Current status of asymmetric synthesis

In the last 30 years the subject of asymmetric synthesis has grown from a little studied academic niche in organic chemistry to an intensely investigated field of commercial importance and heightened general interest. Impressive advances have been made in several areas, notably catalytic asymmetric homogeneous hydrogenation, catalytic asymmetric epoxidation of allyl alcohols and stereochemical control of carbon-carbon bond-forming reactions. Asymmetric synthesis must now be deliberately considered along with other available methods as a practical strategy for the synthesis of any chiral compound.     

Liquid chromatographic determination and identification of morantel-related residues as precursors of 3-(3-methyl-2-thienyl) acrylic acid (CP-20,107) in bovine milk

A simple liquid chromatographic (LC) method was developed to determine and identify incurred morantel-related residues in bovine milk by converting them to 3-(3-methyl-2-thienyl) acrylic acid (CP-20, 107). Key techniques in this method involve short-term digestion of milk in HCl to release residues convertible to CP-20, 107, isolation and alkaline hydrolysis of these precursors to CP-20, 107, and recovery of the product for LC analysis. Photochemical conversion of CP-20, 107 to its cis-isomer and separation by LC identifies the residue. A homolog (pyrantel), which is used as an internal standard, is hydrolyzed to 3-(2-thienyl) acrylic acid. These acrylic acid isomers are readily resolved by LC. The method was evaluated over the 1-4 ppb (ng/mL) range for accuracy and precision to assess its utility for withdrawal studies. Bovine milk supplemented with morantel at 1, 2, and 4 ppb and assayed in replicate (n = 7-8) over 4 trials gave mean values and standard deviations of 1.0 +/- 0.11, 2.0 +/- 0.24, and 4.0 +/- 0.44 ppb, respectively. A milk specimen containing physiologically incurred residues of morantel assayed 2.1 +/- 0.19 ppb in replicate (n = 5).     

Duplication, deletion, and polymorphism in the sex-determining region of the mouse Y chromosome

The ZFY gene in the sex-determining region of the human Y chromosome encodes a "zinc-finger" protein that may be the testis-determining factor, TDF. Although the Y chromosomes of most placental mammals carry a single homolog of ZFY, the mouse Y chromosome has two homologs, both in the sex-determining (Sxr) region. Zfy-1 alone may suffice to determine maleness; Zfy-2 is dispensable, as it was deleted in an Sxr variant that retains sex-determining function but has lost other genes. Both loci mapped near the centromere of the mouse Y chromosome. The Y chromosomes of the subspecies Mus musculus musculus and M. m. domesticus were distinguishable by a Zfy-1 restriction fragment polymorphism, which can be used to study their differing interactions with autosomal sex-determining genes.     

A single IGF1 allele is a major determinant of small size in dogs

The domestic dog exhibits greater diversity in body size than any other terrestrial vertebrate. We used a strategy that exploits the breed structure of dogs to investigate the genetic basis of size. First, through a genome-wide scan, we identified a major quantitative trait locus (QTL) on chromosome 15 influencing size variation within a single breed. Second, we examined genetic variation in the 15-megabase interval surrounding the QTL in small and giant breeds and found marked evidence for a selective sweep spanning a single gene (IGF1), encoding insulin-like growth factor 1. A single IGF1 single-nucleotide polymorphism haplotype is common to all small breeds and nearly absent from giant breeds, suggesting that the same causal sequence variant is a major contributor to body size in all small dogs.     

Fitness cost, cross resistance and realized heritability of resistance to imidacloprid in Spodoptera litura (Lepidoptera: Noctuidae)

Imidacloprid has been used as a key insecticide for controlling sucking insect pests of cotton, whereas Spodoptera litura also has been indirectly exposed to this insecticide in Pakistan. To evaluate the risk of resistance evolution and to develop a better resistance management strategy, a field collected population was selected with imidacloprid in the laboratory. Thereafter, fitness cost, realized heritability and cross resistance of imidacloprid resistance in S. litura were investigated. After 14 generations of selection with imidacloprid, S. litura developed a 137.48-fold resistance to the insecticide. Bioassay revealed that this strain showed cross-resistance to acetamiprid (RR 8.52) and a little to lamdacyhalothrin (1.92) but negative cross-resistance was found to methomyl (−0.19). The resistant strain had a relative fitness of 0.38, with substantially lower rates of larval survival, larval duration, male pupal duration, development time, emergence rate of healthy adults, fecundity, hatchability, and prolonged larval and pupal duration. Mean relative growth rate of the larvae, intrinsic rate of population increase, and biotic potential was lower for the selected populations. The estimated realized heritability (h²) of imidacloprid resistance was 0.15 in the resistant strain of S. litura. Development of the resistance may cost significant fitness for the resistant population. This study provided valuable information for further understanding the impact of imidacloprid resistance on physiological parameters of S. litura and for facilitating the development of resistance management strategies.     

