bluuebunny/crossref_metadata_2025_split huggingface dataset:
ZFAND5/ZNF216 is an activator of the 26S proteasome that stimulates overall protein degradation
Authors: Lee Donghoon , Takayama Shinichi , Goldberg Alfred L. 
Published: September 2018

Significance
ZFAND5/ZNF216, a member of the ubiquitous ZFAND protein family, contains two zinc finger domains. It is induced in skeletal muscle during atrophy and was shown to be essential for the resulting large loss of muscle mass. We show here that purified ZFAND5 stimulates the 26S proteasomes’ capacity to degrade peptides and ubiquitinated proteins. In cells, it promotes the degradation of endogenous cell proteins through its ubiquitin-binding zinc finger domain (A20). Unlike several ZFAND proteins, it is not induced in proteotoxic stresses. Unlike other proteasome activators, ZFAND5 actually stimulates overall protein breakdown by the ubiquitin proteasome pathway.
A single phosphorylation site of SIK3 regulates daily sleep amounts and sleep need in mice
Authors: Honda Takato , Fujiyama Tomoyuki , Miyoshi Chika , Ikkyu Aya , Hotta-Hirashima Noriko , Kanno Satomi , Mizuno Seiya , Sugiyama Fumihiro , Takahashi Satoru , Funato Hiromasa , Yanagisawa Masashi 
Published: September 2018

Significance
The neural substrate for “sleepiness,” as well as the molecular mechanisms determining daily sleep amounts, remain mysterious. Here, we found that a single amino acid, S551, of the protein kinase SIK3 has a crucial role in the regulation of sleep need and daily nonrapid-eye movement sleep amounts. Importantly, S551 in SIK3 is evolutionally conserved as a PKA phosphorylation site from nematodes and fruit flies to mice and humans. These findings implicate SIK3 in the molecular basis of homeostatic sleep/wake regulation.
Blood-derived plasminogen drives brain inflammation and plaque deposition in a mouse model of Alzheimer’s disease
Authors: Baker Sarah K. , Chen Zu-Lin , Norris Erin H. , Revenko Alexey S. , MacLeod A. Robert , Strickland Sidney 
Published: September 2018

SignificanceWe demonstrate that depletion of blood plasminogen is sufficient to protect against both innate immune cell activation in the brain and Alzheimer’s disease (AD) pathology in a mouse model of AD. This work provides a molecular mechanism for initiation of AD-related brain inflammation and for regulation of β-amyloid deposition, and could lead to therapeutic strategies in human AD patients, including the targeting of systemic molecules.
The Cross-sectional and Longitudinal Associations Between IL-6, IL-10, and TNFα and Cognitive Outcomes in the Mayo Clinic Study of Aging
Authors: Wennberg Alexandra M V , Hagen Clinton E , Machulda Mary M , Knopman David S , Petersen Ronald C , Mielke Michelle M 
Published: September 2018

Abstract

Background
Chronic inflammation has been linked with geriatric-related conditions, including dementia. Inflammatory cytokine levels, including interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF) α, in the blood have been associated with cognitive impairment and decline. However, evidence has been mixed.

Methods
We examined the cross-sectional and longitudinal associations between baseline-measured IL-6, IL-10, and TNFα levels and the ratio of IL-6/IL-10 with cognitive test performance and mild cognitive impairment (MCI) among 1,602 community-dwelling older adults (median age = 72.8) enrolled in the Mayo Clinic Study of Aging. Approximately half (46.5%) of participants were female and 98.6% were white. At baseline and follow-up visits (occurring at 15-month intervals), participants completed neuropsychological testing, blood draws, and had a clinical consensus diagnosis.

Results
In multivariable cross-sectional analyses, we did not observe an association between inflammatory cytokine levels and global or domain-specific cognitive z scores; however, higher IL-6 and IL-10 levels were associated with greater odds of a MCI diagnosis. Longitudinally, we did not observe any association between inflammatory cytokine levels and cognitive test performance or risk of MCI. Sex, age, cognitive status, APOE ε4 genotype, diabetes, depression, and cerebral amyloid-beta deposition were not effect modifiers.

