Leukemia-mutated proteins PHF6 and PHIP form a chromatin complex that represses myeloid leukemia stemness.

Myeloid leukemias are heterogeneous cancers with a diverse mutational landscape. Though many mutated genes fall within common protein complexes, some lack known functional partners and have unclear roles. PHF6 is a poorly-understood chromatin-binding protein with recurrent mutations that confer an unfavorable prognosis in acute and chronic myeloid leukemias.

PHF6 suppresses self-renewal of leukemic stem cells in AML.

Acute myeloid leukemia is characterized by uncontrolled proliferation of self-renewing myeloid progenitors accompanied by a differentiation arrest. PHF6 is a chromatin-binding protein mutated in myeloid leukemias, and its isolated loss increases mouse HSC self-renewal without malignant transformation. We report here that Phf6 knockout increases the aggressiveness of Hoxa9-driven AML over serial transplantation, and increases the frequency of leukemia initiating cells.

PHF6 suppresses self-renewal of leukemic stem cells in AML.

Acute myeloid leukemia is characterized by uncontrolled proliferation of self-renewing myeloid progenitors. PHF6 is a chromatin-binding protein mutated in myeloid leukemias, and its loss increases mouse HSC self-renewal without malignant transformation. We report here that knockout increases the aggressiveness of -driven AML over serial transplantation, and increases the frequency of leukemia initiating cells.

FISH-Flow to quantify nascent and mature ribosomal RNA in mouse and human cells.

FISH-Flow (fluorescence in situ hybridization-flow cytometry) involves hybridizing fluorescent oligos to RNA and quantifying fluorescence at a single-cell level using flow cytometry. Here, we present a FISH-Flow protocol to quantify nascent 47S and mature 18S and 28S rRNAs in mouse and human cells, including rRNA quantification across cell cycle stages using DNA staining. We describe steps for cell preparation, hybridization of fluorescent probes against rRNA, and DNA staining.

Control of ribosomal RNA synthesis by hematopoietic transcription factors.

Ribosomal RNAs (rRNAs) are the most abundant cellular RNAs, and their synthesis from rDNA repeats by RNA polymerase I accounts for the bulk of all transcription. Despite substantial variation in rRNA transcription rates across cell types, little is known about cell-type-specific factors that bind rDNA and regulate rRNA transcription to meet tissue-specific needs. Using hematopoiesis as a model system, we mapped about 2,200 ChIP-seq datasets for 250 transcription factors (TFs) and chromatin proteins to human and mouse rDNA and identified robust binding of multiple TF families to canonical TF motifs on rDNA.

HectD1 controls hematopoietic stem cell regeneration by coordinating ribosome assembly and protein synthesis.

Impaired ribosome function is the underlying etiology in a group of bone marrow failure syndromes called ribosomopathies. However, how ribosomes are regulated remains poorly understood, as are approaches to restore hematopoietic stem cell (HSC) function loss because of defective ribosome biogenesis. Here we reveal a role of the E3 ubiquitin ligase HectD1 in regulating HSC function via ribosome assembly and protein translation.

Fidelity of start codon selection influences 3-amino-1,2,4-triazole sensitivity in GTPase activating protein function defective eIF5.

The eIF5 protein plays an important role in the fidelity of AUG start codon selection. However, the hyper GTPase eIF5 mutation in yeast causes preferential utilization of UUG as initiation codon and is termed as suppressor of initiation codon (Sui) phenotype. The eIF5G31R mutant recognizes upUUG initiation codon from the 5' regulatory leader region of GCN4 transcript and dominantly represses expression thereby conferring sensitivity to 3-amino-1,2,4-triazole (3AT)-induced starvation.

Efficacy of Tramadol or Dexamethasone as an Adjuvant to Levobupivacaine in Ultrasound-guided Supraclavicular Plexus Block for Upper Limb Surgery: A Randomized Double-blinded Controlled Study.

Aims And Objectives: To evaluate the efficacy of tramadol or dexamethasone as an adjuvant to levobupivacaine in ultrasound-guided supraclavicular brachial plexus block in terms of onset time of complete sensory and motor blockade, duration of motor blockade, duration of analgesia, and any complication.

Settings And Design: This was a randomized controlled trial conducted in the Department of Anesthesiology, a tertiary care hospital.

Materials And Methods: Sixty consecutive patients of the American Society of Anesthesiologists physical status Class I and II who were posted for upper limb surgeries were recruited.

Efficacy of Dexmedetomidine Infusion for Procedural Comfort and Intraoperative Sedation in Patients Undergoing Surgeries with Subarachnoid Block: A Randomized Double-blind Clinical Trial.

Introduction: There is increasing evidence to include sedation as an integral part of regional anesthesia to ensure patient comfort. This may compromise patient cooperation, an important component of regional anesthesia. We decided to determine the efficacy of dexmedetomidine (0.

Clinical embryology teaching: is it relevant anymore?

Background: Embryology finds itself jostling for precious space in the crowded medical curriculum, yet remains important for helping students understand birth defects. It has been suggested that teaching embryology through clinical scenarios can increase its relevance and interest. The aim of this research was to determine the attitudes of final-year medical students to learning embryology and whether clinical scenarios aid understanding.

Traumatic posterior urethral disruptions in boys: experience with the perineal/perineal-transpubic approach in ten cases.

The management of traumatic posterior urethral disruption in children has ranged from primary realignment/repair to delayed urethroplasty. The operative approach may be perineal or transpubic; the advocates of either cite comparable outcome. The anatomic considerations in a child differ from the adult and the management is individualized.