Ligands of the transforming growth factor-β (TGF-β) superfamily are important targets for therapeutic intervention but present challenges because they signal combinatorially and exhibit overlapping activities in vivo. To obtain agents capable of sequestering multiple TGF-β superfamily ligands with novel selectivity, we generated soluble, heterodimeric ligand traps by pairing the extracellular domain (ECD) of the native activin receptor type IIB (ActRIIB) alternately with the ECDs of native type I receptors activin receptor-like kinase 4 (ALK4), ALK7, or ALK3. Systematic analysis of these heterodimeric constructs by surface plasmon resonance, and comparison with their homodimeric counterparts, revealed that each type I receptor partner confers a distinct ligand-binding profile to the heterodimeric construct.
View Article and Find Full Text PDFMammals have extremely limited regenerative capabilities; however, axolotls are profoundly regenerative and can replace entire limbs. The mechanisms underlying limb regeneration remain poorly understood, partly because the enormous and incompletely sequenced genomes of axolotls have hindered the study of genes facilitating regeneration. We assembled and annotated a de novo transcriptome using RNA-sequencing profiles for a broad spectrum of tissues that is estimated to have near-complete sequence information for 88% of axolotl genes.
View Article and Find Full Text PDFThe ability to introduce DNA elements into host cells and analyze the effects has revolutionized modern biology. Here we describe a protocol to generate Moloney murine leukemia virus (MMLV)-based, replication-incompetent pseudotyped retrovirus capable of infecting axolotls and incorporating genetic information into their genome. When pseudotyped with vesicular stomatitis virus (VSV)-G glycoprotein, the retroviruses can infect a broad range of proliferative axolotl cell types.
View Article and Find Full Text PDFRegeneration (Oxf)
February 2015
Loss-of-function genetics provides strong evidence for a gene's function in a wild-type context. In many model systems, this approach has been invaluable for discovering the function of genes in diverse biological processes. Axolotls are urodele amphibians (salamanders) with astonishing regenerative abilities, capable of regenerating entire limbs, portions of the tail (including spinal cord), heart, and brain into adulthood.
View Article and Find Full Text PDFStudy Objectives: The relationship between sleep and immune function is not well understood at a functional or molecular level. We therefore used a genetic approach in Drosophila to manipulate sleep and evaluated effects on the ability of flies to fight bacterial infection.
Setting: Laboratory.
Study Objectives: Sleep is known to increase as an acute response to infection. However, the function of this behavioral response in host defense is not well understood. To address this problem, we evaluated the effect of acute sleep deprivation on post-infection sleep and immune function in Drosophila.
View Article and Find Full Text PDFA complex interaction between the immune response and host behavior has been described in a wide range of species. Excess sleep, in particular, is known to occur as a response to infection in mammals (1) and has also recently been described in Drosophila melanogaster(2). It is generally accepted that sleep is beneficial to the host during an infection and that it is important for the maintenance of a robust immune system(3,4).
View Article and Find Full Text PDFBackground: Immune challenge impacts behavior in many species. In mammals, this adaptive behavior is often manifested as an increase in sleep. Sleep has therefore been proposed to benefit the host by enhancing immune function and thereby overcome the challenge.
View Article and Find Full Text PDFExtensive use of pharmaceuticals and growth hormone in farm animal and live stocks has resulted in their frequent detection in soils, groundwater, and wastewater. The fate and transport of these compounds are strongly affected by their sorptive behavior to the soil minerals and humic materials. In this research, we conducted the sorption of tetracycline (TC), a common antibiotic, on palygorskite (PFL-1), a fibrous clay mineral of high surface area and high sorptivity towards organic compounds.
View Article and Find Full Text PDFHuman hepatitis B virus (HBV) can cause acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HBV e antigen (HBeAg), a secreted protein and not required for viral replication, is thought to play an immunoregulatory role during viral infection. However, the functional involvement of HBeAg in host immune response has not been fully elucidated.
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