High-resolution GTG-banding and nucleolar organizer regions of chromosomes of two vole species: Microtus rossiaemeridonionalis and M. transcaspicus (Rodentia, Arvicolidae)

Two lines of White Leghorns that had undergone long-term selection for high (HH) or low (LL) antibody response to sheep red blood cell antigen(s) formed the nuclear lines for this experiment. Matings were made in a full diallel cross to produce in a single hatch from age-contemporary breeders the parental lines, reciprocal F1 and F2 crosses, and backcrosses for 16 progeny types. For males and females, there were parental line differences in BW to 42 d of age, after which there was decline between lines for males. Differences in BW between reciprocal F1 crosses and maternal heterosis declined with age, primarily reflecting dissipation of effects of egg weight. Heterosis of BW was dependent on the particular F1 cross and recombination effects were not important. At 50 d of age chicks were inoculated with either a 1 or 10% suspension of spleen extract from chickens infected with marble spleen disease virus (MSDV). A third group served as uninjected controls. Response to MSDV was evaluated by spleen weight 6 d after inoculation. Spleen weights relative to BW of control chicks were heavier for the HH than LL line with evidence from the crosses of sexlinkage and negative heterosis. Line LL chicks were more resistant to MSDV than Line HH chicks was F1 crosses intermediate to and different from either parental line with no evidence of heterosis.     

Selection for growth does not affect apparent energetic efficiency of jejunal glucose uptake in mice

Five-wk-old male mice from high growth (M16) and randomly bred control (ICR) lines, plus their reciprocal crosses, ICR x M16 and M16 x ICR, were used to investigate whether whole-body O2 consumption, jejunal respiration, jejunal glucose absorption and the apparent energetic efficiency of jejunal active glucose uptake in mice are altered by genetic selection for growth as well as by heterosis and maternal effects. Whole-body O2 consumption was measured in 12 mice from each line or cross. The mice were later killed for measurement of jejunal O2, using tissue respiration chambers and jejunal glucose transport determined by 3H-3-O-methylglucose accumulation. No heterosis or maternal effects were detected in jejunal glucose active transport and active glucose uptake. Selection for growth (M16 vs. ICR) increased daily gain (1.54 vs. 1.09 g, P < 0.001), small intestinal length and weight, but did not enhance jejunal glucose transport. The apparent energetic efficiency of jejunal active glucose uptake among lines was not different (54.0, 50.4, 51.6 and 47.1 nmol ATP expended/nmol glucose uptake for M16, ICR, M16 x ICR and ICR x M16, respectively, P > 0.63). Selection for growth in mice did not result in more energetically efficient jejunal glucose absorption.     

Effects of inbreeding and heterozygosity on preweaning traits in a closed population of Herefords under selection

Records of five inbred lines at the Livestock and Range Research Laboratory were used to evaluate effects of inbreeding and heterozygosity on preweaning traits. Members of each line were descendants of a single founder Hereford bull. A total of 8,065 records of birth weight and 7,380 records of preweaning daily gain and weaning weight were analyzed by derivative-free REML using a model that included fixed effects of sex, combination of year and month of birth and parity of dam, with covariates for direct and maternal genetic fractions of inheritance from the genetic groups, inbreeding, and heterozygosity fractions. Heterozygosity fractions were computed for crosses between lines. The random model effects were direct and maternal genetic and uncorrelated maternal permanent environmental and temporary environmental. Direct inbreeding and heterozygosity fractions averaged .098 and .343, and maternal inbreeding and heterozygosity fractions averaged .075 and .294. Regression coefficients of traits on direct and maternal inbreeding fractions were -5.8 +/- 1.1 and -4.7 +/- 1.3 for birth weight, -.189 +/- .031 and -.252 +/- .039 for preweaning daily gain, and -44.5 +/- 6.6 and -56.1 +/- 8.4 kg for weaning weight. Estimates for direct heritability, maternal heritability, and direct-maternal genetic correlations were .37, .12, and -.01 for birth weight; .16, .25, and -.27 for daily gain; and .17, .26, and -.21 for weaning weight. Results suggest that heterosis represents recovery of accumulated inbreeding depression. Results also indicate that selection can overcome inbreeding depression and antagonism exists between direct and maternal genetic effects for preweaning traits.     

