A near infrared fluorescent probe for hypoxia based on dicyanoisophorone and its application in Hela cells imaging.

Hypoxia will accelerate tumors metastasis and deterioration, thereby limiting the effects of chemotherapy or radiotherapy. Thus, developing efficient techniques for detecting hypoxia in tumor cells is extremely important for cancer diagnosis and therapy. In this work, we reported a dicyanoisophorone-based probe (DCI-Azo) that specifically switched on its near infrared emission with hypoxia up-regulated azo-reductase (AzoR).

Transient neonatal hemolytic anemia due to the novel gamma globin gene mutation HBG2:C.290T>C, p.Leu97Pro (hemoglobin Wareham).

Unstable gamma globin variants can cause transient neonatal hemolytic anemia. We have identified a novel variant in a newborn who presented with jaundice and anemia requiring phototherapy and red blood cell transfusion. The patient was found to be heterozygous for the mutation HGB2:c.

Editing aberrant splice sites efficiently restores β-globin expression in β-thalassemia.

The thalassemias are compelling targets for therapeutic genome editing in part because monoallelic correction of a subset of hematopoietic stem cells (HSCs) would be sufficient for enduring disease amelioration. A primary challenge is the development of efficient repair strategies that are effective in HSCs. Here, we demonstrate that allelic disruption of aberrant splice sites, one of the major classes of thalassemia mutations, is a robust approach to restore gene function.

A Mild Phenotype of Severe β+ Thalassemia in a 16-Month-Old Boy.

β thalassemia is characterized by a deficient production of functional β-globin chains and a relative excess of α-globin chains. An extremely diverse clinical spectrum-asymptomatic to transfusion-dependent-is primarily due to homozygosity or compound heterozygosity for the very large number of β-thalassemia-causing mutations, along with interacting mutations that affect the α-globin and γ-globin genes and their expression. We report a case of a 16-month-old boy who was initially diagnosed with iron deficiency anemia until he was later found to be homozygous for a severe β-thalassemia genotype with a mild hematologic phenotype.

A long noncoding RNA from the HBS1L-MYB intergenic region on chr6q23 regulates human fetal hemoglobin expression.

The HBS1L-MYB intergenic region (chr6q23) regulates erythroid cell proliferation, maturation, and fetal hemoglobin (HbF) expression. An enhancer element within this locus, highlighted by a 3-bp deletion polymorphism (rs66650371), is known to interact with the promoter of the neighboring gene, MYB, to increase its expression, thereby regulating HbF production. RNA polymerase II binding and a 50-bp transcript from this enhancer region reported in ENCODE datasets suggested the presence of a long noncoding RNA (lncRNA).

A Comprehensive, Ethnically Diverse Library of Sickle Cell Disease-Specific Induced Pluripotent Stem Cells.

Sickle cell anemia affects millions of people worldwide and is an emerging global health burden. As part of a large NIH-funded NextGen Consortium, we generated a diverse, comprehensive, and fully characterized library of sickle-cell-disease-specific induced pluripotent stem cells (iPSCs) from patients of different ethnicities, β-globin gene (HBB) haplotypes, and fetal hemoglobin (HbF) levels. iPSCs stand to revolutionize the way we study human development, model disease, and perhaps eventually, treat patients.

A candidate transacting modulator of fetal hemoglobin gene expression in the Arab-Indian haplotype of sickle cell anemia.

Fetal hemoglobin (HbF) levels are higher in the Arab-Indian (AI) β-globin gene haplotype of sickle cell anemia compared with African-origin haplotypes. To study genetic elements that effect HbF expression in the AI haplotype we completed whole genome sequencing in 14 Saudi AI haplotype sickle hemoglobin homozygotes-seven selected for low HbF (8.2% ± 1.

Diverse hematological phenotypes of β-thalassemia carriers.

Most β-thalassemia carriers have mild anemia, low mean corpuscular volume and mean corpuscular hemoglobin, and elevated hemoglobin α2 (HbA2 ). However, there is considerable variability resulting from coinheritance with α- and/or δ-globin gene mutations, dominant inheritance of β-thalassemia mutations, highly unstable variant globin chains, large deletions removing part or all of the β-globin gene cluster, loss of heterozygosity of the β-globin gene cluster during development, or concomitant erythroid enzyme or membrane protein abnormalities. Recognition of the specific abnormality and correct diagnosis can allay anxiety and unnecessary investigation, help formulate treatment programs, and deliver appropriate genetic and family counseling.

The genetic basis of asymptomatic codon 8 frame-shift (HBB:c25_26delAA) β(0) -thalassaemia homozygotes.

Two 21-year old dizygotic twin men of Iraqi descent were homozygous for HBB codon 8, deletion of two nucleotides (-AA) frame-shift β(0) -thalassaemia mutation (FSC8; HBB:c25_26delAA). Both were clinically well, had splenomegaly, and were never transfused. They had mild microcytic anaemia (Hb 120-130 g/l) and 98% of their haemoglobin was fetal haemoglobin (HbF).

Therapeutic fetal-globin inducers reduce transcriptional repression in hemoglobinopathy erythroid progenitors through distinct mechanisms.

