A new protein domain was found in several proteins involved in apoptosis, inflammation, cancer and immune responses. Its location within these proteins and predicted fold suggests that it functions ...as a protein–protein interaction domain, possibly uniting different signaling pathways.
We cloned a novel cDNA derived from the CARD6 gene locus on chromosome 5p12 of 311 amino acids in length. By immunoprecipitation we detected specific binding of this CARD6-encoding protein to Nod1 ...(CARD4), Cardiak (Rip2/Rick), NAC (NALP1/DEFCAP/CARD7), and TUCAN (CARD8/Cardinal/NDPP/Dakar), caspase recruitment domain (CARD)-containing proteins implicated in NF-κB and caspase-1 activation but not to other CARD family proteins. Cardiak and Nod1 (but not other CARD proteins) also exhibited opposing effects on CARD6 protein phosphorylation and expression, providing further evidence of functional interactions among these proteins in cells. In transfection experiments, the CARD6 protein suppressed NF-κB induction by Nod1 or Cardiak but did not interfere with NF-κB activation by the CARD-containing adapter protein Bcl10 or the cytokine tumor necrosis factor-α, demonstrating specificity of CARD6 for Nod-1 and Cardiak-dependent pathways. In contrast to its effects on Nod1- and Cardiak-dependent NF-κB activation, CARD6 did not interfere with caspase-1-dependent interleukin-1β secretion induced by Cardiak or Nod1. CARD6 also did not affect caspase activation and apoptosis induced by overexpression of Fas, Bax, or other pro-apoptotic stimuli. Thus, CARD6 represents a selective modulator of NF-κB activation by Cardiak and Nod1, adding to the repertoire of CARD-family proteins implicated in inflammatory responses and innate immunity.
The Ets family of transcription factors, of which there are now about 35 members regulate gene expression during growth and development. They share a conserved domain of around 85 amino acids which ...binds as a monomer to the DNA sequence 5'-C/AGGAA/T-3'. We have determined the crystal structure of an ETS domain complexed with DNA, at 2.3-A resolution. The domain is similar to alpha + beta (winged) 'helix-turn-helix' proteins and interacts with a ten-base-pair region of duplex DNA which takes up a uniform curve of 8 degrees. The domain contacts the DNA by a novel loop-helix-loop architecture. Four of amino acids that directly interact with the DNA are highly conserved: two arginines from the recognition helix lying in the major groove, one lysine from the 'wing' that binds upstream of the core GGAA sequence, and another lysine, from the 'turn' of the 'helix-turn-helix' motif, which binds downstream and on the opposite strand.
In the rapidly evolving realm of Virtual Reality (VR), the integration of video content with 3D modeling presents various challenges and opportunities. This paper introduces a methodology that ...incorporates glTF models directly into video files, offering a holistic and immersive multimedia experience. By utilizing a custom Blender plugin and a Unity-based video player, we enable seamless synchronization between video content and 3D animations. Our approach utilizes steganography, specifically the Least Significant Bit (LSB) technique, to hide 3D models within video files without significantly compromising video quality. The Blender plugin facilitates the creative process by allowing users to synchronize video and glTF animations, while the Unity video player ensures real-time rendering and interactivity during playback. Our results, showcased through user perspective views, highlight the transformative potential of our methodology, setting the stage for a paradigm shift in VR entertainment and beyond.
Caspase-associated recruitment domains (CARDs) are protein interaction domains that participate in activation or suppression of CARD-carrying members of the caspase family of apoptosis-inducing ...proteases. A novel CARD-containing protein was identified that is overexpressed in some types of cancer and that binds and suppresses activation of procaspase-9, which we term TUCAN (tumor-up-regulated CARD-containing antagonist of caspase nine). The CARD domain of TUCAN selectively binds itself and procaspase-9. TUCAN interferes with binding of Apaf1 to procaspase-9 and suppresses caspase activation induced by the Apaf1 activator, cytochrome c. Overexpression of TUCAN in cells by stable or transient transfection inhibits apoptosis and caspase activation induced by Apaf1/caspase-9-dependent stimuli, including Bax, VP16, and staurosporine, but not by Apaf1/caspase-9-independent stimuli, Fas and granzyme B. High levels of endogenous TUCAN protein were detected in several tumor cell lines and in colon cancer specimens, correlating with shorter patient survival. Thus, TUCAN represents a new member of the CARD family that selectively suppresses apoptosis induced via the mitochondrial pathway for caspase activation.
