bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract MP124: De-palmitoylation of Cysteine 202 of Cyclophilin-D by Calcium is Important for the Activation of the Permeability Transition Pore
Authors: Amanakis Georgios , Sun Junhui , Fergusson Maria , Liu Chengyu , Molkentin Jeff D , Murphy Elizabeth
Published: October 2020

Cyclophilin-D (CypD) is a well-known regulator of the mitochondrial permeability transition pore (PTP), the main effector of cardiac ischemia/reperfusion (I/R) injury characterized by oxidative stress and calcium overload. However, the mechanism by which CypD activates PTP is poorly understood. Cysteine 202 of CypD (C202) is highly conserved across species and can undergo redox-sensitive post-translational modifications, such as S-nitrosylation and oxidation. To study the importance of C202, we developed a knock-in mouse model using CRISPR where CypD-C202 was mutated to a serine (C202S). Hearts from these mice are protected against I/R injury. We found C202 to be abundantly S-palmitoylated under baseline conditions while C202 was de-palmitoylated during ischemia in WT hearts. To further investigate the mechanism of de-palmitoylation during ischemia, we considered the increase of matrix calcium, oxidative stress and uncoupling of ATP synthesis from the electron transport chain. We tested the effects of these conditions on the palmitoylation of CypD in isolated cardiac mitochondria. The palmitoylation of CypD was assessed using a resin-assisted capture (Acyl-RAC). We report that oxidative stress (phenylarsenide) and uncoupling (CCCP) had no effect on CypD palmitoylation (p>0.05, n=3 and n=7 respectively). However, calcium overload led to de-palmitoylation of CypD to the level observed at the end ischemia (1±0.10 vs 0.63±0.09, p=0.012, n=9). To further test the hypothesis that calcium regulates S-palmitoylation of CypD we measured S-palmitoylation of CypD in non-perfused heart lysates from global germline mitochondrial calcium uniporter knock-out mice (MCU-KO), which have reduced mitochondrial calcium and we found an increase in S-palmitoylation of CypD (WT 1±0.04 vs MCU-KO 1.603±0.11, p<0.001, n=6). The data are consistent with the hypothesis that C202 is important for the CypD mediated activation of PTP. Ischemia leads to increased matrix calcium which in turn promotes the de-palmitoylation of CypD on C202. The now free C202 can further be oxidized during reperfusion leading to the activation of PTP. Thus, S-palmitoylation and oxidation of CypD-C202 possibly target CypD to the PTP, making them potent regulators of cardiac I/R injury.
Abstract MP131: The CDK2-FOXO1 Axis Mediates Doxorubicin-induced Cardiomyocyte Apoptosis and Atrophy
Authors: Xia Peng , Chen Jingrui , Liu Yuening , Fletcher Maya , Jensen Brian C , Cheng Zhaokang
Published: October 2020

Recent clinical investigations indicate that anthracycline-based chemotherapy induces early declines in heart mass in cancer patients. A decline in heart mass can be caused by a decrease in cardiac cell number due to exaggerated cell death, and/or a reduction in cell size via atrophy. Our previous study reveals that the anthracycline doxorubicin (DOX) induces apoptotic death of cardiomyocytes through activation of cyclin-dependent kinase 2 (CDK2). However, the signaling pathway downstream of CDK2 remains to be characterized. In addition, it is unclear whether the same pathway also mediates cardiac atrophy. Here we demonstrated that DOX exposure induced CDK2-dependent phosphorylation of forkhead box O1 (FOXO1) at S249, leading to transcription of its pro-apoptotic target gene Bim. In cultured cardiomyocytes, treatment with the small molecule FOXO1 inhibitor AS1842856, or transfection with FOXO1-specific siRNAs protected against DOX-induced apoptosis and mitochondrial damage. Oral administration of AS1842856 in mice hindered apoptosis and prevented DOX-induced decline in left ventricular systolic function. Intriguingly, pharmacologic inhibition of FOXO1 also attenuated DOX-induced cardiac atrophy, likely due to repression of MuRF1, a pro-atrophic FOXO1 target gene. In conclusion, DOX exposure induces CDK2-dependent FOXO1 activation, resulting in cardiomyocyte apoptosis and atrophy. Our results identify FOXO1 as a promising drug target for DOX-induced cardiotoxicity. FOXO1 inhibitors may represent a novel class of therapeutics for cardioprotection during chemotherapy.
Abstract MP133: Development of β-arrestin-biased Positive Allosteric Modulators for the β
1
Adrenergic Receptor
Authors: Wang Jialu , Gokhan Ilhan , Xiong Xinyu , Kahsai Alem W , Jiang Haoran , Pfeiffer Conrad T , Tian William , Pani Biswaranjan , Ahn Seungkirl , Lefkowitz Robert J , Rockman Howard A
Published: October 2020

The β
1
adrenergic receptor (β
1
AR) is a central regulator of cardiac function and an important therapeutic target for cardiac diseases. Two emerging areas of receptor biology are biased agonism: ligand directed selective engagement of a receptor toward either a G protein or β-arrestin transducer; and allosteric modulation: ligands that bind to topographically distinct sites on the receptor to modulate its activity. Advances in these areas have the potential to yield new drugs that precisely enhance cardioprotective effects while limiting untoward detrimental actions.

Compound 6 (Cmpd6) is a newly discovered positive allosteric modulator (PAM) for the β
2
AR. Interestingly, we now show that Cmpd6 has the unique property to enhance the binding affinity of the β-arrestin-biased agonist carvedilol to both the β
2
AR and the β
1
AR, while having minimal effect on the affinity of a panel of agonists and antagonists of the β
1
AR. We further tested the effect of Cmpd6 on β
1
AR signaling induced by a broad range of ligands. Cmpd6 selectively enhanced carvedilol-stimulated ERK activation in a β-arrestin-dependent signaling fashion, while having no effect on carvedilol-induced G protein-dependent cAMP production.

