Genetic and other effects on antibody and cell mediated immune response in swine leucocyte antigen (SLA)-defined miniature pigs

Summary. Miniature pigs of eight swine leucocyte antigens (SLA) haplotypes were immunized with sheep erythrocytes (SRBC), hen egg white lysozyme (HEWL) and the synthetic peptide (T, G)-A–L to induce antibody. Bacillus Calmette Geurin (BCG) and dinitrochlorobenzene (DNCB) were used to induce cell mediated immune response (CMI). Analysis of variance by least squares was used to assess the effects of SLA haplotype, sire, dam, litter and sex of pig on the magnitude of the primary and secondary antibody response and on dermal delayed type hypersensitivity induced by purified protein derivative of tuberculin (PPD) and DNCB-induced contact hypersensitivity.
The statistical model accounted for 43.50–77.30% of the observed variability in antibody and CMI at various times after immunization or challenge. While SLA had a significant effect on both antibody and CMI to some antigens at some, but not all times, sire, dam and litter were more frequently significant and to a greater degree.
Haplotypes dd, dg and gg produced more antibody to SRBC and (T, G)-A–L while dg and gg had higher primary, but not secondary antibody response to HEWL. Delayed hypersensitivity to PPD was most marked in pigs of dd, dg and gg haplotypes while contact hypersensitivity to DNCB was expressed least in the dg and gg haplotype pigs.
Heritability estimates were high for response to (T, G)-A–L and HEWL indicating feasibility of selective breeding for these traits.     

Genetic and other effects on antibody and cell mediated immune response in swine leucocyte antigen (SLA)-defined miniature pigs

Miniature pigs of eight swine leucocyte antigens (SLA) haplotypes were immunized with sheep erythrocytes (SRBC), hen egg white lysozyme (HEWL) and the synthetic peptide (T, G)-A--L to induce antibody. Bacillus Calmette Geurin (BCG) and dinitrochlorobenzene (DNCB) were used to induce cell mediated immune response (CMI). Analysis of variance by least squares was used to assess the effects of SLA haplotype, sire, dam, litter and sex of pig on the magnitude of the primary and secondary antibody response and on dermal delayed type hypersensitivity induced by purified protein derivative of tuberculin (PPD) and DNCB-induced contact hypersensitivity. The statistical model accounted for 43.50-77.30% of the observed variability in antibody and CMI at various times after immunization or challenge. While SLA had a significant effect on both antibody and CMI to some antigens at some, but not all times, sire, dam and litter were more frequently significant and to a greater degree. Haplotypes dd, dg and gg produced more antibody to SRBC and (T, G)-A--L while dg and gg had higher primary, but not secondary antibody response to HEWL. Delayed hypersensitivity to PPD was most marked in pigs of dd, dg and gg haplotypes while contact hypersensitivity to DNCB was expressed least in the dg and gg haplotype pigs. Heritability estimates were high for response to (T, G)-A--L and HEWL indicating feasibility of selective breeding for these traits.     

Immune reactivity in cattle with ocular squamous cell carcinoma after intralesional BCG immunotherapy

