Identification and smart design of peptide binders recognizing target biomarkers

There is an urgent need for novel diagnostic methods capable of non-invasive, sensitive and feasible early prediction of colorectal adenoma-to-carcinoma progression over conventional techniques. In this paper, we describe for the first time the use of phage display for the identification of novel peptide motifs that specifically recognize colorectal cancer (CRC) biomarkers for the prediction of colorectal adenoma-to-carcinoma progression. We performed a biopanning of phage displayed peptide library to identify novel peptide sequences specific for promising CRC biomarker, LRG1 and TTR. The peptides specific for LRG1 that is upregulated proteins in carcinoma had an amino acid sequence with QHIMHLPHINTL, while the peptides specific for TTR that is downregulated proteins in adenoma had an amino acid sequence with VHDDFRQDWQPS. ELISA assays were used to evaluate binding affinity for their targets. As a consequence, both phage-displayed peptides were found to be sub-picomolar binding affinities for their proteins. A quartz crystal microbalance (QCM) is used as a diagnosis tool during biosensor development, and electrochemical techniques (cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS)) and surface-enhanced Raman scattering (SERS) are used as the detection methods in the biosensor. Overall these results demonstrate a simple platform for developing sensitive peptide-based biosensors for almost any desired protein target. Please click Additional Files below to see the full abstract

Wide-ranging functions of E2F4 in transcriptional activation and repression revealed by genome-wide analysis

The E2F family of transcription factors has important roles in cell cycle progression. E2F4 is an E2F family member that has been proposed to be primarily a repressor of transcription, but the scope of its binding activity and functions in transcriptional regulation is not fully known. We used ChIP sequencing (ChIP-seq) to identify around 16 000 E2F4 binding sites which potentially regulate 7346 downstream target genes with wide-ranging functions in DNA repair, cell cycle regulation, apoptosis, and other processes. While half of all E2F4 binding sites (56%) occurred near transcription start sites (TSSs), ∼20% of sites occurred more than 20 kb away from any annotated TSS. These distal sites showed histone modifications suggesting that E2F4 may function as a long-range regulator, which we confirmed by functional experimental assays on a subset. Overexpression of E2F4 and its transcriptional cofactors of the retinoblastoma (Rb) family and its binding partner DP-1 revealed that E2F4 acts as an activator as well as a repressor. E2F4 binding sites also occurred near regulatory elements for miRNAs such as let-7a and mir-17, suggestive of regulation of miRNAs by E2F4. Taken together, our genome-wide analysis provided evidence of versatile roles of E2F4 and insights into its functions

Tgif1 Counterbalances The Activity Of Core Pluripotency Factors In Mouse Embryonic Stem Cells

Core pluripotency factors, such as Oct4, Sox2, and Nanog, play important roles in maintaining embryonic stem cell (ESC) identity by autoregulatory feedforward loops. Nevertheless, the mechanism that provides precise control of the levels of the ESC core factors without indefinite amplification has remained elusive. Here, we report the direct repression of core pluripotency factors by Tgif1, a previously known terminal repressor of TGF beta/activin/nodal signaling. Overexpression of Tgif1 reduces the levels of ESC core factors, whereas its depletion leads to the induction of the pluripotency factors. We confirm the existence of physical associations between Tgif1 and Oct4, Nanog, and HDAC1/2 and further show the level of Tgif1 is not significantly altered by treatment with an activator/inhibitor of the TGF beta/activin/nodal signaling. Collectively, our findings establish Tgif1 as an integral member of the core regulatory circuitry of mouse ESCs that counterbalances the levels of the core pluripotency factors in a TGF beta/activin/nodal-independent manner.Cancer Prevention Research Institute of Texas (CPRIT) R1106Molecular Bioscience

Structure and spectral features of H+(H2O)(7): Eigen versus Zundel forms

The two dimensional (2D) to three dimensional (3D) transition for the protonated water cluster has been controversial, in particular, for H+(H2O)(7). For H+(H2O)(7) the 3D structure is predicted to be lower in energy than the 2D structure at most levels of theory without zero-point energy (ZPE) correction. On the other hand, with ZPE correction it is predicted to be either 2D or 3D depending on the calculational levels. Although the ZPE correction favors the 3D structure at the level of coupled cluster theory with singles, doubles, and perturbative triples excitations [CCSD(T)] using the aug-cc-pVDZ basis set, the result based on the anharmonic zero-point vibrational energy correction favors the 2D structure. Therefore, the authors investigated the energies based on the complete basis set limit scheme (which we devised in an unbiased way) at the resolution of the identity approximation Moller-Plesset second order perturbation theory and CCSD(T) levels, and found that the 2D structure has the lowest energy for H+(H2O)(7) [though nearly isoenergetic to the 3D structure for D+(D2O)(7)]. This structure has the Zundel-type configuration, but it shows the quantum probabilistic distribution including some of the Eigen-type configuration. The vibrational spectra of MP2/aug-cc-pVDZ calculations and Car-Parrinello molecular dynamics simulations, taking into account the thermal and dynamic effects, show that the 2D Zundel-type form is in good agreement with experiments. (c) 2006 American Institute of Physics.open353

