bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haematopoietic PI3-kinase delta deficiency profoundly impairs regulatory T-cell biology and thereby protection against atherosclerosis
Authors: Zierden M , Millarg C , Berghausen E.M , Feik L , Baldus S , Vantler M , Rosenkranz S 
Published: November 2020

Abstract

Introduction and purpose
Atherosclerosis is a chronic inflammatory disease of arteries, critically involving leukocytes like macrophages as well as T and B lymphocytes. Macrophages are major drivers of disease through the ingestion of lipoproteins, foam cell formation, and secretion of inflammatory mediators. Although macrophages outnumber other leukocytes in atherosclerotic plaques, T and B cells can shape the course of disease by promoting or mitigating inflammatory responses. Leukocytes highly express the phosphoinositide 3-kinase isoform delta (PI3Kd), exerting a key role in the regulation of immune responses including activation, proliferation, differentiation, and effector functions. Therefore, PI3Kd represents a promising target for the modulation of inflammatory diseases. Consequently, we aimed to analyse the role of PI3Kd in leukocytes during atherogenesis.

Methods and results
To investigate the role of PI3Kd in atherosclerosis, bone marrow from PI3Kd−/− or PI3Kd+/+ mice was transplanted into LDLR−/− mice. After a 6-weeks-challenge by high fat diet, PI3Kd−/− recipient LDLR−/− mice displayed profoundly impaired CD4+ and CD8+ T-cell numbers, CD4+ T-cell activation, CD4+ effector T-cell differentiation, and proatherogenic CD4+ T-helper (Th) 1 responses in para-aortic lymph nodes and spleen compared with PI3Kd+/+ transplanted controls. Surprisingly, the net effect of PI3Kd deficiency was a substantial increase of aortic inflammation and atherosclerosis in LDLR−/− mice. Whereas plaque content and functions of macrophages including foam cell formation, efferocytosis, and cytokine secretion remained unaffected, haematopoietic PI3Kd ablation strongly reduced mature B cells and serum immunoglobulins in LDLR−/− mice. Importantly, PI3Kd deficiency severely impaired numbers and immunosuppressive functions of regulatory CD4+ T cells (Tregs) in spleen, para-aortic lymph nodes, and plaques of LDLR−/− mice. Consequently, adoptive transfer of PI3Kd+/+ Tregs fully constrained the plaque burden in PI3Kd−/− transplanted LDLR−/− mice without affecting B-cell numbers and serum immunoglobulins, whereas adoptively transferred PI3Kd−/− Tregs were unable to relieve atherosclerosis progression.

Conclusions
Here, we demonstrate that PI3Kd plays a crucial role in Tregs, Th1 cells, and B cells during atherogenesis. Lack of PI3Kd signalling specifically in atheroprotective Treg responses outplays its impact on proatherogenic Th1 and B-cell responses, thus leading to aggravated atherosclerosis. Hence, PI3Kd is a key regulator of Treg biology and thereby protects against atherosclerosis.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): Marga and Walter Boll Foundation
Sirt6 regulates autophagy in AGE-treated endothelial cells via KLF4
Authors: Tong J , Chen F , Tang J.N , Ye Z , Liu X.B 
Published: November 2020

Abstract

Aims
To explore Sirt6 regulating autophagy in endothelial cells and the specific mechanism of this function with involvement of KLF4.

Materials and methods
Human umbilical vein endothelial cells were cultured with advanced glycation end products (AGE) treatment. Adv-Sirt6, LV-Sirt6 and LV-KLF4 were used to knockup Sirt6 and knockdown Sirt6 and KLF4 respectively. qPCR and Western Blotting were used to detect the mRNA and protein expression of Sirt6 and KLF4. Laser scanning confocal microscope was used to observe the LC3-II marked autophagosomes. Wildlife BALB/c mice were treated with STZ to produce diabetic mice model. AAV-Sirt6 was injected by tail vein injection to achieve Sirt6 knockdown. HE staining and scanning electron microscope were used to observe the aortic intima condition and autophagosomes number respectively.

