Adrenergic orchestration of immune cell dynamics in response to cardiac stress.

Immune cells contribute approximately 5-10 % of the heart's total cell population, including several myeloid cell and lymphocyte cell subsets, which, despite their relatively small percentages, play important roles in cardiac homeostasis and remodeling responses to various forms of injury and long-term stress. Pathological cardiac stress activates the sympathetic nervous system (SNS), resulting in the release of the catecholamines epinephrine and norepinephrine either systemically or from sympathetic nerve terminals within various lymphoid organs. Acting at α- or β-adrenergic receptors (αAR, βAR), catecholamines regulate immune cell hematopoiesis, egress and migration in response to stress.

Mechanism of hydrophobic gating in the acetylcholine receptor channel pore.

Neuromuscular acetylcholine receptors (AChRs) are hetero-pentameric, ligand-gated ion channels. The binding of the neurotransmitter acetylcholine (ACh) to two target sites promotes a global conformational change of the receptor that opens the channel and allows ion conduction through the channel pore. Here, by measuring free-energy changes from single-channel current recordings and using molecular dynamics simulations, we elucidate how a constricted hydrophobic region acts as a "gate" to regulate the channel opening in the pore of AChRs.

Loss of Myeloid Cell-Specific β2-Adrenergic Receptor Expression Ameliorates Cardiac Function and Remodeling after Acute Ischemia.

Myeloid cells, including neutrophils, monocytes and macrophages, accumulate quickly after ischemic injury in the heart where they play integral roles in the regulation of inflammation and repair. We previously reported that deletion of β2-adrenergic receptor (β2AR) in all cells of hematopoietic origin resulted in generalized disruption of immune cell responsiveness to injury, but with unknown impact on myeloid cells specifically. To investigate this, we crossed floxed β2AR (F/F) mice with myeloid cell-expressing Cre (LysM-Cre) mice to generate myeloid cell-specific β2AR knockout mice (LB2) and subjected them to myocardial infarction (MI).

DMF-Net: a deep multi-level semantic fusion network for high-resolution chest CT and X-ray image de-noising.

Medical images such as CT and X-ray have been widely used for the detection of several chest infections and lung diseases. However, these images are susceptible to different types of noise, and it is hard to remove these noises due to their complex distribution. The presence of such noise significantly deteriorates the quality of the images and significantly affects the diagnosis performance.

Myeloid cell-specific deletion of epidermal growth factor receptor aggravates acute cardiac injury.

Myeloid cells, including macrophages, play important roles as first responders to cardiac injury and stress. Epidermal growth factor receptor (EGFR) has been identified as a mediator of macrophage responsiveness to select diseases, though its impact on cardiac function or remodeling following acute ischemic injury is unknown. We aimed to define the role of myeloid cell-specific EGFR in the regulation of cardiac function and remodeling following acute myocardial infarction (MI)-induced injury.

Bispidine as a Versatile Scaffold: From Topological Hosts to Transmembrane Transporters.

The development of designer topological structures is a synthetically challenging endeavor. We present herein bispidine as a platform for the design of molecules with various topologies and functions. The bispidine-based acyclic molecule, which shows intriguing S-shape topology, is discussed.

Rehabilitation using implants in free fibula flap of a patient with ameloblastoma: Case report with 4-year follow-up.

Ameloblastoma is a locally invasive odontogenic tumor of the jaw. It can advance to large size resulting in facial deformity, loose teeth, and in severe cases pathologic fracture of the jaws. As ameloblastoma shows local invasiveness and tendency for recurrence, radical surgery which includes marginal resection or segmental resection are preferred.

DNA Damage Response Signaling Is Crucial for Effective Chikungunya Virus Replication.

Viruses utilize a plethora of strategies to manipulate the host pathways and hijack host machineries for efficient replication. Several DNA and few RNA viruses are reported to interact with proteins involved in DNA damage responses (DDRs). As the DDR pathways have never been explored in alphaviruses, this investigation intended to understand the importance of the DDR pathways in chikungunya virus (CHIKV) infection , , and models.

Comparative evaluation of transpalatal arch and vertical holding appliance at different heights.

Objectives: An effective method for controlling vertical dysplasia remains a concern for orthodontists. This study aims to compare the stresses on the maxillary first molars while changing the height of the loop/acrylic pad of the transpalatal arch (TPA) and vertical holding appliance (VHA) during swallowing using finite element analysis.

Methods: Head and neck computed tomography (CT) of a patient with levelled and aligned maxillary teeth was taken for a three-dimensional reconstruction.

Protein engineering and design in ion channels and receptors.

Acetylcholine receptors (AChRs) expressed at the neuromuscular junction synapses are typical allosteric proteins that shuttle between at least two stable conformational states: Closed (C) and Open (O). Agonist binding to their target sites on the receptor in the extracellular domain triggers a global C→O conformational change that results in an open channel pore that allows ion conduction. How the receptor senses the chemical signal of an agonist and communicates it to the channel pore, located ~50Å away, are key to understanding the receptor function.

