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Low-stress along with high-stress vocal range possess diverse outcomes about glucocorticoid response.
0% at baseline) and 16.9% reported CO-verified PPA. A positive attitude toward a SFH policy was associated with increased odds of SFH adoption (Adjusted Odds Ratio [AOR] 8.68, 95% CI 2.42, 31.17). Voluntary SFH adoption was associated with increased PPA (AOR 26.27, 95% CI 3.43, 201.30). PSH staff reported improved attitudes toward and self-efficacy in delivering cessation care, and decreased barriers to discussing smoking cessation among PSH residents between baseline and 3-months follow-up. CONCLUSIONS In this single-arm study, a brief intervention increased SFH adoption and PPA among PSH residents. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail [email protected] instability resulting from defective DNA damage responses or repair causes several abnormalities, including progressive cerebellar ataxia, for which the molecular mechanisms are not well understood. Here, we report a new murine model of cerebellar ataxia resulting from concomitant inactivation of POLB and ATM. POLB is one of key enzymes for the repair of damaged or chemically modified bases, including methylated cytosine, but selective inactivation of Polb during neurogenesis affects only a subpopulation of cortical interneurons despite the accumulation of DNA damage throughout the brain. However, dual inactivation of Polb and Atm resulted in ataxia without significant neuropathological defects in the cerebellum. ATM is a protein kinase that responds to DNA strand breaks, and mutations in ATM are responsible for Ataxia Telangiectasia, which is characterized by progressive cerebellar ataxia. In the cerebella of mice deficient for both Polb and Atm, the most downregulated gene was Itpr1, likely because of misregulated DNA methylation cycle. ITPR1 is known to mediate calcium homeostasis, and ITPR1 mutations result in genetic diseases with cerebellar ataxia. Our data suggest that dysregulation of ITPR1 in the cerebellum could be one of contributing factors to progressive ataxia observed in human genomic instability syndromes. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.BACKGROUND Over the past several decades, treatment of cancer in adolescents and young adults (AYAs) has evolved substantially, leading to steady improvements in estimated five-year survival at diagnosis. However, the impact on late mortality in this population is largely unexamined. We investigated temporal trends in mortality among five-year AYA cancer survivors. METHODS The Surveillance, Epidemiology, and End Results database was used to identify AYAs (age 15-39) diagnosed with cancer during 1975-2011 who survived ≥5 years beyond diagnosis. Survival months were accrued from five years post-diagnosis until death or end of 2016. Cumulative mortality from all causes, the primary cancer, other cancers, and noncancer/nonexternal causes (i.e. excluding accidents, suicide, homicide) were estimated according to diagnosis era. RESULTS Among 282,969 five-year AYA cancer survivors, five-year mortality (i.e. from 5 through 10 years post-diagnosis) from all causes decreased from 8.3% (95% CI 8.0%-8.6%) among those diagnosed in 1975-1984 to 5.4% (95% CI 5.3%-5.6%) among those diagnosed in 2005-2011. This was largely explained by decreases in mortality from the primary cancer (6.8% to 4.2%) between these periods. However, for specific cancer types, including colorectal, bone, sarcomas, cervical/uterine, and bladder, cumulative mortality curves demonstrated little improvement in primary cancer-mortality over time. Some reduction in late mortality from noncancer/nonexternal causes was apparent for Hodgkin lymphoma, leukemia, kidney cancer, head and neck cancers, and trachea, lung, and bronchus cancers. CONCLUSION Over the past four decades, all-cause and cancer-specific mortality have decreased among five-year AYA cancer survivors overall, but several cancer types have not shared in these improvements. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email [email protected] time series transcriptome analysis is a powerful tool to study development, evolution, aging, disease progression and cancer prognosis. We develop TimeMeter, a statistical method and tool to assess temporal gene expression similarity, and identify differentially progressing genes where one pattern is more temporally advanced than the other. We apply TimeMeter to several datasets, and show that TimeMeter is capable of characterizing complicated temporal gene expression associations. Interestingly, we find (i) the measurement of differential progression provides a novel feature in addition to pattern similarity that can characterize early developmental divergence between two species; (ii) genes exhibiting similar temporal patterns between human and mouse during neural differentiation are under strong negative (purifying) selection during evolution; (iii) analysis of genes with similar temporal patterns in mouse digit regeneration and axolotl blastema differentiation reveals common gene groups for appendage regeneration with potential implications in regenerative medicine. