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At least 1,369 records · Page 76Linked to original sources
PubMed2000

Sequence diversity of intervening sequences (IVSs) in the 23S ribosomal RNA in Salmonella spp.

Intervening sequences (IVSs) occur sporadically in the rrl (ribosomal RNA large) genes for 23S ribosomal RNA (rRNA) at helix-25 (base pair 550) and helix 45 (base pair 1170) in several bacterial genera, including Salmonella, Yersinia, Proteus, and Providencia, representing the Enterobacteriaceae, but are missing from other genera such as Escherichia. These sequences are transcribed, but later excised without re-ligation during RNaseIII processing of the rRNA, resulting in fragmented 23S rRNA. The IVSs from 22 strains of the SARB (Salmonella Reference Collection B) set were amplified by PCR and sequenced.IVSs with 90% or more sequence identity were placed in the same family; Salmonella has three families of IVSs in helix-25 (A, B, and C) and two in helix-45 (M and O). The rRNA secondary structure for the IVSs predicted from the mfold program reveals a primary stem of about 14bp, which is the postulated RNaseIII cleavage site, and a secondary region of stems and loops. The primary stem is considerably well conserved, with a high rate of compensatory mutations (positional covariants), confirming the reality of the secondary structure and indicating that removal of the IVSs exerts a positive selective pressure to retain the secondary structure. The pattern of possession and presence of families of IVSs was diverse and could not be related to the proposed ancestry of the strains as revealed by the multi-locus enzyme electrophoresis pattern of the strains, suggesting that the IVSs are transferred between strains by lateral transfer. Helix-25 IVSs from families A, B, and C of Salmonella and D of Proteus, which share almost identical primary stems, are placed in superfamily I, while the primary stems of other IVSs from Proteus and Providencia are unrelated to superfamily I and are thus placed into superfamily II; this indicates lateral transfer of members of superfamily I between Proteus and Salmonella, but an independent origin of IVSs of superfamily II in Proteus and Providencia.

Base Sequence↗
PubMed2005

Genetics of efficient feed utilization and national cattle evaluation: a review.

Selection for the wide range of traits for which most beef breed associations calculate expected progeny differences focus on increasing the outputs of the production system, thereby increasing the genetic potential of cattle for reproductive rates, weights, growth rates, and end-product yield. Feed costs, however, represent a large proportion of the variable cost of beef production and genetic improvement programs for reducing input costs should include traits related to feed utilization. Feed conversion ratio, defined as feed inputs per unit output, is a traditional measure of efficiency that has significant phenotypic and genetic correlations with feed intake, growth rate, and mature size. One limitation is that favorable decreases in feed to gain either directly or due to correlated response to increasing growth rate do not necessarily relate to improvement in efficiency of feed utilization. Residual feed intake is defined as the difference between actual feed intake and that predicted on the basis of requirements for maintenance of body weight and production. Phenotypic independence of residual feed intake with growth rate, body weight, and other energy depots can be forced. However, genetic associations may remain when a phenotypic prediction approach is used. Heritability estimates for phenotypic residual feed intake have been moderate, ranging from 0.26 to 0.43. Genetic correlations of phenotypic residual feed intake with feed intake have been large and positive, suggesting that improvement would produce a correlated response of decreased feed intake. Residual feed intake estimated by genetic regression results in a zero genetic correlation with its predictors, which reduces concerns over long-term antagonistic responses such as increased mature size and maintenance requirements. The genetic regression approach requires knowledge of genetic covariances of feed intake with weight and production traits. Cost of individual feed intake measurements on potential replacements must be considered in implementation of national cattle evaluations for efficiency of feed utilization. These costs need to be compared to expected, and, if possible, realized rates of genetic change and the associated reduction in feed input requirements.

Animal Feed↗
PubMed2005

Tag SNP selection in genotype data for maximizing SNP prediction accuracy.

