Biomedical subjects

H T Blair

Publications and source records attributed to H T Blair.

At least 19 recordsLinked to original sources

PubMed2006

'Ovar-Mhc' - ovine major histocompatibility complex: structure and gene polymorphisms.

The major histocompatibility complex (MHC) in sheep, Ovar-Mhc, is poorly characterised, when compared to other domestic animals. However, its basic structure is similar to that of other mammals, comprising class I, II and III regions. Currently, there is evidence for the existence of four class I loci. The class II region is better characterised, with evidence of one DRA, four DRB (one coding and three non-coding), one DQA1, two DQA2, and one each of the DQB1, DQB2, DNA, DOB, DYA, DYB, DMA, and DMB genes in the region. The class III region is the least characterised, with the known presence of complement cascade (C4, C2 and Bf), TNFalpha and CYP21 genes. Products of the class I and II genes, MHC molecules, play a pivotal role in antigen presentation required for eliciting immune responses against invading pathogens. Several studies have focused on polymorphisms of Ovar-Mhc genes and their association with disease resistance. However, more research emphasis is needed on characterising the remaining Ovar-Mhc genes and developing simplified and cost-effective methods to score gene polymorphisms. Haplotype screening, employing multiple markers rather than single genes, would be more meaningful in MHC-disease association studies, as it is well known that most of the MHC loci are tightly linked, exhibiting very little recombination. This review summarises the current knowledge of the structure of Ovar-Mhc and polymorphisms of genes located in the complex.

Animals↗

PubMed2006

Ovar-Mhc--ovine major histocompatibility complex: role in genetic resistance to diseases.

Research on the structure of the ovine major histocompatibility complex (MHC), Ovar-Mhc, and its association with resistance to various diseases in sheep has received increasing attention during recent years. The term 'resistance' is used to denote the capacity of an animal to defend itself against disease or to withstand the effects of a harmful environmental agent. The Ovar-Mhc is poorly characterised when compared to MHCs of other domestic animals. However, its basic structure is similar to that of other animals, comprising Class I, II and III regions. Products of the Class I and II genes, the histocompatibility molecules, are of paramount importance as these present antigens to T-lymphocytes, thereby eliciting immune responses. Several studies have been conducted in sheep on the involvement of MHC genes/antigens in genetic resistance to diseases, the majority being concerned with gastrointestinal nematodes. Studies on resistance to footrot, Johne's disease and bovine leukaemia virus (BLV)-induced leukaemogenesis have also been reported. Genes of all three regions were implicated in the disease association studies. In addition to disease resistance, Ovar-Mhc genes have been found to be associated with traits such as marbling and birthweight. The use of genetic markers from within the Ovar-Mhc may be useful, via marker-assisted selection, for increasing resistance to various diseases provided they do not impact negatively on other economically-important traits. This review summarises current knowledge of the role of Ovar-Mhc in genetic resistance to diseases in sheep.

Animals↗

PubMed2005

The lateral amygdala processes the value of conditioned and unconditioned aversive stimuli.

The amygdala is critical for acquiring and expressing conditioned fear responses elicited by sensory stimuli that predict future punishment, but there is conflicting evidence about whether the amygdala is necessary for perceiving the aversive qualities of painful or noxious stimuli that inflict primary punishment. To investigate this question, rats were fear conditioned by pairing a sequence of auditory pips (the conditioned stimulus, or CS) with a brief train of shocks to one eyelid (the unconditioned stimulus, or US). Conditioned responding to the CS was assessed by measuring freezing responses during a test session conducted 24 h after training, and unconditioned responding to the US was assessed by measuring head movements evoked by the eyelid shocks during training. We found that pre-training electrolytic lesions of the amygdala's lateral (LA) nucleus blocked acquisition of conditioned freezing to the CS, and also significantly attenuated unconditioned head movements evoked by the US. Similarly, bilateral inactivation of the amygdala with the GABA-A agonist muscimol impaired acquisition of CS-evoked freezing, and also attenuated US-evoked responses during training. However, when amygdala synaptic plasticity was blocked by infusion of the NR2B receptor antagonist ifenprodil, acquisition of conditioned freezing was impaired but shock reactivity was unaffected. These findings indicate that neural activity within the amygdala is important for both predicting and perceiving the aversive qualities of noxious stimuli, and that synaptic plasticity within LA is the mechanism by which the CS becomes associated with the US during fear conditioning.

