bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted mutagenesis of the ryanodine receptor by Platinum TALENs causes slow swimming behaviour in Pacific bluefin tuna (Thunnus orientalis)
Authors: Higuchi Kentaro , Kazeto Yukinori , Ozaki Yuichi , Yamaguchi Toshiya , Shimada Yukinori , Ina Yoshiaki , Soma Satoshi , Sakakura Yoshitaka , Goto Rie , Matsubara Takahiro , Nishiki Issei , Iwasaki Yuki , Yasuike Motoshige , Nakamura Yoji , Matsuura Aiko , Masuma Shukei , Sakuma Tetsushi , Yamamoto Takashi , Masaoka Tetsuji , Kobayashi Takanori , Fujiwara Atushi , Gen Koichiro 
Published: September 2019

AbstractIn bluefin tuna aquaculture, high mortalities of hatchery-reared juveniles occur in sea cages owing to wall collisions that are caused by high-speed swimming in panic due to changes in illuminance. Here, we report that targeted gene mutagenesis of the ryanodine receptor (RyR1b), which allows the sarcoplasmic reticulum to release Ca2+ in fast skeletal muscle, using highly active Platinum TALENs caused slow swimming behaviour in response to external stimuli in Pacific bluefin tuna (PBT) larvae. This characteristic would be a useful trait to prevent wall collisions in aquaculture production. A pair of Platinum TALENs targeting exons 2 and 43 of the PBT ryr1b gene induced deletions in each TALEN target site of the injected embryos with extremely high efficiency. In addition, ryr1b expression was significantly decreased in the mutated G0 larvae at 7 days after hatching (DAH). A touch-evoked escape behaviour assay revealed that the ryr1b-mutated PBT larvae swam away much less efficiently in response to mechanosensory stimulation at 7 DAH than did the wild-type larvae. Our results demonstrate that genome editing technologies are effective tools for determining the functional characterization of genes in a comparatively short period, and create avenues for facilitating genetic studies and breeding of bluefin tuna species.
Extracorporeal Life Support Enhances the Forward Pressure Wave to Cause a Mismatch between Cardiac Oxygen Demand and Supply
Authors: Wang Chih-Hsien , Chang Ru-Wen , Wu En- Ting , Hsiao Yi-Jing , Wu Ming-Shiou , Yu Hsi-Yu , Chen Yih-Sharng , Lai Liang-Chuan , Yu Sung-Liang 
Published: September 2019

AbstractExtracorporeal life support (ECLS) is a world-famous life-saving method. Until now, changes in arterial wave properties due to ECLS have remained unexamined. In this study, we determined the effects of ECLS on arterial wave properties and ventricular/arterial coupling in male Wistar rats with the measured aortic pressure alone. Ascending aortic pressure signals were measured before ECLS and at 30, 60, and 90 min after weaned off. The aortic pressure signal then calculated by fourth-order derivative to obtain an assumed triangular flow wave. The ratio of mean systolic pressure to mean diastolic pressure (Pms/Pmd), a parameter for evaluating the matching condition between myocardial oxygen demand and supply, was significantly higher after ECLS. The magnitude of forward pressure (|Pf|) augmented by ECLS prevailed over the backward pressure (|Pb|), leading to a decline in wave reflection factor. Pms/Pmd was positively linearly correlated with |Pf| (Pms/Pmd = 0.9177 + 0.0078 × |Pf|, r = 0.8677; P < 0.0001). These findings suggest that |Pf| was a predominant factor responsible for the mismatch between the myocardial oxygen demand and supply in rats after ECLS phase of experiment.
Age- and sex-dependent role of osteocytic pannexin1 on bone and muscle mass and strength
Authors: Aguilar-Perez Alexandra , Pacheco-Costa Rafael , Atkinson Emily G. , Deosthale Padmini , Davis Hannah M. , Essex Alyson L. , Dilley Julian E. , Gomez Leland , Rupert Joseph E. , Zimmers Teresa A. , Thompson Roger J. , Allen Matthew R. , Plotkin Lilian I. 
Published: September 2019