MOTIVATION: The search for genetic regions associated with complex diseases, such as cancer or Alzheimer's disease, is an important challenge that may lead to better diagnosis and treatment. The existence of millions of DNA variations, primarily single nucleotide polymorphisms (SNPs), may allow the fine dissection of such associations. However, studies seeking disease association are limited by the cost of genotyping SNPs. Therefore, it is essential to find a small subset of informative SNPs (tag SNPs) that may be used as good representatives of the rest of the SNPs. RESULTS: We define a new natural measure for evaluating the prediction accuracy of a set of tag SNPs, and use it to develop a new method for tag SNPs selection. Our method is based on a novel algorithm that predicts the values of the rest of the SNPs given the tag SNPs. In contrast to most previous methods, our prediction algorithm uses the genotype information and not the haplotype information of the tag SNPs. Our method is very efficient, and it does not rely on having a block partition of the genomic region. We compared our method with two state-of-the-art tag SNP selection algorithms on 58 different genotype datasets from four different sources. Our method consistently found tag SNPs with considerably better prediction ability than the other methods. AVAILABILITY: The software is available from the authors on request.

Algorithms↗
PubMed2004

Association of a common variant of the CASP8 gene with reduced risk of breast cancer.

Apoptosis, or programmed cell death, is perturbed in many cancers. We tested the hypothesis that coding polymorphisms of the death receptor 4 (DR4), caspase-8 (CASP8), and caspase-10 (CASP10) genes might act as low-penetrance breast cancer genes. Single-nucleotide polymorphisms (SNPs) of these genes were genotyped in a series of 999 breast cancer case patients and 996 control subjects from Sheffield, U.K., and in a second, independent U.K. population of 2192 case patients and 2262 control subjects from East Anglia. In the Sheffield study, the rare H allele of CASP8, D302H, was associated with a reduced risk of breast cancer in a dose-dependent manner (P(trend) = .007). Furthermore, the CASP8 D302H association, but not that of the other CASP8 SNPs examined (T21914C, G50121A, and G50358A), was replicated in the East Anglian study. The combined adjusted odds ratios for breast cancer were 0.83 (95% confidence interval [CI] = 0.74 to 0.94) for the DH heterozygote and 0.58 (95% CI = 0.39 to 0.88) for the HH homozygote (P(trend) = .0002, adjusted for study). The reproducible, dose-dependent association of CASP8 D302H with breast cancer indicates the potential importance of inherited variation in the apoptosis pathway in breast cancer susceptibility.

Aspartic Acid↗
PubMed2006

Creation of a pair of stereochemically complementary biocatalysts.

N-Acetylneuraminic acid lyase (NAL) exhibits poor facial selectivity during carbon-carbon formation, and as such, its utility as a catalyst for use in synthetic chemistry is limited. For example, the NAL-catalyzed condensation between pyruvate and (2R,3S)-2,3-dihydroxy-4-oxo-N,N-dipropylbutyramide yields ca. 3:1 mixtures of diastereomeric products under either kinetic or thermodynamic control. Engineering the stereochemical course of NAL-catalyzed reactions could remove this limitation. We used directed evolution to create a pair of stereochemically complementary variant NALs for the synthesis of sialic acid mimetics. The E192N variant, a highly efficient catalyst for aldol reactions of (2R,3S)-2,3-dihydroxy-4-oxo-N,N-dialkylbutyramides, was chosen as a starting point. Initially, error-prone PCR identified residues in the active site of NAL that contributed to the stereochemical control of an aldolase-catalyzed reaction. Subsequently, an intense structure-guided program of saturation and site-directed mutagenesis was used to identify a complementary pair of variants, E192N/T167G and E192N/T167V/S208V, which were approximately 50-fold selective toward the cleavage of the alternative 4S- and 4R-configured condensation products, respectively. It was shown that wild-type NAL could not be used for the highly stereoselective synthesis of a 6-dipropylamide sialic acid mimetic because the 4S-configured product was only approximately 3-fold kinetically favored and only approximately 3-fold thermodynamically favored over the alternative 4R-configured product. However, the complementary 4R- and 4S-selective variants allowed the highly (>98:<2) diastereoselective synthesis of both 4S- and 4R-configured products under kinetic control from the same starting materials. Conversion of an essentially nonselective aldolase into a pair of complementary biocatalysts will be of enormous interest to synthetic chemists. Furthermore, since residues identified as critical for stereoselectivity are conserved among members of the NAL superfamily, the approach might be extended to the evolution of other useful biocatalysts for the stereoselective synthesis of biologically active molecules.

Aldehydes↗
PubMed1983

A multivariate genetic analysis of ridge count data from the offspring of monozygotic twins.

