Exendin-(9-39) is an inverse agonist of the murine glucagon-like peptide-1 receptor: implications for basal intracellular cyclic adenosine 3',5'-monophosphate levels and beta-cell glucose competence

The effect of exendin-(9-39), a described antagonist of the glucagon-like peptide-1 (GLP-1) receptor, was evaluated on the formation of cAMP- and glucose-stimulated insulin secretion (GSIS) by the conditionally immortalized murine betaTC-Tet cells. These cells have a basal intracellular cAMP level that can be increased by GLP-1 with an EC50 of approximately 1 nM and can be decreased dose dependently by exendin-(9-39). This latter effect was receptor dependent, as a beta-cell line not expressing the GLP-1 receptor was not affected by exendin-(9-39). It was also not due to the endogenous production of GLP-1, because this effect was observed in the absence of detectable preproglucagon messenger RNA levels and radioimmunoassayable GLP-1. Importantly, GSIS was shown to be sensitive to this basal level of cAMP, as perifusion of betaTC-Tet cells in the presence of exendin-(9-39) strongly reduced insulin secretion. This reduction of GSIS, however, was observed only with growth-arrested, not proliferating, betaTC-Tet cells; it was also seen with nontransformed mouse beta-cells perifused in similar conditions. These data therefore demonstrated that 1) exendin-(9-39) is an inverse agonist of the murine GLP-1 receptor; 2) the decreased basal cAMP levels induced by this peptide inhibit the secretory response of betaTC-Tet cells and mouse pancreatic islets to glucose; 3) as this effect was observed only with growth-arrested cells, this indicates that the mechanism by which cAMP leads to potentiation of insulin secretion is different in proliferating and growth-arrested cells; and 4) the presence of the GLP-1 receptor, even in the absence of bound peptide, is important for maintaining elevated intracellular cAMP levels and, therefore, the glucose competence of the beta-cells.     

Depletion of antibiotics from the mammary gland of goats

Four intramammary infusion products were tested in 10 normal goats to determine their rates of depletion from milk. The products tested, which are marketed for treatment of mastitis in the bovine, contained the single active ingredient erythromycin, oxytetracycline, penicillin, or cephapirin. Each mammary gland was infused, after the goats were milked, with the maximum recommended dose of test product (dosing frequency and quantity) for administration to lactating dairy cattle. With one exception, no antibiotics could be detected in the milk by the end of the bovine milk-discard period. Penicillin was detectable in the milk of one goat for 72 h after the last dose of product containing this antibiotic was given (60-h withdrawal period). Only the product containing oxytetracycline produced significant adverse reactions in the mammary gland. The applicator tips of the products were too large for atraumatic insertion into the teat opening of some goats. Overall, results of this limited study indicated that some intramammary infusion products can be used to treat mastitis in the goat if instructions for use in the bovine are followed.     

Local versus Global in Quasi-Conformal Mapping for Medical Imaging

A method and algorithm of flattening folded surfaces, for two-dimensional representation and analysis of medical images, are presented. The method is based on an application to triangular meshes of classical results of Gehring and Väisälä regarding the existence of quasi-conformal and quasi-isometric mappings.The proposed algorithm is basically local and, therefore, suitable for extensively folded surfaces encountered in medical imaging. The theory and algorithm guarantee minimal distance, angle and area distortion. Yet, the algorithm is relatively simple, robust and computationally efficient, since it does not require computational derivatives. Both random-starting-point and curvature-based versions of the algorithm are presented.We demonstrate the algorithm using medical data obtained from real CT images of the colon and MRI scans of the human cortex. Further applications of the algorithm, for image processing in general are also considered. The globality of this algorithm is also studied, via extreme length methods for which we develop a technique of computing straightest geodesics on polyhedral surfaces.     

On the decoding of convolutional codes on an unknown channel

An algorithm is proposed for universal decoding of convolutional/trellis codes employed over unknown channels. On discrete memoryless channels and at rates below the channel's computational cutoff rate (for a uniform input distribution), the algorithm achieves an asymptotic complexity-performance tradeoff similar to the tradeoff achieved by the Viterbi (1979) algorithm, but with the benefit that the algorithm's implementation does not require knowledge of the channel law. The algorithm is also applicable to channels with memory, and in particular to intersymbol interference (ISI) channels, to channels with nonlinear ISI, and even to general finite-state channels     

Circulating Tumor DNA in Precision Oncology and Its Applications in Colorectal Cancer

Circulating tumor DNA (ctDNA) is a component of cell-free DNA (cfDNA) that is shed by malignant tumors into the bloodstream and other bodily fluids. ctDNA can comprise up to 10% of a patient’s cfDNA depending on their tumor type and burden. The short half-life of ctDNA ensures that its detection captures tumor burden in real-time and offers a non-invasive method of repeatedly evaluating the genomic profile of a patient’s tumor. A challenge in ctDNA detection includes clonal hematopoiesis of indeterminate potential (CHIP), which can be distinguished from tumor variants using a paired whole-blood control. Most assays for ctDNA quantification rely on measurements of somatic variant allele frequency (VAF), which is a mutation-dependent method. Patients with certain types of solid tumors, including colorectal cancer (CRC), can have levels of cfDNA 50 times higher than healthy patients. ctDNA undergoes a precipitous drop shortly after tumor resection and therapy, and rising levels can foreshadow radiologic recurrence on the order of months. The amount of tumor bulk required for ctDNA detection is lower than that for computed tomography (CT) scan detection, with ctDNA detection preceding radiologic recurrence in many cases. cfDNA/ctDNA can be used for tumor molecular profiling to identify resistance mutations when tumor biopsy is not available, to detect minimal residual disease (MRD), to monitor therapy response, and for the detection of tumor relapse. Although ctDNA is not yet implemented in clinical practice, studies are ongoing to define the appropriate way to use it as a tool in the clinic. In this review article, we examine the general aspects of ctDNA, its status as a biomarker, and its role in the management of early (II–III) and late (IV; mCRC) stage colorectal cancer (CRC).     

