Development of a Novel Mathematical Model That Explains SARS-CoV-2 Infection Dynamics in Caco-2 Cells

Mathematical modeling is widely used to study within-host viral dynamics. However, to the best of our knowledge, for the case of SARS-CoV-2 such analyses were mainly conducted with the use of viral load data and for the wild type (WT) variant of the virus. In addition, only few studies analyzed models for in vitro data, which are less noisy and more reproducible. In this work we collected multiple data types for SARS-CoV-2-infected Caco-2 cell lines, including infectious virus titers, measurements of intracellular viral RNA, cell viability data and percentage of infected cells for the WT and Delta variants. We showed that standard models cannot explain some key observations given the absence of cytopathic effect in human cell lines. We propose a novel mathematical model for in vitro SARS-CoV-2 dynamics, which included explicit modeling of intracellular events such as exhaustion of cellular resources required for virus production. The model also explicitly considers innate immune response. The proposed model accurately explained experimental data. Attenuated replication of the Delta variant in Caco-2 cells could be explained by our model on the basis of just two parameters: decreased cell entry rate and increased cytokine production rate

Genome sequence of the pattern forming Paenibacillus vortex bacterium reveals potential for thriving in complex environments

<p>Abstract</p> <p>Background</p> <p>The pattern-forming bacterium <it>Paenibacillus vortex </it>is notable for its advanced social behavior, which is reflected in development of colonies with highly intricate architectures. Prior to this study, only two other <it>Paenibacillus </it>species (<it>Paenibacillus </it>sp. JDR-2 and <it>Paenibacillus larvae</it>) have been sequenced. However, no genomic data is available on the <it>Paenibacillus </it>species with pattern-forming and complex social motility. Here we report the <it>de novo </it>genome sequence of this Gram-positive, soil-dwelling, sporulating bacterium.</p> <p>Results</p> <p>The complete <it>P. vortex </it>genome was sequenced by a hybrid approach using 454 Life Sciences and Illumina, achieving a total of 289× coverage, with 99.8% sequence identity between the two methods. The sequencing results were validated using a custom designed Agilent microarray expression chip which represented the coding and the non-coding regions. Analysis of the <it>P. vortex </it>genome revealed 6,437 open reading frames (ORFs) and 73 non-coding RNA genes. Comparative genomic analysis with 500 complete bacterial genomes revealed exceptionally high number of two-component system (TCS) genes, transcription factors (TFs), transport and defense related genes. Additionally, we have identified genes involved in the production of antimicrobial compounds and extracellular degrading enzymes.</p> <p>Conclusions</p> <p>These findings suggest that <it>P. vortex </it>has advanced faculties to perceive and react to a wide range of signaling molecules and environmental conditions, which could be associated with its ability to reconfigure and replicate complex colony architectures. Additionally, <it>P. vortex </it>is likely to serve as a rich source of genes important for agricultural, medical and industrial applications and it has the potential to advance the study of social microbiology within Gram-positive bacteria.</p

Cumulative prognostic power of laminin genes in colorectal cancer.

BACKGROUND: Laminins are a major family of extracellular matrix proteins and the main component of basement membranes. Laminins are involved in many if not all stages of cancer progression, and expression of laminin genes has prognostic value in various types of cancer, including colorectal. Only single laminin genes or components of a single laminin trimer with significant differential expression have been regarded as potential biomarkers to date. RESULTS: Here we compared prognostic power of classifiers constructed from sets of laminin genes with that of any single laminin gene. The analysis showed that cumulative prognostic power of sets of laminin genes was higher and was achieved already with pairs and triples of the genes. Interestingly, components of the pairs and the triples did not belong to any known laminin trimer, but, taken together with the gene weights, suggested higher LAMA4/LAMA5 expression ratio in patients with poor prognosis. CONCLUSIONS: Analysis of the laminin expression profile rather than expression of the single genes or components of laminin trimers is useful for colorectal cancer prognosis in patients. High LAMA4/LAMA5 ratio is associated with increased permeability of basement membranes suggesting that basement membranes produced by colorectal tumors might be an important hindrance to their own dissemination in patients

Greedy Expansions with Prescribed Coefficients in Hilbert Spaces

Greedy expansions with prescribed coefficients, which have been studied by V. N. Temlyakov in Banach spaces, are considered here in a narrower case of Hilbert spaces. We show that in this case the positive result on the convergence does not require monotonicity of coefficient sequence C. Furthermore, we show that the condition sufficient for the convergence, namely, the inclusion C∈l2∖l1, can not be relaxed at least in the power scale. At the same time, in finite-dimensional spaces, the condition C∈l2 can be replaced by convergence of C to zero

utomated real-time classification of functional states: the significance of individual tuning stage

