The metabolic basis of inherited neutropenias.

Neutrophils are the shortest-lived blood cells, which requires a prodigious degree of proliferation and differentiation to sustain physiologically sufficient numbers and be poised to respond quickly to infectious emergencies. More than 10 neutrophils are produced every minute in an adult bone marrow-a process that is tightly regulated by a small group of cytokines and chemical mediators and dependent on nutrients and energy. Like granulocyte colony-stimulating factor, the primary growth factor for granulopoiesis, they stimulate signalling pathways, some affecting metabolism.

Ataluren improves myelopoiesis and neutrophil chemotaxis by restoring ribosome biogenesis and reducing p53 levels in Shwachman-Diamond syndrome cells.

Shwachman-Diamond syndrome (SDS) is characterized by neutropenia, exocrine pancreatic insufficiency and skeletal abnormalities. SDS bone marrow haematopoietic progenitors show increased apoptosis and impairment in granulocytic differentiation. Loss of Shwachman-Bodian-Diamond syndrome (SBDS) expression results in reduced eukaryotic 80S ribosome maturation.

SBDS rescues survival of zebrafish in a dose-dependent manner independently of Tp53.

Defects in ribosomal biogenesis profoundly affect organismal development and cellular function, and these ribosomopathies produce a variety of phenotypes. One ribosomopathy, Shwachman-Diamond syndrome (SDS) is characterized by neutropenia, pancreatic exocrine insufficiency, and skeletal anomalies. SDS results from biallelic mutations in , which encodes a ribosome assembly factor.

Sperm and northern bottlenose whale interactions with deep-water trawlers in the western North Atlantic.

Commercial fisheries have increased in all the world's oceans with diverse unintended impacts on marine ecosystems. As a result of resource overlap, interactions between cetaceans and fisheries are a common occurrence and, in many cases, can give rise to significant conservation issues. Research on the distribution and types of such interactions is important for efficient management.

Shwachman-Diamond syndromes: clinical, genetic, and biochemical insights from the rare variants.

Shwachman-Diamond syndrome is a rare inherited bone marrow failure syndrome characterized by neutropenia, exocrine pancreatic insufficiency, and skeletal abnormalities. In 10-30% of cases, transformation to a myeloid neoplasm occurs. Approximately 90% of patients have biallelic pathogenic variants in the SBDS gene located on human chromosome 7q11.

Neuronal expression of ndst3 in early zebrafish development is responsive to Wnt signaling manipulation.

Heparan sulfate proteoglycans (HSPGs) are constituents of the cell surface and extracellular matrix and are vital for various activities within the cell. The N-deacetylase/N-sulfotransferase (heparin glucosaminyl) family of enzymes, or NDST, modifies heparan sulfate (HS) by catalyzing both the N-deacetylation and the N-sulfation of N-acetylglucosamine residues. In zebrafish, a single ndst3 gene is an orthologue of both mammalian NDST3 and NDST4 genes.

Loss of Sbds in zebrafish leads to neutropenia and pancreas and liver atrophy.

Shwachman-Diamond syndrome (SDS) is characterized by exocrine pancreatic insufficiency, neutropenia, and skeletal abnormalities. Biallelic mutations in SBDS, which encodes a ribosome maturation factor, are found in 90% of SDS cases. Sbds-/- mice are embryonic lethal.

Peering through zebrafish to understand inherited bone marrow failure syndromes.

Inherited bone marrow failure syndromes are experiments of nature characterized by impaired hematopoiesis with cancer and leukemia predisposition. The mutations associated with inherited bone marrow failure syndromes affect fundamental cellular pathways, such as DNA repair, telomere maintenance, or proteostasis. How these disturbed pathways fail to produce sufficient blood cells and lead to leukemogenesis are not understood.

SRP54 and a need for a new neutropenia nosology.

In this issue of , Bellanné-Chantelot et al noted that mutations in signal recognition particle 54 () cause an inherited neutropenia in 23 individuals with features of both severe congenital neutropenia (SCN) and Shwachman-Diamond syndrome (SDS).

New monogenic disorders identify more pathways to neutropenia: from the clinic to next-generation sequencing.

Neutrophils are the most common type of leukocyte in human circulating blood and constitute one of the chief mediators for innate immunity. Defined as a reduction from a normal distribution of values, neutropenia results from a number of congenital and acquired conditions. Neutropenia may be insignificant, temporary, or associated with a chronic condition with or without a vulnerability to life-threatening infections.

Synonymous mutation in TP53 results in a cryptic splice site affecting its DNA-binding site in an adolescent with two primary sarcomas.

Pathologic variants in TP53 are known risk factors for the development of cancer. We report a 17-year-old male who presented with two primary sarcomas. Germline sequencing revealed a novel TP53 c.

Use of gnotobiotic zebrafish to study Vibrio anguillarum pathogenicity.

We evaluated the use of the gnotobiotic zebrafish system to study the effects of bacterial infection, and analyzed expression of genes involved in zebrafish innate immunity. Using a GFP-labeled strain of Vibrio anguillarum, we fluorescently monitored colonization of the zebrafish intestinal tract and used gene expression analysis to compare changes in genes involved in innate immunity between nongnotobiotic and gnotobiotic larvae. The experiments performed with the gnotobiotic zebrafish reveal new insights into V.