Prestonmcculloch6400
Prothrombin-related thrombophilia is a genetic disorder produced by a substitution of a single DNA base pair, replacing guanine with adenine, and is detected mainly by polymerase chain reaction (PCR). A suitable alternative that could detect the single point mutation without requiring sample amplification is the surface plasmon resonance (SPR) technique. SPR biosensors are of great interest they offer a platform to monitor biomolecular interactions, are highly selective, and enable rapid analysis in real time. Oligonucleotide-based SPR biosensors can be used to differentiate complementary sequences from partially complementary or noncomplementary strands. In this work, a glass chip covered with an ultrathin (50 nm) gold film was modified with oligonucleotide strands complementary to the mutated or normal (nonmutated) DNA responsible for prothrombin-related thrombophilia, forming two detection platforms called mutated thrombophilia (MT) biosensor and normal thrombophilia (NT) biosensor. Varespladib show that the hybridization response is obtained in 30 min, label free and with high reproducibility. The sensitivity obtained in both systems was approximately 4 ΔμRIU/nM. The dissociation constant and limits of detection calculated were 12.2 nM and 20 pM (3 fmol), respectively, for the MT biosensor, and 8.5 nM and 30 pM (4.5 fmol) for the NT biosensor. The two biosensors selectively recognize their complementary strand (mutated or normal) in buffer solution. In addition, each platform can be reused up to 24 times when the surface is regenerated with HCl. This work contributes to the design of the first SPR biosensor for the detection of prothrombin-related thrombophilia based on oligonucleotides with single point mutations, label-free and without the need to apply an amplification method.Digital dermatitis (DD) causes lameness in dairy cattle. To detect the quantitative trait loci (QTL) associated with DD, genome-wide association studies (GWAS) were performed using high-density single nucleotide polymorphism (SNP) genotypes and binary case/control, quantitative (average number of FW per hoof trimming record) and recurrent (cases with ≥2 DD episodes vs. controls) phenotypes from cows across four dairies (controls n = 129 vs. FW n = 85). Linear mixed model (LMM) and random forest (RF) approaches identified the top SNPs, which were used as predictors in Bayesian regression models to assess the SNP predictive value. The LMM and RF analyses identified QTL regions containing candidate genes on Bos taurus autosome (BTA) 2 for the binary and recurrent phenotypes and BTA7 and 20 for the quantitative phenotype that related to epidermal integrity, immune function, and wound healing. Although larger sample sizes are necessary to reaffirm these small effect loci amidst a strong environmental effect, the sample cohort used in this study was sufficient for estimating SNP effects with a high predictive value.Eukaryotic 5-methylcytosine RNA methyltransferases catalyze the transfer of a methyl group to the fifth carbon of a cytosine base in RNA sequences to produce 5-methylcytosine (m5C). m5C RNA methyltransferases play a crucial role in the maintenance of functionality and stability of RNA. Viruses have developed a number of strategies to suppress host innate immunity and ensure efficient transcription and translation for the replication of new virions. One such viral strategy is to use host m5C RNA methyltransferases to modify viral RNA and thus to affect antiviral host responses. Here, we summarize the latest findings concerning the roles of m5C RNA methyltransferases, namely, NOL1/NOP2/SUN domain (NSUN) proteins and DNA methyltransferase 2/tRNA methyltransferase 1 (DNMT2/TRDMT1) during viral infections. Moreover, the use of m5C RNA methyltransferase inhibitors as an antiviral therapy is discussed.Rho GTPase signaling promotes proliferation, invasion, and metastasis in a broad spectrum of cancers. Rho GTPase activity is regulated by the deleted in liver cancer (DLC) family of bona fide tumor suppressors which directly inactivate Rho GTPases by stimulating GTP hydrolysis. In addition to a RhoGAP domain, DLC proteins contain a StAR-related lipid transfer (START) domain. START domains in other organisms bind hydrophobic small molecules and can regulate interacting partners or co-occurring domains through a variety of mechanisms. In the case of DLC proteins, their START domain appears to contribute to tumor suppressive activity. However, the nature of this START-directed mechanism, as well as the identities of relevant functional residues, remain virtually unknown. Using the Catalogue of Somatic Mutations in Cancer (COSMIC) dataset and evolutionary and structure-function analyses, we identify several conserved residues likely to be required for START-directed regulation of DLC-1 and DLC-2 tumor-suppressive capabilities. This pan-cancer analysis shows that conserved residues of both START domains are highly overrepresented in cancer cells from a wide range tissues. Interestingly, in DLC-1 and DLC-2, three of these residues form multiple interactions at the tertiary structural level. Furthermore, mutation of any of these residues is predicted to disrupt interactions and thus destabilize the START domain. As such, these mutations would not have emerged from traditional hotspot scans of COSMIC. We propose that evolutionary and structure-function analyses are an underutilized strategy which could be used to unmask cancer-relevant mutations within COSMIC. Our data also suggest DLC-1 and DLC-2 as high-priority candidates for development of novel therapeutics that target their START domain.Power efficiency is becoming a critical aspect of IoT devices. #link# In this paper, we present a compact object-detection coprocessor with multiple cores for multi-scale/type classification. This coprocessor is capable to process scalable block size for multi-shape detection-window and can be compatible with the frame-image sizes up to 2048 × 2048 for multi-scale classification. A memory-reuse strategy that requires only one dual-port SRAM for storing the feature-vector of one-row blocks is developed to save memory usage. Eventually, a prototype platform is implemented on the Intel DE4 development board with the Stratix IV device. The power consumption of each core in FPGA is only 80.98 mW.