Comparison of performance and fitness traits in German Angler, Swedish Red and Swedish Polled with Holstein dairy cattle breeds under organic production

Although the use of local breeds is recommended by organic regulations, breed comparisons performed under organic production conditions with similar production intensities are scarce. Therefore, we compared data of local and widely used Holstein dairy cattle breeds from 2011 to 2015 regarding production, fertility and health from German and Swedish organic farms with similar management intensities within country. In Germany, the energy-corrected total milk yield tended to be lower in the local breed Original Angler Cattle (AAZ, 5193 kg) compared to the modern German Holstein Friesian breed (HO, 5620 kg), but AAZ showed higher milk fat and protein contents (AAZ v. HO: 5.09% v. 4.18% and 3.61% v. 3.31%, respectively). In Sweden, the widely used modern Swedish Holstein (SH) breed had the highest milk yield (9209 kg, fat: 4.10%, protein: 3.31%), while the local Swedish Polled (SKB) showed highest milk yield, fat and protein contents (6169 kg, 4.47%, 3.50%, respectively), followed by the local breed Swedish Red (SRB, 8283 kg, 4.33%, 3.46%, respectively). With regard to fertility characteristics, the German breeds showed no differences, but AAZ tended to have less days open compared to HO (−17 days). In Sweden, breeds did not differ with regard to calving interval, but both local breeds showed a lower number of days open (−10.4 in SRB and −24.1 in SKB compared to SH), and SKB needed fewer inseminations until conception (−0.5 inseminations) compared to SH. Proportion of test day records with a somatic cell count content of ≥100 000 cells per ml milk did not reveal breed differences in any of the two countries. German breeds did not differ regarding the proportion of cows with veterinary treatments. In Sweden, SRB showed the lowest proportion of cows with general veterinary treatment as well as specific treatment due to udder problems (22.8 ± 6.42 and 8.05 ± 2.18, respectively), but the local breed SKB did not differ from SH in either of the two traits. In Sweden, we found no breed differences regarding veterinary treatments due to fertility problems or diagnosis of claw or leg problems during claw trimming. Our results indicate a stronger expression of the antagonism between production and functional traits with increasing production intensity. Future breed comparisons, therefore, need to consider different production intensities within organic farming in order to derive practical recommendations as to how to implement European organic regulations with regard to a suitable choice of breeds

Imprinted Zac1 in neural stem cells.

Neural stem cells (NSCs) and imprinted genes play an important role in brain development. On historical grounds, these two determinants have been largely studied independently of each other. Recent evidence suggests, however, that NSCs can reset select genomic imprints to prevent precocious depletion of the stem cell reservoir. Moreover, imprinted genes like the transcriptional regulator Zac1 can fine tune neuronal vs astroglial differentiation of NSCs. Zac1 binds in a sequence-specific manner to pro-neuronal and imprinted genes to confer transcriptional regulation and furthermore coregulates members of the p53-family in NSCs. At the genome scale, Zac1 is a central hub of an imprinted gene network comprising genes with an important role for NSC quiescence, proliferation and differentiation. Overall, transcriptional, epigenomic, and genomic mechanisms seem to coordinate the functional relationships of NSCs and imprinted genes from development to maturation, and possibly aging

Discovery of the VHE gamma-ray source HESS J1641-463

A new TeV source, HESS J1641-463, has been serendipitously discovered in the Galactic plane by the High Energy Stereoscopic System (H.E.S.S.) at a significance level of 8.6 standard deviations. The observations of HESS J1641-463 were performed between 2004 and 2011 and the source has a moderate flux level of 1.7% of the Crab Nebula flux at E > 1 TeV. HESS J1641-463 has a rather hard photon index of 1.99 +- 0.13_stat +- 0.20_sys. HESS J1641-463 is positionally coincident with the radio supernova remnant SNR G338.5+0.1, but no clear X-ray counterpart has been found in archival Chandra observations of the region. Different possible VHE production scenarios will be discussed in this contribution.Comment: 5 pages, 5 figures, 2012 Fermi Symposium proceedings - eConf C12102

