Targeting CHAF1B Enhances IFN Activity against Myeloproliferative Neoplasm Cells.

Unlabelled: Interferons (IFNs) are cytokines with potent antineoplastic and antiviral properties. IFNα has significant clinical activity in the treatment of myeloproliferative neoplasms (MPN), but the precise mechanisms by which it acts are not well understood. Here, we demonstrate that chromatin assembly factor 1 subunit B (CHAF1B), an Unc-51-like kinase 1 (ULK1)-interactive protein in the nuclear compartment of malignant cells, is overexpressed in patients with MPN.

αI-spectrin represents evolutionary optimization of spectrin for red blood cell deformability.

Spectrin tetramers of the membranes of enucleated mammalian erythrocytes play a critical role in red blood cell survival in circulation. One of the spectrins, αI, emerged in mammals with enucleated red cells after duplication of the ancestral α-spectrin gene common to all animals. The neofunctionalized αI-spectrin has moderate affinity for βI-spectrin, whereas αII-spectrin, expressed in nonerythroid cells, retains ancestral characteristics and has a 10-fold higher affinity for βI-spectrin.

Familial Haploidentical Stem Cell Transplant in Children and Adolescents With High-Risk Sickle Cell Disease: A Phase 2 Clinical Trial.

This phase 2 clinical trial in patients with high-risk sickle cell disease assesses the feasibility, safety, and 1-year event-free survival after myeloimmunoablative conditioning and familial haploidentical stem cell transplant.

A natural "GA" insertion mutation in the sequence encoding the 3'UTR of CXCL12/SDF-1α: Identification, characterization, and functional impact on mRNA splicing.

The CXCL12 gene produces a series of transcript variants through alternative splicing at the 3' end of its pre-mRNA. This study explores the biological activities of these alternative transcripts and the mechanisms involved in the regulation of CXCL12 transcription and RNA splicing. We identified a "GA" insertion mutation in the region of CXCL12α DNA encoding the conserved 3'UTR.

Antiviral Activity of Dual-acting Hydrocarbon-stapled Peptides against HIV-1 Predominantly Circulating in China.

Objective: New rationally designed i,i+7-hydrocarbon-stapled peptides that target both HIV-1 assembly and entry have been shown to have antiviral activity against HIV-1 subtypes circulating in Europe and North America. Here, we aimed to evaluate the antiviral activity of these peptides against HIV-1 subtypes predominantly circulating in China.

Methods: The antiviral activity of three i,i+7-hydrocarbon-stapled peptides, NYAD-36, NYAD-67, and NYAD-66, against primary HIV-1 CRF07_BC and CRF01_AE isolates was evaluated in peripheral blood mononuclear cells (PBMCs).

1970s and 'Patient 0' HIV-1 genomes illuminate early HIV/AIDS history in North America.

The emergence of HIV-1 group M subtype B in North American men who have sex with men was a key turning point in the HIV/AIDS pandemic. Phylogenetic studies have suggested cryptic subtype B circulation in the United States (US) throughout the 1970s and an even older presence in the Caribbean. However, these temporal and geographical inferences, based upon partial HIV-1 genomes that postdate the recognition of AIDS in 1981, remain contentious and the earliest movements of the virus within the US are unknown.

Red blood cells stored 35 days or more are associated with adverse outcomes in high-risk patients.

Background: Clinical trials have shown that longer red blood cell (RBC) storage duration does not worsen outcomes; however, these studies included few RBCs near the end of the 42-day storage limit. We tested the hypothesis that these "oldest" RBCs are associated with adverse outcomes.

Study Design And Methods: In a retrospective study, 28,247 transfused patients given 129,483 RBC units were assessed.

The reason sickle reticulocytes expose PS.

In this issue of Blood, Mankelow et al link phosphatidylserine (PS) exposure in sickle erythrocytes to a physiological event in reticulocyte maturation. This discovery has implications for efforts to prevent thrombosis in sickle cell disease (SCD).

Babesia divergens apical membrane antigen-1 (BdAMA-1): A poorly polymorphic protein that induces a weak and late immune response.

Babesiosis is an important veterinary and zoonotic tick borne disease caused by the hemoprotozoan Babesia spp. which infects red blood cell of its vertebrate host. In order to control the infection, vaccination that targets molecules involved in the invasion process of red blood cells could provide a good alternative to chemotherapy.

Human and murine erythropoiesis.

Purpose Of Review: Research into the fundamental mechanisms of erythropoiesis has provided critical insights into inherited and acquired disorders of the erythrocyte. Studies of human erythropoiesis have primarily utilized in-vitro systems, whereas murine models have provided insights from in-vivo studies. This report reviews recent insights into human and murine erythropoiesis gained from transcriptome-based analyses.

Crystal structures of HIV-1 gp120 envelope glycoprotein in complex with NBD analogues that target the CD4-binding site.

