Search results for " biology."
showing 10 items of 33717 documents
PTC124-mediated translational readthrough of a nonsense mutation causing Usher syndrome type 1C.
2011
We investigated the therapeutic potential of the premature termination codon (PTC) readthrough-inducing drug PTC124 in treating the retinal phenotype of Usher syndrome, caused by a nonsense mutation in the USH1C gene. Applications in cell culture, organotypic retina cultures, and mice in vivo revealed significant readthrough and the recovery of protein function. In comparison with other readthrough drugs, namely the clinically approved readthrough-inducing aminoglycoside gentamicin, PTC124 exhibits significant better retinal biocompatibility. Its high readthrough efficiency in combination with excellent biocompatibility makes PTC124 a promising therapeutic agent for PTCs in USH1C, as well a…
STAT1 and Its Crucial Role in the Control of Viral Infections
2022
The signal transducer and activator of transcription (STAT) 1 protein plays a key role in the immune response against viruses and other pathogens by transducing, in the nucleus, the signal from type I, type II and type III IFNs. STAT1 activates the transcription of hundreds of genes, some of which have been well characterized for their antiviral properties. STAT1 gene deletion in mice and complete STAT1 deficiency in humans both cause rapid death from severe infections. STAT1 plays a key role in the immunoglobulin class-switch recombination through the upregulation of T-bet; it also plays a key role in the production of T-bet+ memory B cells that contribute to tissue-resident humoral memory…
Why viruses sometimes disperse in groups?
2019
AbstractMany organisms disperse in groups, yet this process is understudied in viruses. Recent work, however, has uncovered different types of collective infectious units, all of which lead to the joint delivery of multiple viral genome copies to target cells, favoring co-infections. Collective spread of viruses can occur through widely different mechanisms, including virion aggregation driven by specific extracellular components, cloaking inside lipid vesicles, encasement in protein matrices, or binding to cell surfaces. Cell-to-cell viral spread, which allows the transmission of individual virions in a confined environment, is yet another mode of clustered virus dissemination. Nevertheles…
SARS-CoV-2 envelope protein topology in eukaryotic membranes
2020
Coronavirus E protein is a small membrane protein found in the virus envelope. Different coronavirus E proteins share striking biochemical and functional similarities, but sequence conservation is limited. In this report, we studied the E protein topology from the new SARS-CoV-2 virus both in microsomal membranes and in mammalian cells. Experimental data reveal that E protein is a single-spanning membrane protein with the N-terminus being translocated across the membrane, while the C-terminus is exposed to the cytoplasmic side (Nt lum /Ct cyt ). The defined membrane protein topology of SARS-CoV-2 E protein may provide a useful framework to understand its interaction with other viral and ho…
Characterization of the autoantigen La (SS-B) as a dsRNA unwinding enzyme
1997
During the analysis of the La (SS-B) autoantigen for catalytic activities an ATP-dependent double-stranded RNA unwinding activity was detected. Both native and recombinant La proteins from different species displayed this activity, which could be inhibited by monospecific anti-La antibodies. La protein was able to melt dsRNA substrates with either two 3'-overhangs or a single 3'- and a 5'-overhang. Double-stranded RNAs with two 5'-overhangs were not unwound, indicating that at least one 3'-overhang is required for unwinding. Sequence elements of the La protein that might be involved in dsRNA unwinding, such as an evolutionarily conserved putative ATP-binding motif and an element that is hom…
Clathrin- and Caveolin-Independent Entry of Human Papillomavirus Type 16—Involvement of Tetraspanin-Enriched Microdomains (TEMs)
2008
BACKGROUND: Infectious entry of human papillomaviruses into their host cells is an important step in the viral life cycle. For cell binding these viruses use proteoglycans as initial attachment sites. Subsequent transfer to a secondary receptor molecule seems to be involved in virus uptake. Depending on the papillomavirus subtype, it has been reported that entry occurs by clathrin- or caveolin-mediated mechanisms. Regarding human papillomavirus type 16 (HPV16), the primary etiologic agent for development of cervical cancer, clathrin-mediated endocytosis was described as infectious entry pathway. METHODOLOGY/PRINCIPAL FINDINGS: Using immunofluorescence and infection studies we show in contra…
Quantitative microscopy reveals stepwise alteration of chromatin structure during herpesvirus infection
2019
During lytic herpes simplex virus 1 (HSV-1) infection, the expansion of the viral replication compartments leads to an enrichment of the host chromatin in the peripheral nucleoplasm. We have shown previously that HSV-1 infection induces the formation of channels through the compacted peripheral chromatin. Here, we used three-dimensional confocal and expansion microscopy, soft X-ray tomography, electron microscopy, and random walk simulations to analyze the kinetics of host chromatin redistribution and capsid localization relative to their egress site at the nuclear envelope. Our data demonstrated a gradual increase in chromatin marginalization, and the kinetics of chromatin smoothening arou…
Tumor targeting of baculovirus displaying a lymphatic homing peptide.
2008
Background Tumor-associated cells and vasculature express attractive molecular markers for site-specific vector targeting. To attain tumor-selective tropism, we recently developed a baculovirus vector displaying the lymphatic homing peptide LyP-1, originally identified by ex vivo/in vivo screening of phage display libraries, on the viral envelope by fusion to the transmembrane anchor of vesicular stomatitis virus G-protein. Methods In the present study, we explored the specificity and kinetics of viral binding and internalization as well as in vivo tumor homing of the LyP-1 displaying virus to elucidate the applicability of baculovirus for targeted therapies. Results We demonstrated that th…
Visual Contrast Modulates Operant Learning Responses in Larval Zebrafish.
2018
The larval zebrafish is a promising vertebrate model organism to study neural mechanisms underlying learning and memory due to its small brain and rich behavioral repertoire. Here, we report on a high-throughput operant conditioning system for zebrafish larvae, which can simultaneously train 12 fish to associate a visual conditioned pattern with electroshocks. We find that the learning responses can be enhanced by the visual contrast, not the spatial features of the conditioned patterns, highlighted by several behavioral metrics. By further characterizing the learning curves as well as memory extinction, we demonstrate that the percentage of learners and the memory length increase as the co…
(A,B) In vivo GCaMP6f signals recorded in layers M1, M5 and M9/10 of Mi1 (A) and Tm3 (B) neurons, before (blue, green) and after (gray, red) applicat…
2019
Sensory systems sequentially extract increasingly complex features. ON and OFF pathways, for example, encode increases or decreases of a stimulus from a common input. This ON/OFF pathway split is thought to occur at individual synaptic connections through a sign-inverting synapse in one of the pathways. Here, we show that ON selectivity is a multisynaptic process in the Drosophila visual system. A pharmacogenetics approach demonstrates that both glutamatergic inhibition through GluClα and GABAergic inhibition through Rdl mediate ON responses. Although neurons postsynaptic to the glutamatergic ON pathway input L1 lose all responses in GluClα mutants, they are resistant to a cell-type-specifi…