Lycorine Carbamate Derivatives for Reversing P-Glycoprotein-Mediated Multidrug Resistance in Human Colon Adenocarcinoma Cells

Multidrug resistance (MDR) is a major challenge in cancer chemotherapy. Aiming at generating a small library of anticancer compounds for overcoming MDR, lycorine (1), a major Amaryllidaceae alkaloid isolated from Pancratium maritimum, was derivatized. Thirty-one new compounds (2–32) were obtained by chemical transformation of the hydroxyl groups of lycorine into mono- and di-carbamates. Compounds 1–32 were evaluated as MDR reversers, through the rhodamine-123 accumulation assay by flow cytometry and chemosensitivity assays, in resistant human colon adenocarcinoma cancer cells (Colo 320), overexpressing P-glycoprotein (P-gp, ABCB1). Significant inhibition of P-gp efflux activity was observed for the di-carbamate derivatives, mainly those containing aromatic substituents, at non-cytotoxic concentrations. Compound 5, bearing a benzyl substituent, and compounds 9 and 25, with phenethyl moieties, were among the most active, exhibiting strong inhibition at 2 µM, being more active than verapamil at 10-fold higher concentration. In drug combination assays, most compounds were able to synergize doxorubicin. Moreover, some derivatives showed a selective antiproliferative effect toward resistant cells, having a collateral sensitivity effect. In the ATPase assay, selected compounds (2, 5, 9, 19, 25, and 26) were shown to behave as inhibitors

Re-purposing Ac/Ds transgenic system for CRISPR/dCas9 modulation of enhancers and non-coding RNAs in zebrafish

Due to its genetic amenability coupled with recent advances in genome editing, the zebrafish serves as an excellent model to examine the function of both coding and non-coding elements. Recently, the non-coding genome has gained prominence due to its critical role in development and disease. Here, we have re-purposed the Ac/Ds maize transposition system to reliably screen and efficiently characterise zebrafish enhancers, with or without germline propagation. We further utilised the system to stably express guide RNAs in microinjected embryos enabling tissue-specific CRISPR/dCas9-interference (CRISPRi) knockdown of lncRNA and enhancer activity without disrupting the underlying genetic sequence. Our study highlights the utility of Ac/Ds transposition for transient epigenome modulation of non-coding elements in zebrafish

Exploring the Monoterpene Indole Alkaloid Scaffold for Reversing P-Glycoprotein-Mediated Multidrug Resistance in Cancer

Dregamine (1), a major monoterpene indole alkaloid isolated from Tabernaemontana elegans, was submitted to chemical transformation of the ketone function, yielding 19 azines (3-21) and 11 semicarbazones (22-32) bearing aliphatic or aromatic substituents. Their structures were assigned mainly by 1D and 2D NMR (COSY, HMQC, and HMBC) experiments. Compounds 3-32 were evaluated as multidrug resistance (MDR) reversers through functional and chemosensitivity assays in a human ABCB1-transfected mouse T-lymphoma cell model, overexpressing P-glycoprotein. A significant increase of P-gp inhibitory activity was observed for most derivatives, mainly those containing azine moieties with aromatic substituents. Compounds with trimethoxyphenyl (17) or naphthyl motifs (18, 19) were among the most active, exhibiting strong inhibition at 0.2 mu M. Moreover, most of the derivatives showed selective antiproliferative effects toward resistant cells, having a collateral sensitivity effect. In drug combination assays, all compounds showed to interact synergistically with doxorubicin. Selected compounds (12, 17, 18, 20, and 29) were evaluated in the ATPase activity assay, in which all compounds but 12 behaved as inhibitors. To gather further insights on drug-receptor interactions, in silico studies were also addressed. A QSAR model allowed us to deduce that compounds bearing bulky and lipophilic substituents were stronger P-gp inhibitors