Results
In AGE treated HUVECs, knockdown of Sirt6 led to impaired autophagy level along with less expression of autophagic markers LC3-II, Beclin-1, Lamp2 and autophagic marker p62. Knockdown and knockup of Sirt6 directly affected KLF4 expression level but KLF4 didn't have any effect on Sirt6 expression. Knockout of KLF4 offset the augmented autophagy caused by overexpression of Sirt6. In high-fat fed diabetic mice, downregulation of Sirt6 led to better cardiac function along with less autophagosomes and impaired aortic intima integrity.

Conclusions
Sirt6 improves autophagy both in vivo and in vitro and Sirt6 regulates autophagy via KLF4 in HUVECs.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China
The role of matrix metalloproteinase-2 on age-dependent arterial stiffness
Authors: Puspitasari Y.M , Diaz-Canestro C , Sudano I , Flammer A , Bonetti N.R , Wuest P , Liberale L , Constantino S , Paneni F , Ruschitzka F , Beer J.H , Hermann M , Luscher T.F , Camici G.G 
Published: November 2020

Abstract

Introduction
Arterial stiffness is a well-characterized sign of vascular aging. It strongly predicts the development of several cardiovascular diseases (CVD), such as hypertension, stroke and heart failure. The age-dependent stiffening of elastic arteries is primarily attributed to the loss of interlaminar elastic fibers and the increase of collagen fibers. This process is regulated by matrix metalloproteinases (MMPs), including MMP-2. A strong correlation between MMP-2 levels and arterial stiffness has been previously described. However, the causative link between age-dependent arterial stiffness and MMP-2 remains unclear.

Purpose
In this study, we aimed to prospectively investigate the effect of MMP-2 gene silencing on the development of age-dependent carotid stiffness in wild type (WT) mice.

Methods
Pulse Wave Velocity (PWV), as the gold standard technique to assess arterial stiffness, was assessed in the right common carotid artery (RCCA) of C57BL/6 WT mice of various ages ranging between 3 and 25 months. Plasma and vascular levels of MMP-2 on RCCA were also measured and correlate with PWV. Moreover, aged WT male mice (18–21-month-old) were treated for 4 weeks with either MMP-2 siRNA or Scr siRNA via tail vein injection every 4 days and PWV was assessed at baseline, 2 and 4 weeks.

Results
Mouse carotid PWV increased and was positively correlated with age in our in vivo longitudinal study. Increases of vascular and circulating MMP-2 levels were also observed in this study. MMP-2 knockdown by siRNA treatment reduced vascular MMP-2 level (Fig. 1), which in turn attenuated age-dependent carotid stiffening (data not shown). siMMP-2 treated animals also showed an increase of elastin to collagen ratio. Furthermore, enhanced phosphorylation of the activatory eNOS Ser1177 was observed in the siMMP-2 group without affecting the level of total eNOS and Akt phosphorylation. Interestingly, co-immunoprecipitation experiments demonstrated that MMP-2 directly interacts with eNOS and this interaction is augmented with age.

Conclusion
The silencing of MMP-2 attenuates age-dependent carotid stiffness by affecting elastin to collagen ratio and interfering with eNOS activation. Thus, MMP-2 may mediate ECM remodeling and endothelial-dependent vasorelaxation in the development of age-dependent vascular stiffness.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): Swiss National Science Foundation, Foundation for Cardiovascular Research-Zurich Heart House
A case report of cardiac toxicity from barracuda ingestion in Mexico
Authors: Haouzi Alice , Khraishah Haitham , Diamond Jamie , Pinto Duane S 
Published: November 2020

Abstract

Background
Ciguatera toxicity is a fish-borne illness that initially manifests with gastrointestinal symptoms, followed by bizarre neurological symptoms including heat-cold sensation alteration, peculiar feeling of loose teeth, and peripheral neuropathy. However, cardiac manifestations are rare and underreported in the literature.

Case summary
A 73-year-old man presented with symptomatic bradycardia and hypotension after ingestion of barracuda fish in Mexico. He received atropine and dopamine with subsequent improvement in his symptoms, but continued to experience peripheral neuropathic and other odd sensations. Four of his family members ingested the same fish and had similar symptoms. He was managed conservatively and did not require temporary or permanent pacing. Within 1 week from toxin exposure, bradycardia had improved. Heart rate was 40–50 b.p.m. at rest, and he was discharged with an ambulatory monitor. Heart rate had increased to 77 b.p.m. at 1-month follow-up on repeat electrocardiogram (ECG).