Calcium antagonists and endothelial function: focus on nitric oxide and endothelin

Replicate high-selected, control, and low-selected lines were crossed at generation 46 of bidirectional selection for thermoregulatory nest-building behavior. Previous analysis of the lines at their limits had revealed multiple responses to uniform selection, where each of the four selected lines responded differently to reverse selection (Laffan, 1989). The reciprocal F1 crosses showed significant heterosis for nest-building behavior compared to the contemporaneous generations of the parental lines. This pattern of heterosis in all three crosses is consistent with the finding that nest-building behavior in each of the four replicate lines had a different genetic basis, in spite of the phenotypic similarity between the two replicate lines in the high and low direction of nesting. This heterosis effect and the larger number of young weaned in all three crosses compared to their respective contemporaneous generation of the parental lines also support earlier findings that larger nests are closely related to fitness.     

Absence of strong heterosis for life span and other life history traits in Caenorhabditis elegans

We have examined crosses between wild-type strains of Caenorhabditis elegans for heterosis effects on life span and other life history traits. Hermaphrodites of all wild strains had similar life expectancies but males of two strains had shorter life spans than hermaphrodites while males of two other strains lived longer than hermaphrodites. F1 hermaphrodite progeny showed no heterosis while some heterosis for longer life span was detected in F1 males. F1 hybrids of crosses between two widely studied wild-type strains, N2 (var. Bristol) and Berg BO (var. Bergerac), were examined for rate of development, hermaphrodite fertility, and behavior; there was no heterosis for these life history traits. Both controlled variation of temperature and uncontrolled environmental variation affected the length of life of all genotypes. Significant G x E effects on life span were observed in comparisons of N2 and Berg BO hermaphrodites, or N2 hermaphrodites and males, or N2 and a Ts mutant strain (DH26). Nevertheless, within an experiment, environmental variation was minimal and life spans were quite replicable.     

Effect of crossing a line selected for increased shank width with two commercial sire lines on performance and walking ability of turkeys

Published research indicated that a line (FL) of turkeys selected for increased shank width and exhibiting good walking ability (WA) and improved leg structure was useful in improving WA of a cross with an unimproved commercial sire line while remaining competitive in BW and body conformation. The purpose of the present study was to determine whether the FL line was useful in improving WA of two improved commercial primary-breeding sire lines and to study the inheritance of BW traits in the pure lines and reciprocal crosses of the pure lines. Samples of a primary breeding sire line from each of two major commercial turkey breeders were obtained as unpedigreed eggs and designated as Lines A and B. Lines A and B were reciprocally crossed with the FL line that had been selected for increased shank width for 16 generations. Pure lines and reciprocal crosses were produced by artificially mating 10 males to 15 females using pooled semen. The same semen pools were used to produce both the pure lines and the crosses. Traits measured included BW at 8, 16, and 20 wk of age, and length, width, and depth of the shank, width of the breast, and WA at 16 wk of age. The A and B lines were larger and had wider breasts and narrower and shorter shanks than the FL line. Line B was larger than Line A. Shank measurements and WA score did not differ between Lines A and B in either sex. Breasts of Line B females were wider than those of Line A females, but there was no sire line difference in breast width of males. Heterosis in BW was greater in Line A crosses (average of 4.6% with a range of 2.5 to 7.2% for BW at different ages) than in Line B crosses (average of 2.2% with a range of 0.1 to 5.3%). Heterosis in WA score was negative (crosses had better WA than pure lines) for males [14% for the Line A and FL crosses (P < or = 0.001) and 4% for the Line B and FL crosses (P < or = 0.05)], but was positive and nonsignificant for females of the above crosses (average of 2.6 %). With one exception, heterosis was not an important source of variation for shank width or shank depth and there was a low level of heterosis for shank length. No heterosis was observed for breast width. Reciprocal effects were an important source of variation in BW and shank measurements for females but not for males in both sets of crosses. The results of the present study indicated that use of the FL line to improve WA of improved primary-breeding commercial sire lines was not a feasible alternative. The slight improvement noted in WA of the male crosses was offset by the reduction in BW and breast width of the crosses relative to the pure commercial sire lines.     

Inheritance of learning ability in mice: A diallel-environmental analysis.

