Effects of phenotype, sex, and diet on plasma lipids in LA/N-cp rats

The LA/N-corpulent (cp) rat is a recently developed congenic strain which exhibits obesity. The effects of phenotype and sex on serum and lipoprotein lipid content were examined in LA/N-cp rats fed either a control or an atherogenic diet high in saturated fat and protein. Obese rats were pair-fed to equivalent lean animals. Results from this study indicate that sex, phenotype, and diet exert significant effects on plasma and lipoprotein cholesterol content. Plasma cholesterol levels were higher in obese compared with lean rats, females than in males, and rats consuming the atherogenic diet compared with the control diet. Plasma and lipoprotein triglyceride levels were significantly increased only in obese compared with lean animals. The increased plasma cholesterol and triglyceride was observed primarily in the chylomicron and very low density lipoprotein fractions. Increased levels of plasma cholesterol were not a result of increased dietary cholesterol absorption or increased liver cholesterol biosynthesis. These data suggest that LA/N-cp rats can serve as a unique rodent model for the study of the interrelationships between hyperlipidemia, obesity, and coronary heart disease.     

Estrogen-inducible and liver-specific expression of the chicken Very Low Density Apolipoprotein II gene locus in transgenic mice.

We have examined the chicken Very Low Density Apolipoprotein II (apoVLDL II) gene locus in transgenic mice. A DNA fragment composed of the transcribed region, 16 kb of 5' flanking and 400 bp of 3' flanking sequences contained all the information sufficient for estrogen-inducible, liver-specific expression of the apoVLDL II gene. The far-upstream region contains a Negative Regulating Element coinciding with a DNaseI-hypersensitive site at -11 kb. In transgenic mice, the NRE at -11 kb is used for downregulating the expression to a lower maximum level. The NRE might be used for modulating apoVLDL II gene expression, and may be involved in the rapid shut-down of the expression after hormone removal.     

HPTN 071 (PopART): A Cluster-Randomized Trial of the Population Impact of an HIV Combination Prevention Intervention Including Universal Testing and Treatment: Mathematical Model

Background

The HPTN 052 trial confirmed that antiretroviral therapy (ART) can nearly eliminate HIV transmission from successfully treated HIV-infected individuals within couples. Here, we present the mathematical modeling used to inform the design and monitoring of a new trial aiming to test whether widespread provision of ART is feasible and can substantially reduce population-level HIV incidence.

Methods and Findings

The HPTN 071 (PopART) trial is a three-arm cluster-randomized trial of 21 large population clusters in Zambia and South Africa, starting in 2013. A combination prevention package including home-based voluntary testing and counseling, and ART for HIV positive individuals, will be delivered in arms A and B, with ART offered universally in arm A and according to national guidelines in arm B. Arm C will be the control arm. The primary endpoint is the cumulative three-year HIV incidence.We developed a mathematical model of heterosexual HIV transmission, informed by recent data on HIV-1 natural history. We focused on realistically modeling the intervention package. Parameters were calibrated to data previously collected in these communities and national surveillance data.We predict that, if targets are reached, HIV incidence over three years will drop by >60% in arm A and >25% in arm B, relative to arm C. The considerable uncertainty in the predicted reduction in incidence justifies the need for a trial. The main drivers of this uncertainty are possible community-level behavioral changes associated with the intervention, uptake of testing and treatment, as well as ART retention and adherence.

Conclusions

The HPTN 071 (PopART) trial intervention could reduce HIV population-level incidence by >60% over three years. This intervention could serve as a paradigm for national or supra-national implementation. Our analysis highlights the role mathematical modeling can play in trial development and monitoring, and more widely in evaluating the impact of treatment as prevention.     

Temporal variation in condition index and meat quality of Lunella undulata (Turbinidae), in relation to the reproductive cycle

ABSTRACT

Lunella undulata is a subtropical-temperate marine gastropod which is harvested commercially from temperate reefs in Australia. This paper aimed to evaluate monthly variation in the condition index (CI) and biochemical composition of the foot tissue of L. undulata in relation to the spawning cycle. The gonadosomatic index (GSI) varied significantly between males and females and across months (P?=?0.0001), ranging from 43% to 70% in males and 41% to 71% for females. The highest GSI, as well as the highest CI for both sexes was recorded in December and April, whilst meat yield peaked in January, September and October. Protein, lipid, fatty acid and heavy metals in the foot tissue also significantly varied between months (P?<?0.05). Throughout all 14 months of sampling, the foot tissue of L. undulata showed good nutritional quality, with high levels of protein and the polyunsaturated fatty acids, docosapentaenoic acid, eicosapentaenoic acid and arachidonic acid. Overall, despite some temporal variability in the biochemical composition, L. undulata could be harvested at any time of the year for human consumption, although it may be best to avoid peak spawning times, which occur around January in northern NSW.     

A relationship between seed development, Arabinogalactan-proteins (AGPs) and the AGP mediated promotion of somatic embryogenesis

Arabinogalactan-protein (AGP) epitopes are known to display developmentally regulated patterns of expression in several plant tissues. Therefore, AGPs have been suggested to play a role in plant development. Somatic embryogenesis is regulated by AGPs as well as by EP3 endochitinases. Using four different methods we have analysed the composition of AGPs in immature carrot seeds. The results obtained show that: (1) the native electrophoretic mobility of such AGPs changes during development; (2) AGP epitopes in immature seeds are developmentally regulated; (3) enzymatically released fragments of AGPs show that the composition of these molecules changes as a function of development; and (4) the biological activity of AGPs on the formation of somatic embryos changes depending on the age of the seeds. Our results suggest that degradation of maternally derived AGPs occurs after fertilization, while cellularization of the endosperm leads to synthesis of a new set of AGPs. The presence of an endochitinase cleavage site as well as the capacity to increase somatic embryogenesis only occurred in AGPs that were isolated from seeds in which the endosperm had been cellularized. Apparently, both EP3 endochitinases and somatic embryogenesis-promoting AGPs are developmentally regulated in immature carrot seeds.     