Influence of Carbon Content and Isothermal Heat Treatment Temperature on the Microstructure and Mechanical Properties of Ultra-High Strength Bainitic Steels

The effect of carbon content and isothermal heat treatment conditions on the microstructure evolution and mechanical properties of ultra-high strength bainitic steels was investigated. A reduction in carbon content from 0.8 wt% to 0.6 wt% in super-bainite steel with typical chemistry effectively improved not only the Charpy impact toughness but also the strength level. This suggests that reducing the carbon content is a very promising way to obtain better mechanical balance between strength and impact toughness. The higher Charpy impact toughness at a lower carbon content of 0.6 wt% is thought to result from a reduction in austenite fraction, and refinement of the austenite grain. The coarse austenite grains have a detrimental effect on impact toughness, by prematurely transforming to deformation-induced martensite during crack propagation. Mechanical properties were also affected by the isothermal treatment temperature. The lower isothermal temperature enhanced the formation of bainitic ferrite with a refined microstructure, which has a beneficial influence on strength, but reduces impact toughness. The lower impact toughness at lower isothermal temperature is attributed to the sluggish redistribution of carbon from the bainitic ferrite into the surrounding austenite. Higher solute carbon in the bainitic ferrite contributes to an increase of strength, but at the same time, encourages a propensity to cleavage fracture.11Ysciescopuskc

Large Oncocytic Adrenocortical Tumor with Uncertain Malignant Potential

Oncocytoma is a neoplasm consisting of oncocytes that is found in the salivary gland, kidney, and thyroid. Adrenocortical oncocytoma is particularly uncommon, and most cases reported are benign and nonfunctioning. Here, we report a 20 cm adrenal mass associated with necrosis that was identified as an oncocytic adrenocortical tumor with uncertain malignant potential through histopathological evaluation after its resection

Visible emission from Ce-doped ZnO nanorods grown by hydrothermal method without a post thermal annealing process

Visible light-emitting Ce-doped ZnO nanorods [NRs] without a post thermal annealing process were grown by hydrothermal method on a Si (100) substrate at a low temperature of 90°C. The structural investigations of Ce-doped ZnO NRs showed that the Ce3+ ions were successfully incorporated into the ZnO lattice sites without forming unwanted Ce-related compounds or precipitates. The optical investigation by photoluminescence spectra shows that the doped Ce3+ ions in the ZnO NRs act as an efficient luminescence center at 540 nm which corresponds to the optical transition of 5d → 4f orbitals in the Ce3+ ions. The photoluminescence intensity of the Ce-doped ZnO NRs increased with the increasing content of the Ce-doping agent because the energy transfer of the excited electrons in ZnO to the Ce3+ ions would be enhanced by increased Ce3+ ions

Computed Tomographic Angiogram of an Anterior Communicating Artery Aneurysm Causing Acute Retrobulbar Optic Neuropathy: A Case Report

Three-dimensional computed tomographic (3D-CT) angiography is a widespread imaging modality for intracranial vascular lesions. However, 3D-CT angiograms of an anterior communicating artery aneurysm associated with acute retrobulbar optic neuropathy have not been previously described. We present 3D-CT angiograms of an aneurysm of the anterior communicating artery that caused subarachnoid hemorrhage and vision loss in a 39-year old man. The 3D-CT angiograms were consistent with findings identified directly during surgery

Positioning of the Fermi Level in Graphene Devices with Asymmetric Metal Electrodes

To elucidate the effect of the work function on the position of the Dirac point, we fabricated graphene devices with asymmetric metal contacts. By measuring the peak position of the resistance for each pair of metal electrodes, we obtained the voltage of the Dirac point VgDirac (V) from the gate response. We found that the position of VgDirac (V) in the hybrid devices was significantly influenced by the type of metal electrode. The measured shifts in VgDirac (V) were closely related to the modified work functions of the metal-graphene complexes. Within a certain bias range, the Fermi level of one of the contacts aligned with the electron band and that of the other contact aligned with the hole band