To test the
in vivo
effect of Cmpd6 on cardiac injury, mice were pretreated with carvedilol with or without Cmpd6, then underwent ischemia/reperfusion through the left anterior descending artery ligation. Cell apoptosis was assessed by TUNEL. Carvedilol decreased the level of I/R-induced apoptosis compared to the vehicle-treated animals, and Cmpd6 significantly positively enhanced the anti-apoptotic effects of carvedilol.

In conclusion, we identified Cmpd6 as a potential β-arrestin-biased PAM for the β
1
AR that enhances the cardioprotective effect of carvedilol. Ongoing studies will test Cmpd6 on heart failure post myocardial infarction.
Abstract MP140: Epigenetic Silencing of SERCA2a by Long Noncoding RNA
Lnc-SYNPO
Contributes to Impaired Ca
2+
Homeostasis and Contractility in the Failing Heart
Authors: You Min-Yi , Ho Pei-Jin , Ku Hui-Chun , Wang Shu-Ping , Yang Kai-chien
Published: October 2020

Abnormal sarcolemmal Ca
2+
handling and impaired contractile function owing to sarcoplasmic reticulum/endoplasmic reticulum ATPase 2a (SERCA2a, encoded by
ATP2A2
) downregulation and/or dysfunction are pathognomonic hallmarks of heart failure (HF). There is, however, no clinically proven HF therapy that targets SERCA2a/
ATP2A2
dysregulation directly. Exploiting gene co-expression network analysis using an RNA sequencing dataset generated from human failing and non-failing left ventricular (LV) tissues, we identified long noncoding RNA
lnc-SYNPO
, transcribed from the 3’ untranslated region of
SYNPO2
, as a potential regulator of SERCA2a/
ATP2A2
. Myocardial
lnc-SYNPO
was markedly upregulated during HF and its expression level showed a strong negative correlation (Pearson correlation coefficient=-0.60) with that of SERCA2a/
ATP2A2
in both mouse and human LV. Knockdown of
lnc-SYNPO
in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) increased, whereas overexpression of
lnc-SYNPO
reduced, SERCA2a/
ATP2A2
expression. In addition,
lnc-SYNPO
knockdown reversed endothelin-1 (ET-1) treatment-induced SERCA2a/
ATP2A2
downregulation, impaired Ca
2+
homeostasis and contractile dysfunction in hiPSC-CM. Mechanistically, the depletion of
lnc-SYNPO,
a chromatin-associated nuclear lncRNA, led to increased H3K4me3 and reduced H3K27me3 occupancy at SERCA2a/
ATP2A2
promoter. Chromatin isolation by RNA purification showed direct physical binding between
lnc-SYNPO
and the promoter of SERCA2a/
ATP2A2
. In addition, RNA pull-down assays showed that
lnc-SYNPO
binds to EZH2 and SUZ12, two core components of the polycomb repressor complex 2 (PRC2), suggesting that
lnc-SYNPO
represses SERCA2a/
ATP2A2
expression by recruiting PRC2 complex to the promoter of SERCA2a/
ATP2A2
, leading to epigenetic silencing of SERCA2a/
ATP2A2
. Taken together, these results unveiled a previously undiscovered epigenetic regulatory mechanism of SERCA2a/
ATP2A2
by
lnc-SYNPO
, contributing to impaired myocardial Ca
2+
homeostasis and contractile dysfunction observed with HF. Targeting
lnc-SYNPO
, therefore, could be a novel therapeutic approach to improve Ca
2+
homeostasis and contractile function in the failing human heart.
Abstract MP145: Potential Functions of the Nuclear Basket Associated With Dilated Cardiomyopathy
Authors: Preston Claudia C , Burdine Ryan D , Storm Emily C , Preston Claudia S
Published: October 2020

Objectives:
NUP153 overexpression is clinically correlated with cardiomyopathies, specifically dilated cardiomyopathy (DCM). In combination with the nuclear pore complex (NPC) proteins TPR and NUP50, all three form the basket structure of the NPC that sits within the nuclear envelope. The nuclear basket regulates chromatin dynamics and nuclear export, yet its potential role in cardiopathological development and progression remains unknown. This study was thus carried out to elucidate possible functional roles for nuclear basket nucleoporins in cardiac biology.

Methods:
Human induced pluripotent stem cells (hiPSCs) with endogenous mEGFP tagged NUP153 were differentiated into cardiomyocytes (hiPSC-CMs) via direct differentiation. Beating started ~ Day 10 and contractile areas were analyzed for contraction velocity and magnitude. NUP153 mobility in hiPSCs and hiPSC-CMs was determined by iFRAP experiments. Bioinformatic analysis of a clinical dilated cardiomyopathy dataset (GSE29819) returned a focused ‘nuclear envelope’ gene list that was uploaded to Ingenuity Pathways Analysis for network analysis.

Results:
Within hiPSC-CM beating foci (A), NUP153 mobility decreased and went from a biphasic to a monophasic decay curve (B). Bioinformatic analysis of a DCM dataset (C) revealed expression changes in
TPR
and
NUP50
, with no significant changes in
NUP153
(D).

