Breakup of 17^{17}F on 208^{208}Pb near the Coulomb barrier

Angular distributions of oxygen produced in the breakup of $^{17}$F incident on a $^{208}$Pb target have been measured around the grazing angle at beam energies of 98 and 120 MeV. The data are dominated by the proton stripping mechanism and are well reproduced by dynamical calculations. The measured breakup cross section is approximately a factor of 3 less than that of fusion at 98 MeV. The influence of breakup on fusion is discussed.Comment: 7 pages, 8 figure

Rosa26-GFP Direct Repeat (RaDR-GFP) Mice Reveal Tissue- and Age-Dependence of Homologous Recombination in Mammals In Vivo

Homologous recombination (HR) is critical for the repair of double strand breaks and broken replication forks. Although HR is mostly error free, inherent or environmental conditions that either suppress or induce HR cause genomic instability. Despite its importance in carcinogenesis, due to limitations in our ability to detect HR in vivo, little is known about HR in mammalian tissues. Here, we describe a mouse model in which a direct repeat HR substrate is targeted to the ubiquitously expressed Rosa26 locus. In the Rosa26 Direct Repeat-GFP (RaDR-GFP) mice, HR between two truncated EGFP expression cassettes can yield a fluorescent signal. In-house image analysis software provides a rapid method for quantifying recombination events within intact tissues, and the frequency of recombinant cells can be evaluated by flow cytometry. A comparison among 11 tissues shows that the frequency of recombinant cells varies by more than two orders of magnitude among tissues, wherein HR in the brain is the lowest. Additionally, de novo recombination events accumulate with age in the colon, showing that this mouse model can be used to study the impact of chronic exposures on genomic stability. Exposure to N-methyl-N-nitrosourea, an alkylating agent similar to the cancer chemotherapeutic temozolomide, shows that the colon, liver and pancreas are susceptible to DNA damage-induced HR. Finally, histological analysis of the underlying cell types reveals that pancreatic acinar cells and liver hepatocytes undergo HR and also that HR can be specifically detected in colonic somatic stem cells. Taken together, the RaDR-GFP mouse model provides new understanding of how tissue and age impact susceptibility to HR, and enables future studies of genetic, environmental and physiological factors that modulate HR in mammals.National Institutes of Health (U.S.) (Program Project Grant P01-CA026731)National Institutes of Health (U.S.) (R33-CA112151)National Institute of Environmental Health Sciences (P30-ES002109)Singapore-MIT Alliance for Research and Technology CenterNational Institutes of Health (U.S.) (P41-EB015871)National Cancer Institute (U.S.) (P30-CA014051

Updates in the Relationship Between Human Rhinovirus and Asthma

Human rhinovirus (HRV) is a nonenveloped, single stranded RNA virus belonging to the family Picornaviridae. HRV infections can cause both upper and lower respiratory illnesses in children and adults. Lower respiratory illnesses are more likely to occur in specific high risk groups, including infants, and children and adults with asthma. The relationships between rates of infection and the risk of clinical illness and exacerbation are not completely understood. Recent studies employing polymerase chain reaction and other molecular techniques indicate that there are new branches on the HRV family tree, and one characteristic of recently detected viruses is that they cannot be detected by standard tissue culture. Here we review the current literature and discuss new advances in understanding the link between HRV and asthma

Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009

Insulin resistance is a hallmark of type 2 diabetes mellitus and is associated with a metabolic and cardiovascular cluster of disorders (dyslipidaemia, hypertension, obesity [especially visceral], glucose intolerance, endothelial dysfunction), each of which is an independent risk factor for cardiovascular disease (CVD). Multiple prospective studies have documented an association between insulin resistance and accelerated CVD in patients with type 2 diabetes, as well as in non-diabetic individuals. The molecular causes of insulin resistance, i.e. impaired insulin signalling through the phosphoinositol-3 kinase pathway with intact signalling through the mitogen-activated protein kinase pathway, are responsible for the impairment in insulin-stimulated glucose metabolism and contribute to the accelerated rate of CVD in type 2 diabetes patients. The current epidemic of diabetes is being driven by the obesity epidemic, which represents a state of tissue fat overload. Accumulation of toxic lipid metabolites (fatty acyl CoA, diacylglycerol, ceramide) in muscle, liver, adipocytes, beta cells and arterial tissues contributes to insulin resistance, beta cell dysfunction and accelerated atherosclerosis, respectively, in type 2 diabetes. Treatment with thiazolidinediones mobilises fat out of tissues, leading to enhanced insulin sensitivity, improved beta cell function and decreased atherogenesis. Insulin resistance and lipotoxicity represent the missing links (beyond the classical cardiovascular risk factors) that help explain the accelerated rate of CVD in type 2 diabetic patients