Conclusions
These results suggest that plasma inflammatory markers may not be useful to ascertain risk for cognitive decline and MCI in the general population.
Chronic Treatment With the ACE Inhibitor Enalapril Attenuates the Development of Frailty and Differentially Modifies Pro- and Anti-inflammatory Cytokines in Aging Male and Female C57BL/6 Mice
Authors: Keller Kaitlyn , Kane Alice , Heinze-Milne Stefan , Grandy Scott A , Howlett Susan E 
Published: September 2018

AbstractStudies on interventions that can delay or treat frailty in humans are limited. There is evidence of beneficial effects of angiotensin converting enzyme (ACE) inhibitors on aspects related to frailty, such as physical function, even in those without cardiovascular disease. This study aimed to longitudinally investigate the effect of an ACE inhibitor on frailty in aging male and female mice. Frailty was assessed with a clinical frailty index (FI) which quantifies health-related deficits in middle-aged (9–13 months) and older (16–25 months) mice. Chronic treatment with enalapril (30 mg/kg/day in feed) attenuated frailty in middle-aged and older female mice, and older male mice, without a long-term effect on blood pressure. Enalapril treatment resulted in a reduction in the proinflammatory cytokines interleukin (IL)-1α, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1a in older female mice, and an increase in the anti-inflammatory cytokine IL-10 in older male mice compared with control animals. These sex-specific effects on inflammation may contribute to the protective effects of enalapril against frailty. This is the first study to examine the longitudinal effect of an intervention on the FI in mice, and provides preclinical evidence that enalapril may delay the onset of frailty, even when started later in life.
Effects of Vitamin D3 Supplementation on Epigenetic Aging in Overweight and Obese African Americans With Suboptimal Vitamin D Status: A Randomized Clinical Trial
Authors: Chen Li , Dong Yanbin , Bhagatwala Jigar , Raed Anas , Huang Ying , Zhu Haidong 
Published: September 2018

Abstract

Background
We have previously shown that vitamin D supplementation increases telomerase activity, suggesting an anti-aging effect. In this study, we aim to test the hypothesis that vitamin D supplementation would slow down epigenetic aging, a new marker of biological aging.

Methods
A randomized clinical trial was previously conducted among 70 overweight/obese African Americans with serum 25-hydroxyvitamin D [25(OH)D] < 50 nmol/L, who were randomly assigned into four groups of 600 IU/d, 2,000 IU/d, 4,000 IU/d of vitamin D3 supplements or placebo followed by 16-week interventions. Whole genome-wide DNA methylation analysis was conducted in 51 participants. DNA methylation ages were calculated according to the Horvath and the Hannum methods. Methylation-based age acceleration index (∆Age) is defined as the difference between DNA methylation age and chronological age in years. Mixed-effects models were used to evaluate the treatment effects.

Results
Fifty-one participants (aged 26.1 ± 9.3 years, 16% are male) were included in the study. After the adjustment of multi-covariates, vitamin D3 supplementation of 4,000 IU/d was associated with 1.85 years decrease in Horvath epigenetic aging compared with placebo (p value = .046), and 2,000 IU/d was associated with 1.90 years decrease in Hannum epigenetic aging (p value = .044). Serum 25(OH)D concentrations were significantly associated with decreased Horvath ∆Age only (p values = .002), regardless of treatments.

Conclusions
Our results suggest that vitamin D supplementation may slow down Horvath epigenetic aging. But the effect on Hannum epigenetic aging is not conclusive. Large-scale and longer duration clinical trials are needed to replicate the findings.
The genome of common long-arm octopus Octopus minor
Authors: Kim Bo-Mi , Kang Seunghyun , Ahn Do-Hwan , Jung Seung-Hyun , Rhee Hwanseok , Yoo Jong Su , Lee Jong-Eun , Lee SeungJae , Han Yong-Hee , Ryu Kyoung-Bin , Cho Sung-Jin , Park Hyun , An Hye Suck 
Published: September 2018

Abstract

Background
The common long-arm octopus (Octopus minor) is found in mudflats of subtidal zones and faces numerous environmental challenges. The ability to adapt its morphology and behavioral repertoire to diverse environmental conditions makes the species a promising model for understanding genomic adaptation and evolution in cephalopods.

Findings
The final genome assembly of O. minor is 5.09 Gb, with a contig N50 size of 197 kb and longest size of 3.027 Mb, from a total of 419 Gb raw reads generated using the Pacific Biosciences RS II platform. We identified 30,010 genes; 44.43% of the genome is composed of repeat elements. The genome-wide phylogenetic tree indicated the divergence time between O. minor and Octopus bimaculoides was estimated to be 43 million years ago based on single-copy orthologous genes. In total, 178 gene families are expanded in O. minor in the 14 bilaterian species.

