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A novel multitarget model of radiation-induced cell killing based on the Gaussian distribution.

J Theor Biol. 2017 Mar 08;:

Authors: Zhao L, Mi D, Sun Y

Abstract
The multitarget version of the traditional target theory based on the Poisson distribution is still used to describe the dose-survival curves of cells after ionizing radiation in radiobiology and radiotherapy. However, noting that the usual ionizing radiation damage is the result of two sequential stochastic processes, the probability distribution of the damage number per cell should follow a compound Poisson distribution, like e.g. Neyman's distribution of type A (N. A.). In consideration of that the Gaussian distribution can be considered as the approximation of the N. A. in the case of high flux, a multitarget model based on the Gaussian distribution is proposed to describe the cell inactivation effects in low linear energy transfer (LET) radiation with high dose-rate. Theoretical analysis and experimental data fitting indicate that the present theory is superior to the traditional multitarget model and similar to the Linear - Quadratic (LQ) model in describing the biological effects of low-LET radiation with high dose-rate, and the parameter ratio in the present model can be used as an alternative indicator to reflect the radiation damage and radiosensitivity of the cells.

PMID: 28284991 [PubMed - as supplied by publisher]

Higher order assembly: folding the chromosome.

Curr Opin Struct Biol. 2017 Mar 08;42:162-168

Authors: Sewitz SA, Fahmi Z, Lipkow K

Abstract
The linear molecules of DNA that constitute a eukaryotic genome have to be carefully organised within the nucleus to be able to correctly direct gene expression. Microscopy and chromosome capture methods have revealed a hierarchical organisation into territories, domains and subdomains that ensure the accessibility of expressed genes and eventually chromatin loops that serve to bring gene enhancers into proximity of their target promoters. A rapidly growing number of genome-wide datasets and their analyses have given detailed information into the conformation of the entire genome, allowing evolutionary insights, observations of genome rearrangements during development and the identification of new gene-to-disease associations. The field is now progressing into using computational models of genome dynamics to investigate the mechanisms that shape genome structure, placing increasing importance on the role of chromatin associated proteins for this process.

PMID: 28284913 [PubMed - as supplied by publisher]

Evidence, Mechanism, and Clinical Relevance of the Transdifferentiation from Lung Adenocarcinoma to Squamous Cell Carcinoma.

Am J Pathol. 2017 Mar 08;:

Authors: Hou S, Zhou S, Qin Z, Yang L, Han X, Yao S, Ji H

Abstract
Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are two distinct subtypes of non-small-cell lung carcinoma. Interestingly, approximately 4% to 9% of human non-small-cell lung carcinoma tumors contain mixed adenomatous and squamous pathologies in a single lesion, clinically termed adenosquamous cell carcinoma. More important, these two different pathological components frequently share identical oncogenic mutations, indicative of a potential transition. Indeed, recent data have provided convincing evidence in supporting the ADC to SCC transdifferentiation in lungs. In the liver kinase B1 (official name STK11)-deficient mouse model, lung ADC can progressively transdifferentiate to SCC through pathologically mixed adenosquamous cell carcinoma as the intermediate status. Mechanistic studies further identify essential roles of extracellular matrix remodeling and metabolic reprogramming during this phenotypic transition. Small molecular compounds, including lysyl oxidase inhibitors and reactive oxygen species-inducing reagents such as phenformin, significantly accelerate the transition from lung ADC to SCC and thus confer lung tumors with drug resistance. Consistent with these findings, recent clinical studies have shown that epidermal growth factor receptor-mutant lung ADC can transdifferentiate to SCC in relapsed cancer patients. Together, these data support that this phenotypic transition from lung ADC to SCC might represent a novel mechanism for drug resistance. This review will summarize our current understanding of the transdifferentiation from lung ADC to SCC.

PMID: 28284717 [PubMed - as supplied by publisher]

Pollen of common ragweed (Ambrosia artemisiifolia L.): Illumina-based de novo sequencing and differential transcript expression upon elevated NO2/O3.

Environ Pollut. 2017 Mar 08;:

Authors: Zhao F, Durner J, Winkler JB, Traidl-Hoffmann C, Strom TM, Ernst D, Frank U

Abstract
Common ragweed (Ambrosia artemisiifolia L.) is a highly allergenic annual ruderal plant and native to Northern America, but now also spreading across Europe. Air pollution and climate change will not only affect plant growth, pollen production and duration of the whole pollen season, but also the amount of allergenic encoding transcripts and proteins of the pollen. The objective of this study was to get a better understanding of transcriptional changes in ragweed pollen upon NO2 and O3 fumigation. This will also contribute to a systems biology approach to understand the reaction of the allergenic pollen to air pollution and climate change. Ragweed plants were grown in climate chambers under controlled conditions and fumigated with enhanced levels of NO2 and O3. Illumina sequencing and de novo assembly revealed significant differentially expressed transcripts, belonging to different gene ontology (GO) terms that were grouped into biological process and molecular function. Transcript levels of the known Amb a ragweed encoding allergens were clearly up-regulated under elevated NO2, whereas the amount of allergen encoding transcripts was more variable under elevated O3 conditions. Moreover transcripts encoding allergen known from other plants could be identified. The transcriptional changes in ragweed pollen upon elevated NO2 fumigation indicates that air pollution will alter the transcriptome of the pollen. The changed levels of allergenic encoding transcripts may have an influence on the total allergenic potential of ragweed pollen.