Raised 189 male mice from 4 inbred strains and their F1 hybrid crosses under either standard laboratory conditions or mildly stressful conditions. Subsequent performance in appetitive -maze and water-escape learning was analyzed by quantitative genetic methods. The -maze time scores and water-escape times showed large additive genetic and nonadditive genetic components. Environmental stress had a marginally significant effect only on water-escape times, and there was no indication of a Genotype * Environment interaction. Both heterosis and developmental homeostasis were found on water-escape times. Genetic correlations were high between the 2 -maze measures (time and errors), which in turn showed lower correlations with water-escape times. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

NH2-terminal structural motifs in staphylokinase required for plasminogen activation

Staphylokinase (Sak) forms an inactive 1:1 stoichiometric complex with plasminogen which requires both conversion of plasminogen to plasmin and hydrolysis of the Lys10-Lys11 peptide bond of Sak to become a potent plasminogen activator (Schlott, B., Guhrs, K.-H., Hartmann, M., Rocker, A., and Collen, D. (1997) J. Biol. Chem. 272, 6067-6072). Exposure of a positively charged NH2-terminal amino acid after hydrolysis of Sak is a major determinant of the plasminogen-activating potential, but in itself is neither necessary nor sufficient. Here, the structural motifs of the NH2-terminal region Lys11-Gly-Asp-Asp-Ala-Ser16-Tyr-Phe-Glu of processed Sak, required for plasminogen activating potential, were studied by deletion and substitution mutagenesis. Expression in Escherichia coli of variants with deletion of 11, 14, 15, or 16 NH2-terminal amino acids yielded correctly processed but inactive molecules. Expression of their homologues with the NH2-terminal amino acid substituted with Lys-generated derivatives from which the NH2-terminal initiation Met was no longer removed, yielding inactive (50%) Sak42DDeltaN14(M), A15K and Sak42DDeltaN15(M),S16K, and inactive Sak42DDeltaN16(M),Y17K. Lys variants without NH2-terminal Met, generated from fusion proteins in which a His6 tag and a factor Xa recognition sequence were linked to the NH2 terminus of the Sak variants, were indistinguishable from their NH2-terminal Met-containing counterparts. All variants studied had intact affinities for plasminogen as measured by biospecific interaction analysis. The activity of Sak42DDeltaN11(M),G12K could be restored by additional substitution of both Asp13 and Asp14 with Asn, yielding active Sak42DDeltaN11(M),G12K, D13N, D14N, whereas substitution in Sak42DDeltaN16(M),Y17K of Phe18 and Glu19 with Asn yielded inactive Sak42DDeltaN16(M),Y17K,F18N,E19N. These data, in combination with the recent finding that the 20 NH2-terminal amino acids of Sak lack secondary structure, suggest that the NH2-terminal region of Sak is not required for binding to plasmin/plasminogen, but that a positively charged amino acid in the ultimate or penultimate NH2-terminal position corresponding to amino acids 11-16 of this flexible region participates in the reconfiguration of the active site of the plasmin molecule to endow it with plasminogen-activating potential.     

Cumulative selection and genetic change for weaning or yearling weight or for yearling weight plus muscle score in Hereford cattle

Selection in three lines of Hereford cattle for 1) weaning weight (WWL), 2) yearling weight (YWL), and 3) an index of yearling weight and muscle score (IXL) was studied. Remnant foundation cows and semen from seven foundation sires were used to establish an unselected control line for the last 11 yr of the experiment. Performance data collected over a 23-yr period on birth weight (BWT), weaning weight (WWT), postweaning gain (PWG), yearling weight (YWT), muscle score (MSC), and an index (IDX) giving equal weight to standard deviations of yearling weight and muscle score were analyzed. Generation interval of midparents was about 4.16 yr in each selected line. Sire and dam selection differentials, in standard deviation units per generation, for primary criteria were, respectively, 1.59 and .33 for WWT in WWL, 1.75 and .25 for YWT in YWL, and 1.42 and .25 for IDX in IXL. Components of direct and maternal genetic variances, direct-maternal covariance, and dam permanent environmental variance were estimated by REML. The average annual response of males and females in actual units for each trait in WWL, YWL, and IXL was, respectively, BWT, .22, .24, and .27 kg; WWT, .98, .63, and 1.26 kg; YWT, 2.43, 2.64, and 3.44 kg; and MSC, .053, .009, and .104 scores. Average selection responses in BWT, WWT, YWT, MSC, and IDX per unit of primary criteria in each selection line (all in standard deviation units) were .22, .20, .31, .10, and .24 for WWT in WWL; .23, .12, .32, .04, and .21 for YWT in YWL; and .27, .22, .40, .20, and .36 for IDX in IXL. Responses in bold type are realized heritability and others are correlated responses. Realized genetic correlations were .78 for WWT and YWT, .87 for WWT and IDX, and .86 for YWT and IDX. Responses for all traits in IXL were greater than in other selected lines.     