AbstractPannexins (Panxs), glycoproteins that oligomerize to form hemichannels on the cell membrane, are topologically similar to connexins, but do not form cell-to-cell gap junction channels. There are 3 members of the family, 1–3, with Panx1 being the most abundant. All Panxs are expressed in bone, but their role in bone cell biology is not completely understood. We now report that osteocytic Panx1 deletion (Panx1Δot) alters bone mass and strength in female mice. Bone mineral density after reaching skeletal maturity is higher in female Panx1Δot mice than in control Panx1fl/fl mice. Further, osteocytic Panx1 deletion partially prevented aging effects on cortical bone structure and mechanical properties. Young 4-month-old female Panx1Δot mice exhibited increased lean body mass, even though pannexin levels in skeletal muscle were not affected; whereas no difference in lean body mass was detected in male mice. Furthermore, female Panx1-deficient mice exhibited increased muscle mass without changes in strength, whereas Panx1Δot males showed unchanged muscle mass and decreased in vivo maximum plantarflexion torque, indicating reduced muscle strength. Our results suggest that osteocytic Panx1 deletion increases bone mass in young and old female mice and muscle mass in young female mice, but has deleterious effects on muscle strength only in males.
Synergy between B cell receptor/antigen uptake and MHCII peptide editing relies on HLA-DO tuning
Authors: Jiang Wei , Adler Lital N. , Macmillan Henriette , Mellins Elizabeth D. 
Published: September 2019

AbstractB cell receptors and surface-displayed peptide/MHCII complexes constitute two key components of the B-cell machinery to sense signals and communicate with other cell types during antigen-triggered activation. However, critical pathways synergizing antigen-BCR interaction and antigenic peptide-MHCII presentation remain elusive. Here, we report the discovery of factors involved in establishing such synergy. We applied a single-cell measure coupled with super-resolution microscopy to investigate the integrated function of two lysosomal regulators for peptide loading, HLA-DM and HLA-DO. In model cell lines and human tonsillar B cells, we found that tunable DM/DO stoichiometry governs DMfreeactivity for exchange of placeholder CLIP peptides with high affinity MHCII ligands. Compared to their naïve counterparts, memory B cells with less DMfreeconcentrate a higher proportion of CLIP/MHCII in lysosomal compartments. Upon activation mediated by high affinity BCR, DO tuning is synchronized with antigen internalization and rapidly potentiates DMfreeactivity to optimize antigen presentation for T-cell recruitment.
RETRACTED ARTICLE: Chondro-protective effects of polydatin in osteoarthritis
through its effect on restoring dysregulated autophagy via modulating MAPK, and PI3K/Akt
signaling pathways
Authors: Wu Zhengyuan , Luan Zhiwei , Zhang Xiaohan , Zou Kai , Ma Shiting , Yang Zhenyi , Feng Wenyu , He Mingwei , Jiang Linhua , Li Jia , Yao Jun 
Published: September 2019

AbstractOsteoarthritis (OA) is a degenerative disease of the cartilage that is
prevalent in the middle-aged and elderly demography. Polydatin (PD), a natural
resveratrol glucoside, has shown significant anti-inflammatory and anti-arthritic
potential in previous studies. This study was designed to evaluate the therapeutic
properties of PD in vitro and in vivo, and elucidate their underlying mechanisms. The
expression levels of all relevant factors were evaluated by qRT-PCR, western
blotting, and immunohistochemistry (IHC) where suitable. Reactive oxygen species
(ROS) and apoptosis were analyzed using the suitable probes and flow cytometry. The
histological evidence of cartilage was assessed in rat models, moreover, the several
serum cytokines levels and autophagy levels were evaluated. The result showed PD
displayed significant chondro-protective effects, inferred in terms of reduced
inflammation and cartilage degradation, apoptosis inhibition, and lower ROS
production. The protective effects were attenuated by the autophagy inhibitor 3-MA,
indicating a mediating role of autophagy in PD action. Mechanistically, PD exerted
its effects by inhibiting the MAPK and PI3K/Akt signaling pathways which led to the
down-regulation of mTOR. In conclusion, PD protects against cartilage degeneration
by activating the autophagy flux in the chondrocytes via the MAPK and PI3K/Akt
signaling pathways.
Challenging judicial impartiality
Authors: Plug H. José 
Published: September 2019

AbstractImpartiality is one of the core values underlying the administration of justice. A complaint about a judge’s supposed lack of impartiality may be filed on the grounds of the judge’s verbal behavior. In this article I will analyze complaints that concern the judge’s use of rhetorical questions during court hearings. I will explore what role these complaints may play in the strategic maneuvering of a party who seeks the judge’s disqualification.
Research Priorities in Family Caregiving: Process and Outcomes of a Conference on Family-Centered Care Across the Trajectory of Serious Illness
Authors: Harvath Theresa A , Mongoven Jennifer M , Bidwell Julie T , Cothran Fawn A , Sexson Kathryn E , Mason Diana J , Buckwalter Kathleen 
Published: September 2019