Two methods have been studied for extending the half-sib model, which was developed by Nance and Corey [34] for the genetic analysis of univariate traits, to include the analysis of multivariate traits. The methods are adaptations of the Bock and Vandenberg procedure [4] and the form of confirmatory maximum likelihood factor analysis which was developed by Jöreskog and Sörbom for the LISREL IV program [22]. These methods were applied to sex-adjusted individual finger ridge count data from the offspring of monozygotic twins. The Bock and Vandenberg procedure was applied to the eigenvalues and eigenvectors from a nested analysis of variance on 30 balanced male twin kinships. The result was a matrix of pure genetic effects which was at least positive semidefinite, and therefore appropriate for factor analytic procedures. Principal components analysis revealed two substantial genetic factors, one with a strong impact on the ridge counts of all ten fingers, with the largest loadings on the three central fingers of each hand, and the other influencing the thumbs and fifth fingers with opposite signs. In both cases, the factor loadings of homologous fingers were nearly equal. Employing the Bock and Vandenberg procedure to analyze multivariate data from MZ twin kinship has both positive and negative features. Its greatest strength is that it is easy to program with the Nested, Matrix, and Factor Procedures of the Statistical Analysis System package [see 44]. Multivariate half-sib data on any traits can be quickly explored for genotypic associations with the availability of this package or others like it. The exploratory findings from this analysis, the LISREL analysis, and the Bock and Vandenberg analysis on MZ and DZ twin pairs, as reported by Nance et al [36] are in agreement. This attests to the validity of the results from the two procedures. Such strong agreement may not be the case for other genetic structures, however, and analysis of other sets of traits or analyses on simulated data should clarify the cases under which the procedures produce concordant results. A negative feature of the Bock and Vandenberg procedure is that it wastes much of the data taken from individuals who attend the Twin Clinic. Both male and female kinships are routinely ascertained, with equal frequencies, although in this analysis we have examined the results from male kinships only. In addition, a substantial number of the male kinships either do not meet the criterion of at least two individuals in each sibship, or else have larger sibships containing individuals who must be excluded from the analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Child↗
PubMed1987

Determinants of a protein fold. Unique features of the globin amino acid sequences.

The three-dimensional structures of globins are known, from crystallographic analyses, to be very similar. Their amino acid sequences, however, differ greatly. Only two residues are absolutely conserved in all sequences, and the residue identities of some pairs of sequences are only 16%. We have determined the nature and exact extent of the sequence variations and the extent to which the conserved features of the globin sequences are unique to this family. The 226 globin sequences now known were aligned and analysed. Because distantly related protein sequences cannot be aligned correctly without the use of structural data, we developed a method that incorporated structural information into the alignment procedure. Analysis of the aligned sequences show that: (1) Although individual chains vary in size between 132 and 157 residues, deletions and insertions result in there being only 102 residue sites common to all globins. These sites form six separate regions. Insertions and deletions between these regions means that their separations can vary in different sequences. (2) Within the conserved regions there are 32 sites that almost always contain hydrophobic residues. In the known structures, these sites are in the protein interior. We measured the variations in the size of the residues that occur in the 226 sequences at these sites. At six sites the residues differ in size by less than 40 A3, at 11 sites they differ by 40 to 100 A3, and at 15 sites they differ by more than 100 A3. There are two other conserved buried sites: one contains the His linked to the haem iron and the other usually contains a His involved with the haem ligand. (3) Within the conserved regions there are another 32 sites that are almost always occupied by charged, polar or small non-polar (Gly or Ala) residues. In the known structures, these sites are on the protein surface. To determine the extent to which the conserved features found for the globin sequences are unique to that protein family, the following procedure was used. The six conserved regions, and the residue restrictions that occur at the 66 sites within these regions, were encoded into two "templates". One was based only on the sequences so far determined; the other was extended to include as yet unobserved substitutions that seemed plausible on the basis of size, hydrophobicity and polarity. Each of the 3286 non-globin sequences in the data bank was then examined by a computer program to see how closely it could be matched to these templates.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1997

Organization and diversity of the 3'-noncoding region of classical swine fever virus genome.