Caspases play an essential role during programmed cell death in all metazoans. These enzymes are cysteine proteases and comprise a multi-gene family with more than a dozen mammalian family members. ...Although caspases have been characterized in many animals, including
Drosophila melanogaster, little is known about the caspases that exist in mosquitoes. Here we describe the identification and characterization of
Aedes Dredd (AeDredd), a novel caspase in the yellow fever mosquito,
Aedes aegypti. AeDredd contains two N-terminal death effector domains and the well conserved caspase catalytic domain. Multiple sequence alignments and functional substrate assays of recombinant protein suggest that AeDredd is an orthologue of
Drosophila Dredd and human caspase-8, both central effectors of the death receptor-mediated apoptotic pathway. AeDredd exhibits substrate specificity most similar to human caspase-8. AeDredd transcripts were found in all developmental stages with highest expression in early pupae. Within adults, AeDredd was found in all the tissues examined, with the highest transcript levels detected in fat body tissues. This is the first functional characterization of a death domain-containing caspase in an insect vector of human disease, and will initiate studies on the role of apoptosis in the innate immune response of vectors towards intracellular parasites such as viruses.
In this paper we present P wave tomographic images of the mantle beneath Italy obtained by inverting ∼6000 teleseismic P and PKP wave arrival times, accurately repicked, recorded in the time period ...1988–1994 by the stations of the National Seismic Network of the Istituto Nazionale di Geofisica. We pay great attention in the data selection and picking procedure of seismic phases to obtain a very high quality data set. The data were inverted with the well‐established Aki‐Christofferson‐Husebye tomographic technique; different reference models and residuals computation have been tried to verify the stability of the results. The high quality of the repicked arrival times allows us to enhance the definition of the deep structures beneath both the Alps and the Apennines, looking for their lateral and vertical continuity down to 800 km depth. The main finding of this study is a continuous high‐velocity body located between 250 and 670 km depth beneath the entire Apenninic system dipping toward the Tyrrhenian area, which continues upward segmented in two main anomalies in the northern Apenninic and the Calabrian Arcs. We interpret this high‐velocity feature as the subducted oceanic lithosphere between the Eurasian and African plates, dipping down to the upper‐lower mantle boundary beneath the Tyrrhenian Sea. The retrieved images of the lithosphere subducting beneath Apennines are reliable in terms of thickness (about 80–90 km) and P wave velocity contrast (2–4% higher than the normal mantle). Furthermore, our tomographic images, which focus on the deep geometry and continuity of the velocity structures, provide new keys to understanding the geodynamic evolution of the Italian region. The segmentation of the high‐velocity slab upward suggests a complex evolution of the arc‐trench system and the initially continuous subduction of the Ionian‐Adriatic plate progressively developed in subordinate arcs, probably due to lateral heterogeneity of the subducting lithosphere.
Rhinella jimi toads (Stevaux, 2002) belong to the Bufonidae family, are endemic in the Brazilian Northeast and are commonly found during rainy periods. In general, amphibians of this family have in ...their poisons different metabolites that show a diversity of pharmacological activities. The isolation and identification of these compounds are of great importance, and techniques such as high-performance liquid chromatography coupled to mass spectrometry are widely used for the discovery of novel and known compounds in these poisons. For R. jimi poison, the ethyl acetate and methanolic extracts were obtained and thirty compounds were identified by combining ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) with direct infusion atmospheric pressure chemical ionization mass spectrometry (DI-APCI-MS/MS) and direct infusion electrospray mass spectrometry (DI-ESI-MS/MS) for each extract, respectively. Marinobufagin (2) and marinobufotoxin (19) were the majorities of each extract, respectively. In addition, other bufadienolides mainly present in the ethyl acetate extract, such other bufotoxins, alkaloids and arginine diacid derivatives were identified in the methanol extract. In a cytotoxic assay by 3-(4,5-dimethylthiazol-2-yl)-2,5‑diphenyltetrazolium bromide (MTT), the extracts and compound 2 demonstrated half-maximal inhibitory concentration (IC50) values better than the positive control doxorubicin, evidencing excellent cytotoxic. This is the most complete study of the chemical composition of R. jimi toad poison and its respective cytotoxic activity, promoting the enrichment of knowledge about this family and species.
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