Conclusions
We found that the O. minor genome was larger than that of closely related O. bimaculoides, and this difference could be explained by enlarged introns and recently diversified transposable elements. The high-quality O. minor genome assembly provides a valuable resource for understanding octopus genome evolution and the molecular basis of adaptations to mudflats.
Perceived Impact of Participation in a One-Time Expressive Arts Workshop
Authors: Morrison Penny , Nishimoto Patricia W , Kim John B , Medina-Dupaix Carolina , Bantum Erin O’Carroll 
Published: September 2018

Abstract

Introduction
This 2015 study examined the use of art to express the experience of the cancer journey of military cancer patients/cancer survivors, family and friends, caregivers, volunteers, and staff members through a one-time art-making workshop, administered by non-art therapists.
Using art to express a medical/cancer journey may give participants, who cannot express their feelings in words, the ability to articulate their experience through art that looks at the creative process rather than the end result – expressive art.

Materials and Methods
This mixed methods study examined the use of art to express the cancer journey of participants. Twenty-eight adults participated in a one-time expressive arts workshop conducted by non-professional art therapists at a military medical center. The five domains of the Emotion Thermometer were analyzed to determine if the pre-event and post-event assessment results would differ. The Silver Drawing Test and Draw-a-Story assessment tools were used to identify emotions and attitudinal stance on six separate five-point scales. A qualitative analysis was done using the phenomenological method of the post-interviews that facilitated open expression to identify themes.

Results
A significant difference was found between the pre-event and post-event analyses using the Emotion Thermometer, with post-assessment results revealing lower levels in the three domains of distress, anxiety, and depression. The Silver Drawing Test and Draw-a-Story were analyzed for six components using a five-point scale, with the highest scores being content/meaning, ability to combine, and creativity. A qualitative analysis was done using the phenomenological method; post-interviews provided information to categorize the experience into four key themes: environment, connection, emotions, and discoveries.

Conclusions
Using art to express one’s journey through cancer allows participants to articulate that journey “beyond language.” This mixed methods study was administered by five non-professional art therapists with three having no expressive arts background. This study established that an expressive arts workshop can effectively be conducted by non-professional art therapists. The team of non-professional art therapists, who facilitated this one-time art-making workshop, demonstrated that a military member’s stress can be decreased by giving them “a voice” through expressive art.
Real-World Effectiveness of Pharmaceutical Smoking Cessation Aids: Time-Varying Effects
Authors: Chaiton Michael , Diemert Lori M , Bondy Susan J , Cohen Joanna E , Fung Michael D , Zhang Bo R , Ferrence Roberta G 
Published: September 2018

Abstract

Background
There are a limited number of studies that have examined the real-world effectiveness of smoking cessation aids and relapse longitudinally in population-representative samples. This study examines the association between use of nicotine gum, patch, bupropion, and varenicline and time to relapse as well as any changes in the association with increased length of abstinence.

Methods
Data of 1821 current adult smokers (18+) making their first serious quit attempt were compiled from 4504 individuals enrolled in the Ontario Tobacco Survey, a representative telephone survey of Ontario adults, which followed smokers every 6 months for up to 3 years. Use of cessation aids at the time of initial report of a quit attempt was analyzed. A flexible parametric survival model was developed to model length of abstinence, controlling for potential confounders.

Results
The best fit model found knots at 3, 13, 43, and 212 days abstinent, suggesting different rates of relapse in the periods marked by those days. Use of the patch and varenicline was associated with lower rates of relapse, but no positive effect was found for bupropion or nicotine gum. The effectiveness of the patch reversed in effect after the first month of abstinence.

Conclusions
This study is one of few reports of long-term quitting in a population-representative sample and demonstrates that the effectiveness of some pharmacological cessation aids (the patch and varenicline can be seen in a population sample). Previous failures in real-world studies of the effectiveness of smoking cessation aids may reflect differences in the products individuals use and differences in the timing of self-reported cessation.

