A stochastic compartmental model with continuous infusion

This paper deals with stochasticm-compartmental systems with continuous time-dependent infusions into all compartments and reversible time-independent flows between any two compartments. A methodology for the first two moments of the distribution of the number of units in the different compartments at any point in time is outlined without resorting to the usual techniques of generating functions and inverse Laplace transforms. A possible application to a systems analysis of the kidney transplant system is discussed.     

Quantitative light microscopic autoradiography. Emulsion sensitivity and latent image fading.

Emulsion sensitivity, latent image fading, and the effects of temperature, humidity, radiation dose and chemography on them were measured for NTB2 autoradiographic emulsion using quantitative methods. Sensitivity of NTB2 emulsion increased as the temperature during exposure increased, with the greatest increase per degree occurring between -20 degrees C. At 4 degrees C, emulsion sensitivity remained constant with time and radiation dose. Direct measurement of latent image fading showed no latent image fading for 60 weeks on slides exposed at 4 degrees C with Drierite. Slides exposed at 27 degrees C showed significant latent image fading and great variation between samples. High humidity decreased emulsion sensitivity and increased latent image fading. No evidence of either positive or negative chemography was found. The practical use of autoradiography requires an internal standard on each slide to correct for fluctuations in temperature and humidity during exposure time.     

Targeted tandem affinity purification of PSD‐95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins

The molecular complexity of mammalian proteomes demands new methods for mapping the organization of multiprotein complexes. Here, we combine mouse genetics and proteomics to characterize synapse protein complexes and interaction networks. New tandem affinity purification (TAP) tags were fused to the carboxyl terminus of PSD‐95 using gene targeting in mice. Homozygous mice showed no detectable abnormalities in PSD‐95 expression, subcellular localization or synaptic electrophysiological function. Analysis of multiprotein complexes purified under native conditions by mass spectrometry defined known and new interactors: 118 proteins comprising crucial functional components of synapses, including glutamate receptors, K⁺ channels, scaffolding and signaling proteins, were recovered. Network clustering of protein interactions generated five connected clusters, with two clusters containing all the major ionotropic glutamate receptors and one cluster with voltage‐dependent K⁺ channels. Annotation of clusters with human disease associations revealed that multiple disorders map to the network, with a significant correlation of schizophrenia within the glutamate receptor clusters. This targeted TAP tagging strategy is generally applicable to mammalian proteomics and systems biology approaches to disease.     

Pro-Leu-Ser/Thr-Pro is a consensus primary sequence for substrate protein phosphorylation. Characterization of the phosphorylation of c-myc and c-jun proteins by an epidermal growth factor receptor threonine 669 protein kinase.

A growth factor-stimulated (MAP2-related) protein kinase, ERT, that phosphorylates the epidermal growth factor receptor at Thr669 has been purified from KB human tumor cells by Northwood and co-workers (Northwood, I. C., Gonzalez, F. A., Wartmann, M., Raden, D. L., and Davis, R. J. (1991) J. Biol. Chem. 266, 15266-15276). The ERT protein kinase has a restricted substrate specificity, and the structural determinants employed for substrate recognition by this enzyme have not been defined. As an approach toward understanding the specificity of substrate phosphorylation, we have used an in vitro assay to identify additional substrates for the ERT protein kinase. In this report we describe two novel substrates: (a) the human c-myc protein at Ser62 and (b) the rat c-jun protein at Ser246. Alignment of the primary sequences surrounding the phosphorylation sites located within the epidermal growth factor receptor (Thr669), Myc (Ser62), and Jun (Ser246) demonstrated a marked similarity. The observed consensus sequence was Pro-Leu-Ser/Thr-Pro. We propose that this sequence forms part of a substrate structure that is recognized by the ERT protein kinase.     

The murine pan T cell marker CD96 is an adhesion receptor for CD155 and nectin-1

The CD155 ligand CD96 is an immunoglobulin-like protein tentatively allocated to the repertoire of human NK receptors. We report here that the CD96/CD155-interaction is preserved between man and mouse although both receptors are only moderately conserved in amino acid sequence. Moreover, murine CD96 (mCD96) binds to nectin-1, a receptor related to CD155. Applying newly generated monoclonal antibodies specifically recognizing mCD96, an expression profile is revealed resembling closely that of human CD96 (hCD96) on cells of hematopoietic origin. A panel of anti-mCD96 but also recently established anti-mCD155 antibodies effectively prevents formation of CD96/CD155-complexes. This was exploited to demonstrate that the only available receptor for mCD96 present on thymocytes is mCD155. Moreover, T cell adhesion to insect cells expressing mCD155 is blocked by these antibodies depending on the T cell subtype. These results suggest a function of the CD96/CD155-adhesion system in T cell biology.     

