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PubMedDate not supplied

Assessing background ground water chemistry beneath a new unsewered subdivision.

Previous site-specific studies designed to assess the impacts of unsewered subdivisions on ground water quality have relied on upgradient monitoring wells or very limited background data to characterize conditions prior to development. In this study, an extensive monitoring program was designed to document ground water conditions prior to construction of a rural subdivision in south-central Wisconsin. Previous agricultural land use has impacted ground water quality; concentrations of chloride, nitrate-nitrogen, and atrazine ranged from below the level of detection to 296 mg/L, 36 mg/L, and 0.8 microg/L, respectively, and were highly variable from well to well and through time. Seasonal variations in recharge, surface topography, aquifer heterogeneities, surficial loading patterns, and well casing depth explain observed variations in ground water chemistry. This variability would not have been detected if background conditions were determined from only a few monitoring wells or inferred from wells located upgradient of the subdivision site. This project demonstrates the importance of characterizing both ground water quality and chemical variability prior to land-use change to detect any changes once homes are constructed.

Agriculture↗

PubMed2006

Heritability of serum resistin and its genetic correlation with insulin resistance-related features in nondiabetic Caucasians.

CONTEXT: Serum levels of resistin are believed to modulate insulin resistance in humans. OBJECTIVE: The aim of this study was to investigate whether serum resistin levels are genetically controlled and whether this control is shared with other insulin resistance traits. DESIGN AND METHODS: The study cohort included 264 nondiabetic probands, Caucasian from Italy, and their 473 adult family members. Phenotypic characterization included anthropometric variables, blood pressure, fasting glucose and insulin, lipid profile, and resistin levels. Genotypes were determined at position g.-420C-->G (rs1862513), IVS2+181G-->A (rs3745367), and GAT((n)) polymorphisms of the resistin (RETN) gene. RESULTS: In the 264 unrelated probands, resistin levels were significantly (P < 0.01) correlated with adiposity, blood pressure, C-reactive protein, and the metabolic syndrome score. In a variance component analysis of the 264 probands and their 473 relatives, about 70% of the observed variation of serum resistin levels was heritable (P < 0.0001). A small, but significant (P = 0.004) proportion of this variance was explained by the G-->A variation at position IVS2+181 of the RETN gene. Significant genetic correlations (P < 0.05) were observed between resistin and body mass index (rho(g) = 0.30), waist circumference (rho(g) = 0.32), the insulin resistance index HOMA(IR) (rho(g) = 0.28), and the metabolic syndrome score (rho(g) = 0.35). CONCLUSIONS: These data indicate that serum resistin is highly heritable and has some common genetic background with traits related to insulin resistance, reinforcing the hypothesis that this adipokine may play a pathogenic role in insulin resistance-related abnormalities, including type 2 diabetes and cardiovascular disease.

Adult↗

PubMed1996

Acoustic input impedance of the stapes and cochlea in human temporal bones.

The acoustic input impedance of the stapes and cochlea ZSC represents the mechanical load driven by the tympanic membrane, malleus and incus. ZSC was calculated from broad-band measurements (20 Hz to 11 kHz) of stapes displacement made with an optical motion sensor and of sound pressure at the stapes head in a human temporal-bone preparation. Measurements were made in 12 fresh temporal bones with the round window insulated from the sound stimulus. Below 1 kHz, the magnitude of ZSC was approximately inversely proportional to frequency, and ZSC angle was between 0.10 and -0.20 periods. This behavior is consistent with a mixed stiffness and resistance. Between 1 and 4 kHz, ZSC was resistance-dominated with a magnitude between 40 and 100 mks acoustic G omega that was roughly independent of frequency, and its angle was between -0.12 and 0 periods. Between 4 and 7 kHz, the magnitude of ZSC was either constant or increased with frequency while ZSC angle was near 0. Between 7 and 8 kHz, both ZSC magnitude and angle decreased sharply with frequency, and both increased somewhat at higher frequencies. The input impedance of the cochlea ZC was estimated in one ear from ZSC measurements made before and after draining the inner ear fluids. ZC was stiffness-dominated below 100 HZ, and resistance-dominated from 100 Hz to 5 kHz. The frequency-dependent magnitude of ZSC in our bones is similar to those reported by other investigators in cadaver temporal bones (Nakamura et al., 1992; Kurokawa and Goode, 1995). Our ZSC measurements are qualitatively similar to theoretical predictions (Zwislocki, 1962; Kringlebotn, 1988), but are a factor of 3 greater in magnitude, implying that ZSC may be more resistive and stiffer than previously thought. We found inter-ear variations of a factor of 4 (12 dB), which may explain some of the clinically observed variations in size of the air bone gap in individuals with middle ear lesions or after middle-ear reconstructive surgery.