Summary Lymphocyte stimulation with Con A and specific immune reactivity to BCG (antibody formation to BCG and DTH reaction to PPD) were determined in BCG-treated, surgically treated and untreated cows with ocular squamous cell carcinoma. In tumor-bearing cows the Con A-induced proliferation of lymphocytes was reduced when compared to healthy controls. This suppression consisted of a reduced blastogenic response to Con A of lymphocytes from tumor-bearing cows, and the presence of a factor in the sera of these animals, as these sera suppressed the blastogenic response of lymphocytes from healthy cows. BCG had only a minor influence on the suppressive activity. Antibodies to BCG were demonstrated in 50% of the BCG-treated animals. The formation of antibodies was not influenced by intradermal injection of PPD of Mycobacterium bovis. Absorption of a BCG antibody containing serum with BOSCC tumor extracts did not reveal the existence of cross reacting antigens between BCG and BOSCC. Pretherapeutic and posttherapeutic Con A reactivity could not be correlated with clinical response. Of the 30 BCG treated cows 29 developed a positive DTH reaction to PPD. Correlation between clinical response and immune reactivity was seen only with regard to the DTH reaction to PPD: this reaction remained positive for a longer period after treatment in animals with a favorable clinical outcome than in nonresponding animals.Animals were maintained under the guidelines laid down by the Faculty of Veterinary Medicine, State University, Utrecht, The NetherlandsGrant recipient of the Koningin Wilhelmina Fonds (Netherlands Cancer Foundation) Abbreviations used: BCG, Bacillus Calmette-Guerin; BOSCC, bovine ocular squamous cell carcinoma PBL peripheral blood leukocytes; PPD, purified protein derivative of Mycobacteria; DTH, delayed type hypersensitivity Con A, concanavalin A; PHA, phytohemagglutinin; PWM, pokeweed mitogen     

Complement Requirement of Neutralizing Antibodies in Different Classes of Immunoglobulin Appearing in Rabbits and Guinea Pigs after Primary and Booster Immunizations with Herpes Simplex Virus

Rabbits and guinea pigs were immunized with herpes simplex virus and bled periodically. The sera were fractionated into slow IgG, fast IgG and IgM by DEAE-cellulose column chromatography, and complement-requiring (CRN) and nonrequiring neutralizing (N) antibody activities were estimated. In early sera of rabbits, the two IgG and IgM fractions possessed about equal CRN activities, although some animals showed a slightly lower activity in fast IgG. In guinea pigs, the early CRN activity resided mainly in slow IgG (7 S γ₂). The early IgG antibody of guinea pigs differed from that of rabbits in that it resembled IgM in resistances to heating at 70 C and to 2-mercaptoethanol. The level of CRN IgM antibody in rabbits declined following a peak reached in 2 to 3 weeks, whereas such a decline was never observed in guinea pigs. N IgG antibody was developed a few weeks after the first immunization in rabbits and much retarded in guinea pigs. In both species, booster immunization quickly evoked N antibody in the two IgG fractions and also CRN IgM antibody, but in the case of rabbits the IgM antibody disappeared soon. It is concluded that IgG plays an important role in humoral immunity from the initial stage of the immunization course.     

Deciphering the proteome of the in vivo diagnostic reagent "purified protein derivative" from Mycobacterium tuberculosis

Purified protein derivative (PPD) has served as a safe and effective diagnostic reagent for 60 years and is the only broadly available material to diagnose latent tuberculosis infections. This reagent is also used as a standard control for a number of in vitro immunological assays. Nevertheless, the molecular composition and specific products that contribute to the extraordinary immunological reactivity of PPD are poorly defined. Here, a proteomic approach was applied to elucidate the gene products in the U.S. Food and Drug Administration (FDA) standard PPD-S2. Many known Mycobacterium tuberculosis T-cell antigens were detected. Of significance, four heat shock proteins (HSPs) (GroES, GroEL2, HspX, and DnaK) dominated the composition of PPD. The chaperone activities and capacity of these proteins to influence immunological responses may explain the exquisite solubility and immunological potency of PPD. Spectral counting analysis of three separate PPD reagents revealed significant quantitative variances. Gross delayed-type hypersensitivity (DTH) responses in M. tuberculosis infected guinea pigs were comparable among these PPD preparations; however, detailed histopathology of the DTH lesions exposed unique differences, which may be explained by the variability observed in the presence and abundance of early secretory system (Esx) proteins. Variability in PPD reagents may explain differences in DTH responses reported among populations.     