Acoustic Stimulation↗

PubMed2005

Inherited chondrodysplasia in Texel sheep.

CASE HISTORY: A skeletal disease characterised by dwarfism, limb deformity and sometimes sudden death occurred over a period of 5 years in lambs born on a commercial sheep farm in Southland. The disease showed variable expression and occurred in crossbred sheep. A genetic aetiology was supported by the birth of affected lambs over two seasons in a flock of putative carrier and affected sheep transported to Massey University. CLINICAL FINDINGS: Affected lambs appeared normal at birth but showed evidence of dwarfism, wide-based stance and exercise intolerance as early as 1 week of age. Most died within the first 3 months of life, often after developing bilateral varus deformity of the forelimbs. Some severely-affected lambs died suddenly of respiratory embarrassment, probably due to tracheal collapse. Mildly-affected individuals had a short, blocky stature and some survived to breeding age. PATHOLOGICAL FINDINGS: Gross and microscopic lesions of variable severity were present in the tracheal, articular, epiphyseal and physeal cartilages. In severe cases, articular cartilage in major joints was eroded from weight-bearing surfaces. The trachea was flaccid, abnormally kinked, and had thickened cartilaginous rings and a narrow lumen. Affected sheep that survived to breeding age eventually developed severe degenerative joint disease. Histologically, chondrocytes were disorganised, surrounded by concentric rings of abnormal fibrillar material, and the matrix often contained focal to coalescing areas of chondrolysis. DIAGNOSIS: Inherited chondrodysplasia of Texel sheep. CLINICAL RELEVANCE AND CONCLUSIONS: This chondrodysplasia differs from those previously described in sheep and is considered to be a newly-recognised, recessively-inherited genetic disease of the Texel breed. A defect in the synthesis of glycosaminoglycans in cartilage matrix is suspected. This disease of sheep may provide a suitable model for studying various forms of therapy for human chondrodysplasias.

Animals↗

PubMed2005

Meat quality traits were unaffected by a quantitative trait locus affecting leg composition traits in Texel sheep.

A QTL affecting leg muscle and fat traits has been identified within the New Zealand Texel population. The QTL maps to a region on OAR 2 with a two-marker haplotype test established at markers BULGE20 and BM81124. These markers encompass the likely position of Growth Differentiation Factor 8 (GDF8). The pleiotropic effects of this QTL on meat quality traits are tested. Objective measures of meat quality including pH, color (L*, a*, and b*), and tenderness (as assessed by Warner-Bratzler shear force measurements) were assessed on longissimus and semi-membranosus muscles of 540 progeny from six Texel sires. Four of these sires were subsequently identified as segregating for leg muscle and fat traits. For these segregating sires, comparison of progeny that had inherited the favorable haplotype from their sire with those that had received the alternate haplotype revealed no significant differences in the meat quality traits assessed. This finding suggests that the muscling QTL does not have pleiotropic effects on meat quality. A general scan for meat quality QTL was carried out using genotype data for eight markers from FCB128 to RM356 flanking 122cM of OAR 2 using Haley-Knott regression. This analysis revealed two QTL for a single sire. A QTL detected in the region of Marker INRA40 for color L* mapped to a site close to the muscling QTL, but there was evidence to suggest it is at a distinct locus. The QTL in the region of Marker RM356 might map distal to Marker RM356, as no peak was observed. This QTL, which seems to affect pH, color a*, color b*, and Warner-Bratzler shear measurements, requires further characterization.

Animals↗

PubMed2005

A directed search in the region of GDF8 for quantitative trait loci affecting carcass traits in Texel sheep.

