Effects of dam breed and dietary source of n-3 polyunsaturated fatty acids on the growth and carcass characteristics of lambs sourced from hill sheep flocks

The objectives of this study were to investigate the effect of dietary lipid source on the growth and carcass characteristics of lambs sourced from a range of crossbred hill ewes. Over a 2-year period, 466 lambs representing the progeny of Scottish Blackface (BF × BF), Swaledale (SW) × BF, North Country Cheviot (CH) × BF, Lleyn (LL) × BF and Texel (T) × BF ewes were sourced from six commercial hill flocks and finished on one of four diets: grass pellets (GP), cereal-based concentrate (CC), CC enriched with oilseed rape (CR) and CC enriched with fish oil (CF). Dry matter intake (DMI) was highest (P < 0.001) in lambs offered GP; however, carcass weight gain (CWG) and feed conversion efficiency were higher (P < 0.001) in lambs fed concentrate-based diets. For lambs offered concentrate-based diets, DMI and live weight gain were lower (P < 0.001) for CF than CC or CR. Lambs with T × BF dams achieved a higher (P < 0.05) daily CWG and CWG/kg DMI than BF × BF, SW × BF or LL × BF dams. When lambs were slaughtered at fat score 3, CH × BF, LL × BF and T × BF dams increased carcass weight by 0.8 to 1.4 kg (P < 0.001) and conformation score (CS) by 0.2 to 0.4 units (P < 0.001) compared with BF × BF or SW × BF dams. However, breed effects on carcass conformation were reduced by 50% when lambs were slaughtered at a constant carcass weight. Diets CC and CR increased carcass weight by 0.8 to 1.6 kg (P < 0.001) and CS by 0.1 to 0.3 units (P < 0.001) compared with GP and CF. Both, dam breed and dietary effects on carcass conformation were associated with an increase (P < 0.001) in shoulder width of the lambs. Lambs fed CF and slaughtered at a constant carcass weight had more subcutaneous fat over the Longissumus dorsi (P < 0.05), Iliocostalis thoracis (P < 0.001) and Obliquus internus abdominis (P < 0.001) compared with those fed CC. However, these effects were removed when lambs were slaughtered at a constant fat score. At both endpoints, lambs from T × BF dams contained less (P < 0.05) perinephric and retroperitoneal fat than SW × BF or LL × BF dams fed GP or CC, respectively. The results from this study show that using crossbred ewes sired by CH, LL or T sires will increase carcass weight and improve carcass conformation of lambs sourced from hill flocks. Inclusion of oilseed rape in lamb finishing diets had only minor effects on performance compared with a standard CC but feeding fish oil or GP impacted negatively on lamb growth and carcass quality.     

Functional conservation and specialization among eukaryotic anti-silencing function 1 histone chaperones

Chromatin disassembly and reassembly, mediated by histone chaperones such as anti-silencing function 1 (Asf1), are likely to accompany all nuclear processes that occur on the DNA template. In order to gain insight into the functional conservation of Asf1 across eukaryotes, we have replaced the budding yeast Asf1 protein with Drosophila Asf1 (dAsf1) or either of the two human Asf1 (hAsf1a and hAsf1b) counterparts. We found that hAsf1b is best able to rescue the growth defect of Saccharomyces cerevisiae lacking Asf1. Moreover, dAsf1 and hAsf1b but not hAsf1a can replace the role of yeast Asf1 in protecting against replicational stress and activating the PHO5 gene, while only hAsf1a can replace the role of Asf1 in protecting against double-stranded-DNA-damaging agents. Furthermore, it appears that the interaction between Asf1 and the DNA damage checkpoint protein Rad53 is not required for Asf1's role in maintaining genomic integrity. In addition to indicating the functional conservation of the Asf1 proteins across species, these studies suggest distinct roles for the two human Asf1 proteins.     

Discovery of human inversion polymorphisms by comparative analysis of human and chimpanzee DNA sequence assemblies

With a draft genome-sequence assembly for the chimpanzee available, it is now possible to perform genome-wide analyses to identify, at a submicroscopic level, structural rearrangements that have occurred between chimpanzees and humans. The goal of this study was to investigate chromosomal regions that are inverted between the chimpanzee and human genomes. Using the net alignments for the builds of the human and chimpanzee genome assemblies, we identified a total of 1,576 putative regions of inverted orientation, covering more than 154 mega-bases of DNA. The DNA segments are distributed throughout the genome and range from 23 base pairs to 62 mega-bases in length. For the 66 inversions more than 25 kilobases (kb) in length, 75% were flanked on one or both sides by (often unrelated) segmental duplications. Using PCR and fluorescence in situ hybridization we experimentally validated 23 of 27 (85%) semi-randomly chosen regions; the largest novel inversion confirmed was 4.3 mega-bases at human Chromosome 7p14. Gorilla was used as an out-group to assign ancestral status to the variants. All experimentally validated inversion regions were then assayed against a panel of human samples and three of the 23 (13%) regions were found to be polymorphic in the human genome. These polymorphic inversions include 730 kb (at 7p22), 13 kb (at 7q11), and 1 kb (at 16q24) fragments with a 5%, 30%, and 48% minor allele frequency, respectively. Our results suggest that inversions are an important source of variation in primate genome evolution. The finding of at least three novel inversion polymorphisms in humans indicates this type of structural variation may be a more common feature of our genome than previously realized.     