Acoustic Impedance Tests↗

PubMed1986

Effects of pregnancy on the inter-individual variations in blood levels of lead, cadmium and mercury.

Blood samples to be analysed for lead, cadmium and mercury were taken from 417 pregnant women not occupationally exposed to these metals. Each subject was paired with a non-pregnant woman of the same age (+/- 2 years), socio-economic status, alcohol and tobacco status. Most of the inter-individual variations observed in earlier studies were confirmed in the control group. Among the pregnant women, however, such variations in blood metal levels appeared to be somewhat different compared to the control women according to the parameters studied: age of the women, alcohol and tobacco consumption. Furthermore, the study of the evolution of blood levels of lead, cadmium and mercury throughout pregnancy revealed a significant decrease in cadmium levels during the first half of pregnancy. A similar tendency was observed for lead but this did not attain statistical significance.

Adolescent↗

PubMed2005

Habiline variation: a new approach using STET.

The problem of whether the hominid fossil sample of habiline specimens is comprised of more than one species has received much attention in paleoanthropology. The core of this debate has critical implications about when and how variation can be explained by taxonomy. In this paper, we examine the problem of whether the observed variation in habiline samples reflects species differences. We test the null hypothesis of no difference by examining the degree of variability in habiline sample in comparison with other single-species early hominid fossil samples from Sterkfontein and Swartkrans (Sterkfontein is earlier than the habiline sample, Swartkrans may be within the habiline time span). We developed a new method for this examination, which we call STandard Error Test of the null hypothesis of no difference (STET). Our sampling statistic is based on the standard error of the slope of regressions between pairs of specimens, relating all of the homologous measurements that each pair shares. We show that the null hypothesis for the habiline sample cannot be rejected. The similarities of specimen pairs within the habiline sample are not more than those observed between the specimens in the australopithecine samples we analyzed.

Animals↗

PubMed2004

Antigenic and genetic variation in human respiratory syncytial virus.

BACKGROUND: Human respiratory syncytial virus (HRSV) is a leading cause of serious pediatric respiratory disease worldwide. Natural infection provides only partial protection as repeat infections occur throughout life. A brief review of the extent of antigenic and genetic variation observed in HRSV clinical isolates is presented. METHODS AND RESULTS: Recent experimental research is reviewed, describing key factors that may explain the ability of HRSV to cause multiple infections in the same individual even in the presence of an existing immune response. It is well-appreciated that variability of the G protein, both between and within antigenic subgroups A and B, is partially responsible for repeat HRSV infections. A high level of nucleotide change resulting in amino acid change provides strong evidence for selective pressure for change in G sequences, thus new HRSV variants. Although little variation in gene-coding sequences is observed in the F protein (the second major protective antigen), new evidence of genetic variation has identified alteration of gene expression levels by selection of changes in the gene end termination signal that precedes the gene encoding the F protein. Due to obligatory sequential transcription, these changes affect downstream gene expression levels. These data suggest that modulation of F protein levels may provide a selective advantage in the presence of a preexisting immune response. CONCLUSIONS: Experimental data in HRSV demonstrate that variation exists not only in gene-coding sequences but also in the signals that control gene expression. Thus alteration in the expression of key proteins provides a second type of antigenic "variation." A better understanding of these differences is critical to the development of an effective vaccine.