Selective breeding of high and Low antibody-responder lines of guinea pigs

High (H) and Low (L) antibody-responder lines of guinea pigs were produced by selective breeding for the character quantitative agglutinin responsiveness to optimal doses of sheep erythrocytes (SE) and chicken erythrocytes (CE). The non cross-reacting SE and CE were alternated with each generation in order to avoid the specific interference of maternally transmitted antibodies. The continuous distribution of the phenotypes in the foundation population (F₀) and the progressive interline divergence during eight consecutive generations of selective breeding demonstrates that the character investigated is submitted to polygenic regulation. The difference in the peak agglutinin titers between the H and L lines of the eighth generation (HF₈/LF₈) is eight fold. The mean heritability (h²) of the character investigated, measured from the interline divergence of the eight generations of selection is 0.18±0.04. The h² value was established by the linear regression of the cumulated response to selection (R) on the cumulated selection differential (S). The selective breeding has a nonspecific effect because it also modifies the antibody responsiveness to other immunogens, such as f and s antigens ofSalmonella typhimurium or human erythrocytes, that are immunologically unrelated to those used in the selection.     

Characterization and genetic control of the immune response to synthetic polypeptide antigens of defined geometry.

Both humoral and cell-mediated immune responses to the synthetic helical hapten-carrier conjugate poly-Glu-Tyr-Lys(TNP)-(Glu-Tyr-Ala)5 were found to be linked to the major histocompatibility locus in mice and guinea pigs. The responder mouse strains (H-2d haplotype) showed a primary IgM response with an IgG component appearing after the secondary immunization. The antibody response was accompanied by a positive DTH reaction in responder strains. Nonresponder mice (H-2b or H-2k haplotypes) showed neither IgM nor IgG antibodies and the DTH reaction was negative. Administration of the antigen as a complex with an immunogenic carrier was not effective in inducing a response in nonresponder mice. In guinea pig studies, it was found that strain 2 animals were able to mount an antibody response against the TNP-hapten and a DTH response against the polypeptide backbone. Strain 13 animals gave no anti-TNP antibodies at the lower dose levels and DTH activity was entirely negative for all doses of immunizing antigen. Replacement of the TNP hapten by the arsanilazo dipeptide derivative, BOC-gly-ARA-tyrosine, converted the nonresponder strain 13 guinea pigs into complete responders showing antibody and DTH reactions to both the hapten and the polypeptide backbone.     

BCG—PPD的制备及应用

用三氯醋酸(TCA)和硫酸铵(AS)综合法,由卡介菌苗(BCG)培养滤液中提纯制得卡介菌素纯蛋白衍生物(BCG—PPD)。BCG—PPD的纯度和结核菌素纯蛋白衍生物国际标准(PPD-S)及中国标准(PPD—C)相近,高于加拿大标准(PPD—CT68)和丹麦标准(PPD—RT23)。在BCG免疫豚鼠中,BCG—PPD的皮肤迟发型变态反应(DTH)大于结核菌素纯蛋白衍生物(PPD)的DTH反应。在结核菌感染豚鼠组中,BCG—PPD的DTH反应小于PPD的DTH反应.在检查333名新生儿接种BCG12周后的免疫     

Ability of dairy cows to be inseminated according to breed and genetic merit for production traits under contrasting pasture-based feeding systems