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.We conducted a molecular survey of Rickettsia in fleas collected from opossums, road-killed and live-trapped in peridomestic and rural settings, state parks, and from pet cats and dogs in Georgia, United States during 1992-2014. The cat flea, Ctenocephalides felis (Bouché) was the predominant species collected from cats and among the archival specimens from opossums found in peridomestic settings. Polygenis gwyni (Fox) was more prevalent on opossums and a single cotton rat trapped in sylvatic settings. Trapped animals were infested infrequently with the squirrel flea, Orchopeas howardi (Baker) and C. felis. TaqMan assays targeting the BioB gene of Rickettsia felis and the OmpB gene of Rickettsia typhi were used to test 291 flea DNAs for Rickettsia. A subset of 53 C. felis collected from a cat in 2011 was tested in 18 pools which were all bioB TaqMan positive (34% minimum infection prevalence). Of 238 fleas tested individually, 140 (58.8%, 95% confidence interval [CI] 52.5-64.9%) DNAs were bioB positive. Detection of bioB was more prevalent in individual C. felis (91%) compared to P. gwyni (13.4%). Twenty-one (7.2%) were ompB TaqMan positive, including 18 C. felis (9.5%) and 3 P. gwyni (3.2%). Most of these fleas were also positive with bioB TaqMan; however, sequencing of gltA amplicons detected only DNA of Rickettsia asembonensis. Furthermore, only the R. asembonensis genotype was identified based on NlaIV restriction analysis of a larger ompB fragment. These findings contribute to understanding the diversity of Rickettsia associated with fleas in Georgia and emphasize the need for development of more specific molecular tools for detection and field research on rickettsial pathogens. © The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America.All rights reserved. For permissions, please e-mail [email protected] have previously shown that the highly prevalent acute myeloid leukemia (AML) mutation, Arg882His, in DNMT3A disrupts its cooperative mechanism and leads to reduced enzymatic activity, thus explaining the genomic hypomethylation in AML cells. However, the underlying cause of the oncogenic effect of Arg882His in DNMT3A is not fully understood. Here, we discovered that DNMT3A WT enzyme under conditions that favor non-cooperative kinetic mechanism as well as DNMT3A Arg882His variant acquire CpG flanking sequence preference akin to that of DNMT3B, which is non-cooperative. We tested if DNMT3A Arg882His could preferably methylate DNMT3B-specific target sites in vivo. Rescue experiments in Dnmt3a/3b double knockout mouse embryonic stem cells show that the corresponding Arg878His mutation in mouse DNMT3A severely impairs its ability to methylate major satellite DNA, a DNMT3A-preferred target, but has no overt effect on the ability to methylate minor satellite DNA, a DNMT3B-preferred target. We also observed a previously unappreciated CpG flanking sequence bias in major and minor satellite repeats that is consistent with DNMT3A and DNMT3B specificity suggesting that DNA methylation patterns are guided by the sequence preference of these enzymes. We speculate that aberrant methylation of DNMT3B target sites could contribute to the oncogenic potential of DNMT3A AML variant. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.BACKGROUND AND IMPORTANCE Superior cerebellar artery (SCA) perforator aneurysms are extremely rare, with only one other case published in the literature. There is no conclusive management strategy for these aneurysms, although endovascular treatment, open surgical treatment with clipping, and antifibrinolytic administration with spontaneous thrombosis have all been discussed. CLINICAL PRESENTATION A 61-yr-old male presented with intraventricular hemorrhage (IVH) primarily in the posterior fossa. He was found to have a dissecting left SCA perforator aneurysm lying on the floor of the fourth ventricle. The aneurysm was not amenable to endovascular treatment, and antifibrinolytic therapy failed to spontaneously thrombose the aneurysm. We performed a suboccipital craniotomy and used a supracerebellar transvermian approach to resect the aneurysm. There was total obliteration of the aneurysm on postoperative cerebral angiogram. CONCLUSION SCA perforator aneurysms represent an extremely uncommon subset of intracranial aneurysms. The best therapeutic strategy has yet to be definitively proven. When pursuing surgical treatment, the supracerebellar transvermian navigated approach can be a useful and safe option, as described and illustrated in this video. Cobimetinib price Copyright © 2020 by the Congress of Neurological Surgeons.Insect symbionts benefit their host and their study requires large spectrum antibiotic use like tetracycline to weaken or suppress symbiotic communities. While antibiotics have a negative impact on insect fitness, little is known about antibiotic effects on insect microbial communities and how long they last. We characterized the bacterial communities of adult cabbage root fly Delia radicum in a Wolbachia-free population and evaluated the effect of tetracycline treatment on these communities over several generations. Three D. radicum generations were used the first- and second-generation flies either ingested tetracycline or not, while the third-generation flies were untreated but differed with their parents and/or grandparents that had or had not been treated. Fly bacterial communities were sequenced using a 16S rRNA gene. Tetracycline decreased fly bacterial diversity and induced modifications in both bacterial abundance and relative frequencies, still visible on untreated offspring whose parents and/or grandparents had been treated, therefore demonstrating long-lasting transgenerational effects on animal microbiomes after antibiotic treatment. Flies with an antibiotic history shared bacterial genera, potentially tetracycline resistant and heritable. Next, the transmission should be investigated by comparing several insect development stages and plant compartments to assess vertical and horizontal transmissions of D. radicum bacterial communities. © FEMS 2020.
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