Specific PCR primers were selected to amplify a 359 bp DNA fragment flanking the 3'-part of the polymerase gene and the 3'-noncoding (3'-NC) region of the genome of classical swine fever virus (CSFV). In RT-PCR the selected fragment was amplified from the genomes of 27 viral strains collected from Europe, America and Asia over a period of a half century as well as from three vaccine strains of CSFV. Eight PCR products were sequenced using an automatic sequencing device. Nucleotide sequence analysis was performed by computer programs DNASTAR and PHYLIP. The comparative studies revealed that the 3'-NC region contains a variable region of nucleotides which is located immediately after the stop codon TGA or TAA. Furthermore, a strongly conserved constant region was identified near to the extreme 3'-terminus. Two imperfect repeated sequences were found both in the variable and in the constant regions. In addition, the variable region was characterized by the occurrence of a 50 bp long poly AT track. Phylogenetic analysis with different mathematical approaches (MegAlign, Neighbor-Joining method, Maximum Likelihood, Parsimony) revealed that the studied CSFV strains were clustered into two main phylogenetic groups. Group I was comprised of the reference strain Brescia, together with old American and European field isolates and a Brazilian vaccine strain. Group II included the reference strain Alfort (Tübingen) and recent European field strains. The Congenital Tremor strain formed a distinct lineage which, although being highly divergent, was more closely related to group I than to group II. In conclusion, the present phylogenetic grouping yielded very similar results as previous studies base on comparison of the E2 (gp55) region. The agreement of the phylogenetic analysis in the two distinct regions confirms the reliability of the genetic grouping of CSFV strains into two main genogroups.

Animals↗
PubMed2001

Protein-protein interaction using tryptophan analogues: novel spectroscopic probes for toxin-elongation factor-2 interactions.

Previously, we characterized the role of the three naturally occurring Trp residues (W-417, -466, and -558) in the catalytic mechanism of the toxin-enzyme produced by Pseudomonas aeruginosa [Beattie and Merrill (1999) J. Biol. Chem. 274, 15646-15654]. However, the use of intrinsic Trp fluorescence to study toxin-eEF-2 interaction is inherently limited since the spectral properties of the various Trp residues in both proteins cannot easily be distinguished. To facilitate the study of the protein-protein interaction by Trp fluorescence spectroscopy, the Trp residues in the catalytic domain of exotoxin A were replaced with the amino acid analogues 4-fluorotryptophan, 5-fluorotryptophan, 5-hydroxytryptophan, and 7-azatryptophan. The incorporation of analogues was achieved by using a tightly regulated promoter, pBAD, and expressing the protein in a Trp auxotrophic strain of Escherichia coli, BL21, in a minimal medium containing the appropriate tryptophan analogue. Quantitative spectral analysis of the analogue-containing proteins using the Decompose program indicated that we had achieved 87-100% incorporation efficiency depending on the Trp analogue being used. Electrospray mass spectrometry analysis verified that we had achieved nearly total replacement of the L-tryptophan residues within the catalytic domain of exotoxin A with the tryptophan analogues 5-fluorotryptophan and 4-fluorotryptophan. The analogue-substituted proteins showed a variation in their catalytic activities with k(cat) values ranging from 6-fold (4-fluorotryptophan) to 260-fold (5-hydroxytryptophan) lower than the natural enzyme, which was in agreement with previous data using site-directed mutagenesis [Beattie et al. (1996) Biochemistry 35, 15134-15142]. However, the analogue-incorporated enzymes did not show any significant change in their ability to bind NAD(+) as substrate, as determined from a fluorescence-binding assay. The spectral properties of the various analogue-incorporated proteins were evaluated and compared with those of the native protein. Furthermore, selective excitation of the 5-hydroxytryptophan-incorporated toxin was exploited to study its interaction with the elongation factor-2 substrate by fluorescence resonance energy transfer to an acceptor chromophore located on the elongation factor-2 protein. The binding between the toxin-enzyme and elongation factor-2 was shown to be independent of the NAD(+) substrate (983 +/- 63 nM) and showed a small dependence upon the ionic strength of the solution.

ADP Ribose Transferases↗
PubMed1993

Mitochondrial DNA sequence polymorphism, VO2max, and response to endurance training.