A conserved negative regulatory region in alphaPAK: inhibition of PAK kinases reveals their morphological roles downstream of Cdc42 and Rac1

AlphaPAK in a constitutively active form can exert morphological effects (E. Manser, H.-Y. Huang, T.-H. Loo, X.-Q. Chen, J.-M. Dong, T. Leung, and L. Lim, Mol. Cell. Biol. 17:1129-1143, 1997) resembling those of Cdc42G12V. PAK family kinases, conserved from yeasts to humans, are directly activated by Cdc42 or Rac1 through interaction with a conserved N-terminal motif (corresponding to residues 71 to 137 in alphaPAK). alphaPAK mutants with substitutions in this motif that resulted in severely reduced Cdc42 binding can be recruited normally to Cdc42G12V-driven focal complexes. Mutation of residues in the C-terminal portion of the motif (residues 101 to 137), though not affecting Cdc42 binding, produced a constitutively active kinase, suggesting this to be a negative regulatory region. Indeed, a 67-residue polypeptide encoding alphaPAK83-149 potently inhibited GTPgammaS-bound Cdc42-mediated kinase activation of both alphaPAK and betaPAK. Coexpression of this PAK inhibitor with Cdc42G12V prevented the formation of peripheral actin microspikes and associated loss of stress fibers normally induced by the p21. Coexpression of PAK inhibitor with Rac1G12V also prevented loss of stress fibers but not ruffling induced by the p21. Coexpression of alphaPAK83-149 completely blocked the phenotypic effects of hyperactive alphaPAKL107F in promoting dissolution of focal adhesions and actin stress fibers. These results, coupled with previous observations with constitutively active PAK, demonstrate that these kinases play an important role downstream of Cdc42 and Rac1 in cytoskeletal reorganization.     

Refined solution structure of 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 opposite CpA in the complementary strand of an oligodeoxynucleotide duplex as determined by 1H NMR

The solution structure of d(CCATCAFBGATCC).d(GGATCAGATGG), containing the 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 adduct, was refined using molecular dynamics restrained by NOE data obtained from 1H NMR. The modified guanosine was positioned opposite cytosine, while the aflatoxin moiety was positioned opposite adenosine in the complementary strand. Sequential 1H NOEs were interrupted between C5 and AFBG6, but intrastrand NOEs were traced through the aflatoxin moiety, via H6a of aflatoxin and H8 of the modified guanine. Opposite the lesion, the NOE between A16 H1' and G17 H8 was weak. A total of 43 NOEs were observed between DNA protons and aflatoxin protons. Molecular dynamics calculations restrained with 259 experimental and empirical distances, and using sp2 hybridization at AFBG6 N7, refined structures with pairwise rms differences < 0.85 A, excluding terminal base pairs. Relaxation matrix calculations yielded a sixth root rms difference between refined structures and NOE intensity data of 7.3 x 10(-2). The aflatoxin moiety intercalated on the 5'-face of the modified guanine. The extra adenine A16 was inserted between base pair AFBG6.C15 and the aflatoxin moiety. A 36 degree bending between the plane of base pair AFBG6.C15 and the plane of the aflatoxin moiety was predicted. The aflatoxin moiety stacked below the top domain of the oligodeoxynucleotide, which consisted of base pairs C1.G21, C2.G20, A3.T19, T4.A18, and C5.G17. The bottom domain consisted of base pairs AFBG6.C15, A7.T14, T8.A13, C9.G12, and C10.G11. The average winding angle between base pair C5.G17, the intercalated aflatoxin moiety, A16, and base pair AFBG6.C15 was reduced to 10 degrees. The preponderance of base pair substitutions in the aflatoxin B1 mutational spectrum, particularly G-->T transversions, suggests that the stability of this modified oligodeoxynucleotide, which models a templated +1 addition mutation, does not reliably predict the frequency of frame shifts.     

