Use of the EM algorithm to detect QTL affecting multiple-traits in an across half-sib family analysis

QTL detection experiments in livestock species commonly use the half-sib design. Each male is mated to a number of females, each female producing a limited number of progeny. Analysis consists of attempting to detect associations between phenotype and genotype measured on the progeny. When family sizes are limiting experimenters may wish to incorporate as much information as possible into a single analysis. However, combining information across sires is problematic because of incomplete linkage disequilibrium between the markers and the QTL in the population. This study describes formulæ for obtaining MLEs via the expectation maximization (EM) algorithm for use in a multiple-trait, multiple-family analysis. A model specifying a QTL with only two alleles, and a common within sire error variance is assumed. Compared to single-family analyses, power can be improved up to fourfold with multi-family analyses. The accuracy and precision of QTL location estimates are also substantially improved. With small family sizes, the multi-family, multi-trait analyses reduce substantially, but not totally remove, biases in QTL effect estimates. In situations where multiple QTL alleles are segregating the multi-family analysis will average out the effects of the different QTL alleles.     

Serum Calcium Response Following Oral Zinc Oxide Administrations in Dairy Cows

Six non-pregnant cows were allocated into 3 groups. Group 1 comprised a pair of lactating cows, whereas groups 2 and 3 each comprised a pair of non-lactating cows. The cows in groups 1 and 2 were dosed intraruminally by stomach tube with zinc oxide at 120 mg Zn per kg of bodyweight at weekly intervals for a period of 33 days. Each cow received a total of 4 doses of zinc oxide. Group 3 served as non-treated control group. Blood samples were collected from all 6 cows daily. Serum was analysed for concentration of calcium. Within 12–24 h of each zinc oxide administration the serum calcium of the lactating cows dropped dramatically indicating the existence of an antagonistic effect between Zn and Ca. The first Zn induced hypocalcaemic episode in the lactating cows was followed by a rise in serum calcium to a level above the pre-dosing level and above the mean value of the control group. The depth of the hypocalcaemic response decreased with the number of zinc oxide dosings. This effect was explained as a response from the stimulation of the calcium homeostatic mechanisms. In the Zn dosed non-lactating cows responses were similar but less clear. The perspective of these findings is discussed in relation to resistance towards parturient hypocalcaemia.     

Milk Fever Control Principles: A Review

Three main preventive principles against milk fever were evaluated in this literature review, and the efficacy of each principle was estimated from the results of controlled investigations. Oral calcium drenching around calving apparently has a mean efficacy of 50%–60% in terms of milk fever prevention as well as prevention of milk fever relapse after intravenous treatment with calcium solutions. However, some drenches have been shown to cause lesions in the forestomacs. When using the DCAD (dietary cation-anion difference) principle, feeding rations with a negative DCAD (measured as (Na + K) – (Cl + S)) significantly reduce the milk fever incidence. Calculating the relative risk (RR) of developing milk fever from controlled experiments results in a mean RR between 0.19 and 0.35 when rations with a negative versus positive DCAD are compared. The main drawback from the DCAD principle is a palatability problem. The principle of feeding rations low in calcium is highly efficient in milk fever prevention provided the calcium intake in the dry period is kept below 20 g per day. Calculating the relative risk (RR) of developing milk fever from controlled experiments results in a very low mean RR (between 0 and 0.20) (daily calcium intake below versus above 20 g/d). The main problem in implementing the low-Ca principle is difficulties in formulating rations sufficiently low in calcium when using commonly available feeds. The use of large doses of vitamin D metabolites and analogues for milk fever prevention is controversial. Due to toxicity problems and an almost total lack of recent studies on the subject this principle is not described in detail. A few management related issues were discussed briefly, and the following conclusions were made: It is important to supply the periparturient cow with sufficient magnesium to fulfil its needs, and to prevent the dry cows from being too fat. Available information on the influence of carbohydrate intake, and on the effect of the length of the dry period and prepartum milking, is at present insufficient to include these factors in control programmes.     

