Recombination between T-DNA insertions to cause chromosomal deletions in Arabidopsis is a rare phenomenon

We previously described the identification of a chromosomal deletion in Arabidopsis thaliana that resulted in the elimination of genomic DNA between two T-DNA insertions located ca. 25 kilobases apart on chromosome IV. The mechanism responsible for this deletion appears to have been recombination between the closely spaced T-DNA elements located in trans in a parent plant. In our original study, we observed one such deletion event after screening ca. 2,000 seedlings using a polymerase chain reaction (PCR) assay. Because a method for precisely deleting a selected region of the Arabidopsis genome would have significant value as a research tool, we were interested in determining the frequency with which this type of T-DNA-directed deletion occurs. To do this we designed a genetic screen that would allow us to phenotypically screen for deletions caused by recombination between T-DNA inserts. This screen involved crossing T-DNA single-mutant lines in order to produce F1 plants in which the two T-DNA insertions flanked a FUSCA (FUS) locus present in the genome. Loss-of-function mutations of FUS genes cause a distinctive developmental phenotype that can be easily scored visually in young seedlings. We used T-DNA lines flanking FUS2, FUS6, FUS7, and FUS11 for this study. Recombination between the T-DNAs in an F1 parent should result in deletion of the FUS gene located between the T-DNAs. Because the deletion would be heterozygous in the F2 generation, we screened the F3 progeny of pooled F2 individuals to search for the fus loss-of-function phenotype. Using this strategy we were able to evaluate a total of 28,314 meioses for evidence of deletions caused by recombination between the T-DNA inserts. No seedlings displaying the fus phenotype were recovered, suggesting that deletions caused by recombination between T-DNA inserts are relatively rare events and may not be a useful tools for genome engineering in Arabidopsis

Ice-Cap: A Method for Growing Arabidopsis and Tomato Plants in 96-well Plates for High-Throughput Genotyping

It is becoming common for plant scientists to develop projects that require the genotyping of large numbers of plants. The first step in any genotyping project is to collect a tissue sample from each individual plant. The traditional approach to this task is to sample plants one-at-a-time. If one wishes to genotype hundreds or thousands of individuals, however, using this strategy results in a significant bottleneck in the genotyping pipeline. The Ice-Cap method that we describe here provides a high-throughput solution to this challenge by allowing one scientist to collect tissue from several thousand seedlings in a single day 1,2. This level of throughput is made possible by the fact that tissue is harvested from plants 96-at-a-time, rather than one-at-a-time

Group Music Intervention Using Percussion Instruments to Reduce Anxiety Among Elderly Male Veterans with Alzheimer Disease

BACKGROUND: This study aimed to assess the impact of a group music intervention on anxiety and depression of elderly male veterans with dementia. MATERIAL AND METHODS: In total, 50 elderly men with Alzheimer disease were randomly divided into intervention and control groups. Patients in the intervention group attended a 60-minute group music session that used percussion instruments with familiar music in the morning once a week for 12 weeks, whereas those in the control group received a rest and reading session at the same intervals and under the same conditions. The Hamilton Anxiety Rating Scale and Geriatric Depression Scale were used to assess anxiety and depression at baseline, week 6, and week 12. The Primary Measures of Music Audiation (PMMA) was used to assess musical aptitude at the baseline. RESULTS: A significant reduction in the anxiety level following the 12-week music sessions was observed in the intervention group (P<.001), but there was no significant change in the control group. However, the change in depressive symptoms between the 2 groups was nonsignificant. In the intervention group, when stratifying patients based on music aptitude determined through PMMA assessment, patients with high PMMA scores had significantly reduced anxiety symptoms over time compared with those with low scores. CONCLUSIONS: For elderly male veterans with dementia, participating in a group music intervention reduced anxiety symptoms. In patients with high musical aptitude, the treatment effects on anxiety reduction were satisfactory. Measures of music aptitude may provide valuable information regarding patients’ response to music intervention

Age- and gender-specific population attributable risks of metabolic disorders on all-cause and cardiovascular mortality in Taiwan

