Widespread subclinical cellular changes revealed across a neural-epithelial-vascular complex in choroideremia using adaptive optics.

Choroideremia is an X-linked, blinding retinal degeneration with progressive loss of photoreceptors, retinal pigment epithelial (RPE) cells, and choriocapillaris. To study the extent to which these layers are disrupted in affected males and female carriers, we performed multimodal adaptive optics imaging to better visualize the in vivo pathogenesis of choroideremia in the living human eye. We demonstrate the presence of subclinical, widespread enlarged RPE cells present in all subjects imaged.

Disrupting the Electrical Circuit: New Onset Atrial Fibrillation in a Patient With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

In December 2019, an outbreak of pneumonia cases in Wuhan, China was attributed to a novel coronavirus that was eventually recognized as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently identified as coronavirus disease 2019 (COVID-19), it has been declared a pandemic by the World Health Organization given its rapid global transmission. Various cardiovascular complications have been reported, including heart failure, myocarditis, acute coronary syndrome and arrhythmias, both atrial and ventricular.

Readmissions on Teaching Versus Non-Teaching Services: Are They Any Different?

Introduction There is a paucity of comparative data on readmissions between teaching services (TS) and nonteaching services (NTS). Therefore, we designed this study to determine if there are any differences in readmissions between the two services. Materials and methods A unique cohort of 384 readmissions during one year was retrospectively examined at Hunter Holmes McGuire Veterans Medical Center.

Seizure: An Adverse Effect of Regadenoson in Myocardial Perfusion Imaging.

Regadenoson is a selective adenosine 2a (A2a) receptor agonist that is used in cardiac stress testing to evaluate for ischemic heart disease and has largely replaced adenosine in the modern era. Since adenosine receptors are involved in synaptic transmission between neurons throughout the central nervous system (CNS) including the cerebral cortex, hippocampus, and other structures as well, regadenoson can lower the seizure threshold in susceptible individuals. Epileptogenic activity is an uncommon yet potentially severe adverse effect of regadenoson use, and therefore, more awareness is required in screening patients at risk and evaluating alternate ways to investigate coronary artery disease (CAD) in susceptible individuals.

Longitudinal adaptive optics fluorescence microscopy reveals cellular mosaicism in patients.

The heterogeneity of individual cells in a tissue has been well characterized, largely using ex vivo approaches that do not permit longitudinal assessments of the same tissue over long periods of time. We demonstrate a potentially novel application of adaptive optics fluorescence microscopy to visualize and track the in situ mosaicism of retinal pigment epithelial (RPE) cells directly in the human eye. After a short, dynamic period during which RPE cells take up i.

Chemokines control naive CD8+ T cell selection of optimal lymph node antigen presenting cells.

Naive antiviral CD8(+) T cells are activated in the draining LN (DLN) by dendritic cells (DCs) presenting viral antigens. However, many viruses infect LN macrophages, which participate in initiation of innate immunity and B cell activation. To better understand how and why T cells select infected DCs rather than macrophages, we performed intravital microscopy and ex vivo analyses after infecting mice with vaccinia virus (VV), a large DNA virus that infects both LN macrophages and DCs.

Knockout of G protein β5 impairs brain development and causes multiple neurologic abnormalities in mice.

Gβ5 is a divergent member of the signal-transducing G protein β subunit family encoded by GNB5 and expressed principally in brain and neuronal tissue. Among heterotrimeric Gβ isoforms, Gβ5 is unique in its ability to heterodimerize with members of the R7 subfamily of the regulator of G protein signaling proteins that contain G protein-γ like domains. Previous studies employing Gnb5 knockout (KO) mice have shown that Gβ5 is an essential stabilizer of such regulator of G protein signaling proteins and regulates the deactivation of retinal phototransduction and the proper functioning of retinal bipolar cells.

Human T-cell leukemia virus type 1 p8 protein increases cellular conduits and virus transmission.

The human T-cell leukemia virus type 1 (HTLV-1) is the cause of adult T-cell leukemia/lymphoma as well as tropical spastic paraparesis/HTLV-1-associated myelopathy. HTLV-1 is transmitted to T cells through the virological synapse and by extracellular viral assemblies. Here, we uncovered an additional mechanism of virus transmission that is regulated by the HTLV-1-encoded p8 protein.

A cell number counting factor alters cell metabolism.

It is still not clear how organisms regulate the size of appendages or organs during development. During development, Dictyostelium discoideum cells form groups of approximately 2 x 10(4) cells. The cells secrete a protein complex called counting factor (CF) that allows them to sense the local cell density.

HIV-1 assembly: viral glycoproteins segregate quantally to lipid rafts that associate individually with HIV-1 capsids and virions.