Abstract
The number of older adults living with functional decline and serious illness is growing exponentially at a time when availability of both family and professional caregivers is strained. Achieving optimal outcomes for this vulnerable population involves advancing the knowledge needed to improve the quality of care delivered by families, health professionals, and community programs. Recent reports from National Institute of Health and the National Academy of Science, Engineering and Medicine have called for the identification of gaps in key areas of family caregiving intervention research. In March 2018, the Family Caregiving Institute at UC Davis convened an invitational meeting of over 50 thought leaders in family caregiving—representing service agencies, funding organizations, and academia—to participate in the Research Priorities in Caregiving Summit: Advancing Family-Centered Care across the Trajectory of Serious Illness. Using an iterative process, attendees identified the top 10 research priorities and created research priority statements that incorporated a definition of the priority topic, rationale for the priority; problem(s) to address; priority population(s); and example research topics. The research priority statements serve as a roadmap for research development that will address the most significant gaps in the caregiving field.
Mucosal Biomarker of Innate Immune Activation Predicts Response to Vedolizumab in Crohn’s Disease
Authors: Osterman Mark T , Gordon Ilyssa O , Davis Elisabeth M , Ciorba Matthew , Glover Sarah C , Abraham Bincy , Khan Freeha , Guo Xueyan , Yee Eric U , Allard Felicia D , Claggett Brian , Shen Bo , Liu Julia J 
Published: September 2019

Abstract

Objective
Mucosal barrier dysfunction plays a crucial role in intestinal inflammation in Crohn’s disease (CD). Intestinal epithelial cell (IEC) death resulting from innate immune activation, termed pyroptosis, was recently found to be a cause of this barrier defect. The aim of this study was to determine the predictive value of pretreatment ileal biopsy pyroptosis as a biomarker for clinical response to vedolizumab in CD.

Design
Crohn’s disease patients ranging 18 to 80 years old from 5 IBD centers with pre-vedolizumab ileal biopsies during colonoscopy were enrolled. Biopsies were stained for activated caspases, and levels of ileal IEC pyroptosis levels were quantified. The primary outcome was clinical response 6 months after therapy, defined as a reduction of Harvey-Bradshaw Index (HBI) of ≥5 points from baseline. Secondary outcomes included clinical remission, defined as HBI &lt;5, and endoscopic improvement, as measured by the Simple Endoscopic Score for Crohn’s Disease (SES-CD).

Results
One hundred CD patients (45 male, 55 female), median age 47 (19, 78) years, were included; clinical response rate was 60%, and clinical remission was 36%. The response rate in patients with ileal pyroptosis &lt;14 positive cells per 1000 IECs was significantly higher than those above the threshold: 89% (25 of 28) vs 49% (35 of 72), odds ratio (OR) 8.8 (95% CI, 2.3–48.6; P &lt; 0.001). Corresponding remission rates were 54% (15 of 28) vs 29% (21 of 72; OR 2.8 [1.03–7.59; P = 0.036]). For endoscopic improvement, ileal pyroptosis of 22 positive cells per 1000 IECs was the optimal threshold that determines the magnitude SES-CD change.

Conclusions
Ileal biopsy IEC pyroptosis was predictive of clinical response and endoscopic improvement to vedolizmab in CD patients.
Melanin Concentrating Hormone Signaling Deficits in Schizophrenia: Association with Memory and Social Impairments and Abnormal Sensorimotor Gating
Authors: Vawter Marquis P , Schulmann Anton , Alhassen Lamees , Alhassen Wedad , Hamzeh Abdul Rezzak , Sakr Jasmine , Pauluk Lucas , Yoshimura Ryan , Wang Xuejie , Dai Qi , Sanathara Nayna , Civelli Olivier , Alachkar Amal 
Published: September 2019

Abstract

Background
Evidence from anatomical, pharmacological, and genetic studies supports a role for the neuropeptide melanin concentrating hormone (MCH) system in modulating emotional and cognitive functions. Genome wide association (GWA) studies revealed a potential association between the MCH receptor (MCHR1) gene locus and schizophrenia and the largest GWA study conducted to date shows a credible GWA.

Methods
We analyze MCHR1 and pro-melanin concentrating hormone (PMCH) RNA-Seq expression in the prefrontal cortex in schizophrenia patients and healthy controls. Disruptions in the MCH system were modeled in the mouse brain by germline deletion of MCHR1 and by conditional ablation of MCH expressing neurons using a Cre-inducible diphtheria toxin (iDTR) system.