MK2a inhibitor CMPD1 abrogates chikungunya virus infection by modulating actin remodeling pathway.

Chikungunya virus (CHIKV) epidemics around the world have created public health concern with the unavailability of effective drugs and vaccines. This emphasizes the need for molecular understanding of host-virus interactions for developing effective targeted antivirals. Microarray analysis was carried out using CHIKV strain (Prototype and Indian) infected Vero cells and two host isozymes, MAPK activated protein kinase 2 (MK2) and MAPK activated protein kinase 3 (MK3) were selected for further analysis.

Inhibition of IRGM establishes a robust antiviral immune state to restrict pathogenic viruses.

The type I interferon (IFN) response is the major host arsenal against invading viruses. IRGM is a negative regulator of IFN responses under basal conditions. However, the role of human IRGM during viral infection has remained unclear.

Erratum: Azimuthal Anisotropy at the Relativistic Heavy Ion Collider: The First and Fourth Harmonics [Phys. Rev. Lett. 92, 062301 (2004)].

This corrects the article DOI: 10.1103/PhysRevLett.92.

Soft-Dielectron Excess in Proton-Proton Collisions at sqrt[s]=13 TeV.

A measurement of dielectron production in proton-proton (pp) collisions at sqrt[s]=13  TeV, recorded with the ALICE detector at the CERN LHC, is presented in this Letter. The data set was recorded with a reduced magnetic solenoid field. This enables the investigation of a kinematic domain at low dielectron (ee) invariant mass m_{ee} and pair transverse momentum p_{T,ee} that was previously inaccessible at the LHC.

Inhibition of herpes simplex virus-1 infection by MBZM-N-IBT: in silico and in vitro studies.

Introduction: The emergence of drug resistance and cross-resistance to existing drugs has warranted the development of new antivirals for Herpes simplex viruses (HSV). Hence, we have designed this study to evaluate the anti-viral activity of 1-[(2-methyl benzimidazole-1-yl) methyl]-2-oxo-indolin-3-ylidene] amino] thiourea (MBZM-N-IBT), against HSV-1.

Method: Molecular docking was performed to assess the affinity of MBZM-N-IBT for HSV-1 targets.

Simlukafusp alfa (FAP-IL2v) immunocytokine is a versatile combination partner for cancer immunotherapy.

Simlukafusp alfa (FAP-IL2v, RO6874281/RG7461) is an immunocytokine comprising an antibody against fibroblast activation protein α (FAP) and an IL-2 variant with a retained affinity for IL-2Rβγ > IL-2 Rβγ and abolished binding to IL-2 Rα. Here, we investigated the immunostimulatory properties of FAP-IL2v and its combination with programmed cell death protein 1 (PD-1) checkpoint inhibition, CD40 agonism, T cell bispecific and antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies. The binding and immunostimulatory properties of FAP-IL2v were investigated and compared with FAP-IL2wt.

Elliptic Flow of Electrons from Beauty-Hadron Decays in Pb-Pb Collisions at sqrt[s_{NN}]=5.02 TeV.

The elliptic flow of electrons from beauty hadron decays at midrapidity (|y|<0.8) is measured in Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV with the ALICE detector at the LHC.

Recent Advances in GPCR-Regulated Leukocyte Responses during Acute Cardiac Injury.

Following acute cardiac injury such as myocardial infarction (MI), the controlled activation and recruitment of various leukocytes to the site of tissue damage significantly impacts chronic changes to cardiac structure and function, and ultimately host survival. While recent research has focused primarily on how leukocytes respond to injury, understanding how to effectively modulate their responsiveness to dampen maladaptive inflammation and promote repair processes is not yet fully understood. The complex spatio-temporal migration and activation of leukocytes are largely controlled by various chemokines and their cognate receptors, belonging to the G protein-coupled receptor (GPCR) family.

Inhibition of transient receptor potential vanilloid 1 (TRPV1) channel regulates chikungunya virus infection in macrophages.

Chikungunya virus (CHIKV), a virus that induces pathogenic inflammatory host immune responses, is re-emerging worldwide, and there are currently no established antiviral control measures. Transient receptor potential vanilloid 1 (TRPV1), a non-selective Ca-permeable ion channel, has been found to regulate various host inflammatory responses including several viral infections. Immune responses to CHIKV infection in host macrophages have been reported recently.

Measurement of the Low-Energy Antideuteron Inelastic Cross Section.

In this Letter, we report the first measurement of the inelastic cross section for antideuteron-nucleus interactions at low particle momenta, covering a range of 0.3≤p<4  GeV/c. The measurement is carried out using p-Pb collisions at a center-of-mass energy per nucleon-nucleon pair of sqrt[s_{NN}]=5.

Probing the Effects of Strong Electromagnetic Fields with Charge-Dependent Directed Flow in Pb-Pb Collisions at the LHC.

The first measurement at the LHC of charge-dependent directed flow (v_{1}) relative to the spectator plane is presented for Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV. Results are reported for charged hadrons and D^{0} mesons for the transverse momentum intervals p_{T}>0.