Mitochondrial DNA sequence variation was determined in 46 sedentary young adult males who took part in ergocycle endurance training programs in two laboratories to assess whether mitochondrial DNA variants were associated with individual differences in maximal oxygen uptake (VO2max) and its response to training. VO2max was obtained from a progressive ergocycle test to exhaustion. White blood cell mitochondrial DNA was characterized with the restriction fragment length polymorphism (RFLP) technique using 22 restriction enzymes and human mitochondrial DNA as a probe for hybridization. Multiple mitochondrial DNA variants were detected with 15 of the enzymes. Some subjects exhibited many RFLPs, while others showed no variation. These RFLPs (morphs) were generated by base substitutions located in gene regions coding for mitochondrial proteins as well as in the noncoding regions. Carriers of three mitochondrial DNA morphs, two in the subunit 5 of the NADH dehydrogenase gene and one in the tRNA for threonine, had a VO2max (ml.kg-1.min-1) in the untrained state significantly higher than noncarriers, while carriers of one mitochondrial DNA morph in subunit 2 of NADH dehydrogenase had a lower initial VO2max. Endurance training increased VO2max by a mean of 0.5 l of O2, with individual differences ranging from gains of 0.06 to 1.03. After adjustment for training site and initial VO2max, a lower response was observed for three carriers of a variant in subunit 5 of the NADH dehydrogenase detected with HincII (mean gain of 0.28 l; P < 0.05). These results suggest that sequence variation in mitochondrial DNA may contribute to individual difference in VO2max and its response to training.

Adolescent↗
PubMed2006

The National Animal Germplasm Program: challenges and opportunities for poultry genetic resources.

In the United States, poultry genetic resources have consolidated because of economic pressures. Such consolidations can potentially jeopardize the poultry industry and the ability of research communities to respond to future challenges. To address the loss of genetic resources for all livestock and aquatic species, USDA established the National Animal Germplasm Program (NAGP) in 1999. Since the initiation of NAGP, population surveys have been conducted on nonindustrial chicken and turkey breeds. These surveys not only provide insight into breed status, but also serve as a benchmark for future comparisons. The survey results revealed that 20 chicken breeds and 9 turkey breeds were in various stages of being lost. The NAGP has initiated an ex situ repository for cryopreserved germplasm and tissue that already contains 59 chicken lines and 2,915 tissue samples. As the NAGP, along with its industry and university partners, continues developing the ex situ collection, there are research opportunities in cryopreserved tissue utilization and studies of genetic diversity. For cryopreserved tissues, several key research areas include improving the cryopreservation protocols for rooster and tom semen by using cryoprotectants other than glycerol and utilizing embryonic cells. Although surveys have been conducted on public research lines and rare breeds, there is a void in understanding the level of genetic diversity present in U.S. poultry populations. Therefore, an opportunity exists to perform a series of genetic diversity studies using molecular- based approaches. Such an evaluation can help clarify population differences between research lines and rare breeds and, thereby, facilitate conservation strategies. There appears to be growing consumer interest in poultry products derived from heritage breeds and/or poultry raised in nonindustrial production systems. Although the depth of such market trends is unknown, such an interest may provide an important niche for rare poultry breeds and, thereby, strengthen the genetic base.

Agriculture↗
PubMed2003

Expression profiling of FSHD muscle supports a defect in specific stages of myogenic differentiation.

The neuromuscular disorder facioscapulohumeral muscular dystrophy (FSHD) results from integral deletions of the subtelomeric repeat D4Z4 on chromosome 4q. A disruption of chromatin structure affecting gene expression is thought to underlie the pathophysiology. The global gene expression profiling of mature muscle tissue presented here provides the first insight into an FSHD-specific defect in myogenic differentiation. FSHD expression profiles generated by oligonucleotide microarrays were compared with those from normal muscle as well as other types of muscular dystrophies (DMD, aSGD) in order to determine FSHD-specific changes. In addition, matched biopsies (affected and unaffected muscle) from individuals with FSHD served to monitor expression changes during the progression of the disease as well as to diminish non-specific changes resulting from individual variability. Among genes altered in an FSHD-specific and highly significant manner, many are involved in myogenic differentiation and suggest a partial block in the normal differentiation program. Indeed, many of the transcripts affected in FSHD represent direct targets of the transcription factor MyoD. Additional mis-expressed genes confirm a diminished capacity to buffer oxidative stress, as demonstrated in FSHD myoblasts. This enhanced vulnerability of proliferative stage myoblasts to reactive oxygen species is also disease-specific, further implicating a defect in FSHD muscle satellite cells. Importantly, none of the genes localizing to the FSHD region at 4q35 were found to exhibit a significantly altered pattern of expression in FSHD muscle. This finding was corroborated by expression analysis of FSHD muscle using a custom cDNA microarray containing 51 genes and ESTs from the 4q35 region. Disruptions in FSHD myogenesis and oxidative capacity may therefore not arise from a position effect mechanism as has been previously suggested, but rather from a global effect on gene regulation. Improper nuclear localization of 4qter is discussed as an alternative model for FSHD gene regulation and pathogenesis.