Self-aggregation of free base porphyrins in aqueous solution and in DMPC vesicles

Free base porphyrin (PPhe), derivatized with aminosulfonyl groups linked to the aromatic amino acid phenylalanine at the meso-positions, was mixed with DMPC vesicles. The resulting interaction was studied by absorption, steady-state and transient state fluorescence, at different pHs. At pH=2 to pH=9, the aforementioned porphyrin predominates as an aggregated species, with a co-facial arrangement of the molecules taking into account the blue shift of the Soret band (414 nm for the monomer and 401 nm for the aggregate). Upon interaction with DMPC vesicles, the competing hydrophobic interactions with the bilayer destabilize the aggregated species in favor of monomer incorporation. Fluorescence lifetimes also show that the long component assigned to the monomer contributes only 30% to the overall decay in solution (e.g. pH=7.0) whereas in DMPC vesicles this contribution increases up to 85% independent of the solution pH, which confirms a location of the probe in an environment "protected" from free water. The picture changes completely in the case of TSPP, an anionic porphyrin which does not incorporate in DMPC vesicles. Remarkably, at pH=2.5 all the experimental findings point to the self-assembling of the porphyrin units in J-aggregates induced at the surface of the DMPC vesicle. In fact, upon removal of the aqueous solvent, we could define by fluorescence lifetime imaging microscopy (FLIM) regions where the fluorescence lifetime is that characteristic of the J-aggregate ( 0.11 ns).     

Isolation of a chromosomally engineered durum wheat line carrying the Aegilops ventricosa pchl gene for resistance to eyespot.

The chromosome 7Dv of Aegilops ventricosa (syn. Triticum ventricosum, 2n = 4x = 28, genome DvDvMvMv) carries the gene Pch1 for resistance to eyespot. This gene has previously been transferred to chromosome 7D of bread wheat, T. aestivum (2n = 6x = 42, genome AABBDD). To (1) enhance the level of resistance of bread wheat by increasing the copy number of Pch1, and (2) create eyespot-resistant triticales, meiotically stable Pch1-carrying durum lines were selected from the backcross progenies of a cross between Ae. ventricosa and T. durum cv. Creso ph1c (2n = 4x = 28, genome AABB). The Pch1 transfer, likely resulting from homoeologous recombination, was located at the distal position on the long arm of chromosome 7A. The 7A microsatellite marker Xgwm 698 was found closely linked in repulsion to the introgression in the resistant recombination lines, and the endopeptidase allele located on chromosome 7A of cv. Creso ph1c was lost.     

The pea late nodulin gene PsNOD6 is homologous to the early nodulin genes PsENOD3/14 and is expressed after the leghaemoglobin genes

The pea late nodulin gene PsNOD6 has been cloned and sequenced. PsNOD6 is homologous to the pea early nodulin genes PsNOD3 and PsENOD14. In situ hybridization experiments showed that, like the PsENOD3 and PsENOD14 genes, the PsNOD6 gene is only expressed in the infected cell type. The PsNOD6 gene is first expressed at the transition of the pre-fixation zone II into the interzone II–III (the amyloplast-rich zone preceding the fixation zone III), whereas the early nodulin genes PsENOD3 and PsENOD14 are already induced in the pre-fixation zone II. Thus these nodulin genes encoding homologous proteins are induced at consecutive stages of nodule development.The expression of the late nodulin genes encoding leghaemoglobin precedes the expression of the late nodulin gene PsNOD6. Therefore these late nodulin genes have to be regulated by different mechanisms despite the fact they are expressed in the same cell type. This conclusion is consistent with the fact that PsNOD6 lacks one of the conserved regions occurring in the promoters of all other late nodulin genes studied.     

Conversion from mitosis to meiosis: morphology and expression of proliferating cell nuclear antigen (PCNA) and Dmc1 during newt spermatogenesis

The conversion from mitosis to meiosis is a phenomenon specific to the cellular progenitors of gametes; however, the mechanism or mechanisms responsible for this conversion are poorly understood. To this end, some morphological and molecular changes that occur during the initiation of meiosis in newt spermatogenesis are reported in the present paper. In situ morphologic studies revealed that spermatogonial stages comprise two phases: early mitotic generations (G1-G4) and late mitotic generations (G5-G8). Morphologic conversion from secondary spermatogonia to primary spermatocytes occurred during the intermediate stage of premeiotic DNA replication. The expression of proliferating cell nuclear antigen (PCNA), a DNA polymerase-delta auxiliary protein, in spermatogonia was weak in G1, highest during DNA synthesis (S), decreased in G2 and was not detectable in dividing cells. Complementary DNA for newt homologs of DMC1 (disrupted meiotic cDNA), which is an Escherichia coli RecA-like protein specifically active during meiosis, were isolated. The newt Dmc1 mRNA was first expressed significantly during the preleptotene stage and this continued into the spermatid stage. These observations present a basis for investigating the mechanism(s) controlling the conversion of newt spermatogonial cells from mitosis to meiosis.