A directed search for QTL affecting carcass traits was carried out in the region of growth differentiation factor 8 (GDF8, also known as myostatin) on ovine chromosome 2 in seven Texel-sired half-sib families totaling 927 progeny. Weights were recorded at birth, weaning, ultrasound scanning, and slaughter. Ultrasonic measures of LM cross-sectional dimensions and s.c. fat above the LM were made, with the same measurements made on the LM after slaughter. Following slaughter, linear measurements of carcass length and width were made on all carcasses, and legs and loins from 540 lambs were dissected. Genotyping was carried out using eight microsatellite markers from FCB128 to RM356 on OAR 2 and analyzed using Haley-Knott regression. There was no evidence for QTL for growth rates or linear carcass traits. There was some evidence for QTL affecting LM dimensions segregating in some sire families, although it was not consistent between ultrasound and carcass measures of the same traits. There was strong and consistent evidence for a QTL affecting muscle and fat traits in the leg that mapped between markers BM81124 and BULGE20 for the four sires that were heterozygous in this region, but not for the three sires that were homozygous. The size of the effect varied across the four sires, ranging from 0.5 to 0.9 of an adjusted SD for weight-adjusted leg muscle traits, and ranging from 0.6 to 1.2 of an adjusted SD for weight-adjusted leg fat traits. The clearest effect shown was for multivariate analysis combining all leg muscle and fat traits analyzed across sires, where the -log(10) probability was 14. Animals carrying the favorable haplotype had 3.3% more muscle and 9.9% less fat in the leg relative to animals carrying other haplotypes. There was evidence for a second peak in the region of marker TEXAN2 for one sire group. It seems that a QTL affecting muscle and fat traits exists within the New Zealand Texel population, and it maps to the region of GDF8 on OAR2.

Adipose Tissue↗

PubMed2004

Genetic disorders of sheep in New Zealand: a review and perspective.

Genetic disorders of sheep that have occurred in New Zealand are reviewed and discussed with regard to phenotype, inheritance and, where known, genotype. Inbreeding was a major factor in the emergence of some of them. The various disorders reflect a continuum, ranging from simple monogenic diseases or malformations due to dysfunctional gene products, those monogenic disorders dependant on environmental interactions, malformations due to homeotic gene dysfunctions, and multifactorial diseases for which genetic factors are associated with disease susceptibility. Chromosomal aberrations, although of limited importance, have contributed to an understanding of the physical chromosome map and derivative linkage map of sheep.

Journal Article↗

PubMed2003

Chondrodysplasia of Texel sheep - a new disease of suspected genetic aetiology (abstract).

A chondrodysplasia characterised by dwarfism and varus deformity of the forelimbs has been recognised over four seasons in Texel and Texel-cross lambs on three related properties. Affected lambs appear normal at birth, but by 2 weeks of age have reduced growth rate, shortened neck and legs, varus forelimb deformities and a progressive reluctance to walk. Most die within the first 4 months of life. Some affected lambs have had normal co-twins. Post mortem examination of two severely affected 3-month-old lambs revealed extensive loss of articular cartilage and exposure of subchondral bone on the weight-bearing surfaces of the proximal humeri and femurs. Articular and physeal cartilages were thicker than normal, suggesting delayed or impaired endochondral ossification. Histopathologically, there was disorganisation of chondrocytes in articular and physeal cartilage of all bones examined. In addition, there were multiple foci of chondrolysis, which coalesced in some areas to form large clefts. The chondroid matrix surrounding chondrocytes had an abnormal fibrillar appearance. One lamb that exhibited early signs of the disease died of an unrelated cause at 3 weeks of age, and although there was no erosion of articular cartilage, characteristic microscopic lesions were present in articular and physeal cartilage. Although most of the affected lambs were born on a commercial property with a mix of different sheep breeds, all had Texel genes on both sire and dam sides of the pedigree. The farmer had been purchasing his Texel rams from the same flock for several seasons. Circumstantial evidence favours a genetic aetiology, characterised by either autosomal recessive inheritance or over dominance. Studies on the genetic and biochemical basis of the disease are continuing.

Journal Article↗

PubMed2001

The anatomical and computational basis of the rat head-direction cell signal.

As a rat navigates through space, neurons called head-direction (HD) cells provide a signal of the rat's momentary directional heading. Although partly guided by landmarks, the cells also show a remarkable ability to track directional heading based on angular head movement. Theoretical models suggest that the HD cells are linked together to form an attractor network, and that cells which signal angular velocity update the directional setting of the attractor. Recently, cell types similar to those required theoretically have been discovered in the lateral mammillary and dorsal tegmental nuclei. Lesion and anatomical data suggest these nuclei might constitute the postulated attractor-path integration mechanism, and that they provide the HD cell signal to cortical areas where it has been observed.