Pharmacologic augmentation of γ-globin expression sufficient to reduce anemia and clinical severity in patients with diverse hemoglobinopathies has been challenging. In studies here, representative molecules from four chemical classes, representing several distinct primary mechanisms of action, were investigated for effects on γ-globin transcriptional repressors, including components of the NuRD complex (LSD1 and HDACs 2-3), and the downstream repressor BCL11A, in erythroid progenitors from hemoglobinopathy patients. Two HDAC inhibitors (MS-275 and SB939), a short-chain fatty acid derivative (sodium dimethylbutyrate [SDMB]), and an agent identified in high-throughput screening, Benserazide, were studied.

Hereditary Persistence of Fetal Hemoglobin Caused by Single Nucleotide Promoter Mutations in Sickle Cell Trait and Hb SC Disease.

Hereditary persistence of fetal hemoglobin (HPFH) can be caused by point mutations in the γ-globin gene promoters. We report three rare cases: a child compound heterozygous for Hb S (HBB: c.20A > T) and HPFH with a novel point mutation in the (A)γ-globin gene promoter who had 42.

The first report of a homozygous codons 9/10 (+T) β-thalassemia mutation in a Turkish patient.

For the first time in Turkey, we report a thalassemic patient with a homozygous codons 9/10 (+T) genotype. Currently, the patient is 3 years and 2 months old and received an initial transfusion at the age of 18 months. After being alloimmunized following this transfusion, he required frequent transfusions, every week to every other week.

Hb Youngstown [β101(G3)Glu → Ala; HBB: c.305A > C]: An unstable hemoglobin variant causing severe hemolytic anemia.

Hb Youngstown is a rare hemoglobin (Hb) variant caused by substitution of glutamic acid with alanine at amino acid residue 101 of the β-globin chain as a result of an A > C transversion on the β-globin gene nucleotide sequences [β101(G3)Glu → Ala; HBB: c.305A > C]. We now report three patients from two different families, one from South Africa and the other from Costa Rica, who are heterozygous for this Hb variant.

Novel dominant β-thalassemia: Hb Boston-Kuwait [codon 139/140(+T)].

Dominant β-thalassemias exhibit a hybrid phenotype of unstable hemoglobin and ineffective erythropoiesis. Most arise from heterozygous β-globin gene mutations in exons 3 or 2 and present in adulthood as thalassemia intermedia. We report a novel, de novo β-globin mutation presenting in a toddler with features of thalassemia major and chromaturia.

Identification of the first mutation in a BRE motif of the β-globin gene and its inheritance with two other α-globin gene mutations in a Lebanese family.

A 7-year old boy presented with a history of recurrent respiratory infections and hypochromic microcytic anemia. Iron profiles were normal thereby prompting genetic analysis of α- and β-globin mutations. The first mutation in a BRE motif of the β-globin gene in the proband, sibling and the mother was identified.

Fetal hemoglobin in sickle cell anemia: genetic studies of the Arab-Indian haplotype.

Sickle cell anemia is common in the Middle East and India where the HbS gene is sometimes associated with the Arab-Indian (AI) β-globin gene (HBB) cluster haplotype. In this haplotype of sickle cell anemia, fetal hemoglobin (HbF) levels are 3-4 fold higher than those found in patients with HbS haplotypes of African origin. Little is known about the genetic elements that modulate HbF in AI haplotype patients.

Hemoglobin Shady Grove: a novel fetal methemoglobin variant.

Recommendations by the US Department of Health and Human Services Secretary's Advisory Committee on Heritable Disorders in Newborns and Children aim to increase congenital heart disease screening by pulse oximetry in the nursery. Here, we describe a novel fetal methemoglobin variant discovered in a newborn found to have oxygen saturations significantly below normal upon pulse oximetry screening for congenital heart disease. As universal newborn screening with pulse oximetry is implemented, hereditary variant hemoglobins should be considered in the diagnostic work-up in otherwise well newborns with low SpO2 .

Massive splenic infarction in an adolescent with hemoglobin S-HPFH.

Hemoglobin sickle-hereditary persistence of fetal hemoglobin (S-HPFH) is a condition in which there is compound heterozygosity for the Hb S mutation and the HPFH deletion. These patients have no anemia, little evidence of hemolysis and generally have a benign clinical course compared to other types of sickle cell anemia. We describe a 19-year-old male with HbS-HPFH who had no history of anemia or vaso-occlusive crisis, who presented with a massive splenic infarct.

TiO2/activated carbon fibers photocatalyst: effects of coating procedures on the microstructure, adhesion property, and photocatalytic ability.

In order to more easily separate TiO(2) photocatalyst from the treated wastewater, TiO(2) film was immobilized on the surface of activated carbon fibers (ACFs) by employing two kinds of coating procedures, dip-coating, and hydrothermal treatment. The effects of coating procedures on microstructure of TiO(2)-coated ACFs (TiO(2)/ACFs), such as morphology, porous property, crystal structure, and light absorption characteristics were investigated in detail. The adhesion property between TiO(2) film and ACFs was evaluated by ultrasonic vibration, and the photocatalytic activity of TiO(2)/ACFs was tested by the photocatalytic decoloration of methylene blue solution.