Results
MCHR1 expression is decreased in the prefrontal cortex of schizophrenia samples (FDR p< 0.05, CommonMind and PsychEncode combined datasets, N = 901) while PMCH is below the detection threshold. MCHR1 expression decreased with aging (p = 6.6E-57) in human dorsolateral prefrontal cortex. The deletion of MCHR1 was found to lead to behavioral abnormalities mimicking schizophrenia-like phenotypes: hyperactivity, increased stereotypic and repetitive behavior, social impairment, impaired sensorimotor gating, and disrupted cognitive functions. Conditional ablation of PMCH neurons increased repetitive behavior and produced a deficit in sensorimotor gating.

Conclusions
Our study indicates that early disruption of the MCH system interferes with neurodevelopmental processes which may contribute to the pathogenesis of schizophrenia. Further neurobiological research on the developmental timing and circuits that are affected by MCH may lead to a therapeutic target for early prevention of schizophrenia.
A full treatment of peculiar velocities on the reionization light cone
Authors: Chapman Emma , Santos Mario G 
Published: September 2019

ABSTRACT
Accurate simulations of the 21-cm signal from the Epoch of Reionization require the generation of maps at specific frequencies given the values of astrophysical and cosmological parameters. The peculiar velocities of the hydrogen atoms producing the 21-cm radiation result in a shift in the observed frequency of the 21-cm radiation and changes the amplitude of the signal itself. This is not an effect we can remove but instead needs to be accurately modelled to ensure we infer the correct physical parameters from an observation. We describe the full calculation of the distortion of the 21-cm signal, and propose a new code that integrates the 21-cm intensity along the line of sight for each individual light cone pixel to fully capture the intensity contributions from multiple redshifts. This algorithm naturally deals with the typical divergences found in standard approaches, allowing for large optical depths and 21-cm absorption events at high redshifts. We find the new method results in up to a 60 per cent decrease in power on the largest scales on the sky, and an increase of over 80 per cent on the smallest scales on the sky. We find that the new implementation of the light cone results in a longer tail of bright temperatures in the brightness temperature distribution, as a result of the successful circumventing of a previous cap that had to be implemented to avoid a divergence in the brightness temperature. We conclude that this full treatment of the evolution of the light cone pixel can be an important effect.
A novel approach for the analysis of the geometry involved in determining light curves of pulsars
Authors: Viganò Daniele , Torres Diego F 
Published: September 2019

ABSTRACT
In this work, we introduce the use of the differential geometry Frenet–Serret equations to describe a magnetic line in a pulsar magnetosphere. These equations, which need to be solved numerically, fix the magnetic line in terms of their tangent, normal, and binormal vectors at each position, given assumptions on the radius of curvature and torsion. Once the representation of the magnetic line is defined, we provide the relevant set of transformations between reference frames; the ultimate aim is to express the map of the emission directions in the star corotating frame. In this frame, an emission map can be directly read as a light curve seen by observers located at a certain fixed angle with respect to the rotational axis. We provide a detailed step-by-step numerical recipe to obtain the emission map for a given emission process, and give a set of simplified benchmark tests. Key to our approach is that it offers a setting to achieve an effective description of the system’s geometry together with the radiation spectrum. This allows to compute multifrequency light curves produced by a specific radiation process (and not just geometry) in the pulsar magnetosphere, and intimately relates with averaged observables such as the spectral energy distribution.
Sleep stage dynamics in young patients with sleep bruxism
Authors: Kishi Akifumi , Haraki Shingo , Toyota Risa , Shiraishi Yuki , Kamimura Mayo , Taniike Masako , Yatani Hirofumi , Kato Takafumi 
Published: September 2019

AbstractStudy ObjectivesWe hypothesized that sleep stage dynamics are different in patients with sleep bruxism (SB) and that these changes are associated with the occurrence of rhythmic masticatory muscle activity (RMMA).MethodsFifteen healthy controls and 15 patients with SB underwent overnight polysomnography. Sleep variables and survival curves of continuous runs of each sleep stage were compared between the groups. Stage transition dynamics and the probability of stage fragmentation were analyzed for three epochs before and after the epoch with RMMA. Survival curves of continuous runs of each sleep stage, terminated with or without RMMA, were also compared.ResultsThere were no significant differences in sleep variables between the groups, except for shorter sleep latency, shorter rapid eye movement (REM) latency, and longer total N1 duration in SB patients than in controls. REM sleep and N2 were significantly less continuous in SB patients than in controls. In the SB group, stage fragmentation probability was significantly increased for the epoch with RMMA compared with the baseline for all stages. Meanwhile, the occurrence of RMMA did not affect the continuity of N2 or REM; however, the occurrence of RMMA was preceded by more continuous N3 runs.ConclusionsSleep stage dynamics differed between SB patients and controls. RMMA does not result in sleep disruption but is likely associated with dissipation of sleep pressure. Less continuity of REM sleep in SB may provide insights into the underlying pathophysiological mechanisms of SB, which may be related to REM sleep processes such as cortical desynchronized states or brainstem activation.
Modeling the cardiometabolic benefits of sleep in older women: exploring the 24-hour day
Authors: Full Kelsie M , Gallo Linda C , Malhotra Atul , Bellettiere John , Kerr Jacqueline , Arredondo Elva , Stone Katie L , Zaslavsky Oleg , Lewis Cora E , Lin Xiaochen , Lacroix Andrea Z 
Published: September 2019