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Analysis of EYFP and EGFP positive control mice and RaDR-GFP tissues.

<p>(A) Histological images of FYDR positive control mice that harbor full-length <i>EYFP</i> sequences within mouse Ch. 1, and RaDR-GFP positive control mice that harbor full-length <i>EGFP</i> at the <i>Rosa</i>26 locus expressed under the same CAG promoter (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004299#s4" target="_blank">Materials and Methods</a>). Brightness/contrast for EYFP filtered images (×10) was adjusted equivalently for all images. (B) Quantification of percentage of cells that are fluorescent within disaggregated pancreas, liver and colon of the FYDR and RaDR-GFP positive control mice (measured using flow cytometry). Almost no cells are fluorescent in liver and colon cells from the positive control FYDR mice, indicating that these tissues cannot be used for analysis of HR in the FYDR mice. Almost all cells from the pancreas, liver and colon of the RaDR-GFP positive control mice are fluorescent, indicating that these tissues can be analyzed for HR frequency in the RaDR-GFP mice. (C) Frequency of HR among 11 different tissues from two months old RaDR-GFP mice is highly variable. The number of recombinant cells per million is reported as individual data points (one data point for each mouse; samples from 9–10 mice were analyzed for each type of tissue). Horizontal lines that capture more than one tissue type indicate that samples within that group are not statistically significantly different from one another. Statistically significant differences between groups (of one or more tissue types) are noted. Bars indicate median frequencies.</p

HR at the RaDR-GFP substrate can give rise to fluorescence following gene conversion, sister chromatid exchange, and replication fork repair, but not following SSA.

<p>Each cassette is missing different essential coding sequences such that neither is able to express EGFP. Gene conversion can lead to transfer of sequence information from one cassette to the other, restoring full-length <i>EGFP</i> coding sequence and giving rise to a fluorescent readout. Each cassette can be the donor or the recipient in a gene conversion event. The entire HR reporter is copied during S phase, making it possible for crossovers between sister chromatids (gene conversion with crossover) to reconstitute full-length <i>EGFP</i>. Note that a long tract gene conversion event would be indistinguishable. Recombination that arises as a consequence of repair of a broken replication fork can also be detected using the RaDR-GFP substrate. A replication fork breakdown arising from a fork moving from left to right is shown. Reinsertion of the broken Δ3<i>egfp</i> end into the Δ5<i>egfp</i> cassette can restore full length EGFP. Note that this figure depicts events wherein the replication fork had been moving from left to right; <i>EGFP</i> can analogously be restored by repair of forks moving in the opposite direction (not shown). Single strand annealing initiated by a DSB between the repeated cassettes can be readily repaired, but these events will not reconstitute full-length EGFP and thus SSA cannot be detected.</p

HR events are induced by exposure to an exogenous DNA damaging agent and are quantifiable using in-house software.

<p>(A) Images of freshly excised liver and colon tissue from control mice and from mice that were exposed to MNU/T3. (B) Images of pancreata from control and MNU/T3 treated RaDR-GFP mice. (C) Analysis of images from part (B) using in-house software to quantify fluorescent foci. Foci identified by the program are indicated by “+”. (D) Frequencies of recombinant foci per cm² in pancreatic, liver and colon tissue quantified using in-house software (controls N = 7–8; treated N = 12–13). Brightness and contrast for all images were optimized for publication. ^*<i>p</i><0.05, Mann–Whitney <i>U</i>-test.</p