4D, N=1\mathcal{N}=1 Matter Gravitino Genomics

Adinkras are graphs that encode a supersymmetric representation's transformation laws that have been reduced to one dimension, that of time. A goal of the supersymmetry ``genomics'' project is to classify all 4D, $\mathcal{N}=1$ off-shell supermultiplets in terms of their adinkras. In~previous works, the genomics project uncovered two fundamental isomer adinkras, the cis- and trans-adinkras, into which all multiplets investigated to date can be decomposed. The number of cis- and trans-adinkras describing a given multiplet define the isomer-equivalence class to which the multiplet belongs. A further refining classification is that of a supersymmetric multiplet's holoraumy: the commutator of the supercharges acting on the representation. The one-dimensionally reduced, matrix representation of a multiplet's holoraumy defines the multiplet's holoraumy-equivalence class. Together, a multiplet's isomer-equivalence and holoraumy-equivalence classes are two of the main characteristics used to distinguish the adinkras associated with different supersymmetry multiplets in higher dimensions. This paper focuses on two matter gravitino formulations, each with 20 bosonic and 20 fermionic off-shell degrees of freedom, analyzes them in terms of their isomer- and holoraumy-equivalence classes, and compares with non-minimal supergravity which is also a 20x20 multiplet. This analysis fills a missing piece in the supersymmetry genomics project, as now the isomer-equivalence and holoraumy-equivalence for representations up to spin two in component fields have been analyzed for 4D, $\mathcal{N}=1$ supersymmetry. To handle the calculations of this research effort, we have used the Mathematica software package called Adinkra.m. This package is open-source and available for download at a GitHub Repository. Data files associated with this paper are also published open-source at a Data Repository also on GitHub.Comment: version 3, added self-gadget analysis, edited some text and references, data available at the GitHub Repository https://hepthools.github.io/Data/ that uses the Adinkra.m package available at https://hepthools.github.io/Adinkra

Particle Motion and Scalar Field Propagation in Myers-Perry Black Hole Spacetimes in All Dimensions

We study separability of the Hamilton-Jacobi and massive Klein-Gordon equations in the general Myers-Perry black hole background in all dimensions. Complete separation of both equations is carried out in cases when there are two sets of equal black hole rotation parameters, which significantly enlarges the rotational symmetry group. We explicitly construct a nontrivial irreducible Killing tensor associated with the enlarged symmetry group which permits separation. We also derive first-order equations of motion for particles in these backgrounds and examine some of their properties.Comment: 16 pages, LaTeX2

Efficacy of Galcanezumab for Migraine Prevention in Patients With a Medical History of Anxiety and/or Depression: A Post Hoc Analysis of the Phase 3, Randomized, Double-Blind, Placebo-Controlled REGAIN, and Pooled EVOLVE-1 and EVOLVE-2 Studies

© 2020 Eli Lilly and Company. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC, on behalf of American Headache Society Objective: This post hoc analysis evaluated the efficacy of galcanezumab for the prevention of migraine in patients with and without comorbid anxiety and/or depression. Background: Patients with migraine have a higher risk of anxiety and/or depression. Given the high prevalence of psychiatric symptoms and their potential negative prognostic impact, determining the efficacy of migraine treatments in patients with these comorbidities is important. Methods: The results of 2 phase 3 episodic migraine studies of patients with 4-14 migraine headache days (MHD) per month were pooled. A third chronic migraine study, which was evaluated separately, enrolled patients with ≥15 headache days per month, of which ≥8 had migraine-like features. Patients in all 3 studies were randomized 2:1:1 to placebo, galcanezumab 120 mg, or galcanezumab 240 mg. The efficacy of galcanezumab on migraine was measured in subgroups of patients with anxiety and/or depression (current or past) and patients without. A repeated measures model was used to compare treatment groups within each subgroup and to test for consistency of treatment effect across the anxiety/depression subgroups (subgroup-by-treatment interaction) during the double-blind treatment phases. Results: Among 1773 intent-to-treat patients with episodic migraine, both doses of galcanezumab demonstrated statistically significant improvements relative to placebo in overall number of MHD for the subgroups of patients with anxiety and/or depression (mean change difference from placebo [95% CI]: −2.07 [−2.81, −1.33] for galcanezumab 120 mg [P \u3c.001], −1.91 [−2.78, −1.04] for 240 mg [P \u3c.001]) and without anxiety and/or depression (mean change difference from placebo [95% CI]: −1.92 [−2.36, −1.47] for 120 mg [P \u3c.001], −1.77 [−2.20, −1.33] for 240 mg [P \u3c.001]), as was observed for the secondary outcomes of MHD with acute medication use and functional impairment. Among 1113 intent-to-treat patients with chronic migraine, those with anxiety and/or depression had significant reductions in overall MHD frequency with the 240-mg dose (mean change difference from placebo [95% CI]: −1.92 [−3.52, −0.33]; P =.018), whereas significant reductions were observed at both the 120-mg (mean change difference from placebo [95% CI]: −2.29 [−3.26, −1.31]; P \u3c.001) and 240-mg (−1.85 [−2.83, −0.87]; P \u3c.001) doses in patients without anxiety and/or depressions. Significant reductions (P \u3c.01) in MHD with acute medication use were observed at both doses within both anxiety/depression subgroups and for overall functional impairment for patients without anxiety and/or depression, though neither dose significantly reduced overall functional impairment beyond placebo in the subgroup with anxiety and/or depression. In the episodic and chronic migraine studies, the subgroup-by-treatment interaction was not statistically significant for MHD, MHD with acute medication use, or functional impairment (chronic study only), suggesting a lack of evidence of differential effect between subgroups. Furthermore, differences between subgroups in the mean change differences from placebo, as well as overlapping 95% confidence intervals for the subgroups, indicated lack of a clinical or statistical difference between subgroups for these outcome variables. There was a significantly higher percentage of patients with episodic migraine attaining ≥50%, ≥75%, and 100% reductions, and a higher percentage of patients with chronic migraine attaining ≥50% and ≥75% reductions from baseline with galcanezumab compared with placebo, regardless of medical history of anxiety and/or depression. Conclusions: A medical history of anxiety and/or depression does not seem to interfere with response to galcanezumab among patients with episodic migraine, and both doses of galcanezumab appear efficacious for these individuals regardless of this psychiatric history. Among patients with chronic migraine and comorbid anxiety and/or depression, the 240-mg dose, but not the 120-mg dose, significantly decreased overall MHD, but neither dose resulted in significantly greater functional improvement. Patients with migraine and comorbid anxiety and/or depression often require additional interventions, and this may be more important in chronic migraine