Animals↗

PubMed2001

Memory consolidation of Pavlovian fear conditioning: a cellular and molecular perspective.

Pavlovian fear conditioning has emerged as a leading behavioral paradigm for studying the neurobiological basis of learning and memory. Although considerable progress has been made in understanding the neural substrates of fear conditioning at the systems level, until recently little has been learned about the underlying cellular and molecular mechanisms. The success of systems-level work aimed at defining the neuroanatomical pathways underlying fear conditioning, combined with the knowledge accumulated by studies of long-term potentiation (LTP), has recently given way to new insights into the cellular and molecular mechanisms that underlie acquisition and consolidation of fear memories. Collectively, these findings suggest that fear memory consolidation in the amygdala shares essential biochemical features with LTP, and hold promise for understanding the relationship between memory consolidation and synaptic plasticity in the mammalian brain.

Animals↗

PubMed2000

Profitabilities of some mating systems for dairy herds in New Zealand.

The aim of this study was to evaluate the profitability of dairy herds under three mating systems involving the Holstein-Friesian, Jersey, and Ayrshire breeds. Mating systems were straight breeding and rotational cross-breeding using two or three breeds. A deterministic model was developed to simulate the nutritional, biological, and economic performance of dairy herds under New Zealand conditions. Expected performances per cow were obtained using estimates of breed group and heterosis effects, age effects, and age distribution in the herd. Requirements for dry matter in feed were estimated per cow for maintenance, lactation, pregnancy, and growth of the replacements. Stocking rate was calculated by assuming 12,000 kg of dry matter utilized annually per hectare. Productivity per hectare was calculated as performance per cow multiplied by stocking rate. Profitability was the difference between income (sale of milk and salvage value of animals) and costs (related to the number of cows in the herd and the land area farmed). Under current market values for milk and meat, all of the rotational crossbred herds showed superior profitability to the straightbred herds (Holstein-Friesian x Jersey, NZ$505/ha; Holstein-Friesian x Jersey x Ayrshire NZ$493/ha; Jersey x Ayrshire, NZ$466/ha; Holstein-Friesian x Ayrshire, NZ$430/ha; Jersey, NZ$430/ha; Holstein-Friesian, NZ$398/ha; and Ayrshire, NZ$338/ha). Changes in the value for fat relative to protein affected profitability more significantly in herds using the Jersey breed, and changes in the value for meat affected profitabiity more significantly in herds using the Holstein-Friesian and Ayrshire breeds. Results suggested that, under New Zealand conditions, the use of rotational crossbreeding systems could increase profitability of dairy herds under the conceivable market conditions.

Animals↗

PubMed2000

Possible effects of 25 years of selection and crossbreeding on the genetic merit and productivity of New Zealand dairy cattle.

A deterministic model was developed to evaluate the concurrent effects of selection and crossbreeding on the rate of genetic gain and productivity of New Zealand dairy cattle over 25 yr. Selection was based on an index, which included estimated breeding values for mature cow live weight and lactation yields of milk, fat, and protein. Mating strategies involving Holstein-Friesian, Jersey, and Ayrshire breeds were evaluated. Effects of heterosis and age were included to calculate live weight and yields of milk, fat, and protein per cow. Feed requirements were estimated for maintenance, lactation, and pregnancy and for replacement heifers. Stocking rate was calculated by assuming 12,000 kg of dry matter annually utilized per hectare. Upgrading to either Jersey or Holstein-Friesian increased the number of potential bull mothers and resulted in genetic gains of 0.27 genetic standard deviations/yr for both options. Rotational crossbreeding of Holstein-Friesian x Jersey decreased the number of potential bull mothers and resulted in a genetic gain of 0.24 genetic standard deviations/yr. Upgrading to Jersey resulted in the least increase in milk (5%) and the greatest increase in fat (16%) and protein (27%) per hectare with a small decrease in stocking rate (0.4%). Upgrading to Holstein-Friesian reduced the stocking rate by 11% and increased production of milk, fat, and protein per hectare by 10, 8, and 21%, respectively. Rotational crossbreeding of Holstein-Friesian x Jersey resulted in greater production per hectare than the intermediate production between upgrading to Jersey and upgrading to Holstein-Friesian. Crossbreeding can be used in combination with selection to exploit the effects of heterosis while maintaining genetic diversity to cover changes in market conditions.

