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At least 1,549 records · Page 86Linked to original sources
PubMed1993

Deficit of HLA homozygotes in a Caucasian isolate.

Deficits of HLA-A, -B homozygotes observed many years ago in two inbred populations suggested negative selection against HLA homozygotes. To determine whether a similar deficiency would be observed in the S-leut Hutterites, a well-characterized Caucasian isolate of European ancestry, and to determine whether selection operated at the allele, locus, or haplotype level, observed and expected numbers of homozygotes were compared in 852 adult Hutterites. Deficits ranging from 11% to 24% were observed for all five loci examined (HLA-A, -B, -C, -DR, and -DQ). However, these deficits were secondary to, and almost completely accounted for by, a 64% loss of individuals homozygous for the haplotype. There was no evidence of deficits affecting only a single allele or locus. The data indicate strong negative selection against HLA homozygotes. This could be due, at least in part, to decreased fecundability among couples sharing HLA-DR. However, these data suggest that additional selective factors acting at the level of the haplotype also operate in this population.

Adult↗
PubMed2006

Time-sharing in pigeons: Independent effects of gap duration, position and discriminability from the timed signal.

Previous data suggest that in a peak-interval procedure with gaps, memory for the pre-gap interval varies with the discriminability of the gap from the to-be-timed signal. Here we extend this finding by manipulating the pre-gap and gap intervals as well as the visual contrast between the gap and the to-be-timed signal. The delay in response function after the gap was found to vary with the duration and position of the gap. However, for each gap duration and position, the delay in response increased with the gap-signal contrast: at 60% gap-signal contrast pigeons continued to accumulate time during the gap, at 80% gap-signal contrast pigeons stopped timing during the gap, and at 100% gap-signal contrast pigeons reset their timing after the gap. Data are accounted for by a time-sharing model assuming two concurrent processes during the gap--time accumulation and memory decay controlled by the salience of the gap--whose interplay results in a continuum of responses in the gap procedure.

Algorithms↗
PubMed1985

The impact of cost sharing on emergency department use.

We studied the effect of insurance coverage on the use of emergency department services, using data from a national trial of cost sharing in health insurance. A total of 3973 persons below the age of 62 years were randomly assigned to fee-for-service health insurance plans with coinsurance rates of 0, 25, 50, or 95 per cent, subject to an income-related upper limit on out-of-pocket expenses. Persons with no cost sharing had emergency department expenses that were 42 per cent higher than those for persons on the 95 per cent plan (P less than 0.01) and about 16 per cent higher than those for persons with smaller amounts of cost sharing. Without cost sharing, emergency department visits for less serious diagnoses (e.g., abrasions) increased three times as much as did visits for more serious diagnoses (e.g., lacerations). After control for insurance, persons in the lower third of the income distribution had emergency department expenses that were 64 per cent higher than those in the upper third (P less than 0.001) and received a greater proportion of their ambulatory care in the emergency department. We conclude that the absence of cost sharing results in significantly greater emergency department use than does insurance with cost sharing. A disproportionate amount of the increased use involves less serious conditions.

Ambulatory Care↗
PubMed2005

Bias of allele-sharing linkage statistics in the presence of intermarker linkage disequilibrium.

Current genome-wide linkage-mapping single-nucleotide polymorphism (SNP) panels with densities of 0.3 cM are likely to have increased intermarker linkage disequilibrium (LD) compared to 5-cM microsatellite panels. The resulting difference in haplotype frequencies versus that predicted may affect multipoint linkage analysis with ungenotyped founders; a common haplotype may be assumed to be rare, leading to inflation of identical-by-descent (IBD) allele-sharing estimates and evidence for linkage. Using data simulated for the Genetic Analysis Workshop 14, we assessed bias in allele-sharing measures and nonparametric linkage (NPL all) and Kong and Cox LOD (KC-LOD) scores in a targeted analysis of regions with and without LD and with and without genes. Using over 100 replicates, we found that if founders were not genotyped, multipoint IBD estimates and delta parameters were modestly inflated and NPL all and KC-LOD scores were biased upwards in the region with LD and no gene; rather than centering on the null, the mean NPL all and KC-LOD scores were 0.51 +/- 0.91 and 0.19 +/- 0.38, respectively. Reduction of LD by dropping markers reduced this upward bias. These trends were not seen in the non-LD region with no gene. In regions with genes (with and without LD), a slight loss in power with dropping markers was suggested. These results indicate that LD should be considered in dense scans; removal of markers in LD may reduce false-positive results although information may also be lost. Methods to address LD in a high-throughput manner are needed for efficient, robust genomic scans with dense SNPs.