Discussion
Although the predominant manifestations of ciguatera toxicity are neurological, cardiac complications tend to be more acute and require attention. Unlike neurological symptoms, bradycardia and hypotension are short-lived, often resolving within a week. Treatment continues to be largely supportive, and patients may require temporary treatment with positive chronotropic agents such as atropine or dopamine.
Assessment of Cognitive-Motor Performance Costs, Task Prioritization, and Adaptation to Dishwashing Under Increased Demand in Older Women With Arthritis
Authors: Mejía Shannon T , Nielsen Karen E , Raichur Vineet , Carmichael Alicia G , Tavares Eugene , Jarvis Jennie , Smith Jacqui , Gonzalez Richard 
Published: November 2020

Abstract

Background and Objectives
Hand arthritis can limit upper-limb instrumental activities of daily living (IADLs) and require the recruitment of additional cognitive and motor resources to support performance. We devised a dual-task protocol for dishwashing to examine cognitive-motor performance costs and prioritizations under increased demands, processes of adaptation, and individual differences in performance costs.

Research Design and Methods
Sixty women with hand arthritis (aged 60–91) completed a standardized dishwashing protocol. Motor demand was increased via the properties of the soap dispenser. Cognitive demand was increased using audial attention and response inhibition tasks. The protocol was completed twice per lab visit on 3 occasions. Response time and dishwashing time provided measures of cognitive and motor task performance. Prioritization was determined by comparing the magnitude of dual-task cost (DTC) across tasks. Adaptation to the dishwashing protocol and novel dispenser was assessed by change in DTC across lab visits. Individual differences in cognitive and physical ability were assessed with the trail making B test and gait speed.

Results
Estimates from linear mixed-effects models revealed that response time increased, whereas dishwashing time decreased, during the dual-task study stages. Cognitive-motor prioritization effects were most pronounced among women with lower cognitive and physical ability. Evidence of prioritization and individual differences in DTC diminished across lab visits.

Discussion and Implications
The pattern of results suggests that older women with arthritis prioritize the motor over cognitive components of dishwashing, a common IADL. Adaptation across lab visits resulted in improved performance, reduced evidence of prioritization, and attenuated differences in DTC across physical and cognitive abilities.
Altruistic Attitudes Among Older Adults: Examining Construct Validity and Measurement Invariance of a New Scale
Authors: Bhatta Tirth R , Kahana Eva , Lekhak Nirmala , Kahana Boaz , Midlarsky Elizabeth 
Published: November 2020

Abstract

Background and Objectives
Scholarly research has established the role of altruism in facilitating human cooperation and prosocial behaviors and highlighted its contribution to psychological well-being. Given the health significance of altruistic attitudes and orientations, we developed a valid and reliable measure of this construct that is suitable for use with older adults.

Research Design and Methods
Based on data from a long-term panel study on adaptation to frailty among older adults (n = 366; mean age = 86 years), we used confirmatory factor analysis to perform construct validation of a five-item Elderly Care Research Center Altruism Scale among older adults (e.g., “Seeing others prosper makes me happy”). Moreover, we examined the invariance of the scale’s factor structure across time and gender using nested models.

Results
Composite reliability (coefficient omega = 0.78), factor loadings (&gt;0.45 with eigenvalue = 2.84) from exploratory factor analysis, and model fit indices (e.g., comparative fit index = 0.999) from confirmatory factor analysis suggest a single factor, supporting a unidimensional reliable construct of altruistic orientation at baseline. The results provided support for configural, metric, and scalar invariance across time. Findings pertaining to measurement invariance across gender confirmed full configural invariance but only offered support for partial metric, scalar, and residual invariance at baseline. Strong correlations among the altruism scale, salient personality traits, psychological well-being, religiosity, and meaning in life help establish construct validity.

Discussion and Implications
The availability of a reliable and valid measure of altruistic attitudes enables a comprehensive evaluation of altruism’s influence on later-life health and well-being.
COVID-19 Pandemic Planning: Simulation Models to Predict Biochemistry Test Capacity for Patient Surges
Authors: Lyon Martha E , Bajkov Andrew , Haugrud Diane , Kyle Barry D , Wu Fang , Lyon Andrew W 
Published: November 2020

Abstract

Background
Patient surges beyond hospital capacity during the initial phase of the COVID-19 pandemic emphasized a need for clinical laboratories to prepare test processes to support future patient care. The objective of this study was to determine if current instrumentation in local hospital laboratories can accommodate the anticipated workload from COVID-19 infected patients in hospitals and a proposed field hospital in addition to testing for non-infected patients.