Automated classification of a human functional state is an important problem, with applications including stress resistance evaluation, supervision over operators of critical infrastructure, teaching and phobia therapy. Such classification is particularly efficient in systems for teaching and phobia therapy that include a virtual reality module, and provide the capability for dynamic adjustment of task complexity. In this paper, a method for automated real-time binary classification of human functional states (calm wakefulness vs. stress) based on discrete wavelet transform of EEG data is considered. It is shown that an individual tuning stage of the classification algorithm — a stage that allows the involvement of certain information on individual peculiarities in the classification, using very short individual learning samples, significantly increases classification reliability. The experimental study that proved this assertion was based on a specialized scenario in which individuals solved the task of detecting objects with given properties in a dynamic set of flying objects

AN INTERACTIVE METHOD OF ANATOMICAL SEGMENTATION AND GENE EXPRESSION ESTIMATION FOR AN EXPERIMENTAL MOUSE BRAIN SLICE

Abstract. We consider the problem of statistical analysis of gene expression in a mouse brain during cognitive processes. In particular we focus on the problems of anatomical segmentation of a histological brain slice and estimation of slice&apos;s gene expression level. The first problem is solved by interactive registration of an experimental brain slice into 3D brain model constructed using Allen Brain Atlas. The second problem is solved by special image filtering and further smart resolution reduction. We also describe the procedure of non-linear correction of atlas slices which improves the quality of the 3D-model significantly. 1 Introduction The analysis of gene expression in a brain is extremely important for cognitive research. Many cognitive functions (e.g. memory consolidation) are regulated by specific genes whose expression starts during some intellectual activity, e.g. training. On the other hand it is known that changes in activity in specific anatomical brain zones reflect the cognitive processes. The combination of anatomical brain map with gene expression patterns and its further statistical processing would allow researchers to discover new genes that are responsible for cognitive processes and new anatomical structures where the functional activity takes place. Up to the current moment gene expression in animal brains is measured using the following technique. A brain is extracted, frozen and then cut into slices. Each slice is double-stained by Nissl method to highlight histology (se

Instrumental Mechanoreceptoric Palpation in Gastrointestinal Surgery

Background and Aims. Small gastric or colorectal tumours can be visually undetectable during laparoscopic surgeries, and available methods still do not provide a 100% localisation rate. Thus, new methods for further improvements in tumour localisation are highly desirable. In this study, we evaluated the usage of the Medical Tactile Endosurgical Complex (MTEC) in gastrointestinal surgery for localisation of tumours. The MTEC provides the possibility of instrumental mechanoreceptoric palpation, which serves as an analogue of conventional manual palpation. Methods. Ninety-six elective surgeries were performed, including 48 open surgeries, 43 laparoscopies, and 5 robot-assisted surgeries. The 20 mm version of the MTEC tactile mechanoreceptor was used in open surgeries, and the 10 mm version in laparoscopic and robot-assisted surgeries. Results. The mean time of instrumental mechanoreceptoric palpation was 3 minutes 12 seconds for open surgeries, which constituted the early stage of the learning curve, and 3 minutes 34 seconds for laparoscopic surgeries. No side effects or postoperative complications related to instrumental mechanoreceptoric palpation were observed, and this procedure provided data sufficient for tumour localisation in more than 95% of cases. Conclusion. Instrumental mechanoreceptoric palpation performed using MTEC is a simple, safe, and reliable method for tumour localisation in gastrointestinal laparoscopic surgery

The Transcriptome of Type I Murine Astrocytes under Interferon-Gamma Exposure and Remyelination Stimulus

Astrocytes are considered to be an important contributor to central nervous system (CNS) disorders, particularly multiple sclerosis. The transcriptome of these cells is greatly affected by cytokines released by lymphocytes, penetrating the blood–brain barrier—in particular, the classical pro-inflammatory cytokine interferon-gamma (IFNγ). We report here the transcriptomal profiling of astrocytes treated using IFNγ and benztropine, a putative remyelinization agent. Our findings indicate that the expression of genes involved in antigen processing and presentation in astrocytes are significantly upregulated upon IFNγ exposure, emphasizing the critical role of this cytokine in the redirection of immune response towards self-antigens. Data reported herein support previous observations that the IFNγ-induced JAK-STAT signaling pathway may be regarded as a valuable target for pharmaceutical interventions