Alleles↗
PubMed1998

Childhood malaria in the Lao People's Democratic Republic.

The idea that malaria in South-East Asia is synonymous with adult malaria is questioned in this paper. In the Lao People's Democratic Republic, community-based malariometric data were collected in Savannakhet Province, which shares borders with Viet Nam in the east and Thailand in the west. The data indicate that endemic malaria is rural and stable in large areas of the province. In these areas, which are rarely subject to malaria control, there is significant childhood malaria. A little more than one-quarter of individuals examined in mass blood surveys carried out in the peak malaria season were parasite-positive. Unlike other studies in the region reporting a declining risk of positive parasitaemia with age, thus suggesting immunity consistent with high and prolonged exposure to malaria, the communities studied in the Lao People's Democratic Republic did not show the expected acquisition of immunity. Further community-based studies on this matter are therefore warranted.

Adolescent↗
PubMed2002

Conserved expression control and shared activity between cognate T-box genes Tbx2 and Tbx3 in connection with Sonic hedgehog signaling during Xenopus eye development.

Tbx2 and Tbx3 are considered to be cognate genes within a Tbx2/3/4/5 subfamily of T-box genes and are expressed in closely overlapping areas in a variety of tissues, including the eye. Herein, we show that misexpression of Tbx2 and Tbx3 in Xenopus embryos gave rise to defective eye morphogenesis, which was reminiscent of the defect caused by attenuated Sonic hedgehog (Shh) signaling. Indeed, Tbx2/3 misexpression suppressed Gli1, Gli2, Ptc2 and Pax2, mediators or targets of Hedgehog (Hh) signals. From these data, Tbx2/3 may have a shared function in inhibiting Gli-dependent Shh signaling during eye development. Conversely, the expression of Tbx2/3 was severely affected by both Shh and a putative dominant negative form of Hh, as well as by both transactivator and transrepressor forms of Gli-fusion proteins, suggesting that the expression of Tbx2/3 may be regulated by a Gli-dependent Hh signal transduction pathway. Because the Shh signal has been considered to play crucial roles in the formation of the proximal-distal and dorsal-ventral axes in the eyes, these findings about the mutual regulatory mechanism between Tbx2/3 and Gli-dependent Hh signaling provide valuable insight into the cause of the localized expression of Tbx2/3 and their role during the formation of these axes. In addition, our findings also imply the conserved regulation and shared activity between the cognate genes of Tbx2 and Tbx3.

Animals↗
PubMed1992

DNA analysis of HLA-DR, DQ, and DP alleles in children with polyarticular juvenile rheumatoid arthritis.

HLA-DR, DQ and DP alleles were determined by restriction fragment length polymorphism analysis and oligonucleotide probe hybridization of polymerase chain reaction amplified genomic DNA in 94 Caucasian children with polyarticular juvenile rheumatoid arthritis (JRA) [13 rheumatoid factor (RF)+ and 81 RF-] and 100 healthy controls. HLA-DRw8, DQw4, DQA1*0401, DQB1*0402 were increased in frequency in those patients with RF seronegative disease, with highest frequencies seen in patients with young age at onset (< 5 years of age). These findings were similar to what we observed in children with pauciarticular JRA, especially those with young age at onset. DPB1*0301 was also found in increased frequency in the RF- group, and in particular those seronegative for antinuclear antibody. In contrast to what is observed in patients with pauciarticular JRA, the frequency of DPB1*0201 was not increased in any polyarticular JRA patient group. These data suggest that polyarticular JRA shares many genetic features with pauciarticular JRA.