Biopsy↗
PubMed1996

Dissociation rates of peptidyl-tRNA from the P-site of E.coli ribosomes.

We studied the dissociation rates of peptidyl-tRNA from the P-site of poly(U)-programmed wild-type Escherichia coli ribosomes, hyperaccurate variants altered in S12 (SmD, SmP) and error-prone variants (Ram) altered in S4 or S5. The experiments were carried out in the presence and absence of streptomycin, and the effects of neomycin were tested in the wild-type ribosomes. Binding of peptidyl-tRNA to the P-site of wild-type ribosomes is much stronger than to their A-site. Addition of streptomycin dramatically reduces its affinity for the P-site. The S12 alternations make the P-site binding of peptidyl-tRNA much tighter, and the S4, S5 alterations make it weaker than in the case of the wild-type. We find that when binding of peptidyl-tRNA to the A-site is weak, then the affinity for the P-site is stronger, and vice versa. From these results, we formulate a hypothesis for the actions of streptomycin and neomycin based on deformations of the 16S rRNA tertiary structure. The results are also used to interpret some in vivo experiments on translational processivity.

Amino Acid Sequence↗
PubMed1983

Uses of available record systems in epidemiologic studies of reproductive toxicology.

The uses of available record systems in epidemiologic studies of reproductive toxicology are described with reference to New York State. The available record systems (and relevant reproductive end points) described include: a newborn screening program for metabolic diseases and hemoglobinopathies (relevant to point mutations); chromosome registries and prenatal cytogenetics (for chromosome anomalies); live birth certificates (for birth defects, birthweight, sex ratio, etc); fetal death certificates (for spontaneous fetal deaths); and a statewide cancer registry (for childhood cancers and transplacental carcinogenesis). The uses and limitations of these record systems are discussed, along with examples of their use in descriptive and analytic epidemiologic studies. Descriptive studies outlined include investigations of temporal and geographic trends in birth defects, birth weight, and fetal deaths, with reference to environmental questions (eg, Love Canal, nuclear power plants). Analytic studies described concern parental occupation in relation to specific birth defects (neural tube defects and Down syndrome) and maternal use of contraceptive drugs.

Abortion, Spontaneous↗
PubMed1998

A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type.

Slow- and fast-twitch myofibers of adult skeletal muscles express unique sets of muscle-specific genes, and these distinctive programs of gene expression are controlled by variations in motor neuron activity. It is well established that, as a consequence of more frequent neural stimulation, slow fibers maintain higher levels of intracellular free calcium than fast fibers, but the mechanisms by which calcium may function as a messenger linking nerve activity to changes in gene expression in skeletal muscle have been unknown. Here, fiber-type-specific gene expression in skeletal muscles is shown to be controlled by a signaling pathway that involves calcineurin, a cyclosporin-sensitive, calcium-regulated serine/threonine phosphatase. Activation of calcineurin in skeletal myocytes selectively up-regulates slow-fiber-specific gene promoters. Conversely, inhibition of calcineurin activity by administration of cyclosporin A to intact animals promotes slow-to-fast fiber transformation. Transcriptional activation of slow-fiber-specific transcription appears to be mediated by a combinatorial mechanism involving proteins of the NFAT and MEF2 families. These results identify a molecular mechanism by which different patterns of motor nerve activity promote selective changes in gene expression to establish the specialized characteristics of slow and fast myofibers.