Methods
Simulation models predicted instrument throughput and turn-around-time for chemistry, ion-selective-electrode, and immunoassay tests using vendor-developed software with different workload scenarios. The expanded workload included tests from anticipated COVID patients in 2 local hospitals and a proposed field hospital with a COVID-specific test menu in addition to the pre-pandemic workload.

Results
Instrumentation throughput and turn-around time at each site was predicted. With additional COVID-patient beds in each hospital, the maximum throughput was approached with no impact on turnaround time. Addition of the field hospital workload led to significantly increased test turnaround times at each site.

Conclusions
Simulation models depicted the analytic capacity and turn-around times for laboratory tests at each site and identified the laboratory best suited for field hospital laboratory support during the pandemic.
Revisiting the Legal Effect of General Assembly Resolutions: Can an Authorising Competence for the Assembly be Grounded in the Assembly’s ‘Established Practice’, ‘Subsequent Practice’ or Customary International Law?
Authors: Barber Rebecca 
Published: November 2020

Abstract
The Security Council’s recent intractability in the face of human rights and humanitarian crises has directed increased attention to the General Assembly’s secondary responsibility for international peace and security. Despite considerable academic attention to the issue, however, significant questions remain regarding the scope of the Assembly’s powers. One of the most significant of these questions is whether the Assembly may authorise conduct that would otherwise be unlawful. This question is important, because while there is good authority to support the proposition that the Assembly may recommend measures up to and including the use of force, if the Assembly is not also competent to authorise such measures, we are left with the unsatisfactory scenario in which the Assembly is legally competent to make recommendations that States may not legally be able to act upon. Drawing on the International Law Commission’s 2018 Draft Articles on Subsequent Agreement and Subsequent Practice, as well as those on Identification of Customary International Law, this article explores whether an authorising competence on the part of the General Assembly can be grounded in the Assembly’s practice. Specifically, it considers whether the Assembly’s practice of recommending and seemingly purporting to authorise coercive measures may amount to ‘established practice’, thus forming part of the ‘rules of the organisation’ within the meaning of the Vienna Convention on the Law of Treaties (VCLT); or alternatively if it can be considered ‘subsequent practice’ within the meaning of the VCLT; or alternatively it may attest to a rule of customary international law.
Using mixture models to examine group difference among jurors: an illustration involving the perceived strength of forensic science evidence
Authors: Kaplan-Damary Naomi , C. Thompson William , Hofstein Grady Rebecca , Stern Hal S 
Published: November 2020

AbstractThe way in which jurors perceive reports of forensic evidence is of critical importance, especially in cases of forensic identification evidence that require examiners to compare items and assess whether they originate from a common source. The current study discusses methods for studying group differences among mock jurors and illustrates them using a reanalysis of data regarding lay perceptions of forensic science evidence. Conventional approaches that consider subpopulations defined a priori are compared with mixture models that infer group structure from the data, allowing detection of subgroups that cohere in unexpected ways. Mixture models allow researchers to determine whether a population comprises subpopulations that respond to evidence differently and then to consider how those subpopulations might be characterized. The reanalysis reported here shows that mixture models can enhance understanding of lay perceptions of an important type of forensic science evidence (DNA and fingerprint comparisons), providing insight into how the perceived strength of that evidence varies as a function of the language forensic experts use to describe their findings. This novel application of mixture models illustrates how such models can be used, more generally, to explore the importance of juror characteristics in jury decision making.
High-cadence, early-time observations of core-collapse supernovae from the TESS prime mission
Authors: Vallely P J , Kochanek C S , Stanek K Z , Fausnaugh M , Shappee B J 
Published: November 2020