Alleles↗
PubMed2026

Sparse phenotyping for wheat grain yield enabled by multiomics prediction.

Grain yield is a central target in wheat breeding, yet accurately predicting it remains challenging because it depends on many genes and responds strongly to environmental variation. Genomic selection (GS) has improved breeding efficiency by enabling genome-based prediction of genetic merit, but predictability (PA) for grain yield is often limited under stress environments. At the same time, advances in high-throughput phenotyping (HTP) using unmanned aerial vehicles (UAVs) provide phenomic data that capture environment-responsive plant performance and may complement genomic information. In this study, we evaluated genomic and phenomic models for predicting grain yield in elite bread wheat lines across irrigated, drought, and heat-stress environments. Using a sparse phenotyping framework, we compared parametric and non-parametric models. PA was evaluated within environments and under cross-environment sparse phenotyping scenarios. Genomic models provided a stable baseline and enabled effective information sharing across environments when phenotypic data were incomplete. Phenomics-only models captured environment-specific plant responses but were more sensitive to environmental context. Multiomics models that integrated genomic and phenomic information consistently achieved the highest PA, with the largest gains observed under stress conditions. Overall, our results demonstrate that integrating genomics and UAV-based phenomics within sparse phenotyping designs offers a practical and scalable approach to improve grain yield prediction in wheat.

Triticum↗
PubMed1981

HLA and disease: predictions for HLA haplotype sharing in families.

An analysis of published data on the segregation of HLA haplotypes in families with more than one individual affected with insulin-dependent diabetes mellitus or multiple sclerosis yields three conclusions: (1) In families with unaffected parents, affected sib pairs are much more often HLA haplotype identical in sibships with two affected sibs than in sibships with three or four affected sibs (P less than .01). (2) In families with unaffected parents and HLA half-identical affected sibs, well siblings more often receive the single haplotype not found in the affected sibs than is expected by chance (P less than .05). (3) In families with one affected parent, well siblings of affected individuals may share with the affected child a haplotype from the unaffected parent less than 50% of the time (P less than .10). These results are consistent with the premise that in some non-Mendelian, familial, HLA-associated disease more than one gene may contribute to susceptibility to the disorder.

Diabetes Mellitus, Type 1↗
PubMed2006

Construction of a nasopharyngeal carcinoma 2D/MS repository with Open Source XML database--Xindice.

BACKGROUND: Many proteomics initiatives require integration of all information with uniformcriteria from collection of samples and data display to publication of experimental results. The integration and exchanging of these data of different formats and structure imposes a great challenge to us. The XML technology presents a promise in handling this task due to its simplicity and flexibility. Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China and Southeast Asia, which has marked geographic and racial differences in incidence. Although there are some cancer proteome databases now, there is still no NPC proteome database. RESULTS: The raw NPC proteome experiment data were captured into one XML document with Human Proteome Markup Language (HUP-ML) editor and imported into native XML database Xindice. The 2D/MS repository of NPC proteome was constructed with Apache, PHP and Xindice to provide access to the database via Internet. On our website, two methods, keyword query and click query, were provided at the same time to access the entries of the NPC proteome database. CONCLUSION: Our 2D/MS repository can be used to share the raw NPC proteomics data that are generated from gel-based proteomics experiments. The database, as well as the PHP source codes for constructing users' own proteome repository, can be accessed at http://www.xyproteomics.org/.

Carcinoma↗
PubMed2004

The ArrayExpress gene expression database: a software engineering and implementation perspective.

MOTIVATION: The lack of microarray data management systems and databases is still one of the major problems faced by many life sciences laboratories. While developing the public repository for microarray data ArrayExpress we had to find novel solutions to many non-trivial software engineering problems. Our experience will be both relevant and useful for most bioinformaticians involved in developing information systems for a wide range of high-throughput technologies. RESULTS: ArrayExpress has been online since February 2002, growing exponentially to well over 10,000 hybridizations (as of September 2004). It has been demonstrated that our chosen design and implementation works for databases aimed at storage, access and sharing of high-throughput data. AVAILABILITY: The ArrayExpress database is available at http://www.ebi.ac.uk/arrayexpress/. The software is open source. CONTACT: ugis@ebi.ac.uk.

