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Found 34901 matches. Displaying 161-170
Frew JW
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Lack of photographic documentation undermines assessment of hidradenitis suppurativa phenotypes: reply from the author

Linked Article: Albrecht et al. Br J Dermatol 2019; 180:749-55.
Piserchio A
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Solution Structure of the Carboxy-Terminal Tandem Repeat Domain of

JOURNAL OF MOLECULAR BIOLOGY 2019 JUL 12; 431(15):2700-2717
Eukaryotic elongation factor 2 kinase (eEF-2K), an atypical
Rao L
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Molecular mechanism of cytoplasmic dynein tension sensing

NATURE COMMUNICATIONS 2019 JUL 26; 10(?):? Article 3332
Cytoplasmic dynein is the most complex cytoskeletal motor protein and is
Castner J, Mammen MJ, Jungquist CR, Licata O, Pender JJ, Wilding GE, Sethi S
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Validation of fitness tracker for sleep measures in women with asthma

JOURNAL OF ASTHMA 2019 JUL 3; 56(7):719-730
Objective: Nighttime wakening with asthma symptoms is a key to assessment and therapy decisions, with no gold standard objective measure. The study aims were to (1) determine the feasibility, (2) explore equivalence, and (3) test concordance of a consumer-based accelerometer with standard actigraphy for measurement of sleep patterns in women with asthma as an adjunct to self-report. Methods: Panel study design of women with poorly controlled asthma from a university-affiliated primary care clinic system was used. We assessed sensitivity and specificity, equivalence and concordance of sleep time, sleep efficiency, and wake counts between the consumer-based accelerometer Fitbit Charge (TM) and Actigraph wGT3X+. We linked data between devices for comparison both automatically by 24-hour period and manually by sleep segment. Results: Analysis included 424 938 minutes, 738 nights, and 833 unique sleep segments from 47 women. The fitness tracker demonstrated 97% sensitivity and 40% specificity to identify sleep. Between device equivalence for total sleep time (15 and 42-minute threshold) was demonstrated by sleep segment. Concordance improved for wake counts and sleep efficiency when adjusting for a linear trend. Conclusions: There were important differences in total sleep time, efficiency, and wake count measures when comparing individual sleep segments versus 24-hour measures of sleep. Fitbit overestimates sleep efficiency and underestimates wake counts in this population compared to actigraphy. Low levels of systematic bias indicate the potential for raw measurements from the devices to achieve equivalence and concordance with additional processing, algorithm modification, and modeling. Fitness trackers offer an accessible and inexpensive method to quantify sleep patterns in the home environment as an adjunct to subjective reports, and require further informatics development.
Butelman ER, McElroy BD, Prisinzano TE, Kreek MJ
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Impact of Pharmacological Manipulation of the kappa-Opioid Receptor System on Self-grooming and Anhedonic-like Behaviors in Male Mice

The kappa (kappa) opioid receptor/dynorphin system modulates depression-like states and anhedonia, as well adaptations to stress and exposure to drugs of abuse. Several relatively short-acting small molecule kappa-receptor antagonists have been synthesized, and their behavioral profile has been examined under some conditions. The hypothesis of this study is that pharmacological manipulations of the kappa-receptor system will result in changes in ethologically relevant anhedonic-like behaviors in mice. Adult male C57BL/6j mice (n = 6-8) were examined for self-grooming behavior in the splash test (in which robust self-grooming is elicited by spraying the dorsum of the mouse with a sucrose solution). The kappa-agonist salvinorin A (0.56-1.8 mg/kg) produced dose-dependent decreases in self-grooming, a marker of anhedonia. The selectivity, potency, and duration of action of two relatively short-acting kappa-antagonists, LY2444296 [(S)-3-fluoro-4-(4-((2-(3-fluorophenyl)pyrrolidin-1-yl)methyl)phenoxy)be nzamide] and LY2795050 [3-chloro-4-(4-(((2S)-2-pyridin-3- ylpyrrolidin-1-yl)methyl) phenoxy)benzamide], were studied for their effectiveness in preventing grooming deficits caused by salvinorin A (1.8 mg/kg). kappa-selective doses of both LY2444296 (0.032-1 mg/kg) and LY2795050 (0.032-0.32 mg/kg) dose- and time-dependently prevented the grooming deficits caused by salvinorin A (1.8 m/kg). We also found that a kappa-selective dose of each of these antagonists decreased immobility in the forced swim test, a common test of anti-anhedonia effects. This study shows that the kappa-receptor system is involved in an ethologically relevant measure of anhedonia, and that kappa-selective doses of these antagonists can produce effects consistent with rapid anti-anhedonia.
Wu YM, Xie L, Meng SY, Hou JH, Fu R, Zheng H, He N, Meyers K
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Mapping Potential Pre-Exposure Prophylaxis Users onto a Motivational Cascade: Identifying Targets to Prepare for Implementation in China