Conclusions:
A switch to monophasic decay kinetics of NUP153 in hiPSC-CMs suggests prioritization of stable slow pools that may reflect changes in global transcriptome regulation. In DCM, differential nucleoporin gene expression changes implicate discrete functional disruptions within the nuclear basket.
Abstract MP150: Inositol 1,4,5-trisphosphate Receptors Selectively Regulate Detrimental Cardiac Fibrosis by Modulating ER-phagy
Authors: Santulli Gaetano , Morelli Marco , Wang Xujun , Ferrante John , Gambardella Jessica
Published: October 2020

Background:
Therapeutic strategies that specifically target excessive post-ischemic cardiac fibrosis are lacking but desperately needed; thus, it is critical to understand the molecular mechanisms underlying these processes. Genome-wide association studies have revealed an association between inositol 1,4,5-trisphosphate receptors (IP3Rs) and ischemic heart disease. However, experimental studies examining the exact role of IP3Rs in post-ischemic cardiac fibrosis are missing.

Aim:
We hypothesize that IP3Rs play a key role in the regulation of cardiac myofibroblasts (myoFBs) in healing the infarcted heart after myocardial infarction (MI).

Methods:
We performed an integrated set of
in vivo, ex vivo
, and
in vitro
experiments aiming at identifying the functional role of cardiac myoFB IP3Rs in post-ischemic cardiac remodeling. We generated cardiac myo-FB-specific Triple IP3R knock-out (IP3R
TKO
) mice (
Cre/lox
recombination technique; Promoter:
Periostin
), allowing us to overcome the difficulties encountered following the KO or KD of a single (of the three existent) IP3Rs, a strategy that has been shown to induce compensatory upregulation of the other isoforms.

Results:
After MI, IP3Rs are significantly upregulated in myoFBs of the remote regions but not in the scar area. IP3R
TKO
mice display a significantly reduced interstitial cardiac fibrosis and a markedly attenuated myocardial dysfunction following MI compared with control IP3R
flox
or Periostin
Cre
littermates. Moreover, FBs lacking IP3Rs exhibit significantly reduced migratory and secretory capacities, a finding confirmed both in murine and human FBs. Mechanistically, we show that IP3Rs modulate endoplasmic reticulum autophagy (ER-phagy) in primary isolated myoFBs following ischemic injury.

Conclusions:
Taken together, our findings indicate for the first time that IP3Rs are essential for the regulation of post-ischemic cardiac fibrosis.
Abstract MP166:
PRKAR1A
Deficiency Abrogates Cardiac Hypertrophy Through Inhibition of Mitochondrial Fission
Authors: Liu Yuening , Xia Peng , Chen Jingrui , Bandettini Patricia W , Kirschner Lawrence S , Stratakis Constantine A , Cheng Zhaokang
Published: October 2020

Protein kinase A (PKA) is pivotal for cardiac function of human heart, and its dysregulation is involved with various cardiac pathologies. PKA regulatory subunit 1α (R1α, encoded by
PRKAR1A
gene) controls PKA kinase activity by sequestering the PKA catalytic subunits. Patients with
PRKAR1A
mutations are often diagnosed with Carney complex (CNC) and may die prematurely from cardiac complications such as heart failure. However, it remains unknown whether
PRKAR1A
deficiency interferes with normal heart growth during postnatal development. Here, we show that left ventricular mass is reduced in young CNC patients with
PRKAR1A
mutations or deletions. To investigate the impact of
PRKAR1A
deficiency on heart growth, we generated cardiac-specific
PRKAR1A
heterozygous knockout mice. Ablation of the
PRKAR1A
gene in mice increased cardiac PKA activity, reduced heart weight to body weight ratio and cardiomyocyte size without altering contractile function. Cardiomyocyte hypertrophy in response to activation of the α1-adrenergic receptor, was completely abolished by silencing of
PRKAR1A
. Mechanistically, depletion of
PRKAR1A
provoked PKA-dependent phosphorylation of the mitochondrial fission protein Drp1 at S637, resulting in impaired mitochondrial fission and diminished cardiomyocyte hypertrophy. In conclusion,
PRKAR1A
deficiency abrogates cardiac hypertrophy during postnatal development, likely through inhibiting Drp1-mediated mitochondrial fission. Our study provides novel mechanistic insights regarding the cardiac mortality associated with CNC.
Abstract MP171: Transcription Start Site Profiling Defines Promoter and Enhancer Regions for Cardiomyopathy Genes
Authors: Gacita Anthony M , Dellefave-Castillo Lisa , Page Patrick G , Barefield David Y , Wasserstrom Andrew , Puckelwartz Megan , Nobrega Marcelo A , McNally Elizabeth M
Published: October 2020

Background:
Mutations in more than 100 genes lead to dilated, hypertrophic and other forms of cardiomyopathy. Autosomal dominant mutations in the
MYH7
and
LMNA
genes cause autosomal dominant hypertrophic and dilated cardiomyopathy, respectively. Individual mutations display a range of clinical expression from severe early onset disease to minimal or no symptoms. Genetic variation in noncoding gene regulatory regions including enhancers is expected to modify expression of cardiomyopathy genes and disease expressivity. In addition, heart failure is associated a fetal gene re-expression program, mediated by genetic regulatory regions. The contribution of noncoding genetic variation to cardiomyopathy and heart failure has been hampered by limited genome wide descriptions of human cardiac regulatory regions.

Methods and Results:
We used
C
ap
A
nalysis of
G
ene
E
xpression by sequencing (CAGE-seq) to profile the transcriptional start sites in healthy and failed human hearts. CAGE-seq detects the unidirectional signals of gene promoters and the bidirectional signal of transcribed enhancer regions. We identified ~17,000 transcriptional start sites associated with gene promoters and ~1,500 putative enhancer regions active in cardiac tissue. These CAGE-defined regulatory regions carried histone modifications and transcription factor binding properties characteristic of enhancers or promoters. We specifically identified promoter switching and differential enhancer usage between healthy and failed hearts. We intersected CAGE-defined enhancers with additional epigenomic datasets to identify regulatory regions for
MYH7
and
LMNA
genes. We identified 13 putative enhancer regions and validated the functionality of a subset of these regulatory regions using reporter assays and gene editing.