Adolescent↗

PubMed1990

Using MZ twins in experimental research to test for the presence of a genotype-environment interaction effect.

Despite some evidence that genotype-environment interaction (G x E) effects may be involved in the variation observed in behavioral and biological traits, few attempts have been made to detect and quantify this component of genetic variation in humans. We propose that one way to achieve this goal is to challenge several genotypes in a similar manner, submitting both members of several MZ twin pairs to an ethically acceptable experimental treatment capable of inducing an adaptative response. In this situation, the G x E effect can be assessed with a two-way analysis of variance for repeated measures on one factor, the treatment effect. In this design, twins are considered nested within the pair, whereas the treatment effect is considered a fixed variable. The intrapair resemblance in the response to the treatment is quantified with an intraclass correlation coefficient computed with between-sibhips and within-sibhips means of squares. To illustrate this approach, changes induced by long-term endurance training were studied in 10 MZ twin pairs. Significant intrapair resemblance in the response of maximal oxygen uptake was observed, with about 7 to 8 times more variance between pairs than within pairs. This design with MZ twins may be helpful in the study of human variation for multifactorial phenotypes.

Environment↗

PubMed2005

Genome-wide linkage identifies novel modifier loci of aganglionosis in the Sox10Dom model of Hirschsprung disease.

Hirschsprung disease (HSCR) is a complex disorder that exhibits incomplete penetrance and variable expressivity due to interactions among multiple susceptibility genes. Studies in HSCR families have identified RET-dependent modifiers for short-segment HSCR (S-HSCR), but epistatic effects in long-segment (L-HSCR) and syndromic cases have not been fully explained. SOX10 mutations contribute to syndromic HSCR cases and Sox10 alleles in mice exhibit aganglionosis and pigmentary anomalies typical of a subset of HSCR patients categorized as Waardenburg-Shah syndrome (WS4, OMIM 277580). Sox10 mutant alleles in mice exhibit strain-dependent variation in penetrance and expressivity of aganglionic megacolon analogous to the variation observed in patients with aganglionosis. In this study, we focused on enteric ganglia deficits in Sox10Dom mice and defined aganglionosis as a quantitative trait in Sox10Dom intercross progeny to investigate the contribution of strain background to variation in enteric nervous system deficits. We observe that the phenotype of Sox10Dom/+ mutants ranges over a continuum from severe aganglionosis to no detectable phenotype in the gut. To systematically identify genes that modulate Sox10-dependent aganglionosis, we performed a single nucleotide polymorphism-based genome scan in Sox10Dom/+ F1 intercross progeny. Our analysis reveals modifier loci on mouse chromosomes 3, 5, 8, 11 and 14 with distinct effects on penetrance and severity of aganglionosis. Three of these loci on chromosomes 3, 8 and 11 do not coincide with previously known aganglionosis susceptibility genes or modifier loci and offer new avenues for elucidating the genetic network that modulates this complex neurocristopathy.

Alleles↗

PubMed1990

Hematological variations at rest and during maximal and submaximal exercise in a cold (0 degree C) environment.

The affect of negative thermal stress on hematological variables at rest, and during submaximal (sub ex) and maximal exercise (max ex) were observed for young males who volunteered in two experimental sessions, performed in cold (0 degree C) and in normal room temperature (20 degrees C). At rest, hematological variables such as RBC and derivates Hb and Hct were significantly increased (P less than 0.05) during cold stress exposure, while plasma volume decreased. The findings of this study suggest that the major factor inducing hypovolemia during low thermal stress can be imputed to local plasma water-shift mechanisms and especially to a transient shift of plasma water from intra- to extravascular compartments. Rest values for WBC and platelets (Pla) were also slightly increased during cold stress exposure. However this increase can partly be related to hemoconcentration but also to the cold induced hyperventilation activating the lung circulation. Maximal exhaustive exercise induced, in both experimental temperatures, significant (P less than 0.05) increments of RBC, Hb, Hct, and WBC while plasma volume decreased. However, Pla increase was less marked. On the other hand, cold stress raised slightly the observed variations of the different hematological variables. Submaximal exercise induced a similar, though non-significant, pattern for the different hematological variables in both experimental conditions. Observed plasma volume (delta PV%) reduction appears during exercise. However cold stress induced resting plasma volume variations that are transferred at every exercise level. Neither exercise nor cold inducement significantly modified the hematological indices (MCH, MCV, MCHC). In conclusion hematological variables are affected by cold stress exposure, even when subjects perform a physical activity.