Strong genetic selection on production traits is considered to be responsible for the declined ability of dairy cows to ensure reproduction. The present study aimed to quantify the effect of genetic characteristics (breeds and genetic merit for production traits) and feeding systems (FS) on the ability of dairy cows to be inseminated. An experiment was conducted during 9 years on Normande and Holstein cows assigned to contrasted pasture-based FS. Diets were based on maize silage in winter and grazing plus concentrate in spring in the High FS; and on grass silage in winter and grazing with no concentrate during spring in the low FS. Within breed, cows were classified into two genetic groups with similar estimated breeding values (EBV) for milk solids: cows with high EBV for milk yield were included in a Milk-Group and those with high EBV for fat and protein contents were included in a Content-Group. Holstein produced more milk throughout lactation than Normande cows (+2294 kg in the High FS and +1280 kg in the Low FS, P<0.001) and lost more body condition to nadir (−1.00 point in the High FS and −0.80 kg in the Low FS, P<0.001). They also showed a poorer ability to be inseminated because of both a delayed commencement of luteal activity (CLA) and delayed first service (more days from start of the breeding season to first service, DAI1). Cows in the Milk-Group produced more milk than cows in the Content-Group, but milk solids production was similar. Cows in the Content-Group had earlier CLA than cows in the Milk-Group (P<0.01). Genetic group neither affected ovulation detection rate nor DAI1. Within breed and FS, cows with high genetic merit for milk yield had later CLA and DAI1. Cows in the High FS produced more milk and lost less condition to nadir than cows in the Low FS. FS did not affect dairy cows’ ability to be inseminated. However, cows with higher milk protein content, and presumably better energy balance, had earlier CLA (P<0.01) and DAI1 (P<0.10). In addition, higher milk yield was associated with poorer ovulation detection rate and oestrus intensity (P<0.05). The study showed that at similar EBV level for milk solids, selection for increased milk fat and protein content resulted in improved cyclicity and similar oestrous expression and submission rates compared with selection for increased milk yield.     

Changes in blastogenic responses and antibody titers of mice infected with Toxoplasma gondii]

This study was performed to observe the cell-mediated and humoral immune responses in mice which were infected with Beverley, Fukaya and ME49 strain of Toxoplasma gondii, respectively. The blastogenic responses of splenocytes using [3H]-thymidine and serum antibody titers were measured weekly up to 10 weeks after infection. The blastogenic responses of splenocytes treated with concanavalin A and Toxoplasma lysate were significantly declined in the 3 strain groups as compared with the non-infected group (p less than 0.05), however lipopolysaccharide-treated blastogenic responses were not significantly different between infected and non-infected groups. The serum IgG antibody titers in the three infected groups increased from 2 weeks after infection, and the serum IgM antibody titers increased until 4 weeks after infection. No significant differences were revealed in blastogenic responses and serum antibody titers among the 3 groups. The present study suggested that cell-mediated immune responses were involved in T. gondii infected mice and blastogenic responses of T lymphocytes were inhibited in acute T. gondii infection.     

On the distance of genetic relationships and the accuracy of genomic prediction in pig breeding

Background

With the advent of genomic selection, alternative relationship matrices are used in animal breeding, which vary in their coverage of distant relationships due to old common ancestors. Relationships based on pedigree (A) and linkage analysis (G_LA) cover only recent relationships because of the limited depth of the known pedigree. Relationships based on identity-by-state (G) include relationships up to the age of the SNP (single nucleotide polymorphism) mutations. We hypothesised that the latter relationships were too old, since QTL (quantitative trait locus) mutations for traits under selection were probably more recent than the SNPs on a chip, which are typically selected for high minor allele frequency. In addition, A and G_LA relationships are too recent to cover genetic differences accurately. Thus, we devised a relationship matrix that considered intermediate-aged relationships and compared all these relationship matrices for their accuracy of genomic prediction in a pig breeding situation.

Methods

Haplotypes were constructed and used to build a haplotype-based relationship matrix (G_H), which considers more intermediate-aged relationships, since haplotypes recombine more quickly than SNPs mutate. Dense genotypes (38 453 SNPs) on 3250 elite breeding pigs were combined with phenotypes for growth rate (2668 records), lean meat percentage (2618), weight at three weeks of age (7387) and number of teats (5851) to estimate breeding values for all animals in the pedigree (8187 animals) using the aforementioned relationship matrices. Phenotypes on the youngest 424 to 486 animals were masked and predicted in order to assess the accuracy of the alternative genomic predictions.

Results

Correlations between the relationships and regressions of older on younger relationships revealed that the age of the relationships increased in the order A, G_LA, G_H and G. Use of genomic relationship matrices yielded significantly higher prediction accuracies than A. G_H and G, differed not significantly, but were significantly more accurate than G_LA.