Conclusions:
This CAGE-seq dataset defines the regulatory environment for heart failure. These promoter and enhancer regions could be used to target heart-failure associated gene expression changes. Additionally, this data can be used to identify enhancer regions regulating cardiomyopathy genes.
Abstract MP172: Y-chromosome Gene, Uty, Confers Male Protection Against Pulmonary Hypertension by Mediating Pro-inflammatory Chemokine Effects
Authors: Cunningham Christine M , Umar Soban , Li Min , Doshi Mitali , Ruffenach Gregoire , HONG JASON , Hrncir Haley , Arnold Arthur , Eghbali Mansoureh
Published: October 2020

Background:
Idiopathic pulmonary arterial hypertension (PAH) is a terminal vascular lung disease characterized by increased PA pressure resulting in right ventricular (RV) failure and death. For reasons largely unknown, PAH is up to 4x more prevalent in females. We published that the Y-Chromosome (Chrm) is protective against hypoxia (Hx)-induced pulmonary hypertension (PH) in mice and identified four Y-Chrm genes expressed in the lung. Here, we identify the protective Y-Chrm gene, investigate its mechanism and demonstrate a novel therapeutic approach.

Methods and Results:
To test the effect of Y-Chrm candidate genes on PH development, we knocked down (KD) each Y-Chrm gene via sequential intratracheal instillation of siRNA in the lungs of male mice exposed to Hx. KD of Y-Chrm gene Uty, but none of the other genes, resulted in more severe PH measured by increased RV systolic pressure (RVSP) and decreased pulmonary arterial acceleration time (PAAT) compared to control (n=4/group; RVSP: Uty-KD= 48.93mmHg, Control= 37.33mmHg, p=0.04; PAAT: Uty-KD= 11.88ms, Control= 14.43ms, p=0.01). RNAseq analysis (Uty-KD vs Control) revealed an increase in pro-inflammatory cytokines Cxcl9 (Log2FC: 1.3, p-adjusted=0.05) and Cxcl10 (Log2FC: 0.9, p-adjusted=0.002). We found Cxcl9/10 significantly upregulated in human PAH lungs vs healthy and female PAH lungs vs male (RT-qPCR). Fluorescent in-situ hybridization revealed Uty and Cxcl9/10 expression co-localized in CD68
+
macrophages within the lung. Treatment of human pulmonary artery endothelial cells (PAEC) with Cxcl9/10 resulted in significantly increased apoptosis. We inhibited Cxcl9/10 activity in female rats 14 days post monocrotaline (MCT) injection by treating them with a small molecular inhibitor. Treated rats (n=6) had less severe PH than vehicle-treated controls (n=5) when measured 28-days post MCT (RVSP: Treated= 36.75mmHg, Vehicle=43.62 mmHg, p=0.03; PAAT: Treated= 26.7ms, Vehicle=20 ms, p=0.01; RV hypertrophy index (RV/(LV+IVS)): Treated= 0.48, Vehicle= 0.35, p=0.01).

Conclusion:
Y-Chrm gene, Uty, is protective against PH. Uty inhibition increases pro-inflammatory cytokines Cxcl9/10 which contribute to PAEC death. Inhibition of Cxcl9/10 activity may provide a novel therapy for the treatment of PH.
Abstract MP173: Loss of DCHS1 Promotes Mitral Valve Prolapse Through Cytoskeleton Destabilization
Authors: Moore Reece , Moore Kelsey , Stairley Rebecca , Fulmer Diana B , Guo Lilong , Norris Russell A
Published: October 2020

Introduction:
Mitral valve prolapse (MVP) is a major source of morbidity and mortality and is becoming one of the most common indications for cardiac surgery. Our group has previously reported that MVP is associated with missense mutations in
DCHS1
, a gene widely implicated in tissue development and organization.

Purpose:
We recently performed two-hybrid screens and co-immunoprecipitation assays that define a novel complex between DCHS1, LIX1L, and SEPT9 (DLS). Our current studies investigate the role of this interaction in mitral valve morphogenesis.

Methods:
Wild-type (WT), DCHS1, and/or LIX1L heterozygous neonate murine heart tissue was isolated for primary culture of cardiac fibroblasts (CFs) and analyzed with immunocytochemistry, collagen, compaction, fibrin pillar to post assays, and actin sedimentation assays. Nuclear morphology and chromatin density were conducted for functional read-outs of cytoskeletal aberrations. Morphologic and functional analyses of murine mitral valves were completed.

Results:
Loss of actin architecture and collagen compaction capability were seen in CFs deficient of DCHS1 and/or LIX1L. Delivery of a peptide that disrupted the LIX1L-SEPT9 binding domain likewise destroyed actin architecture and reduced ECM compaction. In-vivo epistasis studies support these findings as mitral valve enlargement was exacerbated in DCHS1/LIX1L compound heterozygote mice compared to DCHS1 and LIX1L heterozygotes. Echocardiography of 11-month DCHS1/LIX1L compound heterozygote mice revealed pronounced MVP and increased left atrium diameter relative to DCHS1 and LIX1L heterozygotes. Filamentous SEPTIN9 localized to the actin ultrastructure and was also lost with disturbance of the DLS complex. Nuclei stretch and chromatin compaction were reduced in DCHS1/LIX1L compound heterozygote CFs. Further, histone H4 modifications were observed in DCHS1 KO mouse embryonic fibroblasts that indicate reductions in gene expression.