Algorithms↗
PubMed2002

Characterization of Clostridium butyricum neurotoxin associated with food-borne botulism.

The neurotoxin of Clostridium butyricum strain LCL155 (BuNT/LCL155) associated with type E food-borne botulism showed antigenic and biological properties different from those of C. botulinum type E (BoNT/E) andC. butyricum strain BL5262 (BuNT/BL5262). The specific toxicity of BuNT/LCL155 was found to be about 10% those of BoNT/E and BuNT/BL5262. Immunological analysis with monoclonal antibodies against BoNT/E showed that the heavy chain of BuNT/LCL155 differs partially from those of BoNT/E and BuNT/BL5262. Binding experiments with rat brain synaptic membrane revealed that BuNT/LCL155 possesses a binding activity lower than either BoNT/E or BuNT/BL5262. There was no difference in the catalytic activity of the three neurotoxins, which had been determined with a recombinant of the intracellular target protein SNAP-25. These data suggest that the BuNT/LCL155 shares the receptor-recognition site structurally different from BoNT/E and BuNT/BL5262, perhaps causing a decreased specific toxicity.

Amino Acid Sequence↗
PubMed1996

HIV risks and risk reduction readiness in hard-to-reach, drug-using African American and Mexican American women: an exploratory study.

In an exploratory study of the HIV risk-taking behaviors and risk reduction readiness of a sample of 74 hard-to-reach, out-of-treatment African American and Mexican American drug-using women who are at high risk for HIV infection, Mexican American women were found to be more likely than African American women to have drug-using sexual partners and to use drugs daily. Cocaine was the drug most commonly used by both groups. Heroin injectors were more likely than nonheroin injectors to use daily and to share needles. Women of both ethnicities expressed considerable readiness for HIV risk reduction. We describe two empirically derived interventions to reduce HIV risks among this population and share our observations regarding collecting data from and intervening with hard-to-reach, drug-using minority women who are at high risk for HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Developmental aspects of anandamide: ontogeny of response and prenatal exposure.

Recent breakthroughs in cannabinoid research, including the identification of two cannabinoid receptors (CB receptors) and a family of endogenous ligands, the anandamides, may shed new light on the sequelae of pre- and perinatal exposure to cannabinoid receptor ligands and enable the experimental manipulation of the endogenous ligand in the developing organism. In the present study we examined the behavioural response to anandamide (ANA) in developing mice from day 13 into adulthood. We observed that depression of ambulation in an open field and the analgetic response to ANA are not fully developed until adulthood. In a separate set of experiments, we administered five daily injections of ANA (SC, 20 mg/kg) during the last trimester of pregnancy. No effects on birth weight, litter size, sex ratio and eye opening were detected after maternal ANA treatment. Further, no effects on open field performance of the offspring were observed until 4 weeks of age. However, from 40 days of age, a number of differences between the prenatal ANA and control offspring were detected. Thus, the offspring from ANA-treated dams showed impaired responsiveness to a challenge with ANA or delta 0-THC expressed as a lack of immobility in the ring test for catalepsy, hypothermia and analgesia. On the other hand, without challenge, they exhibited a spontaneous decrease in open field activity, catalepsy, hypothermia and a hypoalgetic tendency. These data suggest that exposure to excessive amounts of ANA during gestation alters the functioning of the ANA-CB receptor system. Further experiments investigating responsivity of the immune system suggest an increased inflammatory response to arachidonic acid, and enhanced hypothermic response to lipopolysaccharide in prenatally treated offspring. The results are discussed in relation to other manipulations of the maternal milieu, especially prenatal stress. It is concluded that alterations induced by prenatal exposure to ANA, cannabinoids and other psychotropic drugs or prenatal stress, share common features, but the data also suggest specific effects on the ANA-CB receptor system.