Conclusions

Our hypothesis that intermediate-aged relationships yield more accurate genomic predictions than G was confirmed for two of four traits, but these results were not statistically significant. Use of estimated genotype probabilities for ungenotyped animals proved to be an efficient method to include the phenotypes of ungenotyped animals.     

Suppression and augmentation of the primary in vitro immune response by different classes of antibodies

The capacity of purified γG₁ and γG₂ anti-sheep red blood cell (SRBC) antibodies to exert antigen-specific feedback regulations on the primary in vitro immune response to SRBC was studied. Antibodies were administered to the culture in the native form, as sheep erythrocyte-antibody complexes or as pepsin-derived F(ab′)₂ antibody fragments. Marked differences in the feedback regulatory effects of γG₁ and γG₂ antibodies were found. Antibodies of the γG₁ class suppressed the immune response to SRBC, whereas γG₂ antibodies isolated from the same serum exerted an augmenting effect on antibody synthesis. These opposing feedback effects on in vitro antibody synthesis were immunologically specific, relatively insensitive to changes in antigen concentrations, and could be elicited by either adding antibodies and antigen separately to the culture or as preformed antigen-antibody complexes. Experiments comparing the activities of the F(ab′)₂ antibody fragments with the parent γG₁ and γG₂ antibodies suggested that the Fc fragments may be involved in these regulatory effects on the immune response. It is concluded that the antigen-specific suppressive and augmenting effects on antibody synthesis shown here are determined by the antibody class. In addition, we suggest that these opposing antibody-mediated feedback effects may represent one of the important elements of the immune response.     

Nasopharyngeal carcinoma patients from Norway show elevated Epstein-Barr virus IgA and IgG antibodies prior to diagnosis

BackgroundIgA antibodies against few Epstein-Barr virus (EBV) proteins are established serological markers for nasopharyngeal carcinoma (NPC). We recently validated a novel, comprehensive EBV marker panel and showed that IgA, but also IgG antibodies against multiple EBV proteins are highly sensitive and specific for EBV-positive NPC at diagnosis. However, data about these novel biomarkers as prospective markers for NPC are sparse.MethodsThis study included 30 incident NPC cases and 60 matched controls from the Norwegian Janus Serum Bank. For 21 NPCs, molecular EBV and human papillomavirus (HPV) status were assessed by EBER-ISH and HPV DNA/RNA testing by PCR, respectively. IgA and IgG serum antibodies against 17 EBV antigens were analyzed in prediagnostic sera of cases (median lead time 14 years) and controls using multiplex serology. Sensitivities were calculated using receiver operating characteristic analysis pre-specified to yield 90% specificity in the control group. From 10 cases, serial samples were available.ResultsQuantitative EBV antibody levels were significantly elevated among all cases (p < 0.05) for three IgA and six IgG antibodies. The highest sensitivities for defining 12 EBER-ISH-positive NPCs were observed for BGLF2 IgA (67%) and BGLF2 IgG (83%). Increased IgA and IgG antibody levels between the first and last draw before diagnosis were observed for EBER-ISH positive, but not for EBER-ISH negative NPCs. Among 21 molecularly analyzed NPCs, 4 EBER-ISH negative NPCs showed concomitant positivity to HPV type-specific DNA and RNA; 3 NPCs were HPV16 and 1 NPC was HPV18 positive.ConclusionBoth, EBV IgA and IgG antibody levels are significantly elevated many years before diagnosis of EBV-positive NPCs in Norway, an NPC low-incidence region. This study provides insights into one of the largest available prospective sample collections of NPCs in a non-endemic country.     