Conclusion:
DCHS1, through its interaction with the septin cytoskeleton, must regulate and stabilize actin dynamics in mitral VICs leading to proper valve development. Non-surgical interventions for MVP may be identified through establishing the downstream effects of
DCHS1
mutations in our model.
Abstract MP175: Disruption of the Genome Architecture at the
PRRX1
Locus is Associated With the Pathogenesis of
LMNA
-related Dilated Cardiomyopathy
Authors: Zhang Yuan , Ameen Mohamed , Perea Gil Isaac , Arthur Jennifer , Gavidia Alexandra A , Bharucha Nike , Wang Kevin C , Karakikes Ioannis
Published: October 2020

Background:
LMNA
, a gene encoding A-type lamin proteins (abbreviated as lamin A), is one of the most frequently mutated genes in dilated cardiomyopathy (DCM). The molecular mechanisms underlying cardiomyocyte dysfunction in
LMNA
-related DCM remain elusive, translating to the lack of disease-specific therapies. Lamin A has been shown to play a critical role in genome organization via interactions with the chromatin at specific regions called lamina-associated domains (LADs). However, little is known about whether DCM-causing
LMNA
mutations rearrange the genome conformation and chromosome accessibility. The overarching goal of this study is to define the role of genome organization in
LMNA
-related DCM.

Methods:
LMNA
-related DCM was modeled
in vitro
using cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) from DCM patients carrying a frameshift mutation in the
LMNA
gene (c. 348_349insG; p. K117fs) and isogenic controls. We combined genome-wide single cell functional genomic and epigenomic mapping analyses to define the gene regulation and cis-regulatory interactions in isogenic iPSC-CMs.

Results:
Single-cell RNA-seq revealed global gene dysregulation in
LMNA
mutant compared to isogenic control iPSC-CMs. The homeodomain transcription factor
PRRX1
was significantly upregulated in mutant cells. We showed that LAD integrity is disrupted at the
PRRX1
locus in mutant iPSC-CMs. In agreement, DNA fluorescence
in situ
hybridization (FISH) revealed that the
PRRX1
locus loses peripheral association and relocates towards the transcriptionally active nuclear interior in mutant iPSC-CMs. Correspondingly, single-cell assay for transposase accessible chromatin (ATAC)-seq showed increased chromatin co-accessibility at the
PRRX1
locus, providing a plausible explanation for ectopic activation of
PRRX1
in
LMNA
mutant iPSC-CMs.

Conclusion:
Our data suggest that
LMNA
haploinsufficiency disrupts the structure of LADs, leading to ectopic promoter interactions and altered gene expression in
LMNA
-related DCM iPSC-CMs. We identified
PRRX1
as a promising candidate locus linking changes in LAD organization with gene dysregulation in
LMNA
-related DCM.
Crude Illumination: A Crude Oil Art Inspection
Authors: Vargas Elia , Siembieda Danielle
Published: October 2020

This statement details Elia Vargas's hybrid research art practice and examines alternative histories of crude oil through the social practice of “Art Inspector” Danielle Siembieda. Using art inspection as a creative framework for understanding the entangled nature and culture of the product Crudoleum, invented by American mystic Edgar Cayce, Siembieda evaluates Vargas's crude oil art practice through an assessment of its environmental impacts. The performative inspection speculatively and empirically examines assumptions about the materiality of oil. The purpose of this statement is twofold: to analyze the constitution of Crudoleum, contextualizing it within a history of other petropractices, and to continue Vargas's ongoing critique of the perspective that fossil fuels are ontologically determinate by humans.
YHW the God of Heaven: An interpretatio persica et aegyptiaca of YHW in Elephantine
Authors: Granerød Gard
Published: October 2020

The article discusses the background and implications of the title “the God of Heaven” used as an epithet for YHW in Elephantine. It argues that one should look for the background in the winged symbol used in both Achaemenid and Egyptian iconography. In the Achaemenid–Egyptian context, the title “the God of Heaven” worked as a transmedial, textual reference to the winged symbol that was common to both Achaemenid and Egyptian iconography. In Egypt during the Achaemenid period, the reference of the winged symbol and the title “the God of Heaven” was ultimately the Achaemenid dynasty god Ahura Mazda and perhaps the Egyptian king-protector Horus-Behdety. In the identification of YHW with “the God of Heaven,” we witness an interpretatio persica et aegyptiaca of YHW into the supreme gods of the Achaemenids and the Egyptians.
Synchronicity Research
Authors: Sacco Robert G.
Published: October 2020

Recent years have seen an increased interest in journal articles and books on the topic of synchronicity. Such scholarly interest is consistent with increased cultural attention given to synchronicity and changes to the social context in which spirituality thrives as a personal search for meaning, which may or may not relate to religion. Based on a review of the extant literature on synchronicity, this paper proposes a new taxonomy for better understanding and analyzing the growing phenomenon of individual and cultural interest in synchronicity. The taxonomy consists of four dimensions of synchronicity: Context, Process, Content, and Explanation. The primary contributions of this paper are (a) description and definition of the concept of synchronicity, (b) preliminary proposal of a taxonomy of synchronicity, and (c) outline of a research agenda to conduct theory-based studies of synchronicity phenomena.
Bridging the Knowledge and Business Ecosystems: Resources and Mechanisms for Regional Entrepreneurial Development
Authors: Oliver Zachary T. , Hogan Michael , Albats Ekaterina
Published: October 2020

This article explores a phenomenon of a regional startup ecosystem—its key elements, resources and mechanisms needed for the ecosystem development and growth. Despite famous success stories of such regional ecosystems as Silicon Valley, the literature suggests multiple problems to emerge on the ecosystem development pathway. One of the common issues is a relative disconnect between the knowledge subsystem represented by research centers or universities and a business subsystem represented by mainly large firms. The current understanding of the underlying mechanisms helping to bridge the gap between knowledge and business ecosystems in entrepreneurial regions remain limited. Studying the case of one of the oldest science and technology parks in the world, Research Triangle Park in North Carolina, usa, we explore the development of a regional ecosystem—its elements, challenges and mechanisms to address those. Our findings reveal the key elements, with entrepreneurial networks being one of the most crucial, and explain the difficulties in the elements’ interaction.
A contribution towards the systematics of Magneuptychia Forster, 1964: Caeruleuptychia francisca (Butler, 1870), n. comb. (Lepidoptera: Nymphalidae: Satyrinae)
Authors: Nakahara Shinichi , Kleckner Kaylin , Lamas Gerardo , Huertas Blanca , Willmott Keith R.
Published: October 2020