LGBT HEALTH 2019 JUL 1; 6(5):250-260
Purpose: China recently commenced several pre-exposure prophylaxis (PrEP) projects, but little work has characterized potential users. This study describes awareness of, intention to use, and uptake of PrEP in a sample of men who have sex with men (MSM), a key population experiencing high rates of HIV in China. Methods: Through a cross-sectional survey administered to 708 MSM in four cities, we mapped respondents onto a Motivational PrEP Cascade. We conducted bivariable and multivariable analysis to examine factors associated with progression through the Cascade. Results: Among 45.6% of MSM who were PrEP eligible, 36% were in Contemplation, 9% were in PrEParation, 2% were in PrEP Action and Initiation, and none reached Maintenance and Adherence. We found no association between individual risk factors and progression through the Cascade. In multivariable analysis, friends' positive attitudes toward PrEP, more frequent sexually transmitted infection testing, and higher scores on the perceived PrEP benefits scale were positively associated with entering PrEP Contemplation. Having higher condom use self-efficacy was associated with decreased odds of entering PrEP Contemplation. Having sex with men and women in the past 6 months, having heard of PrEP from medical providers, and knowing a PrEP user were positively associated with entering PrEParation. Conclusion: We found a high proportion of MSM who were PrEP eligible and identified several intervention targets to prepare for PrEP introduction in China: community education to increase accurate knowledge, gain-framed messaging for PrEP and sexual health, and provider trainings to build MSM-competent services that can support shared decision-making for PrEP initiation.
Valverde DP, Yu SL, Boggavarapu V, Kumar N, Lees JA, Walz T, Reinisch KM, Melia TJ
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ATG2 transports lipids to promote autophagosome biogenesis

JOURNAL OF CELL BIOLOGY 2019 JUN; 218(6):1787-1798
During macroautophagic stress, autophagosomes can be produced continuously and in high numbers. Many different organelles have been reported as potential donor membranes for this sustained autophagosome growth, but specific machinery to support the delivery of lipid to the growing autophagosome membrane has remained unknown. Here we show that the autophagy protein, ATG2, without a clear function since its discovery over 20 yr ago, is in fact a lipid-transfer protein likely operating at the ER-autophagosome interface. ATG2A can bind tens of glycerophospholipids at once and transfers lipids robustly in vitro. An N-terminal fragment of ATG2A that supports lipid transfer in vitro is both necessary and fully sufficient to rescue blocked autophagosome biogenesis in ATG2A/ATG2B KO cells, implying that regulation of lipid homeostasis is the major autophagy-dependent activity of this protein and, by extension, that protein-mediated lipid transfer across contact sites is a principal contributor to autophagosome formation.
Clijsters L, Hoencamp C, Calis JJA, Marzio A, Handgraaf SM, Cuitino MC, Rosenberg BR, Leone G, Pagano M
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Cyclin F Controls Cell-Cycle Transcriptional Outputs by Directing the Degradation of the Three Activator E2Fs

MOLECULAR CELL 2019 JUN 20; 74(6):1264-1277.e7
E2F1, E2F2, and E2F3A, the three activators of the E2F family of transcription factors, are key regulators of the G1/S transition, promoting transcription of hundreds of genes critical for cell-cycle progression. We found that during late S and in G2, the degradation of all three activator E2Fs is controlled by cyclin F, the substrate receptor of 1 of 69 human SCF ubiquitin ligase complexes. E2F1, E2F2, and E2F3A interact with the cyclin box of cyclin F via their conserved N-terminal cyclin binding motifs. In the short term, E2F mutants unable to bind cyclin F remain stable throughout the cell cycle, induce unscheduled transcription in G2 and mitosis, and promote faster entry into the next S phase. However, in the long term, they impair cell fitness. We propose that by restricting E2F activity to the S phase, cyclin F controls one of the main and most critical transcriptional engines of the cell cycle.
Varble A, Marraffini LA
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Three New Cs for CRISPR: Collateral, Communicate, Cooperate

TRENDS IN GENETICS 2019 JUN; 35(6):446-456
Clustered regularly interspaced short palindromic repeats (CRISPR) loci and their associated (cas) genes provide protection against invading phages and plasmids in prokaryotes. Typically, short sequences are captured from the genome of the invader, integrated into the CRISPR locus, and transcribed into short RNAs that direct RNA-guided Cas nucleases to the nucleic acids of the invader for their degradation. Recent work in the field has revealed unexpected features of the CRISPR-Cas mechanism: (i) collateral, nonspecific, cleavage of host nucleic acids; (ii) secondary messengers that amplify the immune response; and (iii) immunosuppression of CRISPR targeting by phage-encoded inhibitors. Here, we review these new and exciting findings.
Varble A, Meaden S, Barrangou R, Westra ER, Marraffini LA
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Recombination between phages and CRISPR-cas loci facilitates horizontal gene transfer in staphylococci

NATURE MICROBIOLOGY 2019 JUN; 4(6):956-963
CRISPR (clustered regularly interspaced short palindromic repeats) loci and their associated (cas) genes encode an adaptive immune system that protects prokaryotes from viral(1) and plasmid(2) invaders. Following viral (phage) infection, a small fraction of the prokaryotic cells are able to integrate a small sequence of the invader's genome into the CRISPR array(1). These sequences, known as spacers, are transcribed and processed into small CRISPR RNA guides(3-5) that associate with Cas nucleases to specify a viral target for destruction(6-9). Although CRISPR-cas loci are widely distributed throughout microbial genomes and often display hallmarks of horizontal gene transfer(10)(-12), the drivers of CRISPR dissemination remain unclear. Here, we show that spacers can recombine with phage target sequences to mediate a form of specialized transduction of CRISPR elements. Phage targets in phage 85, Phi NM1, Phi NM4 and Phi 12 can recombine with spacers in either chromosomal or plasmid-borne CRISPR loci in Staphylococcus, leading to either the transfer of CRISPR-adjacent genes or the propagation of acquired immunity to other bacteria in the population, respectively. Our data demonstrate that spacer sequences not only specify the targets of Cas nucleases but also can promote horizontal gene transfer.