Expression and Immunogenicity of Enterotoxigenic <Emphasis Type="Italic">Escherichia</Emphasis> <Emphasis Type="Italic">coli</Emphasis> Heat-Labile Toxin B Subunit in Transgenic Rice Callus

Enterotoxigenic Escherichia coli is one of the leading causes of diarrhea in developing countries, and the disease may be fatal in the absence of treatment. Enterotoxigenic E. coli heat-labile toxin B subunit (LTB) can be used as an adjuvant, as a carrier of fused antigens, or as an antigen itself. The synthetic LTB (sLTB) gene, optimized for plant codon usage, has been introduced into rice cells by particle bombardment-mediated transformation. The integration and expression of the sLTB gene were observed via genomic DNA PCR and western blot analysis, respectively. The binding activity of LTB protein expressed in transgenic rice callus to G_M1-ganglioside, a receptor for biologically active LTB, was confirmed by G_M1-ELISA. Oral inoculation of mice with lyophilized transgenic rice calli containing LTB generated significant IgG antibody titers against bacterial LTB, and the sera of immunized mice inhibited the binding of bacterial LTB to G_M1-ganglioside. Mice orally immunized with non-transgenic rice calli failed to generate detectable anti-LTB IgG antibody titers. Mice immunized with plant-produced LTB generated higher IgG1 antibody titers than IgG2a, indicating a Th2-type immune response. Mice orally immunized with lyophilized transgenic rice calli containing LTB elicited higher fecal IgA antibody titers than mice immunized with non-transgenic rice calli. These experimental results demonstrate that LTB proteins produced in transgenic rice callus and given to mice by oral administration induce humoral and secreted antibody immune responses. We suggest that transgenic rice callus may be suitable as a plant-based edible vaccine to provide effective protection against enterotoxigenic E. coli heat-labile toxin.     

Deregressed EBV as the response variable yield more reliable genomic predictions than traditional EBV in pure-bred pigs

Background

Genomic selection can be implemented by a multi-step procedure, which requires a response variable and a statistical method. For pure-bred pigs, it was hypothesised that deregressed estimated breeding values (EBV) with the parent average removed as the response variable generate higher reliabilities of genomic breeding values than EBV, and that the normal, thick-tailed and mixture-distribution models yield similar reliabilities.

Methods

Reliabilities of genomic breeding values were estimated with EBV and deregressed EBV as response variables and under the three statistical methods, genomic BLUP, Bayesian Lasso and MIXTURE. The methods were examined by splitting data into a reference data set of 1375 genotyped animals that were performance tested before October 2008, and 536 genotyped validation animals that were performance tested after October 2008. The traits examined were daily gain and feed conversion ratio.

Results

Using deregressed EBV as the response variable yielded 18 to 39% higher reliabilities of the genomic breeding values than using EBV as the response variable. For daily gain, the increase in reliability due to deregression was significant and approximately 35%, whereas for feed conversion ratio it ranged between 18 and 39% and was significant only when MIXTURE was used. Genomic BLUP, Bayesian Lasso and MIXTURE had similar reliabilities.

Conclusions

Deregressed EBV is the preferred response variable, whereas the choice of statistical method is less critical for pure-bred pigs. The increase of 18 to 39% in reliability is worthwhile, since the reliabilities of the genomic breeding values directly affect the returns from genomic selection.     

Effects of dietary fish meal and soybean meal on the ovine innate and acquired immune response during pregnancy and lactation