Risk of Infection with Leishmania spp. in the Canine Population in the Netherlands

The dog is the main reservoir of Leishmania infantum, the causative agent of visceral leishmaniasis (VL) in humans in Southern Europe. In order to identify the risk of dogs from a Leishmania non-endemic area traveling to a Leishmania -endemic area becoming infected and the risk of transmitting infection to humans in non-endemic areas an investigation was performed, in which the results of a questionnaire were combined with the results of a serologic survey.     

A structure-activity study on the bradykinin B1 antagonist desArg10-HOE 140: The alanine scan

It has recently been shown that the biological activity of the second generation kinin B1 receptor selective antagonist, desArg10 HOE 140, can be improved by specific amino acid substitutions. Starting from this observation, we undertook a systematic structure-activity relationship study of this antagonist, based on the alanine-scan technique, in order to obtain useful information for the rational design of more analogues. Our data indicate that the sequence of desArg10 HOE 140 does not tolerate the replacement by Ala of most of its residues, with the exception of Ser in position 7 and, to a lesser extent, D-Arg in position 1 and Hyp in position 4. The most critical residues appear to be Pro in position 3 and the C-terminal dipeptide DTic-Oic; Ala replacement at these positions resultes in a total loss of activity. Moreover, replacement by Ala of Gly in position 5 reverts the activity of desArg10 HOE 140 to that of an agonist.     

Vγ9/Vδ2 T lymphocytes in Italian patients with Beh?et's disease: evidence for expansion, and tumour necrosis factor receptor II and interleukin-12 receptor β1 expression in active disease

Beh?et's disease is a multisystem disease in which there is evidence of immunological dysregulation. It has been proposed that γ/δ T cells are involved in its pathogenesis. The aim of the present study was to assess the capacity of γ/δ T cells with phenotype Vγ9/Vδ2, from a group of Italian patients with Beh?et's disease, to proliferate in the presence of various phosphoantigens and to express tumour necrosis factor (TNF) and IL-12 receptors. Twenty-five patients and 45 healthy individuals were studied. Vγ9/Vδ2 T cells were analyzed by fluorescence activated cell sorting, utilizing specific monoclonal antibodies. For the expansion of Vγ9/Vδ2 T cells, lymphocytes were cultured in the presence of various phosphoantigens. The expression of TNF receptor II and IL-12 receptor β₁ was evaluated with the simultaneous use of anti-TNF receptor II phycoerythrin-labelled (PE) or anti-IL-12 receptor β₁ PE and anti-Vδ2 T-cell receptor fluorescein isothiocyanate. There was a certain hierarchy in the response of Vγ9/Vδ2 T cells toward the different phosphoantigens, with the highest expansion factor obtained with dimethylallyl pyrophosphate and the lowest with xylose 1P. The expansion factor was fivefold greater in patients with active disease than in those with inactive disease or in control individuals. TNF receptor II and IL-12 receptor β₁ expressions were increased in both patients and control individuals. The proportion of Vγ9/Vδ2 T cells bearing these receptors was raised in active disease when Vγ9/Vδ2 T cells were cultured in the presence of dimethylallyl pyrophosphate. These results indicate that Vγ9/Vδ2 T cell activation is correlated with disease progression and probably involved in the pathogenesis.     

CTLA4-Ig interacts with cultured synovial macrophages from rheumatoid arthritis patients and downregulates cytokine production

Introduction  

Co-stimulatory signal B7(CD80/CD86):CD28 is needed in order to activate T cells in immune response. Cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (CTLA4-Ig) binding to the B7 molecules on antigen-presenting cells downregulates this activation and represents a recent biological treatment in rheumatoid arthritis (RA). Objectives of the study were to investigate the presence of the B7.2 (CD86) molecule and its masking by CTLA4-Ig on cultures of both RA synovial macrophages (RA SM), and of macrophages differentiated from THP-1 cells (M). In addition, the anti-inflammatory effects of CTLA4-Ig on co-cultures of RA SM and M with activated T cells were tested.