We here transfer an euptychiine taxon hitherto placed in the polyphyletic genus Magneuptychia
Forster, 1964, to Caeruleuptychia
Forster, 1964. Caeruleuptychia francisca (Butler, 1870), n. comb. is reclassified based on a morphology-based maximum likelihood analysis, which is consistent with ongoing analyses of molecular data. Two putative synapomorphic characters are identified for the “Caeruleuptychia umbrosa clade”, one of which appears to be an unusual characteristic of euptychiine butterflies and is tested by optimizing onto the maximum likelihood tree. We also discuss the systematic placement of three additional enigmatic Caeruleuptychia species. A lectotype is designated for Euptychia francisca, and the genitalia of this species are illustrated here for the first time.
Between “Essential Services” and Culpable Homicide
Authors: Boaz Danielle N.
Published: October 2020

On March 11, 2020, the World Health Organization declared covid-19—the disease caused by the novel coronavirus—a global pandemic. As this coronavirus spread throughout the world, most countries implemented restrictions on public gatherings that greatly limited religious communities’ ability to engage in collective worship. Some religious leaders objected to these regulations, opining that faith would spare their congregants from illness or that their religious freedom is paramount to public health. Meanwhile, growing numbers of covid-19 infections were being traced back to religious leaders or gatherings.

This article explores how governments have balanced freedom of worship and public health during the 2020 pandemic. Through the comparison of controversies in South Korea, India, Brazil and the United States, it highlights the paradoxes in debates about whether to hold religious communities accountable for the spread of this highly contagious and deadly disease.
Impact of population size at a rate of morphological and molecular evolution – the use of an object-oriented model
Authors: Sokół Miłosława
Published: October 2020

A generalization of Moran model of evolution is created using object-oriented method of modelling. A population consists of individuals which have a genotype and a phenotype. The genotype is inherited by descendants and it can mutate. The phenotype is dependent on the genotype. Moreover, the phenotype causes changes in the fitness of the individuals (natural selection which four kinds are defined and analysed). Evolution of the population appears spontaneously. This model is used to analyse how population size influence the rate of evolution. Evolution is manifested by two processes: the increase of the phenotype size (morphological evolution) and number of mutations accumulated on genes (molecular evolution). The rate of evolution increases if population size increases. An adaptive natural selection causes nonlinear changes in the phenotype size and number of mutations accumulated on genes. A competitive natural selection causes linear evolution. A surviving natural selection causes the faster evolution than a reproductive natural selection.
A new species of Miccolamia Bates, 1884 (Coleoptera: Cerambycidae: Lamiinae) from northeast India, with comments on related species
Authors: Sreedevi Kolla , AGOSSADOU ANETTE HOUEFA , KUMAR UMESH , GHATE HEMANT V.
Published: October 2020

A new species of Cerambycidae, Miccolamia (Miccolamia) arunachalensis Sreedevi & Ghate sp. nov. (Lamiinae: Desmiphorini) is described from northeast India. This is the fourth species of Miccolamia from India. Additionally, an updated key to the Indian species is also provided along with comments on related species of the subgenus.
Study of Bonded Wafers by Using a Synchrotron Radiation Transmission X-ray Microscopy for Three-Dimensional Integrated Circuit
Authors: Kim Youn-Jang , Lim Jae-Hong , Choi Kyeong-Keun
Published: October 2020

Synchrotron radiation transmission X-ray microscopy (SRTXM) was applied for visualization of the interfacial layer in bonded wafer pairs. The X-ray energy of 6.54 keV with a monitoring window was utilized to enhance a resolution of transmission X-ray microscopy (TXM). The monitoring
window was designed a locally uncovered area of the bonded wafer pairs to make the thickness of bonded wafers less than 200 μm. The experimental results showed that the technique has sub-micron meter resolution. Also this technique can improve the resolution of the synchrotron X-ray
for nanoelectronics application.
Optoelectronic Hybrid Network Architecture and Its Performance Analysis
Authors: Sun Liping , Liu Xiaozhi
Published: October 2020

Optoelectrical hybrid network technology is introduced into a network based on pure electrical packet switching, which increases network capacity and reduces power consumption. However, the problems of long configuration time and complex management of optical circuit switches affect
the performance of hybrid optoelectrical networks. A new type of hybrid optoelectronic network architecture (HOEP) cooperated by Ethernet packet switching network and optical wavelength routing network was designed in the study. The optical routing network transmitted and received optical
signals by using a circular array waveguide grating router, and transmitted the optical signal carrying data to the target port based on the characteristics of wavelength cyclic routing. The entire process only needed to modulate the data signal, and did not need to configure the optical wavelength
routing network. At the same time, in order to further improve the resource utilization of optical nodes, a kind of intelligent node dynamic reconstruction (RC) algorithm was designed. Combining with network link utilization, cache occupancy, and network load value, this method could dynamically
adjust the usage distribution of optical nodes for reconstruction. During the experiment, the RC algorithm was applied to the HOEP network architecture. Compared with other typical network architectures, the HOEP network proposed in the study can effectively reduce the network cost, power
consumption, and improve network throughput. Moreover, the introduction of RC algorithm and network equipment can make the cost remain within the controllable range, while it can further increase the network throughput and reduce the power consumption of the HOEP network, thereby meeting the
dynamic demand for network bandwidth with larger data traffic.
Analysis and Optimization of Surface Acoustic Wave Floating Electrode Unidirectional Transducers Using Coupling-of-Mode Theory and Finite-Element Method
Authors: Chen C. , Jin J. W. , Xie Y. T.
Published: October 2020

