Molecular Variation in \u3ci\u3eAVP\u3c/i\u3e and \u3ci\u3eAVPR1a\u3c/i\u3e in New World Monkeys (Primates, Platyrrhini): Evolution and Implications for Social Monogamy

The neurohypophysial hormone arginine vasopressin (AVP) plays important roles in fluid regulation and vascular resistance. Differences in AVP receptor expression, particularly mediated through variation in the noncoding promoter region of the primary receptor for AVP (AVPR1a), may play a role in social phenotypes, particularly social monogamy, in rodents and humans. Among primates, social monogamy is rare, but is common among New World monkeys (NWM). AVP is a nonapeptide and generally conserved among eutherian mammals, although a recent paper demonstrated that some NWM species possess a novel form of the related neuropeptide hormone, oxytocin. We therefore characterized variation in the AVP and AVPR1a genes in 22 species representing every genus in the three major platyrrhine families (Cebidae, Atelidae and Pitheciidae). For AVP, a total of 16 synonymous substitutions were detected in 15 NWM species. No non-synonymous substitutions were noted, hence, AVP is conserved in NWM. By contrast, relative to the human AVPR1a, 66 predicted amino acids (AA) substitutions were identified in NWM. The AVPR1a N-terminus (ligand binding domain), third intracellular (Gprotein binding domain), and C-terminus were variable among species. Complex evolution of AVPR1a is also apparent in NWM. A molecular phylogenetic tree inferred from AVPR1a coding sequences revealed some consensus taxonomic separation by families, but also a mixed group composed of genera from all three families. The overall dN/dS ratio of AVPR1a was 0.11, but signals of positive selection in distinct AVPR1a regions were observed, including the N-terminus, in which we identified six potential positive selection sites. AA substitutions at positions 241, 319, 399 and 409 occurred uniquely in marmosets and tamarins. Our results enhance the appreciation of genetic diversity in the mammalian AVP/AVPR1a system, and set the stage for molecular modeling of the neurohypophyseal hormones and social behavior in primates

a structure-activity correlation

The polymerization of octamethylcyclotetrasiloxane (D4) is investigated using several five-, six- and seven-membered N-heterocyclic carbenes (NHCs). The catalysts are delivered in situ from thermally susceptible CO2 adducts. It is demonstrated that the polymerization can be triggered from a latent state by mild heating, using the highly nucleophilic 1,3,4,5-tetramethylimidazol-2-ylidene as organocatalyst. This way, high molecular weight PDMS is prepared (up to >400 000 g/mol, 1.6 < ÐM < 2.5) in yields >95%, using low catalyst loadings (0.2–0.1 mol %). Furthermore, the results suggest that a nucleophilic, zwitterionic mechanism is in operation, in preference to purely anionic polymerization

Ontogenetic alterations in molecular and structural correlates of dendritic growth after developmental exposure to polychlorinated biphenyls.

ObjectivePerinatal exposure to polychlorinated biphenyls (PCBs) is associated with decreased IQ scores, impaired learning and memory, psychomotor difficulties, and attentional deficits in children. It is postulated that these neuropsychological deficits reflect altered patterns of neuronal connectivity. To test this hypothesis, we examined the effects of developmental PCB exposure on dendritic growth.MethodsRat dams were gavaged from gestational day 6 through postnatal day (PND) 21 with vehicle (corn oil) or the commercial PCB mixture Aroclor 1254 (6 mg/kg/day). Dendritic growth and molecular markers were examined in pups during development.ResultsGolgi analyses of CA1 hippocampal pyramidal neurons and cerebellar Purkinje cells indicated that developmental exposure to PCBs caused a pronounced age-related increase in dendritic growth. Thus, even though dendritic lengths were significantly attenuated in PCB-treated animals at PND22, the rate of growth was accelerated at later ages such that by PND60, dendritic growth was comparable to or even exceeded that observed in vehicle controls. Quantitative reverse transcriptase polymerase chain reaction analyses demonstrated that from PND4 through PND21, PCBs generally increased expression of both spinophilin and RC3/neurogranin mRNA in the hippocampus, cerebellum, and cortex with the most significant increases observed in the cortex.ConclusionsThis study demonstrates that developmental PCB exposure alters the ontogenetic profile of dendritogenesis in critical brain regions, supporting the hypothesis that disruption of neuronal connectivity contributes to neuropsychological deficits seen in exposed children