Toll-like receptor-7 agonist administered subcutaneously in a prolonged dosing schedule in heavily pretreated recurrent breast, ovarian, and cervix cancers

Background

The primary objective was to study the antitumor activity of prolonged subcutaneous dosing of systemic 852A, a Toll-like receptor-7 agonist (TLR-7), in recurrent breast, ovarian and cervix cancer. Secondary objectives included assessment of safety and immune system activation.

Methods

Adults with recurrent breast, ovarian or cervix cancer failing multiple therapies received 0.6 mg/m² of 852A subcutaneously twice weekly for 12 weeks. Doses increased by 0.2 mg/m²/week to a maximum of 1.2 mg/m². Serum was collected to assess immune activation.

Results

Fifteen patients enrolled: 10 ovarian, 2 cervix and 3 breast. Three completed all 24 injections. There were two grade 2 (decreased ejection fractions), nine grade 3 (1 cardiovascular, 1 anorexia, 3 dehydration, 2 infections, 2 renal) and two grade 4 (hepatic and troponin elevation) unanticipated toxicities. Cardiac toxicities included three cardiomyopathies (2 asymptomatic) and one stress-related non-ST elevated myocardial infarction. Five patients discontinued therapy due to possibly associated side effects. One who had stable disease (SD) following 24 doses received 17 additional doses. A cervix patient with SD following 24 doses received chemotherapy after progressing 3 months later, and remains disease free at 18 months. Immune activation, as evidenced by increased IP-10 and IL-1ra, was observed.

Conclusions

In this first human experience of a TLR-7 agonist delivered subcutaneously using a prolonged dosing schedule, 852A demonstrated sustained tolerability in some patients. Clinical benefit was modest, but immune activation was seen suggesting further study of antitumor applications is warranted. Because of cardiac toxicity; 852A should be used cautiously in heavily pretreated patients.     

Normal calves produced after transfer of in vitro fertilized embryos cultured with an antiviral compound

Bovine viral diarrhea virus (BVDV) replicates in embryo co-culture systems and remains associated with developing IVF bovine embryos, despite washing and trypsin treatment. Previous research demonstrated that 2-(4-[2-imidazolinyl]phenyl)-5-(4-methoxyphenyl)furan (DB606) inhibits replication of BVDV in cultured cells. The objective of this study was to evaluate the capability of IVF embryos to develop into normal, weaned calves after exposure to antiviral concentrations of DB606 during IVC. Oocytes were obtained from cows via transvaginal, ultrasound-guided follicular aspiration. Presumptive zygotes (n = 849) that resulted from fertilization of these oocytes were cultured for 7 d in medium supplemented with 0.4 microM DB606 or medium lacking antiviral agent. All blastocysts (n = 110) were transferred individually into the uterus of a synchronized recipient. The pregnancy status of recipients was determined using transrectal ultrasonography at 21-23 d after embryo transfer. Additional pregnancies as controls (n = 21) were initiated by natural breeding. Developing fetuses and resulting calves were evaluated every 27-34 d. Blastocyst development, pregnancies per transferred embryo, pregnancies maintained per pregnancies established, gestation length, gender ratio, birth weights, viability of neonates, complete blood counts, and serum chemistry profiles at 3 mo of age and adjusted 205 d weaning weights were compared for research treatments. Development to weaning after exposure to DB606 did not differ significantly from controls. In conclusion, bovine embryo cultures can be safely supplemented with antiviral concentrations of DB606; addition of DB606 agent might prevent viral transmission if BVDV were inadvertently introduced into the embryo culture system.     

Morphological and genetic variation indicate cryptic species within Lamarck's little sea star, Parvulastra (=Patiriella) exigua

The asterinid sea star Parvulastra exigua (Lamarck) is a common member of temperate intertidal marine communities from geographically widespread sites around the southern hemisphere. Individuals from Australian populations lay benthic egg masses (through orally directed gonopores) from which nonplanktonic offspring hatch and metamorphose without a dispersing planktonic larval phase. Scattered reports in the taxonomic literature refer to a similar form in southern Africa with aborally directed gonopores (and possibly broadcast spawning of planktonic eggs and larvae); such differences would be consistent with cryptic species variation. Surveys of morphology and mtDNA sequences have revealed cryptic species diversity in other asterinid genera. Here we summarize the taxonomic history of Lamarck's "Astérie exigu?" and survey morphological variation (the location of the gonopores) for evidence that some P. exigua populations include cryptic species with a different mode of reproduction. We found strong evidence for multiple species in the form of two phenotypes and modes of reproduction (oral and aboral gonopore locations) in populations from southern Africa and islands in the Atlantic and Indian oceans. Both modes of reproduction have broad geographic ranges. These results are consistent with previously published genetic data that indicate multiple species in African and island (but not Australian) populations.