Implications
While a large number of randomized controlled trials have shown the efficacy of many pharmaceutical smoking cessation aids, evidence of their effectiveness in observational studies in the real world is ambiguous. This study uses a longitudinal cohort of a representative sample of smokers to show that the effectiveness of pharmaceutical cessation aids can be demonstrated in real-world use situations, but effectiveness varies by product type and has time-varying effects.
Who Wants to Switch? Gauging Patient Interest in Novel Antiretroviral Therapies
Authors: Derrick Caroline B , Ostermann Jan , Weissman Sharon B , Hobbie Amy , Alshareef Noor , Weinhold Andrew , Yelverton Valerie , Thielman Nathan M 
Published: September 2018

Abstract
Study participants were asked about their interest in switching to novel drug delivery systems that reduce the dosing frequency of antiretroviral regimens. Across a diverse, treatment-experienced cohort, we describe greatest interest in switching to an oral regimen taken once weekly, followed by injections taken every other month and twice-annual implants.
Frequencies and severity of injection-site lesions in muscles from rounds of cow carcasses
Authors: Pfeiffer Morgan M , Mafi Gretchen G , Ramanathan Ranjith , Neilson Taylor M , VanOverbeke Deborah L 
Published: September 2018

AbstractThe frequency and severity of injection-site lesions in the outside round muscles of both beef and dairy cattle were evaluated through a series of audits. Audits were conducted in 2017 on 1,300 rounds from dairy and beef cows from seven locations throughout the United States. Outside round muscles were butterfly cut into 1.25-cm slices and, if present, lesions were counted, measured, and categorized. Rounds from beef (7%) and dairy cattle (15%) had at least one injection-site lesion present. The most common location of injection-site lesions was quadrant 2 and 3, which contained both the biceps femoris and semitendinosus muscles. Injection-site lesions were more frequent (P &lt; 0.05) in the biceps femoris for both beef and dairy rounds. Clear lesions accounted for 57% of injection-sites in both beef and dairy rounds, whereas metallic lesions made up 23% of the total in beef and 25% in dairy. Overall, there was a dramatic decline in the frequency (P &lt; 0.05) of injection-site lesions since the 1998 (24 and 45 percentage units greater in beef and dairy rounds, respectively) and 2000 audits (13 and 20 percentage units greater in beef and dairy rounds, respectively). Educational programs, such as Beef Quality Assurance (BQA) and requirements for BQA training, have resulted in substantial improvements in beef management practices for both the beef and dairy industries.
Single Molecule Visualization of Cardiac Myosin-Binding Protein C N-terminal Fragments Interacting with Thin Filaments: Mechanisms of Calcium Sensitization
Authors: Inchingolo Alessio V. , Previs Samantha Beck , Previs Michael J. , Warshaw David M. , Kad Neil M. 
Published: September 2018

AbstractCardiac muscle contraction is activated by calcium binding to troponin and the consequent motion of tropomyosin on actin within the sarcomere. These movements permit myosin binding, filament sliding and motion generation. One potential mechanism by which the N-terminal domains of cardiac myosin-binding protein C (cMyBP-C) play a modulatory role in this activation process is by cMyBP-C binding directly to the actin-thin filament at low calcium levels to enhance the movement of tropomyosin. To determine the molecular mechanisms by which cMyBP-C enhances myosin recruitment to the actin-thin filament, we directly visualized fluorescently-labelled cMyBP-C N-terminal fragments and GFP-labelled myosin molecules binding to suspended actin-thin filaments in a fluorescence-based single molecule microscopy assay. Binding of the C0C3 N-terminal cMyBP-C fragment to the thin filament enhanced myosin association at low calcium levels. However, at high calcium levels, C0C3 bound cooperatively, blocking myosin binding. Dynamic imaging of thin filament-bound Cy3-C0C3 molecules demonstrated that these fragments diffuse along the thin filament before statically binding, suggesting a mechanism that utilizes a weak-binding mode to search for access to the thin filament and a tight-binding mode to sensitize the thin filament to calcium and thus, enhance myosin binding. Although shorter N-terminal fragments (Cy3-C0C1 and Cy3-C0C1f) bound to the thin filaments and displayed modes of motion on the thin filament similar to that of the Cy3-C0C3 fragment, the shorter fragments were unable to sensitize the thin filament. Therefore, the longer N-terminal fragment (C0C3) must possess the requisite domains needed to bind specifically to the thin filament in order for the cMyBP-C N terminus to modulate cardiac contractility.
Neurochemical correlates of scene processing in the precuneus/posterior cingulate cortex: a multimodal fMRI and 1H-MRS study
Authors: Costigan Alison G. , Umla-Runge Katja , Evans C. John , Hodgetts Carl J. , Lawrence Andrew D. , Graham Kim S. 
Published: September 2018