Pharmacokinetics of oral meloxicam in ruminant and preruminant calves

The pharmacokinetics of oral meloxicam has been studied in ruminant, but not preruminant calves. Oral meloxicam was administered at 0.5 mg/kg to six ruminant calves via gavage (RG); to six preruminant calves via gavage (PRG); and to six preruminant calves via suckling in milk replacer (PRF). Plasma drug concentrations, determined over 120-h postadministration, were analyzed by compartmental and noncompartmental methods. The rate of drug absorption was faster (P<0.01) in PRF (0.237±0.0478/h) than RG calves (0.0815±0.0188/h), while absorption in PRG calves (0.153±0.128/h) was not different from other groups. C(max) was lower (P=0.03) in PRF (1.27±0.430 μg/mL) than in PRG calves (2.20±0.467 μg/mL), while C(max) of RG calves (1.95±0.955 μg/mL) was not different from other groups. V/F was higher in PRF calves (365±57 mL/kg) than either PRG (177±63 mL/kg, P<0.01) or RG (232±83 mL/kg, P=0.01) calves. These observations were likely due to differences in bioavailability, physiological maturity, and timing of the drug delivery into different compartments of the ruminant gastrointestinal tract. Results suggest that an adjustment in meloxicam dose may be necessary when administered with milk replacer.     

Source of fiber influences growth,immune responses,gut barrier function and microbiota in weaned piglets fed antibiotic-free diets

This study examined the impacts of different fiber sources on growth, immune status and gut health in weaned piglets fed antibiotic-free diets. Sixty piglets (BW = 8.18 ± 1.35 kg) were assigned to 3 dietary treatments based on BW and gender in a randomized complete block design (5 replicates/treatment and 4 piglets [2 barrows and 2 gilts]/replicate): (1) an antibiotic-free diet (control, CON); (2) CON + 6% wheat bran (WB); (3) CON + 4% sugar beet pulp (SBP). Dietary WB supplementation tended to increase ADG compared with CON from d 1 to 14 (P = 0.051) and from d 1 to 28 (P = 0.099). Supplementation of WB increased (P < 0.05) G:F compared with CON and SBP from d 1 to 14 and from d 1 to 28. Compared with CON, the addition of WB reduced (P < 0.05) diarrhea rate from d 1 to 14 and tended (P = 0.054) to reduce diarrhea rate from d 1 to 28. The addition of WB decreased (P < 0.05) serum diamine oxidase activity on d 14, and up-regulated (P < 0.05) ileal mRNA levels of occludin on d 28 when compared with CON. Piglets fed WB showed decreased (P < 0.05) serum interleukin-6 levels compared to those fed SBP and decreased (P < 0.05) ileal interleukin-8 levels compared to those fed CON and SBP on d 28. Supplementation of WB increased (P < 0.05) serum levels of immunoglobulin A (IgA), IgG and IgM compared with SBP on d 14, and increased (P < 0.05) the levels of serum IgA and ileal sIgA compared with CON and SBP on d 28. Piglets fed WB showed an enhanced (P < 0.05) α-diversity of cecal microbiota than those fed SBP, while piglets fed SBP showed reduced (P < 0.05) α-diversity of cecal microbiota than those fed CON. Compared with CON, the addition of WB elevated (P < 0.05) the abundance of Lachnospira and cecal butyric acid level. Piglets fed WB also showed increased (P < 0.05) abundances of Lachnospira and unclassified_f_Lachnospiraceae compared with those fed SBP. Collectively, the supplementation of WB to antibiotic-free diets improved performance, immune responses, gut barrier function and microbiota compared with the CON and SBP fed piglets. Therefore, supplementing weaned piglets with WB was more effective than SBP.