Investigation of Electrochemical Properties of Xanthine, Adenine and Thymine on a Glassy Carbon Electrode by Voltammetry

In this paper for investigation of electrochemical properties of nitrogenous bases by voltammetry xanthine (Xa), adenine (A) and thymine (T) with constant-current potential sweep with differentiation were used. The electrochemical behavior of Xa, A and T on the surface of a glassy carbon electrode were investigated. The conditions of registration of their joint detecting in the solution were defined. It is demonstrated that the oxidation peak currents of Xa, A and T increased linearly with their concentration in the range of 4.0 10{-8} - 1 10{-4} mol/dm{3} for Xa, 3.0 10{-7} – 1.0 10{-4} mol/dm{3} for A, and 1.0 10{-5}– 1.1 10{-3} mol/dm{3} for T with correlation coefficients of 0.996, 0.996 and 0.999, respectively

The Salmonella enterica PhoP Directly Activates the Horizontally Acquired SPI-2 Gene sseL and Is Functionally Different from a S. bongori Ortholog

To establish a successful infection within the host, a pathogen must closely regulate multiple virulence traits to ensure their accurate temporal and spatial expression. As a highly adapted intracellular pathogen, Salmonella enterica has acquired during its evolution various virulence genes via numerous lateral transfer events, including the acquisition of the Salmonella Pathogenicity Island 2 (SPI-2) and its associated effectors. Beneficial use of horizontally acquired genes requires that their expression is effectively coordinated with the already existing virulence programs and the regulatory set-up in the bacterium. As an example for such a mechanism, we show here that the ancestral PhoPQ system of Salmonella enterica is able to regulate directly the SPI-2 effector gene sseL (encoding a secreted deubiquitinase) in an SsrB-independent manner and that PhoP plays a part in a feed-forward regulatory loop, which fine-tunes the cellular level of SseL. Additionally, we demonstrate the presence of conserved cis regulatory elements in the promoter region of sseL and show direct binding of purified PhoP to this region. Interestingly, in contrast to the S. enterica PhoP, an ortholog regulator from a S. bongori SARC 12 strain was found to be impaired in promoting transcription of sseL and other genes from the PhoP regulon. These findings have led to the identification of a previously uncharacterized residue in the DNA-binding domain of PhoP, which is required for the transcriptional activation of PhoP regulated genes in Salmonella spp. Collectively our data demonstrate an interesting interface between the acquired SsrB regulon and the ancestral PhoPQ regulatory circuit, provide novel insights into the function of PhoP, and highlight a mechanism of regulatory integration of horizontally acquired genes into the virulence network of Salmonella enterica

Sensing what fish feel about passage through three different low-head hydropower turbines

Knowing the kinds of physical stress experienced by fish passing through hydropower turbines can help optimise technologies and improve fish passage. This paper assesses the hydraulic conditions experienced through three different low-head turbines, taken using an autonomous sensor: a VLH, Archimedes screw and horizontal Kaplan turbine. A total of 127 Sensor Fish deployments were undertaken across all three turbines, generating 82 valid datasets. Decompression was rare at the VLH and screw turbines and rarely fell more than 10 kPa below atmospheric pressure. In contrast, the Kaplan was capable of generating pressures as low as 55.5 kPa (approximately 45 kPa below atmospheric pressure), over shorter periods of time. Severer ratios of pressure changes could therefore be expected for both surface and depth acclimated fish at the Kaplan when compared to the other turbines. Strike was another possible source of fish injury (detected in 69-100% of deployments), and although strike severity was highest at the Kaplan, strike was more likely to be encountered at the screw and VLH than the Kaplan turbine. Shear only occurred near the blades of the Kaplan and not at severe levels. The results demonstrate that low-head hydropower facilities are not without their risks for downstream migrating fish

Chiral cationic polyamines for chiral microcapsules and siRNA delivery

Reported herein is the use of chiral cationic polyamines for two intriguing applications: fabrication of chiral covalently-linked microcapsules, and enantiospecific delivery of siRNA to Huh 7 cells. The microcapsules are easily fabricated from homochiral polymers, and the resulting architectures can be used for supramolecular chiral catalysis and many other potential applications. Enantiospecific delivery of siRNA to Huh 7 cells is seen by one ‘enantiomer’ of the polymers delivering siRNA with significantly improved transfection efficiency and reduced toxicity compared to the ‘enantiomeric’ polymer and commercially available transfection reagents. Taken together, the use of these easily accessible polyamine structures for diverse applications is highlighted in this Letter herein and can lead to numerous future research efforts. [Refer to PDF for graphical abstract

