The composition of the human intestinal microbiota is linked to health status. The aim was to analyze the microbiota of normal and colon cancer patients in order to establish cancer-related ...dysbiosis.
Stool bacterial DNA was extracted prior to colonoscopy from 179 patients: 60 with colorectal cancer, and 119 with normal colonoscopy. Bacterial genes obtained by pyrosequencing of 12 stool samples (6 Normal and 6 Cancer) were subjected to a validated Principal Component Analysis (PCA) test. The dominant and subdominant bacterial population (C. leptum, C. coccoides, Bacteroides/Prevotella, Lactobacillus/Leuconostoc/Pediococcus groups, Bifidobacterium genus, and E. coli, and Faecalibacterium prausnitzii species) were quantified in all individuals using qPCR and specific IL17 producer cells in the intestinal mucosa were characterized using immunohistochemistry.
Pyrosequencing (Minimal sequence 200 nucleotide reads) revealed 80% of all sequences could be assigned to a total of 819 taxa based on default parameter of Classifier software. The phylogenetic core in Cancer individuals was different from that in Normal individuals according to the PCA analysis, with trends towards differences in the dominant and subdominant families of bacteria. Consequently, All-bacteria log(10) (bacteria/g of stool) in Normal, and Cancer individuals were similar 11.88±0.35, and 11.80±0.56, respectively, (P = 0.16), according to qPCR values whereas among all dominant and subdominant species only those of Bacteroides/Prevotella were higher (All bacteria-specific bacterium; P = 0.009) in Cancer (-1.04±0.55) than in Normal (-1.40±0.83) individuals. IL17 immunoreactive cells were significantly expressed more in the normal mucosa of cancer patients than in those with normal colonoscopy.
This is the first large series to demonstrate a composition change in the microbiota of colon cancer patients with possible impact on mucosal immune response. These data open new filed for mass screening and pathophysiology investigations.
We introduce a new solution concept for models of coalition formation, called the myopic stable set (MSS). The MSS is defined for a general class of social environments and allows for an infinite ...state space. An MSS exists and, under minor continuity assumptions, it is also unique. The MSS generalizes and unifies various results from more specific applications. It coincides with the coalition structure core in coalition function form games when this set is nonempty; with the set of stable matchings in the Gale-Shapley matching model; with the set of pairwise stable networks and closed cycles in models of network formation; and with the set of pure strategy Nash equilibria in pseudo-potential games and finite supermodular games. We also characterize the MSS for the class of proper simple games.
Most of the Human diseases affecting westernized countries are associated with dysbiosis and loss of microbial diversity in the gut microbiota. The Western way of life, with a wide use of antibiotics ...and other environmental triggers, may reduce the number of bacterial predators leading to a decrease in microbial diversity of the Human gut. We argue that this phenomenon is similar to the process of ecosystem impoverishment in macro ecology where human activity decreases ecological niches, the size of predator populations, and finally the biodiversity. Such pauperization is fundamental since it reverses the evolution processes, drives life backward into diminished complexity, stability, and adaptability. A simple therapeutic approach could thus be to reintroduce bacterial predators and restore a bacterial diversity of the host microbiota.
Understanding whether and how environmental conditions may impact food web structure at a global scale is central to our ability to predict how food webs will respond to climate change. However, such ...an understanding is nascent. Using the best resolved available food webs to date, I address whether latitude, temperature, or both, explain the number of species and feeding interactions, the proportion of basal and top species, as well as the degree of omnivory, connectance and the number of trophic levels across food webs. I found that temperature is a more parsimonious predictor of food web structure than latitude. Temperature directly reduces the number of species, the proportion of basal species and the number of interactions while it indirectly increases omnivory levels, connectance and trophic level through its direct effects on the fraction and number of basal species. While direct impacts of temperature are routinely taken into account to predict how ecosystems may respond to global climate change, indirect effects have been largely overlooked. These results thus suggest that food webs may be affected by a combination of biotic and abiotic conditions, both directly and indirectly, in a changing world.
We consider a situation in which agents have mutual claims on each other, summarized in a liability matrix. Agents’ assets might be insufficient to satisfy their liabilities, leading to defaults. In ...case of default, bankruptcy rules are used to specify the way agents are going to be rationed. A clearing payment matrix is a payment matrix consistent with the prevailing bankruptcy rules that satisfies limited liability and priority of creditors. Since clearing payment matrices and the corresponding values of equity are not uniquely determined, we provide bounds on the possible levels equity can take. Unlike the existing literature, which studies centralized clearing procedures, we introduce a large class of decentralized clearing processes. We show the convergence of any such process in finitely many iterations to the least clearing payment matrix. When the unit of account is sufficiently small, all decentralized clearing processes lead essentially to the same value of equity as a centralized clearing procedure. As a policy implication, it is not necessary to collect and process all the sensitive data of all the agents simultaneously and run a centralized clearing procedure.
This paper was accepted by Yinyu Ye, optimization.