The performance of a floating-electrode unidirectional transducer (FEUDT) with acoustic wavelength of 30 μm is analyzed by coupling-of-mode (COM) theory. In order to extract the COM parameters, a finite element model is developed. The obtained dispersion curve shows frequencies
of four stopband edges different from one another which meets the necessary condition for FEUDT. The phase shift of reflection and transduction centers is derived from the standing wave distributions of electric potential in the whole substrate. When a/p= 0.92 (electrode width/period)
and h/p = 0.015 (electrode height/period), the value of ϕ–ψ = 44.8° (ϕ and ψ are phase angle of reflection and transduction centers, respectively) can be obtained fairly close to the 45°. By analyzing SAW energy transportation
characteristics, FEUDT is found that the more periods it has, the better directivity it exhibits.
Predictability of El Niño Duration Based on the Onset Timing
Authors: Wu Xian , Okumura Yuko M. , DiNezio Pedro N.
Published: October 2020

Analysis of observational data and a long control simulation of the Community Earth System Model, version 1 (CESM1), shows that El Niño events developing in boreal spring to early summer usually terminate after peaking in winter, whereas those developing after summer tend to persist into the second year. To test the predictability of El Niño duration based on the onset timing, perfect model predictions were conducted for three El Niño events developing in April or September in the CESM1 control simulation. For each event, 30-member ensemble simulations are initialized with the same oceanic conditions in the onset month but with slightly different atmospheric conditions and integrated for 2 years. The CESM1 successfully predicts the termination of El Niño after the peak in 95% of the April-initialized simulations and the continuation of El Niño into the second year in 83% of the September-initialized simulations. The predictable component of El Niño duration arises from the initial oceanic conditions that affect the timing and magnitude of negative feedback within the equatorial Pacific, as well as from the Indian and Atlantic Oceans. The ensemble spread of El Niño duration, on the other hand, originates from surface wind variability over the western equatorial Pacific in spring following the peak. The wind variability causes a larger spread in the September-initialized than the April-initialized ensemble simulations due to weaker negative feedback in spring. These results indicate potential predictability of El Niño events beyond the current operational forecasts by 1 year.
Exploratory Geovisualization of the Character and Distribution of American Climate Change Beliefs
Authors: Sugg Johnathan W.
Published: October 2020

Americans remain polarized about climate change. However, recent scholarship reveals a plurality of climate change opinions among the public, with nontrivial support for a range of awareness, risk perceptions, and policy prescriptions. This study uses publicly available opinion estimates to examine the geographic variability of American climate change opinions and maps them as regions that share similarities or differences in the character of their beliefs. The exploratory geovisual environment of a self-organizing map is used to compare the support for 56 different climate opinions across all counties in the United States and arrange them into a spatially coherent grid of nodes. To facilitate the exploration of the patterns, a statistical cluster analysis groups together counties with the most similar climate beliefs. Choropleth maps visualize the clustering results from the self-organizing map. This study finds six groups of climate beliefs in which member counties exhibit a distinct regionality across the United States and share similarities in the magnitude of support for specific opinions. Groups that generally exhibit high or low levels of support for climate change awareness, risk perceptions, and policy prescriptions vary in their relative support for specific opinions. The results provide a nuanced understanding of different types of climate change opinions and where they exist geographically.
Bronchiolitis obliterans organizing pneumonia as the pulmonary manifestation of lupus: A review of three cases
Authors: Baisya Ritasman , Devarasetti Phani Kumar , Uppin Shantveer G , Narayanan Ramakrishna , Rajasekhar Liza , Sreejitha KS
Published: October 2020

Objective

Bronchiolitis obliterans organizing pneumonia (BOOP) is a clinico-patho-radiological diagnosis which rarely presents as a pulmonary manifestation of lupus. In this concise report, organizing pneumonia was found as the sole pulmonary manifestation of SLE in different age groups.

Method

All three patients diagnosed with SLE according to SLICC 2012 classification criteria, were admitted in rheumatology ward of NIMS hospital, Hyderabad, India from May to November, 2018. Their diagnosis of BOOP was either biopsy proven or imaging guided. Review of literature was done with MeSH terms (SLE, BOOP) in PubMed and approximately 10 articles were reviewed including latest of 2019 published in Scientific Reports.

Result

There were three patients – one juvenile lupus and two adults. Two patients were male and one female. All three patients had SLE with high disease activity. They all had organising pneumonia as pulmonary manifestation with other organ involvement. Juvenile patient had a fatal outcome while the others had a good recovery with steroid and immunosuppressive.