In recent years, livestock producers have been supplementing animal diets with fish meal (FM) to produce value-added products for health conscious consumers. As components of FM have unique neuroendocrine–immunomodulatory properties, we hypothesize that livestock producers may be influencing the overall health of their animals by supplementing diets with FM. In this study, 40 pregnant ewes were supplemented with rumen protected (RP) soybean meal (SBM: control diet) or RP FM, commencing gestation day 100 (gd100), in order to evaluate the impact of FM supplementation on the innate and acquired immune response and neuroendocrine response of sheep during pregnancy and lactation. On gd135, half the ewes from each diet (n = 10 FM, n = 10 SBM) were challenged iv with lipopolysaccharide (LPS) to simulate a systemic bacterial infection and the febrile, respiratory and neuroendocrine responses were monitored over time; the other half (n = 10 FM, n = 10 SBM) of the ewes received a saline injection as control. On lactation day 20 (ld20), all ewes (n = 20 FM, n = 20 SBM) were sensitized with hen egg white lysozyme (HEWL) and the serum haptoglobin (Hp) response was measured over time. The cutaneous hypersensitivity response (CHR) to HEWL challenge was measured on ld30 (n = 20 FM, n = 20 SBM), and blood samples were collected over time to measure the primary and secondary immunoglobulin G (IgG) response to HEWL. There was an attenuated trend in the LPS-induced febrile response by the FM treatment when compared with the SBM treatment (P = 0.06), as was also true for the respiratory response (P = 0.07), but significant differences in neuroendocrine function (serum cortisol and plasma ACTH) were not observed between treatments. Basal Hp levels were significantly lower in the FM supplemented ewes when compared with the SBM supplemented ewes (P < 0.01), and the Hp response to HEWL sensitization differed significantly over time between treatments (P < 0.01). The CHR to HEWL was also significantly attenuated in the FM treatment compared with the SBM (P < 0.01); however, treatment differences in the primary and secondary IgG responses to HEWL were not observed. These results indicate that FM supplementation differentially affects the innate and acquired immune responses in pregnant and lactating sheep compared with a typical SBM diet of commercial flocks. The long-term implications of this immunomodulation warrant further investigation.     

Breeding Potential of Introgression Lines Developed from Interspecific Crossing between Upland Cotton (Gossypium hirsutum) and Gossypium barbadense: Heterosis,Combining Ability and Genetic Effects

Upland cotton (Gossypium hirstum L.), which produces more than 95% of the world natural cotton fibers, has a narrow genetic base which hinders progress in cotton breeding. Introducing germplasm from exotic sources especially from another cultivated tetraploid G. barbadense L. can broaden the genetic base of Upland cotton. However, the breeding potential of introgression lines (ILs) in Upland cotton with G. barbadense germplasm integration has not been well addressed. This study involved six ILs developed from an interspecific crossing and backcrossing between Upland cotton and G. barbadense and represented one of the first studies to investigate breeding potentials of a set of ILs using a full diallel analysis. High mid-parent heterosis was detected in several hybrids between ILs and a commercial cultivar, which also out-yielded the high-yielding cultivar parent in F₁, F₂ and F₃ generations. A further analysis indicated that general ability (GCA) variance was predominant for all the traits, while specific combining ability (SCA) variance was either non-existent or much lower than GCA. The estimated GCA effects and predicted additive effects for parents in each trait were positively correlated (at P<0.01). Furthermore, GCA and additive effects for each trait were also positively correlated among generations (at P<0.05), suggesting that F₂ and F₃ generations can be used as a proxy to F₁ in analyzing combining abilities and estimating genetic parameters. In addition, differences between reciprocal crosses in F₁ and F₂ were not significant for yield, yield components and fiber quality traits. But maternal effects appeared to be present for seed oil and protein contents in F₃. This study identified introgression lines as good general combiners for yield and fiber quality improvement and hybrids with high heterotic vigor in yield, and therefore provided useful information for further utilization of introgression lines in cotton breeding.     

Predictive ability of selected subsets of single nucleotide polymorphisms (SNPs) in a moderately sized dairy cattle population