Acute-Phase Reaction↗
PubMed1975

Operant conditioning and behavioral analyses using a minicomputer.

An operant conditioning and data analysis software system was developed for use on a PDP-12A minicomputer. The operant software functions in quasi time-sharing fashion to control and acquire data from any peripheral device that operates in the binary mode. In addition to independently running different experiments in near simultaneous fashion, the program also provides information on the current status of each experiment using a cathode ray-tube display. Response data from each experimental subject is stored on magnetic tape and analyzed, off-line, by the data analysis portion of the software system. A discussion of the operation of this system is given for one possible application: visual discrimination training.

Animals↗
PubMed1999

The effects of k-space data undersampling and discontinuities in keyhole functional MRI.

The effects of the k-space data undersampling and the discontinuities associated with the keyhole approach in functional magnetic resonance imaging (fMRI) have been addressed. Undersampling of high k-space data increases the high spatial-frequency noise by a factor of square root m, where m is the number of images sharing the high k-space data. However, the effects of the noise can be effectively removed using clustered-pixel statistical analysis. The amplitude and phase discontinuities may result in an increase in the low spatial-frequency noise level, which has no impact on specificity and only a minimal impact on sensitivity. Although dramatically reducing acquisition time and preserving the spatial resolution of functional magnetic resonance imaging, the keyhole technique may have a limited capability in detecting highly focal activations.

Algorithms↗
PubMed1999

Association of the TNF +489 polymorphism with susceptibility and radiographic damage in rheumatoid arthritis.

Multiple genetic factors contribute to susceptibility to rheumatoid arthritis (RA). The extent of variability in disease presentation in RA may be related to genetic heterogeneity. In this study we investigated the association of the TNF gene polymorphism at position +489 with susceptibility to and severity of RA. Analysis of the frequency of the +489 A and G alleles in a group of 293 consecutive RA patients and 138 healthy controls revealed a significant decrease of the A allele. The +489 GA patients had a 3.9 times decreased chance of having erosive disease than +489 GG patients. These results were confirmed in a prospective study using a cohort of 112 patients who were followed for 12 years. The progression rate of the erosion score over 12 years expressed as Sharp score for X-rays of hands and feet was 3.4 per year for the GA-genotyped patients and 12.1 for the GG-genotyped patients. These associations were independent of rheumatoid factor and HLA-shared epitope positivity. In conclusion, these data suggest that the intron TNF +489 polymorphism is associated with susceptibility to and disease severity of RA independently of HLA-shared epitope-positive alleles.

Adult↗
PubMed2000

Biodegradation of carbazole by Ralstonia sp. RJGII.123 isolated from a hydrocarbon contaminated soil.

The use of microorganisms for bioremediation of contaminated soils may be enhanced with an understanding of the pathways involved in their degradation of hazardous compounds. Ralstonia sp. strain RJGII.123 was isolated from soil located at a former coal gasification plant, based on its ability to mineralize carbazole, a three-ring N-heterocyclic pollutant. Experiments were carried out with strain RJGHII.123 and 14C-carbazole (2 mg/L and 500 mg/L) as the sole organic carbon source. At 15 days, 80% of the 2 mg/L carbazole was recovered as CO2, and <1% remained as undegraded carbazole, while 24% of the 500 mg/L carbazole was recovered as CO2 and approximately 70% remained as undegraded carbazole. Several stable intermediates were formed during this time. These intermediates were separated by high performance liquid chromatography (HPLC) and were characterized using high resolution mass spectroscopy (HR-MS) and gas chromatography - mass spectroscopy (GC-MS). At least 10 ring cleavage products of carbazole degradation were identified; four of these were confirmed as anthranilic acid, indole-2-carboxylic acid, indole-3-carboxylic acid, and (1H)-4-quinolinone by comparison with standards. These data indicate that strain RJGII.123 shares aspects of carbazole degradation with previously described Pseudomonas spp., and may be useful in facilitating the bioremediation of NHA from contaminated soils.

Betaproteobacteria↗