Parameter estimates for direct, maternal, and grandmaternal genetic effects for birth weight and weaning weight in Hereford cattle

Birth and weaning weights adjusted for age of dam from four lines of Hereford cattle were analyzed to determine the relationships among grandmaternal, maternal, and direct genetic effects. Three lines were selected for 1) weaning weight (WWL), 2) yearling weight (YWL), and 3) an index of yearling weight and muscle score (IXL). The fourth line was an unselected control line (CTL). Numbers of observations ranged from 1,699 (CTL) to 2,811 (WWL), and number of animals in the pedigree file ranged from 2,266 to 3,192. Two animal models were used to obtain estimates by REML using an average information method. Model 1 included random direct and maternal genetic, permanent maternal environmental, and residual environmental effects, and fixed sex x year effects. Model 2 additionally included random grandmaternal genetic and permanent grandmaternal environmental effects. For birth weight, Models 1 and 2 gave almost identical estimates for direct and maternal heritability, and for the fraction of variance that was due to maternal permanent environmental effects. Estimates for grandmaternal heritability could be obtained only for IXL (.03) and CTL (.01). For weaning weight, estimates for direct heritability were similar from both models. Estimates for maternal heritability from Model 1 were .18, .20, .13, and .20, and corresponding estimates from Model 2 were .34, .31, .13, and .34 for WWL, YWL, IXL, and CTL, respectively. For IXL, estimates for variances that were due to grandmaternal genetic and grandmaternal permanent environmental variances could not be obtained and were set to zero. Grandmaternal heritability estimates for WWL, YWL, and CTL were .05, .09, and .12. Estimates of correlations between direct and maternal genetic effects were -.13, -.44, -.11, and -.26 for WWL, YWL, IXL, and CTL. Estimates of correlations between direct and grandmaternal genetic effects were .21, .83, and .55, and those between maternal and grandmaternal genetic effects were -.99, -.84, and -.76 for WWL, YWL, and CTL, respectively. These results indicate that grandmaternal effects may be important for weaning weight and that maternal heritability may be underestimated if grandmaternal effects are not included in the model.     

Ascaris suum: a revision of its early migratory path and implications for human ascariasis

The genetic diversity in a group of Escherichia coli strains belonging to serogroup O6 but expressing different H antigens was investigated by random amplification of polymorphic DNA (RAPD). Isolates of serotypes H16, H1, H31, and non-motile (NM) strains were typed using a set of 3 primers with different G + C contents. The amplified band arrays allowed the identification of 3 main clonal clusters corresponding to each O:H serotype analyzed. Based on their RAPD profiles NM strains could be assigned to either H1 or H31 serotypes. The results indicate that the flagellar antigen and the RAPD fingerprint represent reliable clonal markers in this E. coli group.     

Selection for rate and efficiency of lean gain in the rat

Full-sib family selection for rate (WP) or efficiency (WP/F) of protein gain in rats from 3 to 9 weeks of age was applied for five generations. Three rats per litter were killed to estimate carcass protein. Standardized response/cumulative selection for WP was .19+/-.10 for WP, .28+/-.10 for 3- to 9-week gain .28+/-.08 for 9-week weight, .16+/-.08 for litter size, .22+/-.12 for skinning loss and -.07+/-.09 for fraction of protein in the live weight. Response from selection for WP/F was .18+/-.16 for WP/F, .20+/-.11 for WP, .21+/-.11 for weight gain, .16+/-.11 for 3-week weight, .21+/-.10 for 9-week weight, but negligible for skinning loss or body protein. Response to WP/F selection was extremely variable among generations, associated with generation differences in weight and composition at 9 weeks. Estimates of heritability from offspring-midparent regression were .20+/-.12 for WP and .24+/-.08 for WP/F. Estimates of genotype-generation environment interaction were large for growth, feed intake and skinning loss. Maternal effects were large for weaning weight, fraction of body protein and WP. Sire component genetic correlations were 1.08+/-.13 for WP with total gain, .92+/-.08 for WP/F with gross efficiency and .29+/-.25 for WP with WP/F. A partitional calorimeter was used to evaluate heat production of rats. Lines differed in average heat loss but not in heat loss per unit actual or metabolic weight. Response to selection has been steady for WP but probably could be improved by selecting for WP/F at a constant weight rather than a constant age.     