Animals↗

PubMed2000

Effects of selection and crossbreeding strategies on industry profit in the New Zealand dairy industry.

The effects of selection and crossbreeding on the New Zealand dairy industry net income were evaluated with a deterministic model over a 25 yr planning horizon. Several mating strategies involving Holstein-Friesian, Jersey and Ayrshire cattle were evaluated. These strategies were straight breeding, upgrading to Holstein-Friesian, upgrading to Jersey, upgrading to Ayrshire, use of the best bulls irrespective of breed and two- and three-breed rotational crossbreeding. Industry productions of milk, fat, protein, and lactose were calculated assuming that 12,000 kg of dry matter per hectare was utilized from 1,224,911 hectares of pasture. Profitability was the difference between income (international sale of whole milk powder, casein, butter, and beef from salvage animals) and costs (farm expenses, milk collection, manufacture, and marketing). Casein and whole milk powder were valued at NZ$8.345 and NZ$3.306/ per kilogram, respectively, over 25 yr. Butter was valued at NZ$2.995/kilogram for base year production levels and NZ$0.45/kilogram for marginal increases in production. Upgrading to Holstein-Friesian resulted in the highest industry net income (NZ$1119 million) followed by straight breeding (NZ$1086 million) and two-breed rotational Holstein-Friesian x Jersey (NZ$1076 million). However, if the marginal value of extra butter production was assumed equal to the average base value, then upgrading to Jersey resulted in the highest industry net income (NZ$1185 million) followed by two-breed rotational Holstein-Friesian x Jersey (NZ$1177 million) and use of the best bulls (NZ$1173 million). Future costs and prices of dairy products have major impact on mating strategies.

Animals↗

PubMed1999

The anterior thalamic head-direction signal is abolished by bilateral but not unilateral lesions of the lateral mammillary nucleus.

Head-direction (HD) cells are neurons that signal a rat's directional heading in the horizontal plane. Evidence suggests that the lateral mammillary nucleus (LMN) may play an important role in generating the HD signal. Here, we examined the role of LMN in the HD circuit by comparing the effects of unilateral and bilateral LMN lesions on the activity of HD cells in the anterodorsal thalamus (AD). HD cells were recorded from AD in freely behaving rats. In the middle of the recording session, the rat received either bilateral or unilateral lesions of LMN. Immediately after the lesion, we continued recording the same HD cell in AD that had been recorded before the lesion. Additional cells were recorded from lesioned animals for up to 3 weeks after the lesion. We found that bilateral lesions of LMN permanently abolish HD cells in AD. After bilateral lesions, AD exhibits unusual rhythmic oscillations and velocity-correlated spike activity. Unilateral lesions of LMN did not abolish HD cells in AD. After unilateral lesions, the firing properties of HD cells in AD become more similar to those of HD cells in the intact hemisphere of LMN. We discuss the implications of these findings for understanding the role of LMN in the HD circuit.

Action Potentials↗

PubMed1998

Role of the lateral mammillary nucleus in the rat head direction circuit: a combined single unit recording and lesion study.

We recorded head direction (HD) cells from the lateral mammillary nucleus (LMN) and anterior thalamus (ATN) of freely behaving rats and also made bilateral lesions of LMN while recording HD cells from ATN. We discovered that the tuning functions of LMN HD cells become narrower during contraversive head turns, but not ipsiversive head turns, compared to when the head is not turning. This narrowing effect does not occur for ATN HD cells. We also found that the HD signal in LMN leads that in ATN by about 15-20 ms. When LMN was lesioned bilaterally, HD cells in ATN immediately lost their directional firing properties and never recovered them. Based on these findings, we argue that LMN may be an essential component of an attractor-integrator network that participates in generating the HD signal.