HIV-1 assembly depends on its structural protein, Gag, which after synthesis on ribosomes, traffics to the late endosome/plasma membrane, associates with HIV Env glycoprotein, and forms infectious virions. While Env and Gag migrate to lipid microdomains, their stoichiometry and specificity of interaction are unknown. Pseudotyped viral particles can be made with one viral core surrounded by heterologous envelope proteins.

Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria.

Haemoglobin C, which carries a glutamate-to-lysine mutation in the beta-globin chain, protects West African children against Plasmodium falciparum malaria. Mechanisms of protection are not established for the heterozygous (haemoglobin AC) or homozygous (haemoglobin CC) states. Here we report a marked effect of haemoglobin C on the cell-surface properties of P.

Rgs1 and Gnai2 regulate the entrance of B lymphocytes into lymph nodes and B cell motility within lymph node follicles.

Signaling by G protein-coupled receptors coupled to Galpha(i) assists in triggering lymphocyte movement into and out of lymph nodes. Here, we show that modulating the signaling output from these receptors dramatically alters B cell trafficking. Intravital microscopy of adoptively transferred B cells from wild-type and Rgs1-/- mice revealed that Rgs1-/- B cells stick better to lymph node high endothelial venules, home better to lymph nodes, and move more rapidly within lymph node follicles than do wild-type B cells.

Infection of specific dendritic cells by CCR5-tropic human immunodeficiency virus type 1 promotes cell-mediated transmission of virus resistant to broadly neutralizing antibodies.

The tropism of human immunodeficiency virus type 1 for chemokine receptors plays an important role in the transmission of AIDS. Although CXCR4-tropic virus is more cytopathic for T cells, CCR5-tropic strains are transmitted more frequently in humans for reasons that are not understood. Phenotypically immature myeloid dendritic cells (mDCs) are preferentially infected by CCR5-tropic virus, in contrast to mature mDCs, which are not susceptible to infection but instead internalize virus into a protected intracellular compartment and enhance the infection of T cells.

Characterization of a dipeptide motif regulating IFN-gamma receptor 2 plasma membrane accumulation and IFN-gamma responsiveness.

The IFN-gammaR complex is composed of two IFN-gammaR1 and two IFN-gammaR2 polypeptide chains. Although IFN-gammaR1 is constitutively expressed on all nucleated cells, IFN-gammaR2 membrane display is selective and tightly regulated. We created a series of fluorescent-tagged IFN-gammaR2 expression constructs to follow the molecule's cell surface expression and intracellular distribution.

Proteomics approach reveals novel proteins on the surface of malaria-infected erythrocytes.

Proteins on the surface of parasite-infected erythrocytes (PIESPs) have been one of the major focuses of malaria research due to their role in pathogenesis and their potential as targets for immunity and drug intervention. Despite intense scrutiny, only a few surface proteins have been identified and characterized. We report the identification of two novel surface proteins from Plasmodium falciparum-infected erythrocytes.

pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN.

The severe acute respiratory syndrome coronavirus (SARS-CoV) synthesizes several putative viral envelope proteins, including the spike (S), membrane (M), and small envelope (E) glycoproteins. Although these proteins likely are essential for viral replication, their specific roles in SARS-CoV entry have not been defined. In this report, we show that the SARS-CoV S glycoprotein mediates viral entry through pH-dependent endocytosis.

The influence of the thymic environment on the CD4-versus-CD8 T lineage decision.

T cell receptor signaling is an essential factor regulating thymocyte selection, but the function of the thymic environment in this process is not clear. In mice transgenic for major histocompatibility complex class II-restricted T cell receptors, every thymocyte is potentially selectable for maturation in the CD4 lineage. To address whether selection frequency affects positive selection, we created hematopoietic chimeras with mixtures of selectable and nonselectable precursors.

The aorta and heart differentially express RGS (regulators of G-protein signalling) proteins that selectively regulate sphingosine 1-phosphate, angiotensin II and endothelin-1 signalling.

Normal cardiovascular development and physiology depend in part upon signalling through G-protein-coupled receptors (GPCRs), such as the angiotensin II type 1 (AT(1)) receptor, sphingosine 1-phosphate (S1P) receptors and endothelin-1 (ET-1) receptor. Since regulator of G-protein signalling (RGS) proteins function as GTPase-activating proteins for the G alpha subunit of heterotrimeric G-proteins, these proteins undoubtedly have functional roles in the cardiovascular system. In the present paper, we show that human aorta and heart differentially express RGS1, RGS2, RGS3S (short-form), RGS3L (long-form), PDZ-RGS3 (PDZ domain-containing) and RGS4.