Characterization of culturable bacterial endophytes of switchgrass (Panicum virgatum L.) and their capacity to influence plant growth

Switchgrass (Panicum virgatum L.) is a perennial warm season grass that is native to the plains of North America and is widely grown as a forage, bioenergy or groundcover crop. Despite its importance, a bottleneck in switchgrass production is poor seedling vigor, which as a perennial crop represents an important time for management. Herein, data identify a suite of culturable bacterial microflora extracted from switchgrass, and show their capability to influence host plant growth and development. A total of 307 bacterial isolates were cultured and isolated from surface sterilized switchgrass biomass and sequence identified into 76 strains (subspecies classification), 36 species and 5 phyla. Approximately 58% of bacterial strains, when reintroduced into surface‐sterilized switchgrass seeds, were documented to increase lamina length (cm from base to tip after 60 days growth) relative to uninoculated controls. Ecologically, Phylum Firmicutes was the most abundant bacterial classification and encompassed 75% of all isolates. Although the culturable bacterial community studies herein represent an unknown and assumedly minor proportion of the total microbiome, by focusing on culturable bacteria, we delineate functional feedback between the presence of isolated bacteria and switchgrass seedling growth.     

An evaluation of cellulose saccharification and fermentation with an engineered Saccharomyces cerevisiae capable of cellobiose and xylose utilization

Commercial-scale cellulosic ethanol production has been hindered by high costs associated with cellulose-to-glucose conversion and hexose and pentose co-fermentation. Simultaneous saccharification and fermentation (SSF) with a yeast strain capable of xylose and cellobiose co-utilization has been proposed as a possible avenue to reduce these costs. The recently developed DA24-16 strain of Saccharomyces cerevisiae incorporates a xylose assimilation pathway and a cellodextrin transporter (CDT) that permit rapid growth on xylose and cellobiose. In the current work, a mechanistic kinetic model of cellulase-catalyzed hydrolysis of cellulose was combined with a multi-substrate model of microbial growth to investigate the ability of DA24-16 and improved cellobiose-consuming strains to obviate the need for exogenously added β-glucosidase and to assess the impact of cellobiose utilization on SSF and separate hydrolysis and fermentation (SHF). Results indicate that improved CDT-containing strains capable of growing on cellobiose as rapidly as on glucose produced ethanol nearly as rapidly as non-CDT-containing yeast supplemented with β-glucosidase. In producing 75 g/L ethanol, SSF with any strain did not result in shorter residence times than SHF with a 12 h saccharification step. Strains with improved cellobiose utilization are therefore unlikely to allow higher titers to be reached more quickly in SSF than in SHF.     

Modeling scenarios for mitigating outbreaks in congregate settings

The explosive outbreaks of COVID-19 seen in congregate settings such as prisons and nursing homes, has highlighted a critical need for effective outbreak prevention and mitigation strategies for these settings. Here we consider how different types of control interventions impact the expected number of symptomatic infections due to outbreaks. Introduction of disease into the resident population from the community is modeled as a stochastic point process coupled to a branching process, while spread between residents is modeled via a deterministic compartmental model that accounts for depletion of susceptible individuals. Control is modeled as a proportional decrease in the number of susceptible residents, the reproduction number, and/or the proportion of symptomatic infections. This permits a range of assumptions about the density dependence of transmission and modes of protection by vaccination, depopulation and other types of control. We find that vaccination or depopulation can have a greater than linear effect on the expected number of cases. For example, assuming a reproduction number of 3.0 with density-dependent transmission, we find that preemptively reducing the size of the susceptible population by 20% reduced overall disease burden by 47%. In some circumstances, it may be possible to reduce the risk and burden of disease outbreaks by optimizing the way a group of residents are apportioned into distinct residential units. The optimal apportionment may be different depending on whether the goal is to reduce the probability of an outbreak occurring, or the expected number of cases from outbreak dynamics. In other circumstances there may be an opportunity to implement reactive disease control measures in which the number of susceptible individuals is rapidly reduced once an outbreak has been detected to occur. Reactive control is most effective when the reproduction number is not too high, and there is minimal delay in implementing control. We highlight the California state prison system as an example for how these findings provide a quantitative framework for understanding disease transmission in congregate settings. Our approach and accompanying interactive website (https://phoebelu.shinyapps.io/DepopulationModels/) provides a quantitative framework to evaluate the potential impact of policy decisions governing infection control in outbreak settings.