Several studies have shown that computation of genomic estimated breeding values (GEBV) with accuracies significantly greater than parent average (PA) estimated breeding values (EBVs) requires genotyping of at least several thousand progeny-tested bulls. For all published analyses, GEBV computed from the selected samples of markers have lower or equal accuracy than GEBV derived on the basis of all valid single nucleotide polymorphisms (SNPs). In the current study, we report on four new methods for selection of markers. Milk, fat, protein, somatic cell score, fertility, persistency, herd life and the Israeli selection index were analyzed. The 972 Israeli Holstein bulls genotyped with EBV for milk production traits computed from daughter records in 2012 were assigned into a training set of 844 bulls with progeny test EBV in 2008, and a validation set of 128 young bulls. Numbers of bulls in the two sets varied slightly among the nonproduction traits. In EFF₁₂, SNPs were first selected for each trait based on the effects of each marker on the bulls’ 2012 EBV corrected for effective relationships, as determined by the SNP matrix. EFF₀₈ was the same as EFF₁₂, except that the SNPs were selected on the basis of the 2008 EBV. In DIF_max, the SNPs with the greatest differences in allelic frequency between the bulls in the training and validation sets were selected, whereas in DIF_min the SNPs with the smallest differences were selected. For all methods, the numbers of SNPs retained varied over the range of 300 to 6000. For each trait, except fertility, an optimum number of markers between 800 and 5000 was obtained for EFF₁₂, based on the correlation between the GEBV and current EBV of the validation bulls. For all traits, the difference between the correlation of GEBV and current EBV and the correlation of the PA and current EBV was >0.25. EFF₀₈ was inferior to EFF₁₂, and was generally no better than PA EBV. DIF_max always outperformed DIF_min and generally outperformed EFF₀₈ and PA. Furthermore, GEBV based on DIF_max were generally less biased than PA. It is likely that other methods of SNP selection could improve upon these results.     

Epstein-Barr virus but not cytomegalovirus is associated with reduced vaccine antibody responses in Gambian infants

Background

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are persistent herpesviruses that have various immunomodulatory effects on their hosts. Both viruses are usually acquired in infancy in Sub-Saharan Africa, a region where childhood vaccines are less effective than in high income settings. To establish whether there is an association between these two observations, we tested the hypothesis that infection with one or both viruses modulate antibody responses to the T-cell independent meningococcal polysaccharide vaccine and the T-cell dependent measles vaccines.

Methodology/Principal Findings

Infection with EBV and CMV was diagnosed by the presence of virus-specific IgM in the peripheral blood or by the presence of IgG at higher levels than that found in umbilical cord blood. Anti-meningococcus IgG and IgM were quantified by ELISA. Anti-measles antibody responses were quantified by haemagglutinin antibody inhibition assay. Infants infected with EBV had reduced IgG and IgM antibody responses to meningococcal polysaccharides and to measles vaccine. Infection with CMV alone predicted no changes in the response to meningococcal polysaccharide. While CMV alone had no discernable effect on the antibody response to measles, the response of infants infected with both CMV and EBV was similar to that of infants infected with neither, suggesting that the effects of CMV infection countered the effects of EBV on measles antibody responses.

Conclusions

The results of this exploratory study indicate that infection with EBV is associated with reduced antibody responses to polysaccharides and to measles vaccine, but suggest that the response to T-cell dependent antigens such as measles haemagglutinin may be restored by infection with CMV.     

Characterization of guinea pig mitogenic factors. I. Evidence that antigen-induced mitogenic factor and mitogenic factor from mixed leukocyte cultures are distinct molecular entities.

Mitogenic factor from BCG-sensitized cells stimulated with antigen (PPD) was found to have a m.w. between 20 and 25,000 daltons and an isoelectric point of about 7.5. The blastogenic activity of this factor was not affected by L-fucose or heating at 56 degrees C for up to 1 hr. Mitogenic factor obtained from supernatants of allogeneic cell mixtures (MLC-MF) on the other hand, had a m.w. at 15 to 18,000 daltons and an isoelectric point of 6.5. The blastogenic activity of MLC-MF was inhibited by 0.1 M L-fucose. The factor was stable at 56 degrees C for 1 hr. An antibody prepared against MLC-MF inhibited the MLC reaction as well as the activity of MLC-MF on non-committed cells. This antibody, however, did not affect the response of lymphocytes to PHA or PPD and had no suppressive effect on PPD-MF. The antibody was not cytotoxic and its suppressive activity in the MLC response could not be absorbed out by lymphoid cells indicating that it is probably directed against a lymphocyte activation product (MLC-MF) rather than membrane antigens. The chemical and immunologic differences exhibited by PPD-MF and MLC-MF indicate that these two lymphokines are distinct molecular entities.