ABSTRACT
We present observations from the Transiting Exoplanet Survey Satellite (TESS) of twenty bright core-collapse supernovae with peak TESS-band magnitudes ≲18 mag. We reduce this data with an implementation of the image subtraction pipeline used by the All-Sky Automated Survey for Supernovae (ASAS-SN) optimized for use with the TESS images. In empirical fits to the rising light curves, we do not find strong correlations between the fit parameters and the peak luminosity. Existing semi-analytic models fit the light curves of the Type II supernovae well, but do not yield reasonable estimates of the progenitor radius or explosion energy, likely because they are derived for use with ultraviolet observations while TESS observes in the near-infrared. If we instead fit the data with numerically simulated light curves, the rising light curves of the Type II supernovae are consistent with the explosions of red supergiants. While we do not identify shock breakout emission for any individual event, when we combine the fit residuals of the Type II supernovae in our sample, we do find a &gt;5σ flux excess in the ∼1 d before the start of the light-curve rise. It is likely that this excess is due to shock breakout emission, and that during its extended mission TESS will observe a Type II supernova bright enough for this signal to be detected directly.
Tidally excited oscillations in hot white dwarfs
Authors: Yu Hang , Fuller Jim , Burdge Kevin B 
Published: November 2020

ABSTRACT
We study the flux variation in helium white dwarfs (WDs) induced by dynamical tides for a variety of WD models with effective temperatures ranging from $T=10\, {\rm kK}$ to $T=26\, {\rm kK}$. At linear order, we find the dynamical tide can significantly perturb the observed flux in hot WDs. If the temperature $T\gtrsim 14\, {\rm kK}$, then the dynamical tide may induce a fractional change in the flux by $\gt 1{{\ \rm per\ cent}}$ when the orbital period is $P_{\rm orb}\simeq 20{\!-\!}60\, {\rm min}$. The ratio between the flux modulation due to the dynamical tide and that due to the equilibrium tide (i.e. ellipsoidal variability) increases as the WD’s radius decreases, and it could exceed $\mathcal {O}(10)$ if the WD has a radius R ≲ 0.03 R⊙. Unlike the ellipsoidal variability which is in phase with the orbital motion, the pulsation caused by the dynamical tide may have a substantial phase shift. A cold WD with $T\simeq 10\, {\rm kK}$, on the other hand, is unlikely to show observable pulsations due to the dynamical tide. At shorter orbital periods, the dynamical tide may break and become highly non-linear. We approximate this regime by treating the waves as one-way travelling waves and find the flux variation is typically reduced to 0.1–1 per cent and the excess phase is ∼90° (though with large uncertainty). Even in the travelling-wave limit, the flux perturbation due to dynamical tide could still exceed the ellipsoidal variability for compact WDs with R ≲ 0.02 R⊙. We further estimate the non-linear flux perturbations oscillating at four times the orbital frequency dominated by a self-coupled parent g-mode driving low-order daughter p modes. The non-linear flux variation could be nearly $50{{\ \rm per\ cent}}$ of the linear variation for very hot WD models with $T\gtrsim 26\, {\rm kK}$ and $1{{\ \rm per\ cent}}$ linear flux variation. We thus predict that both the linear and non-linear flux variations due to dynamical tides are likely to have significant observational signatures.
Satellites and central galaxies in SDSS: the influence of interactions on their properties
Authors: Mesa Valeria , Alonso Sol , Coldwell Georgina , Lambas Diego García , Nilo Castellon J L 
Published: November 2020

ABSTRACT
We use SDSS-DR14 to construct a sample of galaxy systems consisting of a central object and two satellites. We adopt projected distance and radial velocity difference criteria and impose an isolation criterion to avoid membership in larger structures. We also classify the interaction between the members of each system through a visual inspection of galaxy images, finding ${\sim}80{{\ \rm per\ cent}}$ of the systems lack evidence of interactions whilst the remaining ${\sim}20{{\ \rm per\ cent}}$ involve some kind of interaction, as inferred from their observed distorted morphology. We have considered separately, samples of satellites and central galaxies, and each of these samples were tested against suitable control sets to analyse the results. We find that central galaxies showing signs of interactions present evidence of enhanced star formation activity and younger stellar populations. As a counterpart, satellite samples show these galaxies presenting older stellar populations with a lower star formation rate than the control sample. The observed trends correlate with the stellar mass content of the galaxies and with the projected distance between the members involved in the interaction. The most massive systems are less affected since they show no star formation excess, possibly due to their more evolved stage and less gas available to form new stars. Our results suggest that it is arguably a transfer of material during interactions, with satellites acting as donors to the central galaxy. As a consequence of the interactions, satellite stellar population ages rapidly and new bursts of star formation may frequently occur in the central galaxy.