21 research outputs found
Enantioselective total synthesis of polyoxygenated cyclohexanoids: (+)-streptol, ent-RKTS-33 and putative '(+)-parasitenone'. identity of parasitenone with (+)-epoxydon
Short, simple and enantioselective syntheses of the natural product (+)-streptol, the non-peptide apoptosis inhibitor ent-RKTS-33 and the putative structure of 'parasitenone' have been accomplished from the readily available chiral building block. 'Parasitenone' has been shown to be identical with the known natural product epoxydon
Synthesis and antimicrobial activity of some new 1-cyclohexyl-3-carbethoxy-2-methyl-5- oxadiazolyl/triazolyl and pyrrolylaminocarbonylmethoxyindoles
2896-2900The exclusive formation of 1-cyclohexyl-3-carbethoxy-2-methylindol-5-yloxyacctic
acid hydrazide 3 when 1-cyclohexyl-3-carbethoxy-5-methoxycarbonylmethoxy-2-methylindole
2 is reacted with hydrazine hydrate, reveals the chemoselectivity of C5-ester
over C3-carbethoxy ester function towards the nucleophilic attack of
hydrazine hydrate. This monocarbohydrazide was treated separately with triethylorthoformate,
acetonylacetone in
boiling absolute ethanol, CS2/KOH
and further on acidification with HCl, CS2/KOH followed by treatment
with hydrazine hydrate, KCNS/HCl and treatment with 10% NaOH, to furnish 1-cyclohexyl-3-carbethoxy
-2-methyl-5-(1,3,4-oxadiazol-2-yl) methoxyindole
4, 1-cyclohexyl-3-carbethoxy-2-methyl-5-(2,5-dimethylpyrrol-1-yl)
aminocarbonylmethoxyi ndole 5, 1-cyclohexyl-3-carbethoxy-2-methyl-5-(5-mercapto-1
,3,4-oxadiazol-2-yl) methoxyindole 6 and 1-cyclohexyl-3-carbethoxy-2-methyl
-5-(4-amino-5-mercaptotriazol-3-yl)methoxyindole 7 and 1-cyclohexyl-3-carbethoxy-2-methyl-5-(4H-5-mercapto-1,2,4-triazol-3-yl)methoxyindole
8, respectively. The newly synthesized compounds have been evaluated for
their antimicrobial activity and their structures have been confirmed on the
basis of analytical and spectral data
Canine embryonic gonad pairs collected for PRO-seq.
<p>Canine embryonic gonad pairs collected for PRO-seq.</p
Embryonic lethality in association with the homozygous insertion at CFA9:6048201 was identified in breeding experiments.
<p>At left are crosses between V4, a fertile GSHP XX DSD and GSHP males (PM6578, V31). At right are crosses between V4 and males from the XX DSD model pedigree (C752, C734), which vary in proportion of American cocker spaniel and beagle genetic background (ACS/BGL). Genotypes at the insertion locus (CFA9:6048201) are homozygous (<i>G+G+</i>), heterozygous (<i>G+/-</i>), or wild type (<i>-/-</i>). Females are indicated by open circles, XX DSD by filled circles, and XY males by squares. Each symbol represents one dog, except those containing a number, which indicates the number of dogs represented by that symbol. None of the offspring had the <i>G+G+</i> genotype. Based on simple Mendelian inheritance, the expected number of <i>-/-</i>, <i>G+/-</i> and <i>G+G+</i> offspring from the <i>G+/-</i> sires and dams is 4.25, 8.5, and 4.25, respectively (N = 17). This is significantly different from the numbers observed (<i>x</i><sup>2</sup> = 8.1776, df = 2, Chi-squared test is significant at p<0.025 since 8.1776>7.38). Similarly, the expected number of <i>G+/-</i> and <i>G+G+</i> offspring from a <i>G+/-</i> dam and <i>G+G+</i> sire (V4 x C734) is 11 and 11, respectively (N = 22). This is a highly significant difference from the numbers observed (<i>x</i><sup>2</sup> = 20.04, calculations include continuity correction for df = 1 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0186331#pone.0186331.ref045" target="_blank">45</a>]; Chi-squared test is significant at p<0.005 since 20.04>7.88). Since all offspring of C734 (<i>G+G+</i>) must have received the <i>G+</i> allele from him, only those receiving the wild type allele from the GSHP V4 dam (<i>G+/-</i>) were born. Together, these results indicated that the <i>G+G+</i> genotype, combined with ≥50% GSHP background, is associated with embryonic lethality.</p
GWAS Manhattan plot for logistic mixed model analysis showing association of XX DSD to CFA9 in the canine model pedigree.
<p>The probability of association [-Log<sub>10</sub> (<i>P</i>)] is shown for single nucleotide polymorphisms (SNPs) on chromosomes 1–40. (Quantile-Quantile plot of the p-values is in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0186331#pone.0186331.s003" target="_blank">S3 Fig</a>).</p
Characteristics of dogs included in GWAS (N = 27).
<p>Characteristics of dogs included in GWAS (N = 27).</p
Purebred pet dog groups genotyped with the custom array of selected WGS variants to identify those that are common to affected dogs of several breeds.
<p>Purebred pet dog groups genotyped with the custom array of selected WGS variants to identify those that are common to affected dogs of several breeds.</p
<i>SOX9</i> expression in canine embryonic gonads was measured by RNA-seq.
<p>(A) At d37-39, <i>SOX9</i> expression was significantly greater in XX DSD gonads at risk (filled triangles) compared to XX age-matched control gonads (open triangles), but <2 fold and primarily due to one sample (C3512). Each open circle represents RNA from one embryonic gonad pair, except for d34, which represents RNA from a gonad pool. Differential expression was statistically tested for XX DSD gonads compared to XX age-matched controls at d37-39 and d42-44 (** p-value ≤ 0.00005). (B) At all ages tested, <i>SOX9</i> expression in XY littermate (filled inverted triangles) and XY age-matched control gonads (open inverted triangles) was much greater than in XX DSD gonads at risk (filled triangles) and XX age-matched controls (open triangles). Each open circle represents RNA from one embryonic gonad pair, except for d34, which represents RNA from a gonad pool. FPKM is Fragments Per Kilobase of transcript per Million mapped reads.</p
<i>RSPO1</i> and <i>WNT4</i> expression in canine embryonic gonads was measured by RNA-seq.
<p>(A) <i>RSP01</i> and (B) <i>WNT4</i> expression were lower in XX DSD gonads at risk (filled triangles) compared to those of XX age-matched controls (open triangles) at d37-39 and d42-44. Neither <i>RSP01</i> nor <i>WNT4</i> expression in XX DSD gonads at risk or those of XX age-matched controls was as low as those of XY littermate controls (filled inverted triangles) or XY age-matched controls (open inverted triangles). Each open circle represents RNA from one embryonic gonad pair, except for d34, which represents RNA from a gonad pool. Differential expression was statistically tested for XX DSD gonads compared to XX controls at d37-39 and d42-44 (* p-value<0.005; ** p-value ≤ 0.00005). FPKM is Fragments Per Kilobase of transcript per Million mapped reads.</p