Animals↗

PubMed1997

Anticipatory time intervals of head-direction cells in the anterior thalamus of the rat: implications for path integration in the head-direction circuit.

Head-direction cells are neurons that signal a rat's directional heading in the horizontal plane. Head-direction cells in the anterior thalamus are anticipatory, so that their firing rate is better correlated with the rat's future head direction than with the present or past head direction. We recorded single-unit activity from head-direction cells in the anterior thalamus of freely moving rats. We measured the time interval by which each individual cell anticipated the rat's future head direction, which we refer to as the cell's anticipatory time interval (ATI). Head-direction cells in the anterior thalamus anticipated the rat's future head direction by an average ATI of approximately 17 ms. However, different anterior thalamic cells consistently anticipated the future head direction by different ATIs ranging between 0 and 50 ms. We found that the ATI of an anterior thalamic head-direction cell was correlated with several parameters of the cell's directional tuning function. First, cells with long ATIs sometimes appeared to have two peaks in their directional tuning function, whereas cells with short ATIs always had only one peak. Second, the ATI of a cell was negatively correlated with the cell's peak firing rate, so that cells with longer ATIs fired at a slower rate than cells with shorter ATIs. Third, a cell's ATI was correlated with the width of its directional tuning function, so that cells with longer ATIs had broader tuning widths than cells with shorter ATIs. These relationships between a cell's ATI and its directional tuning parameters could not be accounted for by artifactual broadening of the tuning function, which occurs for cells that fire in correlation with the future (rather than present) head direction. We found that when the rat's head is turning, the shape of an anterior thalamic head-direction cell's tuning function changes in a systematic way, becoming taller, narrower, and skewed. This systematic change in the shape of the tuning function may be what causes anterior thalamic cells to effectively anticipate the rat's future head direction. We propose a neural circuit mechanism to account for the firing behavior we have observed in our experiments, and we discuss how this circuit might serve as a functional component of a neural system for path integration of the rat's directional heading.

Analysis of Variance↗

PubMed1996

Neural network modeling of the hippocampal formation spatial signals and their possible role in navigation: a modular approach.

Cells throughout the hippocampal formation show striking spatial firing correlates as a rat navigates through space. These cells are thought to play a critical role in orchestrating the navigational abilities of the animals, since damage to the hippocampal formation causes spatial learning deficits. Here, we present a theoretical framework aimed at explaining how the different spatial signals are generated, as well as how they may help guide navigational behavior. Earlier work from our laboratory has presented a simple model for how the location-related signals exhibited by hippocampal place cells could be generated, based on convergent sensory information. Here, the results of this work are combined with two more recent models, to provide a more comprehensive theoretical framework. Specifically, we present 1) A neural network model of head direction cells, based on the idea that the directional signals are generated using a path integration mechanism. Cells which combine directional and angular head velocity information project onto the head direction cells, to "update" the current directional signal. This model reproduces the basic phenomenon of direction-specific firing, as well as the anticipatory nature of this firing, reported for some head direction cells. 2) A network simulation of how the hippocampal spatial signals could be used to orchestrate instrumental learning. Here, place and directional signals converge onto motor cells, each of which are thus driven to fire to specific combinations of location and directional heading. Each active motor cell generates a small leftward or rightward "step" of the simulated animal. When the simulated goal is encountered, recently active synapses are strengthened, so that goal-directed trajectories are "stamped in". We have found these models useful in helping to clarify our thinking about the proposed theoretical principles, as well as in generating testable predictions.

Animals↗

PubMed1996

Visual and vestibular influences on head-direction cells in the anterior thalamus of the rat.

As a rat navigates through space, head-direction cells provide an ongoing signal of its momentary directional heading. This directional signal is thought to be generated, in part, by a dead-reckoning mechanism that uses angular motion information to constantly update the directional representation. This study investigated what kinds of angular motion information might be used for dead reckoning. Anterior thalamic head-direction cells were recorded from rats in a rotatable, cylindrical chamber, which could independently deliver visual motion cues and vestibular cues. Results suggest that both of these angular motion cues have an influence on head-direction cells and may thus be used for dead reckoning. The authors conclude that vestibular and visual movement cues work interactively, along with visual landmarks and motor signals, to determine the directional frame of reference.

Animals↗