramedullary lesions in all cases. Diagnosis was confirmed by extra‐neural tissue biopsies in all cases, including mediastinoscopy (two patients), coelioscopy (one patient), bronchoscopy (one patient), salivary gland biopsy (one patient) and skin biopsy (two patients). The average follow‐up for the group was 49.4 months. All patients responded to corticosteroid therapy with a median reduction of MRS of one point. Five patients received immunosuppressive therapy: cyclophosphamide (two patients), methotrexate (two patients), azathioprine (one patient), mycophenolate mofetyl (one patient), with an inconstant benefit. Patients who received cyclophosphamide presented severe fungaemia.Conclusion:  Based on our study and literature analysis, we propose an algorithm for treatment of spinal cord sarcoidosis.
Age of puberty and the risk of multiple sclerosis: a population based study
Authors: Ramagopalan S. V. , Valdar W. , Criscuoli M. , DeLuca G. C. , Dyment D. A. , Orton S.‐M. , Yee I. M. , Ebers G. C. , Sadovnick A. D. ,   for the Canadian Collaborative Study Group
Published: December 2008

Background and purpose:  Genetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility. Given a potential role for sex hormones in MS, we have investigated whether or not the age of puberty influences the risk of developing MS in a population‐based cohort.Methods:  We identified 5493 MS index cases and 1759 spousal controls with age of puberty information from the Canadian Collaborative Project on Genetic Susceptibility to MS. Age of puberty was compared between index cases and controls, and any effect of age of puberty on the age of onset of MS was also investigated.Results:  There were no significant differences between male index cases and controls with respect to age of puberty, P = 0.70. However, a significant difference was observed between female index cases and female controls, with average age of puberty being 12.4 and 12.6 years respectively, P = 0.00017, providing a relative risk decrease of 0.9 per year increase of age of puberty. There was no effect of the age of puberty on the age of MS onset in either sex.Conclusions:  Earlier age at menarche increases the risk of MS in women. Whether this association is a surrogate for a disease causative factor or directly involved in MS disease aetiology needs to be uncovered.
Separation of phasic arousal and expectancy effects in a speeded reaction time task via fMRI
Authors: Hackley Steven A. , Langner Robert , Rolke Bettina , Erb Michael , Grodd Wolfgang , Ulrich Rolf 
Published: December 2008

AbstractSixteen neurologically normal volunteers performed a 2‐choice speeded reaction time (RT) task in which the imperative was the change in color of a clock hand. During trial blocks with low temporal uncertainty (good clock condition), this imperative stimulus occurred at a fixed location (e.g., 2:00). In the bad clock condition, the clock was unpredictive of imperative onset. On half of both good and bad clock trials, a task‐irrelevant, cutaneous accessory stimulus accompanied the imperative. The speeding of reactions by the accessory was associated with activation primarily in and near the supramarginal gyrus of the parietal lobe. Contrasts of good‐ versus bad‐clock conditions revealed activation in a variety of perceptual, motor, and executive control regions. Apart from interactions within the cerebellum and left anterior insula, there was little overlap between structures influenced by the arousal and expectancy manipulations.
Gamma‐band activity in the human superior temporal sulcus during mentalizing from nonverbal social cues
Authors: Cohen Michael X , David Nicole , Vogeley Kai , Elger Christian E. 
Published: December 2008

AbstractThe posterior superior temporal sulcus (pSTS) is a key structure for our ability to infer others' mental states based on social cues including facial expressions, body posture, and gestures (“mentalizing”), but the neural mechanisms of this ability remain largely unknown. We recorded electrocorticogram directly from the pSTS in humans to show that enhanced neural oscillations in the gamma frequency range (35–55 Hz) accompany mentalizing. One patient with a lesion in pSTS was tested behaviorally on this task; he was unable to infer a virtual character's preferences from nonverbal social cues. Enhanced coherent gamma oscillations in the patients with intact pSTS may reflect a process by which social signals are bound into a unified representation to support mentalizing. This may be relevant for other social cognitive processes, as well as to the study of autism spectrum disorders, for which both mentalizing deficits and abnormal gamma activity have been reported.