False Negative/Positive Control for SAM on Noisy Medical Images

The Segment Anything Model (SAM) is a recently developed all-range foundation model for image segmentation. It can use sparse manual prompts such as bounding boxes to generate pixel-level segmentation in natural images but struggles in medical images such as low-contrast, noisy ultrasound images. We propose a refined test-phase prompt augmentation technique designed to improve SAM's performance in medical image segmentation. The method couples multi-box prompt augmentation and an aleatoric uncertainty-based false-negative (FN) and false-positive (FP) correction (FNPC) strategy. We evaluate the method on two ultrasound datasets and show improvement in SAM's performance and robustness to inaccurate prompts, without the necessity for further training or tuning. Moreover, we present the Single-Slice-to-Volume (SS2V) method, enabling 3D pixel-level segmentation using only the bounding box annotation from a single 2D slice. Our results allow efficient use of SAM in even noisy, low-contrast medical images. The source code will be released soon

Open-channel structure of a pentameric ligand-gated ion channel reveals a mechanism of leaflet-specific phospholipid modulation

Pentameric ligand-gated ion channels (pLGICs) mediate synaptic transmission and are sensitive to their lipid environment. The mechanism of phospholipid modulation of any pLGIC is not well understood. We demonstrate that the model pLGIC, ELIC (Erwinia ligand-gated ion channel), is positively modulated by the anionic phospholipid, phosphatidylglycerol, from the outer leaflet of the membrane. To explore the mechanism of phosphatidylglycerol modulation, we determine a structure of ELIC in an open-channel conformation. The structure shows a bound phospholipid in an outer leaflet site, and structural changes in the phospholipid binding site unique to the open-channel. In combination with streamlined alchemical free energy perturbation calculations and functional measurements in asymmetric liposomes, the data support a mechanism by which an anionic phospholipid stabilizes the activated, open-channel state of a pLGIC by specific, state-dependent binding to this site

Tree-formed Verification Data for Trusted Platforms

The establishment of trust relationships to a computing platform relies on validation processes. Validation allows an external entity to build trust in the expected behaviour of the platform based on provided evidence of the platform's configuration. In a process like remote attestation, the 'trusted' platform submits verification data created during a start up process. These data consist of hardware-protected values of platform configuration registers, containing nested measurement values, e.g., hash values, of loaded or started components. Commonly, the register values are created in linear order by a hardware-secured operation. Fine-grained diagnosis of components, based on the linear order of verification data and associated measurement logs, is not optimal. We propose a method to use tree-formed verification data to validate a platform. Component measurement values represent leaves, and protected registers represent roots of a hash tree. We describe the basic mechanism of validating a platform using tree-formed measurement logs and root registers and show an logarithmic speed-up for the search of faults. Secure creation of a tree is possible using a limited number of hardware-protected registers and a single protected operation. In this way, the security of tree-formed verification data is maintained.Comment: 15 pages, 11 figures, v3: Reference added, v4: Revised, accepted for publication in Computers and Securit

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

Survey of Tyrosine Kinase Signaling Reveals ROS Kinase Fusions in Human Cholangiocarcinoma

Cholangiocarcinoma, also known as bile duct cancer, is the second most common primary hepatic carcinoma with a median survival of less than 2 years. The molecular mechanisms underlying the development of this disease are not clear. To survey activated tyrosine kinases signaling in cholangiocarcinoma, we employed immunoaffinity profiling coupled to mass spectrometry and identified DDR1, EPHA2, EGFR, and ROS tyrosine kinases, along with over 1,000 tyrosine phosphorylation sites from about 750 different proteins in primary cholangiocarcinoma patients. Furthermore, we confirmed the presence of ROS kinase fusions in 8.7% (2 out of 23) of cholangiocarcinoma patients. Expression of the ROS fusions in 3T3 cells confers transforming ability both in vitro and in vivo, and is responsive to its kinase inhibitor. Our data demonstrate that ROS kinase is a promising candidate for a therapeutic target and for a diagnostic molecular marker in cholangiocarcinoma. The identification of ROS tyrosine kinase fusions in cholangiocarcinoma, along with the presence of other ROS kinase fusions in lung cancer and glioblastoma, suggests that a more broadly based screen for activated ROS kinase in cancer is warranted