Fragile X-associated tremor ataxia syndrome (FXTAS) results from a CGG repeat expansion in the 5′ UTR of FMR1. This repeat is thought to elicit toxicity as RNA, yet disease brains contain ...ubiquitin-positive neuronal inclusions, a pathologic hallmark of protein-mediated neurodegeneration. We explain this paradox by demonstrating that CGG repeats trigger repeat-associated non-AUG-initiated (RAN) translation of a cryptic polyglycine-containing protein, FMRpolyG. FMRpolyG accumulates in ubiquitin-positive inclusions in Drosophila, cell culture, mouse disease models, and FXTAS patient brains. CGG RAN translation occurs in at least two of three possible reading frames at repeat sizes ranging from normal (25) to pathogenic (90), but inclusion formation only occurs with expanded repeats. In Drosophila, CGG repeat toxicity is suppressed by eliminating RAN translation and enhanced by increased polyglycine protein production. These studies expand the growing list of nucleotide repeat disorders in which RAN translation occurs and provide evidence that RAN translation contributes to neurodegeneration.
•CGG repeats in the 5′ UTR of FMR1 elicit AUG-independent (RAN) translation•This produces an aggregation-prone polyglycine protein found in patients•CGG RAN translation explains pathologic differences in FXTAS mice•CGG RAN translation is critical for CGG repeat toxicity in fly disease models
CGG repeat expansions underlie the neurodegenerative disorder fragile X-associated tremor ataxia syndrome. Todd et al. describe how CGG repeats trigger non-AUG-initiated translation, producing a polyglycine protein that accumulates in FXTAS brains and contributes to toxicity in model systems.
We consider a matching with contracts model in which buyers face financial constraints. In this model, a competitive equilibrium may fail to exist. We therefore propose the new notion of ...quantity‐constrained competitive equilibrium (QCCE). At a QCCE, buyers form expectations about the expected supply of trades. A buyer may expect that a trade is not to be supplied if the corresponding financial constraint is binding. We show the existence of QCCEs via a dynamic process that updates prices and quantity constraints, the equivalence between QCCE outcomes and stable outcomes, and some other properties of QCCEs like the lattice property.
Removing nonviable cells from a cell suspension is crucial in biotechnology and biomanufacturing. Label-free microfluidic cell separation devices based on dielectrophoresis, acoustophoresis, and ...deterministic lateral displacement are used to remove nonviable cells. However, their volumetric throughputs and test cell concentrations are generally too low to be useful in typical bioreactors in biomanufacturing. In this study, we demonstrate the efficient removal of small (<10 μm) nonviable cells from bioreactors while maintaining viable cells using inertial microfluidic cell sorting devices and characterize their performance. Despite the size overlap between viable and nonviable cell populations, the devices demonstrated 3.5-28.0% dead cell removal efficiency with 88.3-83.6% removal purity as well as 97.8-99.8% live cell retention efficiency at 4 million cells per mL with 80% viability. Cascaded and parallel configurations increased the cell concentration capacity (10 million cells per mL) and volumetric throughput (6-8 mL min-1). The system can be used for the removal of small nonviable cells from a cell suspension during continuous perfusion cell culture operations.
AbstractObjectiveTo understand the epidemiology and burden of severe coronavirus disease 2019 (covid-19) during the first epidemic wave on the west coast of the United States.DesignProspective cohort ...study.SettingKaiser Permanente integrated healthcare delivery systems serving populations in northern California, southern California, and Washington state.Participants1840 people with a first acute hospital admission for confirmed covid-19 by 22 April 2020, among 9 596 321 healthcare plan enrollees. Analyses of hospital length of stay and clinical outcomes included 1328 people admitted by 9 April 2020 (534 in northern California, 711 in southern California, and 83 in Washington).Main outcome measuresCumulative incidence of first acute hospital admission for confirmed covid-19, and subsequent probabilities of admission to an intensive care unit (ICU) and mortality, as well as duration of hospital stay and ICU stay. The effective reproduction number (RE) describing transmission dynamics was estimated for each region.ResultsAs of 22 April 2020, cumulative incidences of a first acute hospital admission for covid-19 were 15.6 per 100 000 cohort members in northern California, 23.3 per 100 000 in southern California, and 14.7 per 100 000 in Washington. Accounting for censoring of incomplete hospital stays among those admitted by 9 April 2020, the estimated median duration of stay among survivors was 9.3 days (with 95% staying 0.8 to 32.9 days) and among non-survivors was 12.7 days (1.6 to 37.7 days). The censoring adjusted probability of ICU admission for male patients was 48.5% (95% confidence interval 41.8% to 56.3%) and for female patients was 32.0% (26.6% to 38.4%). For patients requiring critical care, the median duration of ICU stay was 10.6 days (with 95% staying 1.3 to 30.8 days). The censoring adjusted case fatality ratio was 23.5% (95% confidence interval 19.6% to 28.2%) among male inpatients and 14.9% (11.8% to 18.6%) among female inpatients; mortality risk increased with age for both male and female patients. Reductions in RE were identified over the study period within each region.ConclusionsAmong residents of California and Washington state enrolled in Kaiser Permanente healthcare plans who were admitted to hospital with covid-19, the probabilities of ICU admission, of long hospital stay, and of mortality were identified to be high. Incidence rates of new hospital admissions have stabilized or declined in conjunction with implementation of social distancing interventions.
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