3T3 Cells↗
PubMedDate not supplied

Report of an International Network of Cancer Treatment and Research workshop on non-Hodgkin's lymphoma in developing countries.

The International Network of Cancer Treatment and Research (INCTR) recently organized a workshop on non-Hodgkin lymphomas (NHLs) in selected developing countries with the purpose of examining existing information relating to the pathology and management of these neoplasms, and identifying potential areas for research. This report provides a summary of the information presented and is focused primarily on the pathology of NHLs in children and adults. In most countries, the WHO classification of lymphomas was used and most participating centers included immunohistochemistry using a wide array of lymphoid antibodies as part of routine diagnosis. Some of the series had been reviewed by an external panel of experts. B-cell lymphomas accounted for 82-88% of all NHLs. The proportions of chronic lymphatic leukemia (4-6%), mantle cell lymphoma (MCL, 3-5%), and plasmacytoma (2-4%) were similar in the series presented. However, there was a significant variation in the proportion of follicular lymphoma (FL), which accounted for 15% and 11% in India and Kuwait, but less than 5% in Pakistan and Egypt. All of these frequencies are significantly lower than those reported in Western series. Diffuse large B-cell lymphoma accounted for about 35% of cases in India but for more 50% in other countries, but this difference was not accounted for by an increased incidence in a single lymphoma subtype in India, but rather an apparent paucity of several subtypes (such as mantle cell and marginal zone lymphomas (MZL)) in other series. There were relatively high frequencies of Burkitt lymphoma in Egypt (7%) and precursor T-cell lymphoblastic lymphoma in India (6-7%). Peripheral T-cell lymphomas (PTCLs) (not otherwise specified and angioimmunoblastic subtypes) accounted for 3-5% of NHLs, and extranodal lymphoma of T/NK cell type was rare (<1%). These differences in the relative proportions of NHL subtypes among developing countries and between developing countries and the rest of the world presumably arise from differences in environmental and genetic factors that influence lymphomagenesis and strongly suggest that more research in developing countries would provide valuable insights into the pathogenesis of lymphoid neoplasms.

Adult↗
PubMed1998

Mate selection by groups.

The two key components in a breeding program can be described as the development of an objective function and the implementation of an algorithm for mate selection to target the objective function. However, mate selection is unacceptably slow for objective functions that involve longer term aims, such as engineering a good connection between herds. This paper proposes animal clustering to facilitate group mate selection, plus a step to refine mate selection for individual animals. Cluster analysis is used to form groups of animals within each sex based on nominated factors such as breed, herd, age, and EBV. Mate selection is then performed on groups, reducing the size of the problem considerably. The example used involved a three-breed crossbred population with a simple objective function to maximize predicted progeny merit. Twenty sires and 500 dams were to be selected from 816 and 1784 candidates. Group mate selection achieved 96.9% efficiency (random selection, 0%; full mate selection, 100%) and took 0.28 s to compute (394.2 s for full mate selection). Permitting more candidates to reach the individual mate selection stage increased efficiency to, for example, 98.9% at the cost of an extra 1.15 s. Efficiency was also improved by permitting more clusters.

Algorithms↗
PubMed1979

Can mutation theories of carcinogenesis set priorities for carcinogen testing programs?

The recent activity in designing, validating and implementing short-term tests for carcinogens has been spurred by the fairly convincing correlation between the carcinogenicity and mutagenicity of chemicals and by the assumption that mutations are somehow involved in neoplastic transformation. Moreover, it has been tacitly assumed that the mutagenic capacity alone of compounds would induce regulatory agencies to pass rules for their removal from man's environment, and would lead the public to avoid them. The actual response, however, is quite different. Government departments shy away from making any decisions on the basis of in vitro test systems, the public at large is becoming irritated by daily announcements that many of their cherished habits could adversely affect their health, and industries feel threatened and may reduce their search for new beneficial chemicals. The reluctance to accept wholeheartedly the mutagenicity tests for the detection of carcinogens is partly due to the uncertainty about the involvement of mutations in the formation of benign and malignant tumors. Following the initial rapid advances in the detection of environmental chemicals with carcinogenic and mutagenic properties, we seem to have arrived at the cross roads: we must now set new priorities for future research, and must make an unbiased assessment of the actual hazard of a compound to man and the human population.

Animals↗