Acclimatization↗

PubMedDate not supplied

Heterogeneities in glaciofluvial deposits using an example from new hampshire.

The strong influence of subsurface heterogeneity on contaminant migration and in situ remediation calls for an improved understanding of its origins and more efficient methods of characterization. Accordingly, an outcrop study of physical and chemical heterogeneity was conducted in a glaciofluvial deposit in Deerfield, New Hampshire, in order to uncover processes controlling the spatial variation of sediment properties and evaluate the extent to which geologic information can be used to characterize the observed variation. The results indicate that physical and chemical properties at the Deerfield site have distinctly different spatial correlation structures. Lithologic facies explain 31% to 60% of the variation in permeability, dithionite citrate (DC)-extractable manganese, and DC-extractable aluminum. Lithofacies bounding surfaces do not separate regions of significantly different DC-extractable iron; instead, 49% of its variation is explained by sediment color. Color also accounts for 34% of the variation in DC-extractable aluminum and 60% of the variation in DC-extractable manganese. Strong relationships with sediment facies and/or color enable detailed mapping of permeability, extractable iron, and extractable manganese. Differences in the geometries of iron and manganese enrichment, petrographic observations, and scanning electron microscope analyses indicate that (hydr)oxide grain coatings originated from the postdepositional weathering of biotite and garnet, coupled with local, redox-driven redistribution of the liberated iron and manganese. The findings suggest that lithofacies and color information can aid the characterization and modeling of heterogeneity at similar carbon-poor glaciofluvial sites.

Aluminum↗

PubMed1993

Accuracy and consistency of absolute pitch.

The accuracy and consistency of absolute pitch (AP) judgments have been measured on three subjects in two longitudinal studies separated by twenty years. The drifts and cyclical variations observed in the earlier study still persisted, and an investigation of two other subjects, one of whom was first studied forty years ago, suggests that they might undergo similar cyclical variations in their pitch perception. Pitch judgments also varied during the day. The detailed observations of these nonrandom fluctuations have been used to determine a value for the underlying consistency of the AP estimates. When the effects of the daytime variations and longer-term drifts were removed, the values for this consistency, as measured by the standard deviation, were calculated to be 3.1, 3.4, 3.7, 4.4, and 4.5 Hz for the five subjects. When an oscillator was used to produce the estimate, the consistency of the judgments was observed to depend on the accuracy of those judgments.

Acoustic Stimulation↗

PubMed2000

Ion channel expression by astrocytes in situ: comparison of different CNS regions.

Patch-clamp recordings were obtained in brain slices from 283 rat astrocytes. The expression of voltage-activated whole-cell currents was compared in four different CNS regions (hippocampus, cerebral cortex, spinal cord, and cerebellum). Our data show that CNS astrocytes do not show significant regional differences in their ion channel complement. With the exception of cerebellar Bergmann glial cells, essentially all astrocytes express a combination of delayed rectifying outward K(+) currents, transient A-type K(+) currents, and small Na(+) currents. Developmentally, an increasing percentage of astrocytes and Bergmann glial cells express inwardly rectifying K(+) currents. We did not observe cells that were passive, i.e., lacking voltage-activated currents. A few cells that appeared "passive" in initial recordings showed voltage-activated K(+) currents after off-line leak subtraction. The heterogeneity observed in the ion channel complement was found to be identical when cell-to-cell variations observed within a given CNS region and between various CNS regions were compared, suggesting a common and fairly stereotypical complement of ion channels in CNS astrocytes. Ion channel expression in Bergmann glial cells differed from that of all other CNS regions studied. These cells typically showed very low input resistances attributable to a significant time- and voltage-independent resting K(+) conductance. However, as with electrophysiologically "passive"-appearing astrocytes, Bergmann glial cells showed expression of delayed rectifying K(+) currents after off-line leak subtraction. Inwardly rectifying K(+) currents were observed in Bergmann glial cells after postnatal day 17. Collectively, our data suggest that all astrocytes contain voltage-gated ion channels that display a common pattern of expression during development.