Genome-wide identification of QTL for age at puberty in gilts using a large intercross F2 population between White Duroc and Erhualian

Puberty is a fundamental development process experienced by all reproductively competent adults, yet the specific factors regulating age at puberty remain elusive in pigs. In this study, we performed a genome scan to identify quantitative trait loci (QTL) affecting age at puberty in gilts using a White Duroc × Erhualian intercross. A total of 183 microsatellites covering 19 porcine chromosomes were genotyped in 454 F2 gilts and their parents and grandparents in the White Duroc × Erhualian intercross. A linear regression method was used to map QTL for age at puberty via QTLexpress. One 1% genome-wise significant QTL and one 0.1% genome-wise significant QTL were detected at 114 cM (centimorgan) on SSC1 and at 54 cM on SSC7, respectively. Moreover, two suggestive QTL were found on SSC8 and SSC17, respectively. This study confirmed the QTL for age at puberty previously identified on SSC1, 7 and 8, and reports for the first time a QTL for age at puberty in gilts on SSC17. Interestingly, the Chinese Erhualian alleles were not systematically favourable for younger age at puberty

Mapping quantitative trait loci for feed consumption and feeding behaviors in a White Duroc × Chinese Erhualian resource population

To identify QTL for feed consumption and feeding behavior traits in pigs, ADFI, feed conversion ratio (FCR), number of visits to the feeder per day (NVD), and average feeding rate (AFR) were recorded in 577 F2 animals from a White Duroc × Chinese Erhualian resource population during the fattening period of 120 to 240 d. A whole genome scan was performed with 183 microsatellites covering the pig genome across the entire resource population. A total of 8 QTL were identified on 5 pig chromosomes, including 3 genome-wide significant QTL for FCR on SSC2, 7, and 9, 1 significant QTL for ADFI on SSC3, and 1 for NVD on SSC7. These QTL were identified for the first time, except for the QTL for FCR on SSC2. Four of the 5 significant QTL were adjacent to the known QTL for growth, carcass, and fat deposition traits, supporting the existence of gene(s) with pleiotropic effects on these traits. White Duroc alleles were generally associated with greater phenotypic values, except for those on SSC7 and 9. Comparison of QTL for feed consumption and feeding behaviors indicated that distinct chromosomes had effects on the 2 types of traits. Characterization of causative gene(s) underlying the identified QTL would shed new light on the genetic basis of feed consumption and feeding behaviors in pigs

Gene changes may minimize masculinizing and defeminizing influences of exposure to male cotwins in female callitrichine primates

Background: Sexual differentiation in female mammals can be altered by the proximity of male littermates in utero, a phenomenon known as the intrauterine position effect (IUP). Among simian primates, callitrichines (marmosets and tamarins) are likely candidates for IUP, since they exhibit obligate dizygotic twinning and fetuses share extensive vascularization in utero. In this paper, we determined whether female reproductive parameters are altered by gestating with a male twin and evaluated changes in genes associated with anti-Müllerian and steroid hormones in twinning callitrichine primates. Methods: We assessed the impact of gestation with male cotwins on reproductive performance and survivorship in female marmosets (Callithrix) and lion tamarins (Leontopithecus), contrasting measures for females gestated with one or more littermates (M+) or no male littermates (0M). We compared targeted coding regions for genes involved in steroidal and anti-Müllerian hormone mediation of sexual differentiation for representatives of twinning callitrichines (Callithrix, Saguinus, and Leontopithecus) with closely related New World primates that produce single births (Saimiri and Callimico). Results: IUP effects in females were absent in female callitrichine primates: age at first ovulation, average litter size, and the proportion of stillborn infants, and lifetime survivorship did not differ between M+ and 0M females. We documented multiple nonsynonymous substitutions in genes associated with steroid synthesis, transport, and cellular action (SRD5A2, CYP19A1, SHBG, and AR) and with anti-Müllerian hormone (AMH and AMHR2) in callitrichines. In the only callitrichine to produce single infants (Callimico), two genes contained nonsynonymous substitutions relative to twinning callitrichines (CYP19A1 and AMRHR2); these substitutions were identical with nontwinning Saimiri and humans, suggesting a reversion to an ancestral sequence.Conclusions: In spite of a shared placental vasculature with opposite-sex twins throughout embryonic and fetal development, female callitrichine primates gestated with a male cotwin exhibit no decrement in reproductive performance relative to females gestated with female cotwins. Hence, IUP effects on female reproduction in callitrichines are modest. We have identified mutations in candidate genes relevant for steroid hormone signaling and metabolism, and especially in AMH-related genes, that are likely to alter protein structure and function in the callitrichines. These mutations may confer protection for females from the masculinizing and defeminizing influences of gestating with a male cotwin

