Selective enzymatic hydrolysis of aromatic diesters using esterase from Brevibacterium imperiale B222

Summary A practical procedure has been developed for the chemoselective microbial hydrolysis of aromatic dicarboxylic esters to give the corresponding monoesters, using cellular lysate and whole cell of Brevibacterium imperiale B222. The produced monoesters can be transformed into hydroxyacids, useful intermediates in the synthesis of polyesters.     

A Bayesian scoring rule on clustered event data for familial risk assessment – An example from colorectal cancer screening

Colorectal cancer screening is well established. The identification of high risk populations is the key to implement effective risk‐adjusted screening. Good statistical approaches for risk prediction do not exist. The family's colorectal cancer history is used for identification of high risk families and usually assessed by a questionnaire. This paper introduces a prediction algorithm to designate a family for colorectal cancer risk and discusses its statistical properties. The new algorithm uses Bayesian reasoning and a detailed family history illustrated by a pedigree and a Lexis diagram. The algorithm is able to integrate different hereditary mechanisms that define complex latent class or random factor structures. They are generic and do not reflect specific genetic models. This is comparable to strategies in complex segregation analysis. Furthermore, the algorithm can integrate different statistical penetrance models for right censored event data. Computational challenges related to the handling of the likelihood are discussed. Simulation studies assess the predictive quality of the new algorithm in terms of ROC curves and corresponding AUCs. The algorithm is applied to data of a recent study on familial colorectal cancer risk. Its predictive performance is compared to that of a questionnaire currently used in screening for familial colorectal cancer. The results of the proposed algorithm are robust against different inheritance models. Using the simplest hereditary mechanism, the simulation study provides evidence that the algorithm improves detection of families with high cancer risk in comparison to the currently used questionnaire. The applicability of the algorithm goes beyond the field of colorectal cancer.     

Sex differences in aging,life span and spontaneous tumorigenesis in 129/Sv mice neonatally exposed to metformin

The perinatal (prenatal and early neonatal) period is a critical stage for hypothalamic programming of sexual differentiation as well as for the development of energy and metabolic homeostasis. We hypothesized that neonatal treatment with antidiabetic drug biguanide metformin would positively modify regulation of growth hormone – IGF-1 – insulin signaling pathway slowing down aging and improving cancer preventive patterns in rodents. To test this hypothesis male and female 129/Sv mice were s.c. injected with metformin (100 mg/kg) at the 3rd, 5th and 7th days after birth. Metformin-treated males consumed less food and water and their body weight was decreased as compared with control mice practically over their entire lifespan. There were no significant differences in age-related dynamics of food and water consumption in females and they were heavier than controls. The fraction of mice with regular estrous cycles decreased with age and demonstrated a tendency to decrease in the females neonatally treated with metformin. Neonatal exposure to metformin practically failed to change the extent of hormonal and metabolic parameters in blood serum of male and female mice. In males, neonatal metformin treatment significantly increased the mean life span (+20%, P < 0.05) and slightly increased the maximum life span (+3.5%). In females, the mean life span and median in metformin-treated groups were slightly decreased (−9.1% and −13.8% respectively, P > 0.05) in comparison to controls, whereas mean life span of last 10% survivors and maximum life span were the same as in controls. Almost half (45%) of control male mice and 71.8% male mice neonatally exposed to metformin survived up to 800 d of age, the same age was achieved by 54.3% of mice in control female group and 30% of metformin-treated females (P < 0.03). Thus, neonatal metformin exposure slows down aging and prolongs lifespan in male but not in female mice.     

New Vectors for Chromosomal Integration Enable High-Level Constitutive or Inducible Magnetosome Expression of Fusion Proteins in Magnetospirillum gryphiswaldense

The alphaproteobacterium Magnetospirillum gryphiswaldense biomineralizes magnetosomes, which consist of monocrystalline magnetite cores enveloped by a phospholipid bilayer containing specific proteins. Magnetosomes represent magnetic nanoparticles with unprecedented magnetic and physicochemical characteristics. These make them potentially useful in a number of biotechnological and biomedical applications. Further functionalization can be achieved by expression of foreign proteins via genetic fusion to magnetosome anchor peptides. However, the available genetic tool set for strong and controlled protein expression in magnetotactic bacteria is very limited. Here, we describe versatile vectors for either inducible or high-level constitutive expression of proteins in M. gryphiswaldense. The combination of an engineered native P_mamDC promoter with a codon-optimized egfp gene (Mag-egfp) resulted in an 8-fold increase in constitutive expression and in brighter fluorescence. We further demonstrate that the widely used P_tet promoter is functional and tunable in M. gryphiswaldense. Stable and uniform expression of the EGFP and β-glucuronidase (GusA) reporters was achieved by single-copy chromosomal insertion via Tn5-mediated transposition. In addition, gene duplication by Mag-EGFP–EGFP fusions to MamC resulted in further increased magnetosome expression and fluorescence. Between 80 and 210 (for single MamC–Mag-EGFP) and 200 and 520 (for MamC–Mag-EGFP–EGFP) GFP copies were estimated to be expressed per individual magnetosome particle.     

Sievoides kocyigiti n. gen., n. sp., Mesoendothyra altineriana n. sp. and Kurnubia feleensis n. sp. from Kimmeridgian shallow water limestones intercalated with alkaline igneous rocks, Western Taurus, Turkey

In the framework of the palaeogeographical reconstruction of the Western Taurus during Jurassic, the study of northern and eastern boundary of the Taurids started. Detailed facies analysis evidenced the position of the Barla Dag ramp between two elevated areas: the southern rimmed shelf extension of the platform system and the northern neritic-beach-land plain. In the basal biostratigraphical and ecological characteristics of the Balcikhisar volcano-sedimentary sequence, correlated with the Fele outcrop, one genus and three new species of foraminifers have been found: Sievoides kocyigiti n. gen., n. sp. and Mesoendothyra altineriana n. sp. from neritic environment, and Kurnubia feleensis n. sp. from rimmed shelf lagoon. Both carbonate sedimentary deposits are intercalated with spilitic-basalt pillow lava flows. The age of the new three species is Kimmeridgian, controlled by some foraminifer golden hooks.