Aging↗

PubMed2002

ITS 2 sequences heterogeneity in Phlebotomus sergenti and Phlebotomus similis (Diptera, Psychodidae): possible consequences in their ability to transmit Leishmania tropica.

An intraspecific study on Phlebotomus sergenti, the main and only proven vector of Leishmania tropica among the members of the subgenus Paraphlebotomus was performed. The internal transcribed spacer 2 (ITS2) sequences of 12 populations from 10 countries (Cyprus, Egypt, Italy, Lebanon, Morocco, Pakistan, Portugal, Spain, Syria, and Turkey) were compared. Samples also included three species closely related to P. sergenti: Phlebotomus similis (three populations from Greece and Malta), Phlebotomus jacusieli and Phlebotomus kazeruni. Our results confirm the validity of the taxa morphologically characterised, and imply the revision of their distribution areas, which are explained through biogeographical events. At the Miocene time, a migration route, north of the Paratethys sea would have been followed by P. similis to colonise the north of the Caucasus, Crimea, Balkans including Greece and its islands, and western Turkey. Phlebotomus sergenti would have followed an Asiatic dispersion as well as a western migration route south of the Tethys sea to colonise North Africa and western Europe. This hypothesis seems to be well supported by high degree of variation observed in the present study, which is not related to colonisation or to intra-populational variation. Two groups can be individualised, one oriental and one western in connection with ecology, host preferences and distribution of L. tropica. We hypothesise that they could be correlated with differences in vectorial capacities.

Africa, Northern↗

PubMed1997

Somatosensory evoked magnetic fields and potentials following passive toe movement in humans.

The somatosensory evoked magnetic fields (SEFs) and evoked potentials (SEPs) following passive toe movement were studied in 10 normal subjects. Five main components were identified in SEFs recorded around the vertex around the foot area of the primary sensory cortex (SI). The first and second components, 1M and 2M, were identified at approximately 35 and 46 ms. Equivalent current dipoles (ECDs) of both 1M and 2M were estimated around SI in the hemisphere contralateral to the movement toe, and were probably generated in area 3a or area 2, which mainly receive inputs ascending through muscle and joint afferents. The large inter-individual difference of 1M and 2M in terms of ECD orientation was probably due to a large anatomical variance of the foot area of SI. The third and fourth components, 3M and 4M, were identified at approximately 62 ms and 87 ms, respectively. They appeared to be a single large long-duration component with two peaks. Since the 3M and 4M components were significantly larger than the 1M and 2M components in amplitude and their ECD location was significantly superior to that of 1M and 2M, we suspected that they were generated in different sites from those of 1M and 2M, probably area 3b or area 4. Four components, 1E, 2E, 3E and 4E, were identified in SEPs, which appeared to correspond to 1M, 2M, 3M and 4M, respectively. The variation observed in the scalp distribution of the primary component, 1E, could be accounted for by the variation of the orientation of ECD of the 1M component. There was a large difference in the waveform of the long-latency component (longer than 100 ms) between SEFs and SEPs. The 5E of SEPs was a large amplitude component, but the 5M of SEFs was small or absent. We speculate that this long-latency component was generated by multiple generators.

Adult↗

PubMed1999

Evidence for a major gene accounting for mild elevation in LDL cholesterol: the NHLBI Family Heart Study.

