Tracking down protein-protein interaction via FRET-system using site-specific thiol-labeling

A novel Cys-specific bioorthogonalized linker was synthesized and applied in combination with bioorthogonally applicable fluorescent markers to track down protein–protein (p38-MK2) interactions by FRET.</p

Correlation of homologous recombination deficiency induced mutational signatures with sensitivity to PARP inhibitors and cytotoxic agents

Homologous recombination (HR) repair deficiency arising from defects in BRCA1 or BRCA2 is associated with characteristic patterns of somatic mutations. In this genetic study, we ask whether inactivating mutations in further genes of the HR pathway or the DNA damage checkpoint also give rise to somatic mutation patterns that can be used for treatment prediction.Using whole genome sequencing of an isogenic knockout cell line panel, we find a universal HR deficiency-specific base substitution signature that is similar to COSMIC signature 3. In contrast, we detect different deletion phenotypes corresponding to specific HR mutants. The inactivation of BRCA2 or PALB2 leads to larger deletions, typically with microhomology, when compared to the disruption of BRCA1, RAD51 paralogs, or RAD54. Comparison with the deletion spectrum of Cas9 cut sites suggests that most spontaneously arising genomic deletions are not the consequence of double-strand breaks. Surprisingly, the inactivation of checkpoint kinases ATM and CHK2 has no mutagenic consequences. Analysis of tumor exomes with biallelic inactivating mutations in the investigated genes confirms the validity of the cell line models. We present a comprehensive analysis of sensitivity of the investigated mutants to 13 therapeutic agents for the purpose of correlating genomic mutagenic phenotypes with drug sensitivity.Our results suggest that no single genomic mutational class shows perfect correlation with sensitivity to common treatments, but the contribution of COSMIC signature 3 to base substitutions, or a combined measure of different features, may be reasonably good at predicting platinum and PARP inhibitor sensitivity

Short communication: Upper critical temperature-humidity index for dairy calves based on physiological stress variables

In this study, upper critical values of the temperature-humidity index (THI) were determined in Holstein bull calves (n = 16) based on noninvasive physiological parameters. Meteorological and animal-based data were recorded for a 4-d period following a 24-h habituation. The estimated upper critical THI values based on the assessment of respiratory rate, rectal temperature, ear temperature, heart rate, and salivary cortisol concentrations were 82.4, 88.1, 83.0, 78.3, and 88.8, respectively. We inferred that welfare of young calves may be compromised above a THI of 78 and that calves experience significant heat stress above a THI of 88. Based on the present findings, upper critical THI should be considered to minimize the duration of impaired welfare during summer heat stress episodes. Key words: upper critical temperature-humidity index, heat stress, dairy calve

Induced acute erythema and late pigmentation may not be correlated: In regards to Perera et al. (Int J Radiat Oncol Biol Phys 2005;62:1283-1290)

peer reviewed[No abstract available

High hydrostatic pressure: Can we trust published data?

Abstract. There are numerous new technologies whose implementation in food industry is hampered by the fact that people hesitate to invest in expensive systems which they cannot be sure will work or at least are questionable in terms of a given product. Until recently, preservation by HHP, high hydrostatic pressure, was such a technology, and still is today in some branches of the food industry. Investigations were conducted to answer the question of whether the literature, the laboratory, and the industrial (or at least pilot plant) measurements and results agree with one another. We compared the literature data with two HHP systems which were significantly different in terms of treatment capacity, but their efficiency in killing microbes was studied under the same treatment parameters. Our results show that in nearly all cases only minimal differences exist between the data in the literature and the measurements taken on the two appliances