Abstract

Study Objectives
Activities throughout the day, including sleep, sedentary behavior (SB), light-intensity physical activity (LIPA), and moderate to vigorous physical activity (MVPA) are independently associated with cardiometabolic health. Few studies have examined interrelationships between sleep and 24-hour activity and associations with cardiometabolic risk. The objective of this study is to understand how replacing time in SB, LIPA, or MVPA with sleep impacts cardiometabolic risk.

Methods
Women’s Health Initiative OPACH Study participants (N = 3329; mean age = 78.5 ± 6) wore ActiGraph GT3X+ accelerometers 24 hours/7 days. Adjusted linear regression estimated the relationship between sleep duration and cardiometabolic markers. Separately for shorter (&lt;8 hours) and longer (≥8 hours) sleepers, isotemporal substitution models estimated the cross-sectional associations with cardiometabolic markers with reallocating time in daytime activities to or from sleep.

Results
Longer sleep duration was associated with higher insulin, HOMA-IR, glucose, total cholesterol, and triglycerides (all p &lt; 0.05). The associations between sleep duration and C-reactive protein, waist circumference, and body mass index (BMI) were U-shaped (both p &lt; 0.05). For shorter sleepers, reallocating 33 minutes of MVPA to sleep was associated with higher values of insulin, HOMA-IR, glucose, triglycerides, waist circumference, and BMI (0.7%–11.5%). Replacing 91 minutes of SB time with sleep was associated with lower waist circumference and BMI (−1.3%, −1.8%). For long sleepers, shifting 91 minutes of sleep to SB was associated with higher waist circumference and BMI (1.3%, 1.4%).

Conclusions
This is one of the first isotemporal analyses to include objectively measured sleep duration. Results illuminate possible cardiometabolic risks and benefits of reallocating time to or from sleep.
Association of sleep-disordered breathing with total healthcare costs and utilization in older men: the Outcomes of Sleep Disorders in Older Men (MrOS Sleep) study
Authors: Vo Tien N , Kats Allyson M , Langsetmo Lisa , Taylor Brent C , Schousboe John T , Redline Susan , Kunisaki Ken M , Stone Katie L , Ensrud Kristine E 
Published: September 2019

Abstract

Study Objectives
To determine the associations of sleep-disordered breathing (SDB) with subsequent healthcare costs and utilization including inpatient and post-acute care facility stays among community-dwelling older men.

Methods
Participants were 1,316 men (mean age 76.1 [SD = 5.7] years) in the Outcomes of Sleep Disorders in Older Men (MrOS sleep) study (from December 2003 to March 2005), who were enrolled in a Medicare Fee-For-Service plan. Primary SDB measures including apnea hypopnea index (AHI) and oxygen desaturation index (ODI) were collected using in-home level 2 polysomnography. Incident healthcare costs and utilization were determined from claims data in the subsequent 3-year period post-MrOS sleep visit.

Results
Five hundred and twenty-nine (40.2%) men had at least one hospitalization in the 3-year period. Compared with those without sleep apnea (AHI &lt; 5/hour), men with moderate to severe sleep apnea (AHI ≥ 15/hour) had a higher odds of all-cause hospitalization (odds ratio [OR] adjusted for age and site 1.43, 95% confidence interval [CI]: 1.07–1.90). This association was slightly attenuated after further adjustment for traditional prognostic factors including education, body mass index, comorbid medical conditions, and health status (OR = 1.36; 95% CI: 1.01–1.83). Similar associations were observed for ODI. However, measures of SDB were not related to subsequent healthcare costs (total or outpatient) or odds of post-acute skilled nursing facility stay.

Conclusions
Older men with SDB have an increased risk of hospitalization, not entirely explained by the greater prevalence of comorbid conditions, but not higher subsequent total healthcare costs. These findings indicate a need to evaluate the impact of SDB treatment on subsequent healthcare utilization.