[[abstract]]ABSTRACT: BACKGROUND: The extent of attributable risks of metabolic syndrome (MetS) and its components on mortality remains unclear, especially with respect to age and gender. We aimed to assess the age- and gender-specific population attributable risks (PARs) for cardiovascular disease (CVD)-related mortality and all-cause mortality for public health planning. METHODS: A total of 2,092 men and 2,197 women 30 years of age and older, who were included in the 2002 Taiwan Survey of Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH), were linked to national death certificates acquired through December 31, 2009. Cox proportional hazard models were used to calculate adjusted hazard ratios and PARs for mortality, with a median follow-up of 7.7 years. RESULTS: The respective PAR percentages of MetS for all-cause and CVD-related mortality were 11.6 and 39.2 in men, respectively, and 18.6 and 44.4 in women, respectively. Central obesity had the highest PAR for CVD mortality in women (57.5%), whereas arterial hypertension had the highest PAR in men (57.5%). For all-cause mortality, younger men and post-menopausal women had higher PARs related to Mets and its components; for CVD mortality, post-menopausal women had higher overall PARs than their pre-menopausal counterparts. CONCLUSIONS: MetS has a limited application to the PAR for all-cause mortality, especially in men; its PAR for CVD mortality is more evident. For CVD mortality, MetS components have higher PARs than MetS itself, especially hypertension in men and waist circumference in post-menopausal women. In addition, PARs for diabetes mellitus and low HDL-cholesterol may exceed 20%. We suggest differential control of risk factors in different subpopulation as a strategy to prevent CVD-related mortality

Tetrac and NDAT Induce Anti-proliferation via Integrin αvβ3 in Colorectal Cancers With Different K-RAS Status

Colorectal cancer is a serious medical problem in Taiwan. New, effective therapeutic approaches are needed. The selection of promising anticancer drugs and the transition from pre-clinical investigations to clinical trials are often challenging. The deaminated thyroid hormone analog (tetraiodothyroacetic acid, tetrac) and its nanoparticulate analog (NDAT) have been shown to have anti-proliferative activity in vitro and in xenograft model of different neoplasms, including colorectal cancers. However, mechanisms involved in tetrac- and NDAT-induced anti-proliferation in colorectal cancers are incompletely understood. We have investigated possible mechanisms of tetrac and NDAT action in colorectal cancer cells, using a perfusion bellows cell culture system that allows efficient, large-scale screening for mechanisms of drug actions on tumor cells. Although integrin αvβ3 in K-RAS wild type colorectal cancer HT-29 cells was far less than that in K-RAS mutant HCT116 cells, HT-29 was more sensitive to both tetrac and NDAT. Results also indicate that both tetrac and NDAT bind to tumor cell surface integrin αvβ3, and the agents may have different mechanisms of anti-proliferation in colorectal cancer cells. K-RAS status appears to play an important role in drug resistance that may be encountered in treatment with this drug combination

Clinical Efficacy and Post-Treatment Seromarkers Associated with the Risk of Hepatocellular Carcinoma among Chronic Hepatitis C Patients

This follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological response (SVR) or nonsustained virological response (NSVR). A total of 4639 patients who received pegylated interferon and ribavirin during 2004–2013 were followed until December 2014. HCC was confirmed through health examinations and data linkage with a national database. A total of 233 HCC cases were reported after 26,163 person-years of follow-up, indicating an incidence of 8.9 per 1000 person-years: 6.9 for SVR and 21.6 for NSVR per 1000 person-years. The associated risk of HCC in patients with SVR was 0.37 (0.22–0.63) for those without cirrhosis and 0.54 (0.31–0.92) for those with cirrhosis compared with their respective counterparts with NSVR. Among patients with SVR, advanced age, male gender, cirrhosis, decreased platelet count, and increased aspartate aminotransferase and α-fetoprotein levels were associated with HCC (p < 0.001). The treatment of chronic hepatitis C patients before they developed cirrhosis showed a higher efficacy than did the treatment of those who had already developed cirrhosis. Patients with SVR may still have a risk of HCC and need to be regularly monitored

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements