Snake venom is an ecologically relevant functional trait directly linked with a snake's fitness and survival, facilitating predation and defence. Snake venom variation occurs at all taxonomic levels, but the study at the intraspecific level is still in its early stages. The common adder () exhibits considerable variation in colour phenotypes across its distribution range.
View Article and Find Full Text PDFThe PDCD1-encoded immune checkpoint receptor PD-1 is a key tumor suppressor in T cells that is recurrently inactivated in T cell non-Hodgkin lymphomas (T-NHLs). The highest frequencies of PDCD1 deletions are detected in advanced disease, predicting inferior prognosis. However, the tumor-suppressive mechanisms of PD-1 signaling remain unknown.
View Article and Find Full Text PDFExpectation-based theories of language processing, such as Surprisal theory, are supported by evidence of anticipation effects in both behavioural and neurophysiological measures. Online measures of language processing, however, are known to be influenced by factors such as lexical association that are distinct from-but often confounded with-expectancy. An open question therefore is whether a specific locus of expectancy related effects can be established in neural and behavioral processing correlates.
View Article and Find Full Text PDFBackground: Biosimilar granulocyte-colony-stimulating factors (G-CSFs) have been available in the European Union since 2008, and Sandoz' biosimilar filgrastim was approved in the United States in March 2015 for all of the reference product's indications except acute radiation syndrome. Biosimilar G-CSFs have been largely embraced by the medical community, except for some reservations about healthy-donor stem cell mobilization, for which use outside of clinical studies was cautioned against by some members of the scientific community.
Study Design And Methods: In a two-center safety surveillance study (National Clinical Trial NCT01766934), 245 healthy volunteer stem cell donors were enrolled.
Curr Opin Hematol
January 2016
Purpose Of Review: With the approval of the first biosimilar granulocyte colony-stimulating factor (G-CSF), biosimilars - copies of therapeutic biologicals whose patent protection has expired - have finally reached the US healthcare market. Its advent is an occasion for a closer look at recent insights into biosimilar G-CSF and an attempt at prognosticating the future (future role) of biosimilars in general.
Recent Findings: Recent literature regarding biosimilar G-CSF orbits significantly around patient access and effects on healthcare expenditure.
The genetics responsible for the inter-individually variable G-CSF responsiveness remain elusive. A single nucleotide polymorphism (SNP) in the 3'UTR of CXCL12, rs1801157, was implicated in X4-tropic HiV susceptibility and later, in two small studies, in G-CSR responsiveness in patients and donors. The position of the SNP in the 3'UTR together with in-silico predictions suggested differential binding of micro-RNA941 as an underlying mechanism.
View Article and Find Full Text PDFBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematopoietic malignancy characterized by dismal prognosis and overall poor therapeutic response. Since the biology of BPDCN is barely understood, our study aims to shed light on the genetic make-up of these highly malignant tumors. Using targeted high-coverage massive parallel sequencing, we investigated 50 common cancer genes in 33 BPDCN samples.
View Article and Find Full Text PDFBackground: Unstimulated mononuclear cell (MNC) apheresis plays a role in the generation of donor lymphocytes (DLIs; healthy donors) and in extracorporeal photopheresis (ECP; patients). The new apheresis system Spectra Optia MNC has been shown in small studies to be capable of performing the desired cell collections, but larger data sets from real-life clinical apheresis procedures are lacking.
Study Design And Methods: Presented are comparative data from DLI collections randomly performed with either the new technology or a clinical standard technology, COBE Spectra MNC, as well as data from patients with chronic graft-versus-host disease undergoing MNC collections alternating between the two apheresis systems to generate products for ECP.
Background: Donor granulocyte concentrates are routinely administered to patients with granulocyte function defects or transient neutropenia and (risk of) bacterial or fungal exacerbations, despite lack of definitive clinical proof for patient-relevant outcome improvement. Granulocytes are collected by apheresis from healthy donors treated with granulocyte-colony-stimulating factor and/or steroids for neutrophil mobilization the evening before apheresis, as well as with hydroxyethyl starch during apheresis, to enhance sedimentation of red blood cells (RBCs) and thus to facilitate accessibility of neutrophils for collection.
Study Design And Methods: Granulocyte apheresis procedures are performed with standard apheresis equipment, including with the frequently used apheresis system for peripheral blood "stem cell" collection, COBE Spectra MNC (Terumo BCT), using the same tubing set as for MNC collection, but a different software protocol, PMN.
E23K, a common polymorphism in the pore-forming subunit K(IR)6.2 of pancreatic beta-cell ATP-sensitive K(+) (K(ATP)) channels, is functionally relevant and thus might play a major role in the pathophysiology of common type 2 diabetes. In this study, we show that in the simultaneous presence of activatory and inhibitory nucleotides, the polymorphism exerts opposite effects on the potencies of these modulators: channel opening through nucleoside diphosphates is facilitated, whereas sensitivity toward inhibition through ATP is slightly decreased.
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