Studies of rare Mendelian disorders of low density lipoprotein cholesterol (LDL-C) metabolism have identified specific genetic mutations in the LDL receptor and apolipoprotein B. Although these rare mutations account for a small proportion of LDL-C variation, twin and adoption studies indicate that at least 50% of the overall LDL-C observed variation is genetically determined. In a heterogeneous sample of 3227 subjects from the NHLBI Family Heart Study collected from four US centres, we find evidence for a common major gene accounting for mild elevations (1.25 standard deviations) in LDL-C. The analysis favored a recessive model with a frequency of 0.52 for the gene influencing elevated LDL-C, phenotypic means of 113 mg/dl for the normal genotypes and 146 mg/dl for the abnormal genotype, and a significant polygenic heritability. This statistically-inferred major gene accounted for 24% of the variation in LDL-C, with polygenes accounting for another 28% of the variation. Using parameters for major gene transmission estimated in the segregation analysis, LDL-C showed no linkage to the LDL receptor gene (LDLR), nor to the apolipoprotein E gene (APOE), nor to the cholesterol 7alpha-hydroxylase gene (CYP7A1), indicating the major gene effect influencing mild elevation in LDL-C is not explained by any of these candidate loci.

Adult↗

PubMed1990

Sporozoite malaria vaccine. Where do we stand?

A sporozoite malaria vaccine which elicits high levels of antibodies to the circumsporozoite (CS) protein may protect part of the human population in areas of low endemicity. Other possible targets of a sporozoite vaccine are the liver stages, but in this case the effector cells are T-lymphocytes which recognize sporozoite-derived peptides in association with products of the major histocompatibility complex. There is no evidence that the variation observed in the CS protein of P. falciparum is driven by immunological pressure, nor that this variation will be a major impediment to vaccine development.

Animals↗

PubMed2000

Hospital factors associated with emergency center patients leaving without being seen.

We developed a statistical model that would identify and quantify the relative contributions of different factors hypothesized to impact the frequency of emergency center (EC) patients who leave without being seen (LWBS). We performed an analysis of the daily counts of patients that registered in our EC during a 21-month period who then LWBS. Candidate predictor variables included the number of patients seen, and the number admitted to the hospital, for each area of our EC, as well as the hours of faculty double coverage, and the day of the week. Univariate analyses were performed using standard methods. Multivariate analysis was performed using the general linear model. A backward selection procedure was used to eliminate statistically insignificant variables until all remaining independent variables had P-values < or = .05. External validation and analysis of the stability of the estimated regression coefficients of the model were evaluated using bootstrap methods. Two-tailed tests and a type I error of 0.05 were used. During the period studied, 133,666 patients were registered in the EC and 9,894 (7.4%) left. Multivariate analysis identified six variables that were significantly associated with LWBS. The fitted model containing all six variables explained 52.8% of the variability observed in LWBS frequency. The most powerful predictor of LWBS was total number of patients cared for in the main ED. This accounted for 46.4% of the observed variation in LWBS. The total number of trauma and resuscitation patients, and the total number of observation unit admissions to the hospital were also associated with increased LWBS. More pediatric cases seen in the main ED, weekends, and additional faculty coverage were associated with fewer patients leaving. Efforts to decrease the LWBS rate will be most successful if they address the issue of main ED volume.

Adolescent↗

PubMed2006

Inference about recombination from haplotype data: lower bounds and recombination hotspots.

Recombination is an important evolutionary mechanism responsible for creating the patterns of haplotype variation observable in human populations. Recently, there has been extensive research on understanding the fine-scale variation in recombination across the human genome using DNA polymorphism data. Historical recombination events leave signature patterns in haplotype data. A nonparametric approach for estimating the number of historical recombination events is to compute the minimum number of recombination events in the history of a set of haplotypes. In this paper, we provide new and improved methods for computing lower bounds on the minimum number of recombination events. These methods are shown to detect a higher number of recombination events for a haplotype dataset from a region in the lipoprotein lipase gene than previous lower bounds. We apply our methods to two datasets for which recombination hotspots have been experimentally determined and demonstrate a high density of detectable recombination events in the regions annotated as recombination hotspots. The programs implementing the methods in this paper are available at www.cs.ucsd.edu/users/vibansal/RecBounds/.

Chromosomes, Human↗