Microsatellite-based Genetic Diversity and Evolutionary Relationships of Six Dog Breeds

The Tibetan Mastiff is one of the most archaic, ferocious and the largest dogs in the world. The Kunming dog is the chief working-dog breed in China. In this study, ten microsatellite loci were used to assess the genetic diversity and evolutionary relationships in six dog breeds, including Tibetan Mastiff, Kunming dog, Belgian Malinois, Labrador Retriever, English Springer Spaniel, and German Shepherd. The highest genetic diversity was exhibited by the Tibetan Mastiff, indicating useful protection and little inbreeding in the modern Tibetan Mastiff. Higher genetic diversity was observed in European breeds, supporting the hypotheses that breeders outcross their pure breed dogs occasionally to avoid deleterious effects in Europe. Evolutionary relationships showed that English Springer Spaniel and Labrador Retriever were clustered together, then with the Tibetan Mastiff, consistent with previous cluster results. German Shepherd and Kunming dog were grouped together, coinciding with the breeding history of Kunming dog. It is the first time that Tibetan Mastiff and Kunming dog have been analyzed with microsatellites

A genome scan for quantitative trait loci affecting male reproductive traits in a White Duroc × Chinese Erhualian resource population

Chinese Erhualian boars have dramatically smaller testes, greater concentrations of circulating androgens, and fewer Sertoli cells than Western commercial breeds. To identify QTL for boar reproductive traits, testicular weight, epididymal weight, seminiferous tubular diameter at 90 and 300 d, and serum testosterone concentration at 300 d were measured in 347 F2 boars from a White Duroc × Chinese Erhualian cross. A whole genome scan was performed with 183 microsatellites covering 19 porcine chromosomes. A total of 16 QTL were identified on 9 chromosomes, including 1% genome-wide significant QTL for testicular weight at 90 and 300 d and seminiferous tubular diameter at 90 d on SSCX, and for epididymal weight and testosterone concentration at 300 d on SSC7. Two 5% genome-wide significant QTL were detected for testicular weight at 300 d on SSC1 and seminiferous tubular diameter at 300 d on SSC16. Nine suggestive QTL were found on SSC1, 2, 3, 5, 7, 13, and 14. Chinese Erhualian alleles were not systematically favorable for greater reproductive performance. This study confirmed the previous significant QTL for testicular weight on SSCX and for epididymal weight on SSC7, and reported QTL for seminiferous tubular diameter and testosterone concentration at the first time. The observed different QTL for the same trait at different ages reflect the involvement of distinct genes in the development of male reproductive traits

Single Nucleotide Polymorphisms of Caudal Type Homeobox 1 and 2 Are Associated with Barrett’s Esophagus

Barrett’s esophagus (BE), the premalignant lesion of esophageal adenocarcinoma, is believed to develop as a result of chronic gastroesophageal reflux disease (GERD). Approximately 10% of subjects with GERD progress to BE. Genetic, epigenetic and other risk factors may contribute to this inter-individual variability. Caudal type homeobox 1 (Cdx1) and Caudal type homeobox 2 (Cdx2) play important regulatory roles in the development of human BE