PMID: 28284545 [PubMed - as supplied by publisher]

Proteome-Scale Human Interactomics.

Trends Biochem Sci. 2017 Mar 08;:

Authors: Luck K, Sheynkman GM, Zhang I, Vidal M

Abstract
Cellular functions are mediated by complex interactome networks of physical, biochemical, and functional interactions between DNA sequences, RNA molecules, proteins, lipids, and small metabolites. A thorough understanding of cellular organization requires accurate and relatively complete models of interactome networks at proteome scale. The recent publication of four human protein-protein interaction (PPI) maps represents a technological breakthrough and an unprecedented resource for the scientific community, heralding a new era of proteome-scale human interactomics. Our knowledge gained from these and complementary studies provides fresh insights into the opportunities and challenges when analyzing systematically generated interactome data, defines a clear roadmap towards the generation of a first reference interactome, and reveals new perspectives on the organization of cellular life.

PMID: 28284537 [PubMed - as supplied by publisher]

The Application of Proteomics to Traumatic Brain and Spinal Cord Injuries.

Curr Neurol Neurosci Rep. 2017 Mar;17(3):23

Authors: Sarkis GA, Mangaonkar MD, Moghieb A, Lelling B, Guertin M, Yadikar H, Yang Z, Kobeissy F, Wang KK

Abstract
Traumatic brain injury (TBI) and traumatic spinal cord injury (SCI), collectively termed neurotrauma, are two parallel neurological conditions that can cause long-lasting neurological impairment and other comorbidities in patients, while at the same time, can create a high burden to society. To date, there are still no FDA-approved therapeutic interventions for either TBI or SCI. Recent advances in proteomic technologies, including tandem mass spectrometry, as well as imaging mass spectrometry, have enabled new approaches to study the differential proteome in TBI and SCI with the use of either animal disease models and/or biosamples from clinical observational studies. Thus, the applications of state-of-the-art proteomic method hold promises in shedding light on identifying clinically useful neurotrauma "biomarkers" and/or in identifying distinct and, otherwise, unobvious systems pathways or "key drivers" that can be further exploited as new therapeutic intervention targets.

PMID: 28283963 [PubMed - in process]

Estimating the Efficiency of Phosphopeptide Identification by Tandem Mass Spectrometry.

J Am Soc Mass Spectrom. 2017 Mar 10;:

Authors: Hsu CC, Xue L, Arrington JV, Wang P, Paez Paez JS, Zhou Y, Zhu JK, Tao WA

Abstract
Mass spectrometry has played a significant role in the identification of unknown phosphoproteins and sites of phosphorylation in biological samples. Analyses of protein phosphorylation, particularly large scale phosphoproteomic experiments, have recently been enhanced by efficient enrichment, fast and accurate instrumentation, and better software, but challenges remain because of the low stoichiometry of phosphorylation and poor phosphopeptide ionization efficiency and fragmentation due to neutral loss. Phosphoproteomics has become an important dimension in systems biology studies, and it is essential to have efficient analytical tools to cover a broad range of signaling events. To evaluate current mass spectrometric performance, we present here a novel method to estimate the efficiency of phosphopeptide identification by tandem mass spectrometry. Phosphopeptides were directly isolated from whole plant cell extracts, dephosphorylated, and then incubated with one of three purified kinases-casein kinase II, mitogen-activated protein kinase 6, and SNF-related protein kinase 2.6-along with (16)O4- and (18)O4-ATP separately for in vitro kinase reactions. Phosphopeptides were enriched and analyzed by LC-MS. The phosphopeptide identification rate was estimated by comparing phosphopeptides identified by tandem mass spectrometry with phosphopeptide pairs generated by stable isotope labeled kinase reactions. Overall, we found that current high speed and high accuracy mass spectrometers can only identify 20%-40% of total phosphopeptides primarily due to relatively poor fragmentation, additional modifications, and low abundance, highlighting the urgent need for continuous efforts to improve phosphopeptide identification efficiency. Graphical Abstract ᅟ.

PMID: 28283928 [PubMed - as supplied by publisher]