Quantitative trait loci affecting body weight and fatness from a mouse line selected for extreme high growth

Quantitative trait loci (QTL) influencing body weight were mapped by linkage analysis in crosses between a high body weight selected line (DU6) and a control line (DUKs). The two mouse lines differ in body weight by 106% and in abdominal fat weight by 100% at 42 days. They were generated from the same base population and maintained as outbred colonies. Determination of line-specific allele frequencies at microsatellite markers spanning the genome indicated significant changes between the lines on 15 autosomes and the X chromosome. To confirm these effects, a QTL analysis was performed using structured F2 pedigrees derived from crosses of a single male from DU6 with a female from DUKs. QTL significant at the genome-wide level were mapped for body weight on chromosome 11; for abdominal fat weight on chromosomes 4, 11, and 13; for abdominal fat percentage on chromosomes 3 and 4; and for the weights of liver on chromosomes 4 and 11, of kidney on chromosomes 2 and 9, and of spleen on chromosome 11. The strong effect on body weight of the QTL on chromosome 11 was confirmed in three independent pedigrees. The effect was additive and independent of sex, accounting for 21-35% of the phenotypic variance of body weight within the corresponding F2 populations. The test for multiple QTL on chromosome 11 with combined data from all pedigrees indicated the segregation of two loci separated by 36 cM influencing body weight.     

Differences in patterns of pup care in Mus musculus: VI. Uses of segregating generations to dissociate behavioral units in retrieving.

A genetic analysis of 2 inbred strains of mice (NZB and CBA/H) and their Mendelian crosses conducted by C. Michard and P. Roubertoux (see record 1985-05922-001) demonstrated genetic correlates for 3 variables selected to measure retrieval behavior (first retrieval latency, move away without transporting pups, and nest with all pups). Because these behavioral phenotypes were intercorrelated in the 11 strains making up the population, the present study tested for correlations among their genetic correlates, that is, whether these variables were functionally dependent or were genetically correlated (pleiotropy, linkage). Findings indicate that the correlations are significant for the nonsegregating generations (parental strains NZB and CBA/H, and their F?s) and decrease significantly in at least some segregating generations (F? and backcrosses). The decrease in correlation implies that the genetic correlates of the 3 variables are different. The physiological mechanisms underlying the maintenance of pup care behavior are discussed. (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Antibody neutralization-resistant primary isolates of human immunodeficiency virus type 1

Although typical primary isolates of human immunodeficiency virus type 1 (HIV-1) are relatively neutralization resistant, three human monoclonal antibodies and a small number of HIV-1(+) human sera that neutralize the majority of isolates have been described. The monoclonal antibodies (2G12, 2F5, and b12) represent specificities that a putative vaccine should aim to elicit, since in vitro neutralization has been correlated with protection against primary viruses in animal models. Furthermore, a neutralization escape mutant to one of the antibodies (b12) selected in vitro remains sensitive to neutralization by the other two (2G12 and 2F5) (H. Mo, L. Stamatatos, J. E. Ip, C. F. Barbas, P. W. H. I. Parren, D. R. Burton, J. P. Moore, and D. D. Ho, J. Virol. 71:6869-6874, 1997), supporting the notion that eliciting a combination of such specificities would be particularly advantageous. Here, however, we describe a small subset of viruses, mostly pediatric, which show a high level of neutralization resistance to all three human monoclonal antibodies and to two broadly neutralizing sera. Such viruses threaten antibody-based antiviral strategies, and the basis for their resistance should be explored.     

Bcl-XL cooperatively associates with the Bap31 complex in the endoplasmic reticulum, dependent on procaspase-8 and Ced-4 adaptor

Bap31 is a polytopic integral membrane protein of the endoplasmic reticulum and forms a complex with Bcl-2/Bcl-XL and procaspase-8 (Ng, F. W. H., Nguyen, M., Kwan, T., Branton, P. E., Nicholson, W. D., Cromlish, J. A., and Shore, G. C. (1997) J. Cell Biol. 139, 327-338). In co-transfected human cells, procaspase-8 is capable of interacting with Ced-4, an important adaptor molecule in Caenorhabditis elegans that binds to and activates the C. elegans procaspase, proCed-3. Here, we show that the predicted death effector homology domain within the cytosolic region of Bap31 interacts with Ced-4 and contributes to recruitment of procaspase-8. Bcl-XL, which binds directly but weakly to the polytopic transmembrane region of Bap31, indirectly and cooperatively associates with the Bap31 cytosolic domain, dependent on the presence of procaspase-8 and Ced-4. Ced-4Deltac does not interact with Bcl-XL but rather displaces it from Bap31, suggesting that an endogenous Ced-4-like adaptor is a normal constituent of the Bap31 complex and is required for stable association of Bcl-XL with Bap31 in vivo. These findings indicate that Bap31 is capable of recruiting essential components of a core death regulatory machinery.