Exfoliated CrPS4 with Promising Photoconductivity

Layered semiconductors have attracted significant attention due to their diverse physical properties controlled by composition and the number of stacked layers. Herein, large crystals of the ternary layered semiconductor chromium thiophosphate (CrPS₄) are prepared by a vapor transport synthesis. Optical properties are determined using photoconduction, absorption, photoreflectance, and photoacoustic spectroscopy exposing the semiconducting properties of the material. A simple, one‐step protocol for mechanical exfoliation onto a transmission electron microscope grid is developed, and multiple layers are characterized by advanced electron microscopy methods, including atomic resolution elemental mapping confirming the structure by directly showing the positions of the columns of different elements' atoms. CrPS₄ is also liquid exfoliated, and in combination with colloidal graphene, an ink‐jet‐printed photodetector is created. This all‐printed graphene/CrPS₄/graphene heterostructure detector demonstrates a specific detectivity of 8.3 × 10⁸ (D*). This study shows a potential application of both bulk crystal and individual flakes of CrPS₄ as active components in light detection, when introduced as ink‐printable moieties with a large benefit for manufacturing.     

To call or not to call—That is the question (while driving)

We studied whether decisions to engage in cell phone conversation while driving and the consequences of such decisions are related to the driver's age, to the road conditions (demands of the driving task), and to the driver's role in initiating the phone call (i.e. the driver as caller vs. as receiver). Two experiments were performed in a driving simulator in which driver age, road conditions and phone conversation, as a secondary task, were manipulated. Engagement in cell phone conversations, performance in the driving and the conversation tasks, and subjective effort assessment were recorded. In general, drivers were more willing to accept incoming calls than to initiate calls. In addition, older and younger drivers were more susceptible to the deleterious effects of phone conversations while driving than middle aged/experienced drivers. While older drivers were aware of this susceptibility by showing sensitivity to road conditions before deciding whether to engage in a call or not, young drivers showed no such sensitivity. The results can guide the development of young driver training programs and point at the need to develop context-aware management systems of in-vehicle cell phone conversations.     

On Finite Memory Universal Data Compression and Classification of Individual Sequences

Consider the case where consecutive blocks of letters of a semi-infinite individual sequence over a finite-alphabet are being compressed into binary sequences by some one-to-one mapping. No a priori information about is available at the encoder, which must therefore adopt a universal data-compression algorithm. It is known that if the universal Lempel-Ziv (LZ) data compression algorithm is successively applied to -blocks then the best error-free compression, for the particular individual sequence is achieved as tends to infinity. The best possible compression that may be achieved by any universal data compression algorithm for finite -blocks is discussed. It is demonstrated that context tree coding essentially achieves it. Next, consider a device called classifier (or discriminator) that observes an individual training sequence . The classifier's task is to examine individual test sequences of length and decide whether the test -sequence has the same features as those that are captured by the training sequence , or is sufficiently different, according to some appropriate criterion. Here again, it is demonstrated that a particular universal context classifier with a storage-space complexity that is linear in , is essentially optimal. This may contribute a theoretical ldquoindividual sequencerdquo justification for the Probabilistic Suffix Tree (PST) approach in learning theory and in computational biology.     

Impact of <Emphasis Type="Italic">in vivo</Emphasis> glycation of LDL on platelet aggregation and monocyte chemotaxis in diabetic <Emphasis Type="Italic">Psammomys obesus</Emphasis>

Psammomys obesus (sand rat) is an appropriate model to highlight the development of hyperinsulinemia, insulin resistance, obesity, and diabetes. This animal species, with genetically predetermined diabetes, acquires non-insulin dependent diabetes mellitus when exposed to energy-rich diets. In the present study, we explored the possibility that glycation of LDL may occur in diabetes-prone P. obesus and affect platelet and macrophage functions. The glycation of LDL, isolated from diabetic animals, was significantly (P<0.05) higher (40%) than that of control animals. The incubation of platelets with glycated LDL enhanced the reactivity of platelets by 32–44% depending on the aggregating agents (thrombin, collagen, ADP). Furthermore, LDL derived from diabetic rats were chemotactic for normal monocytes and stimulated the incorporation of [¹⁴C]oleate into cellular cholesteryl esters. The enhancement of platelet aggregation and cholesterol esterification in monocytes may contribute toward the accelerated development of atherosclerotic cardiovascular disease in diabetic P. obesus animals. This study also illustrates the relevance of studying atherosclerosis in the P. obesus animal model, as it shows an increased tendency to develop dietinduced diabetes, which is associated with cardiovascular disorders.     

Cloning and analysis of CoEXG1, a secreted 1,3-beta-glucanase of the yeast biocontrol agent Candida oleophila

Lytic enzymes may have a role in the biological control of fungi. The yeast biocontrol agent, Candida oleophila, is an excellent subject to research this matter. In the present study, CoEXG1, which encodes for a secreted 1,3-beta-glucanase, is the first gene to be cloned from C. oleophila. It was isolated from a partial genomic library and analysed. Its open reading frame and putative promoter were expressed in baker's yeast, Saccharomyces cerevisiae. The reading frame, expressed under the inducible GAL1 promoter, caused an increased secretion of beta-glucanase, and the putative promoter region activated the lacZ reporter gene, to which it was fused. Sequencing analysis revealed that CoEXG1 carries the signature pattern of the 5 glycohydrolases family and has a putative secretion leader, as well as a high degree of identity to yeast 1,3-beta-glucanases. The GenBank Accession No. of CoEXG1 is AF393806.