Conclusion

BOOP is a rare pulmonary manifestation in lupus. It can be diagnosed early with more precision using computerised tomography of lung without waiting for biopsy report. This will result in a better prognosis by rapid initiation of corticosteroid and immunosuppressive treatment.
Zur Evaluation eines interkulturellen Trainings in einem deutschen Großunternehmen
Authors: Podsiadlowski Astrid , Spieß Erika
Published: October 2020

Die Effektivität von Trainings in einem multinationalen Unternehmen zur Entwicklung interkultureller Fähigkeiten wurde in einer qualitativen Einzelfallstudie multimethodal untersucht. Das Forschungsdesign bestand aus vier Untersuchungsgruppen: Trainingsteilnehmer vs. Nichttrainingsteilnehmer sowie Deutsche und Amerikaner. 42 Fragebögen wurden ausgewertet. Der Fragebogen enthält drei Themenbereiche: Allgemeine Erfahrungen mit der deutschen bzw. amerikanischen Kultur (erhoben über einen projektiven Test und ein Polaritätenprofil bzw. semantisches Differential), Beurteilen und Lösen eines interkulturellen Konfliktes (anhand eines Fallbeispiels mit offenen Fragen) und Erfahrungen in der interkulturellen Zusammenarbeit (offene Fragen). Die Auswertung mit Hilfe eines Kategorienschemas ergab, daß sich Trainingsteilnehmer durch deutlich höhere interkulturelle Kompetenz auszeichnen. Somit zeigte sich, daß Trainings erfolgreich interkulturelle Kompetenz fördern. Besonders empfehlenswert ist, junge Mitarbeiter schon zu Beginn einer interkulturellen Projektarbeit in solche Trainings zu schicken.
Ovary resorption in the Norway lobster (Nephrops norvegicus) and its possible causes with special reference to sperm storage
Authors: Becker Carola , Dick Jaimie T. A. , Mánus Cunningham E. , Lundy Mathieu , Bell Ewen , Eagling Lawrence , Sigwart Julia D.
Published: October 2020

The Norway lobster, Nephrops norvegicus, is an important fisheries species in the North-East Atlantic area. In some circumstances, mature females of Nephrops norvegicus can resorb their ovary rather than completing spawning, but the implications of this phenomenon to reproductive biology and fisheries sustainability are not known. To understand after effects of ovary resorption, we studied long-term demographic data sets (1994–2017) collected from the western Irish Sea and the North Sea. Our considerations focused on potential correlations among the frequency of resorption, female insemination, and body size of resorbing females. Resorption was continuously rare in the western Irish Sea (less than 1%); whereas much higher rates with considerable year-to-year variation were observed in the North Sea (mean 9%). Resorption started in autumn after the spawning season (summer) had passed. The frequency stayed high throughout winter and declined again in spring. As sperm limitation can occur in male-biased fisheries, we expected a lack of insemination could be responsible for resorption, but affected females were indeed inseminated. Resorbing females were significantly larger than other sexually mature females in the North Sea, but the opposite trend was observed in the western Irish Sea. It is therefore possible that other, environmental factors or seasonal shifts, may trigger females to resorb their ovaries instead of spawning. Resorption may as well represent a natural phenomenon allowing flexibility in the periodicity of growth and reproduction. In this sense, observations of annual versus biennial reproductive cycles in different regions may be closely linked to the phenomenon of ovary resorption.
Migraine and sleep disorders: a systematic review
Authors: Tiseo Cindy , Vacca Alessandro , Felbush Anton , Filimonova Tamara , Gai Annalisa , Glazyrina Tatyana , Hubalek Irina Anna , Marchenko Yelena , Overeem Lucas Hendrik , Piroso Serena , Tkachev Alexander , Martelletti Paolo , Sacco Simona ,   on behalf of the European Headache Federation School of Advanced Studies (EHF-SAS)
Published: October 2020

Migraine and sleep disorders are common and often burdensome chronic conditions with a high prevalence in the general population, and with considerable socio-economic impact and costs.

The existence of a relationship between migraine and sleep disorders has been recognized from centuries by clinicians and epidemiological studies. Nevertheless, the exact nature of this association, the underlying mechanisms and interactions are complex and not completely understood. Recent biochemical and functional imaging studies identified central nervous system structures and neurotransmitters involved in the pathophysiology of migraine and also important for the regulation of normal sleep architecture, suggesting a possible causative role, in the pathogenesis of both disorders, of a dysregulation in these common nervous system pathways.

This systematic review summarizes the existing data on migraine and sleep disorders with the aim to evaluate the existence of a causal relationship and to assess the presence of influencing factors. The identification of specific sleep disorders associated with migraine should induce clinicians to systematically assess their presence in migraine patients and to adopt combined treatment strategies.
Genome-wide association studies and whole-genome prediction reveal the genetic architecture of KRN in maize
Authors: An Yixin , Chen Lin , Li Yong-Xiang , Li Chunhui , Shi Yunsu , Zhang Dengfeng , Li Yu , Wang Tianyu
Published: October 2020

Background

Kernel row number (KRN) is an important trait for the domestication and improvement of maize. Exploring the genetic basis of KRN has great research significance and can provide valuable information for molecular assisted selection.

Results

In this study, one single-locus method (MLM) and six multilocus methods (mrMLM, FASTmrMLM, FASTmrEMMA, pLARmEB, pKWmEB and ISIS EM-BLASSO) of genome-wide association studies (GWASs) were used to identify significant quantitative trait nucleotides (QTNs) for KRN in an association panel including 639 maize inbred lines that were genotyped by the MaizeSNP50 BeadChip. In three phenotyping environments and with best linear unbiased prediction (BLUP) values, the seven GWAS methods revealed different numbers of KRN-associated QTNs, ranging from 11 to 177. Based on these results, seven important regions for KRN located on chromosomes 1, 2, 3, 5, 9, and 10 were identified by at least three methods and in at least two environments. Moreover, 49 genes from the seven regions were expressed in different maize tissues. Among the 49 genes, ARF29 (Zm00001d026540, encoding auxin response factor 29) and CKO4 (Zm00001d043293, encoding cytokinin oxidase protein) were significantly related to KRN, based on expression analysis and candidate gene association mapping. Whole-genome prediction (WGP) of KRN was also performed, and we found that the KRN-associated tagSNPs achieved a high prediction accuracy. The best strategy was to integrate all of the KRN-associated tagSNPs identified by all GWAS models.

Conclusions

These results aid in our understanding of the genetic architecture of KRN and provide useful information for genomic selection for KRN in maize breeding.