Efforts to develop therapeutic agents that inhibit HIV-1 entry have led to the identification of several small molecule leads. One of the most promising is the NBD series, which binds within a conserved gp120 cavity and possesses para-halogen substituted aromatic rings, a central oxalamide linker, and a tetramethylpiperidine moiety. In this study, we characterized structurally the interactions of four NBD analogues containing meta-fluoro substitution on the aromatic ring and various heterocyclic ring replacements of the tetramethylpiperidine group.

Dual-acting stapled peptides target both HIV-1 entry and assembly.

Background: Previously, we reported the conversion of the 12-mer linear and cell-impermeable peptide CAI to a cell-penetrating peptide NYAD-1 by using an i,i + 4 hydrocarbon stapling technique and confirmed its binding to the C-terminal domain (CTD) of the HIV-1 capsid (CA) protein with an improved affinity (K(d) ~ 1 μM) compared to CAI (K(d) ~ 15 μM). NYAD-1 disrupts the formation of both immature- and mature-like virus particles in in vitro and cell-based assembly assays. In addition, it displays potent anti-HIV-1 activity in cell culture against a range of laboratory-adapted and primary HIV-1 isolates.

Antiviral activity of α-helical stapled peptides designed from the HIV-1 capsid dimerization domain.

Background: The C-terminal domain (CTD) of HIV-1 capsid (CA), like full-length CA, forms dimers in solution and CTD dimerization is a major driving force in Gag assembly and maturation. Mutations of the residues at the CTD dimer interface impair virus assembly and render the virus non-infectious. Therefore, the CTD represents a potential target for designing anti-HIV-1 drugs.

Erythroblastic islands, terminal erythroid differentiation and reticulocyte maturation.

This review summarizes our current understanding of the role of erythroblastic islands in erythropoiesis, membrane assembly during terminal erythroid differentiation and cellular and membrane reorganization during reticulocyte maturation.

Virtual screening based identification of novel small-molecule inhibitors targeted to the HIV-1 capsid.

The hydrophobic cavity of the C-terminal domain (CTD) of HIV-1 capsid has been recently validated as potential target for antiviral drugs by peptide-based inhibitors; however, there is no report yet of any small molecule compounds that target this hydrophobic cavity. In order to fill this gap and discover new classes of ant-HIV-1 inhibitors, we undertook a docking-based virtual screening and subsequent analog search, and medicinal chemistry approaches to identify small molecule inhibitors against this target. This article reports for the first time, to the best of our knowledge, identification of diverse classes of inhibitors that efficiently inhibited the formation of mature-like viral particles verified under electron microscope (EM) and showed potential as anti-HIV-1 agents in a viral infectivity assay against a wide range of laboratory-adapted as well as primary isolates in MT-2 cells and PBMC.

The erythroid niche: molecular processes occurring within erythroblastic islands.

Erythroblasts terminally differentiate within specialized niches composed of erythroblast islands nesting in extracellular matrix proteins. A number of adhesion molecules active in erythroid island attachments have been identified. We have recently observed a receptor/counter receptor interaction that appears to maintain island integrity: erythroid ICAM-4 interacting with macrophage alphaV integrin.

Hereditary spherocytosis and hereditary elliptocytosis: aberrant protein sorting during erythroblast enucleation.

During erythroblast enucleation, membrane proteins distribute between extruded nuclei and reticulocytes. In hereditary spherocytosis (HS) and hereditary elliptocytosis (HE), deficiencies of membrane proteins, in addition to those encoded by the mutant gene, occur. Elliptocytes, resulting from protein 4.

High genetic and antigenic similarity between a swine H3N2 influenza A virus and a prior human influenza vaccine virus: a possible immune pressure-driven cross-species transmission.

In late April of 2009, a global outbreak of human influenza was reported. The causative agent is a highly unusual reassortant H1N1 influenza virus carrying genetic segments derived from swine, human and avian influenza viruses. In this study, we compared the HA, NA and other gene segments of a swine H3N2 influenza A virus, A/Swine/Guangdong/z5/2003, which was isolated from pigs in 2003 in Guangdong Province, China, to the predominant human and swine H3N2 viruses.

PfRH5: a novel reticulocyte-binding family homolog of plasmodium falciparum that binds to the erythrocyte, and an investigation of its receptor.

Multiple interactions between parasite ligands and their receptors on the human erythrocyte are a condition of successful Plasmodium falciparum invasion. The identification and characterization of these receptors presents a major challenge in the effort to understand the mechanism of invasion and to develop the means to prevent it. We describe here a novel member of the reticulocyte-binding family homolog (RH) of P.

Evidence for protection against chronic hepatitis C virus infection in chimpanzees by immunization with replicating recombinant vaccinia virus.

Given the failures of nonreplicating vaccines against chronic hepatitis C virus (HCV) infection, we hypothesized that a replicating viral vector may provide protective immunity. Four chimpanzees were immunized transdermally twice with recombinant vaccinia viruses (rVV) expressing HCV genes. After challenge with 24 50% chimpanzee infective doses of homologous HCV, the two control animals that had received only the parental VV developed chronic HCV infection.