Ancient cattle genomics, origins, and rapid turnover in the Fertile Crescent.

Genome-wide analysis of 67 ancient Near Eastern cattle, Bos taurus, remains reveals regional variation that has since been obscured by admixture in modern populations. Comparisons of genomes of early domestic cattle to their aurochs progenitors identify diverse origins with separate introgressions of wild stock. A later region-wide Bronze Age shift indicates rapid and widespread introgression of zebu, Bos indicus, from the Indus Valley. This process was likely stimulated at the onset of the current geological age, ~4.2 thousand years ago, by a widespread multicentury drought. In contrast to genome-wide admixture, mitochondrial DNA stasis supports that this introgression was male-driven, suggesting that selection of arid-adapted zebu bulls enhanced herd survival. This human-mediated migration of zebu-derived genetics has continued through millennia, altering tropical herding on each continent.

Adjuvant chemotherapy-Radiotherapy-Chemotherapy sandwich protocol in resectable soft tissue sarcoma: An updated single-center analysis of 104 cases.

Adjuvant therapy of local soft tissue sarcomas (STS) after wide surgical excision still is a topic under controversial scientific debate. In this single center report we have offered an adjuvant "sandwich" therapy protocol consisting of 4 cycles of doxorubicin (75 mg/m2 i.v. over 1 h on day 1) followed by ifosfamide (5 g/m2 i.v. over 24 h starting on day 1) and local radiotherapy scheduled between chemotherapy cycles 2 and 3 to 104 consecutive patients after wide surgical excision (R0) of histologically proven high-grade STS. After a mean follow-up of 39 months (range 5-194 months) relapse free survival (RFS) at 2 and 5 years was 68.1% (95% CI, 58.5-77.7%) and 61.2% (95% CI, 50.4-71.6%). When analyzing the 82 STS cases of the extremities only 2- and 5-year RFS was 74.0% (95% CI, 64.0-84.0%) and 65.3% (95% CI, 53.7-76.9%). By intent-to-treat analysis, the overall survival (OS) at 2 years was 87.3% (95% CI, 80.5-94.1%) and 75.6% (95% CI, 65.2-86.0%) at 5 years, while OS for STS of the extremities only cohort was 90.5% (95% CI, 83.7-97.3%) and 79.0% (95% CI, 68.4-89.6%), respectively. Tolerability of the treatment was good. This analysis demonstrates the feasibility of adjuvant chemoradiotherapy and reflects the results of the long lasting intensive multidisciplinary team approach at our "high-volume" sarcoma center. The long-term survival in our patients is among the highest reported and the low local and distant recurrence rate in high-risk STS is at least comparable to the published data.

Polyhydroxyalkanoate production from whey by Pseudomonas hydrogenovora.

Whey permeate from dairy industry was hydrolyzed enzymatically to cleave its main carbon source, lactose, to glucose and galactose. The hydrolysis products were chosen as carbon sources for the production of poly-3-hydroxybutyric acid (PHB) by Pseudomonas hydrogenovora. In shaking flask experiments, the utilization of whey permeate as a cheap substrate was compared to the utilization of pure glucose and galactose for bacterial growth under balanced conditions as well as for the production of PHB under nitrogen limitation. After determination of the inhibition constant Ki for sodium valerate on biomass production (Ki=1.84 g/l), the biosynthesis of PHA co-polyesters containing 3-hydroxybutyrate (3HB) and 3-hydroxyvalerate (3HV) units from hydrolyzed whey permeate and valerate was investigated. The application of hydrolyzed whey permeate turned out to be advantageous compared with the utilization of pure sugars. Therefore, fermentation under controlled conditions in a bioreactor was performed with hydrolyzed whey permeate to obtain detailed kinetic data (maximum specific growth rate, mu max=0.291/h, maximum polymer concentration, 1.27 g/l PHB), values for molecular mass distribution (weight average molecular weight Mw=353.5 kDa, polydispersity index PDI=3.8) and thermo analytical data. The fermentation was repeated with co-feeding of valerate (maximum specific growth rate, mu(max)=0.201/h, maximum polymer concentration, 1.44 g/l poly-(3HB-co-21%-3HV), weight average molecular weight M(w)=299.2 kDa, polydispersity index PDI=4.3).

Potential of various archae- and eubacterial strains as industrial polyhydroxyalkanoate producers from whey.

Three different microbial wild-type strains are compared with respect to their potential as industrial scale polyhydroxyalkanoate (PHA) producers from the feed stock whey lactose. The halophilic archaeon Haloferax mediterranei as well as two eubacterial strains (Pseudomonas hydrogenovora and Hydrogenophaga pseudoflava) are investigated. H. mediterranei accumulated 50 wt.-% of poly-3-(hydroxybutyrate-co-8%-hydroxyvalerate) from hydrolyzed whey without addition of 3-hydroxyvalerate (3HV) precursors (specific productivity q(p): 9.1 mg x g(-1) x h(-1)). Using P. hydrogenovora, the final percentage of poly-3-hydroxybutyrate (PHB) amounted to 12 wt.-% (q(p): 2.9 mg x g(-1) x h(-1)). With H. pseudoflava, it was possible to reach 40 wt.-% P-3(HB-co-5%-HV) on non-hydrolyzed whey lactose plus addition of valeric acid as 3HV precursor (q(p): 12.5 mg x g(-1) x h(-1)). A detailed characterization of the isolated biopolyesters and an evaluation with regard to the economic feasibility completes the study.

Assessment of formal and low structured kinetic modeling of polyhydroxyalkanoate synthesis from complex substrates.

A formal kinetic mathematical model for poly-(3-hydroxybutyrate-co-3-hydroxyvalerate-co-4-hydroxybutyrate) [P(3HB-co-3HV-co-4HB)] terpolyester synthesis from glucose and galactose derived from whey permeate supplemented with gamma-butyrolactone by the archaeon Haloferax mediterranei was created. Further, a low structured mathematical model for poly-3-hydroxybutyrate synthesis from whey permeate by Pseudomonas hydrogenovora was developed. In both cases, biosyntheses for obtaining the experimental data used for compiling the models were performed via fed-batch cultivations. The model developed for H. mediterranei consists of 10 differential and 11 algebraic equations, including 27 kinetic constants. The model compiled for P. hydrogenovora encompasses 10 differential and 3 algebraic equations, including 36 kinetic constants. Both models were solved by Runge-Kuta variable step numerical integration with Monte Carlo parameter optimization procedure. Difficulties arising from the modeling of redirection of metabolic fluxes from biomass growth toward polyhydroxyalkanoate synthesis and byproducts are discussed.