X-ray structure of a soluble Rieske-type ferredoxin from Mus musculus

The X-ray crystal structure of a soluble Rieske ferredoxin from M. musculus was solved at 2.07 Å resolution, revealing an iron–sulfur cluster-binding domain with similar architecture to the Rieske-type domains of bacterial aromatic dioxygenases. The ferredoxin was also shown to be capable of accepting electrons from both eukaryotic and prokaryotic oxidoreductases

Resolvin D1 prevents injurious neutrophil swarming in transplanted lungs

Neutrophils are the primary cell type involved in lung ischemia-reperfusion injury (IRI), which remains a frequent and morbid complication after organ transplantation. Endogenous lipid mediators that become activated during acute inflammation-resolution have gained increasing recognition for their protective role(s) in promoting the restoration of homeostasis, but their influence on early immune responses following transplantation remains to be uncovered. Resolvin D1,

Fibroblast growth factor receptor 1 signaling in adult cardiomyocytes increases contractility and results in a hypertrophic cardiomyopathy

Fibroblast growth factors (FGFs) and their receptors are highly conserved signaling molecules that have been implicated in postnatal cardiac remodeling. However, it is not known whether cardiomyocyte-expressed FGF receptors are necessary or sufficient for ventricular remodeling in the adult heart. To determine whether cardiomyocytes were competent to respond to an activated FGF receptor, and to determine if this signal would result in the development of hypertrophy, we engineered a doxycycline (DOX)-inducible, cardiomyocyte-specific, constitutively active FGF receptor mouse model (αMHC-rtTA, TRE-caFgfr1-myc). Echocardiographic and hemodynamic analysis indicated that acute expression of caFGFR1 rapidly and directly increased cardiac contractility, while chronic expression resulted in significant hypertrophy with preservation of systolic function. Subsequent histologic analysis showed increased cardiomyocyte cross-sectional area and regions of myocyte disarray and fibrosis, classic features of hypertrophic cardiomyopathy (HCM). Analysis of downstream pathways revealed a lack of clear activation of classical FGF-mediated signaling pathways, but did demonstrate a reduction in Serca2 expression and troponin I phosphorylation. Isolated ventricular myocytes showed enhanced contractility and reduced relaxation, an effect that was partially reversed by inhibition of actin-myosin interactions. We conclude that adult cardiomyocytes are competent to transduce FGF signaling and that FGF signaling is sufficient to promote increased cardiomyocyte contractility in vitro and in vivo through enhanced intrinsic actin-myosin interactions. Long-term, FGFR overexpression results in HCM with a dynamic outflow tract obstruction, and may serve as a unique model of HCM

Network analysis of large-scale ImmGen and Tabula Muris datasets highlights metabolic diversity of tissue mononuclear phagocytes

The diversity of mononuclear phagocyte (MNP) subpopulations across tissues is one of the key physiological characteristics of the immune system. Here, we focus on understanding the metabolic variability of MNPs through metabolic network analysis applied to three large-scale transcriptional datasets: we introduce (1) an ImmGen MNP open-source dataset of 337 samples across 26 tissues; (2) a myeloid subset of ImmGen Phase I dataset (202 MNP samples); and (3) a myeloid mouse single-cell RNA sequencing (scRNA-seq) dataset (51,364 cells) assembled based on Tabula Muris Senis. To analyze such large-scale datasets, we develop a network-based computational approach, genes and metabolites (GAM) clustering, for unbiased identification of the key metabolic subnetworks based on transcriptional profiles. We define 9 metabolic subnetworks that encapsulate the metabolic differences within MNP from 38 different tissues. Obtained modules reveal that cholesterol synthesis appears particularly active within the migratory dendritic cells, while glutathione synthesis is essential for cysteinyl leukotriene production by peritoneal and lung macrophages

Human cardiac pericytes are susceptible to SARS-CoV-2 infection

COVID-19 is associated with serious cardiovascular complications, with incompletely understood mechanism(s). Pericytes have key functions in supporting endothelial cells and maintaining vascular integrity. We demonstrate that human cardiac pericytes are permissive to SARS-CoV-2 infection in organotypic slice and primary cell cultures. Viral entry into pericytes is mediated by endosomal proteases, and infection leads to up-regulation of inflammatory markers, vasoactive mediators, and nuclear factor kappa-B-dependent cell death. Furthermore, we present evidence of cardiac pericyte infection in COVID-19 myocarditis patients. These data demonstrate that human cardiac pericytes are susceptible to SARS-CoV-2 infection and suggest a role for pericyte infection in COVID-19