AbstractPrecuneus/posterior cingulate cortex (PCu/PCC) are key components of a midline network, activated during rest but also in tasks that involve construction of scene or situation models. Despite growing interest in PCu/PCC functional alterations in disease, the underlying neurochemical modulators of PCu/PCC’s task-induced activity are largely unstudied. Here, a multimodal imaging approach was applied to investigate whether inter-individual differences in PCu/PCC fMRI activity, elicited during perceptual discrimination of scene stimuli, were correlated with local brain metabolite levels, measured during resting-state 1H-MRS. Forty healthy young adult participants (12 male) completed an fMRI perceptual odd-one-out task for scenes, objects and faces. 1H-MRS metabolites N-acetyl-aspartate (tNAA), glutamate (Glx) and γ-amino-butyric acid (GABA+) were quantified via PRESS and MEGA-PRESS scans in a PCu/PCC voxel and an occipital (OCC) control voxel. Whole brain fMRI revealed a cluster in right dorsal PCu/PCC that showed a greater BOLD response to scenes versus faces and objects. When extracted from an independently defined PCu/PCC region of interest, scene activity (versus faces and objects and also versus baseline) was positively correlated with PCu/PCC, but not OCC, tNAA. A complementary fMRI analysis restricted to the PCu/PCC MRS voxel area identified a significant PCu/PCC cluster, confirming the positive correlation between scene-related BOLD activity and PCu/PCC tNAA. There were no correlations between PCu/PCC fMRI activity and Glx or GABA+ levels. These results demonstrate, for the first time, that scene activity in PCu/PCC is linked to local tNAA levels, identifying a neurochemical influence on inter-individual differences in the task-driven activity of a key brain hub.
Streptococcus salivarius - a potential salivary biomarker for orofacial granulomatosis and Crohn’s disease?
Authors: Goel Rishi M. , Prosdocimi Erica M. , Amar Ariella , Omar Yasmin , Escudier Michael P. , Sanderson Jeremy D. , Wade William G. , Prescott Natalie J. 
Published: September 2018

AbstractObjectiveOrofacial granulomatosis (OFG) is a rare disease characterised by chronic, non-caseating, granulomatous inflammation primarily affecting the oral cavity. Histologically, it is similar to Crohn’s disease (CD) and a proportion of patients have both OFG and CD. The cause of OFG remains elusive but it has been suggested that microbial interactions may be involved. The aim of this study was to compare the salivary microbial composition of subjects with OFG and/or CD and healthy controls.Design261 subjects were recruited, of whom 78 had OFG only, 40 had both OFG and CD, 97 had CD only with no oral symptoms and 46 were healthy controls. Bacterial community profiles were obtained by sequencing the V1-V3 region of the 16S rRNA gene.ResultsThere were no differences in richness or diversity of the salivary bacterial communities between patient groups and controls. The relative abundance of the Streptococcus salivarius-group were raised in patients with OFG or CD only compared to controls while that of the Streptococcus mitis -group was lower in CD compared to both OFG and controls. One S. salivarius oligotype made the major contribution to the increased proportions seen in patients with OFG and CD.ConclusionThe salivary microbiome of individuals with OFG and CD was similar to that found in health although the proportions of S. salivarius, a common oral Streptococcus were raised. One specific strain-level oligotype was found to be primarily responsible for the increased levels seen.
A Cortico-Basal Ganglia Model for choosing an optimal rehabilitation strategy in Hemiparetic Stroke
Authors: Narayanamurthy Rukhmani , Jayakumar Samyukta , Elango Sundari , Muralidharan Vignesh , Chakravarthy V. Srinivasa 
Published: September 2018

AbstractTo facilitate the selection of an optimal therapy for a stroke patient with upper extremity hemiparesis, we propose a cortico-basal ganglia model capable of performing reaching tasks under normal and stroke conditions. The model contains two hemispherical systems, each organized into an outer sensory-motor cortical loop and an inner basal ganglia (BG) loop, controlling their respective hands. In addition to constraint induced movement therapy (CIMT), the model performs both unimanual and bimanual reaching tasks and the simulation results are in congruence with the experiment conducted by Rose et al (2004). Based on our study on the effect of lesion size on arm performance, we hypothesize that the effectiveness of a therapy could greatly depend on this factor. By virtue of the model’s ability to capture the experimental results effectively, we believe that it can serve as a benchmark for the development and testing of various rehabilitation strategies for stroke.