Distinguishing Infections on Different Graph Topologies

The history of infections and epidemics holds famous examples where understanding, containing and ultimately treating an outbreak began with understanding its mode of spread. Influenza, HIV and most computer viruses, spread person to person, device to device, through contact networks; Cholera, Cancer, and seasonal allergies, on the other hand, do not. In this paper we study two fundamental questions of detection: first, given a snapshot view of a (perhaps vanishingly small) fraction of those infected, under what conditions is an epidemic spreading via contact (e.g., Influenza), distinguishable from a "random illness" operating independently of any contact network (e.g., seasonal allergies); second, if we do have an epidemic, under what conditions is it possible to determine which network of interactions is the main cause of the spread -- the causative network -- without any knowledge of the epidemic, other than the identity of a minuscule subsample of infected nodes? The core, therefore, of this paper, is to obtain an understanding of the diagnostic power of network information. We derive sufficient conditions networks must satisfy for these problems to be identifiable, and produce efficient, highly scalable algorithms that solve these problems. We show that the identifiability condition we give is fairly mild, and in particular, is satisfied by two common graph topologies: the grid, and the Erdos-Renyi graphs

Microbiome-derived carnitine mimics as previously unknown mediators of gut-brain axis communication

Alterations to the gut microbiome are associated with various neurological diseases, yet evidence of causality and identity of microbiome-derived compounds that mediate gut-brain axis interaction remain elusive. Here, we identify two previously unknown bacterial metabolites 3-methyl-4-(trimethylammonio)butanoate and 4-(trimethylammonio)pentanoate, structural analogs of carnitine that are present in both gut and brain of specific pathogen–free mice but absent in germ-free mice. We demonstrate that these compounds are produced by anaerobic commensal bacteria from the family Lachnospiraceae (Clostridiales) family, colocalize with carnitine in brain white matter, and inhibit carnitine-mediated fatty acid oxidation in a murine cell culture model of central nervous system white matter. This is the first description of direct molecular inter-kingdom exchange between gut prokaryotes and mammalian brain cells, leading to inhibition of brain cell function

Identification and phenotypic characterization of γδ T cells in rat lymph

γδ T cells represent an unconventional subset of T lymphocytes that are abundant in epithelial tissues and serve as an early immune defense against microbes. We have, for the first time, identified γδ T cells in steady-state thoracic duct lymph (TDL) from rats. The lymph contains γδ T cells expressing CD8 but not CD4, CD25, MHC-II or CD103. The percentage of TDL γδ T cells in rats does not change when the mesenteric lymph nodes (MLN) are surgically removed. Our data suggest that a proportion of γδ T cells migrate from the intestine into rat TDL, under steady-state conditions

Routing over Multi-hop Wireless Networks with Non-ergodic Mobility

Abstract—Routing to mobile nodes in a wireless network is conventionally performed by associating a static IP address (or a geographic location) to each node, and routing to that address using routing tables at intermediate nodes that are updated periodically to reflect mobility-induced network topology changes. This mode of routing works when the mobiles ’ speeds as well as the number of mobiles are small. However, in the presence of large number of fast-moving mobiles, such approaches are infeasible and can lead to excessive overheads, routing failures and hence, throughput loss. In this paper, we consider a wireless network over a domain with a collection of static nodes (that form a connected cover of the domain) and mobile nodes, where the mobile nodes can move in an arbitrary (non-ergodic) manner over sub-domains of the network. For such a system, we develop new routing algorithms (based on a spatial multi-resolution search) that we show are efficient both in terms of routing overheads and throughput. In particular, we show that the achievable rate region of the proposed algorithm is within a poly-logarithmic constant of the optimal rate region with non-ergodic mobility. I

Characterization of conventional and atypical receptors for the chemokine CCL2 on mouse leukocytes

Chemokine-directed leukocyte migration is crucial for effective immune and inflammatory responses. Conventional chemokine receptors (cCKRs) directly control cell movement; atypical chemokine receptors (ACKRs) regulate coexpressed cCKRs; and both cCKRs and ACKRs internalize chemokines to limit their abundance in vivo, a process referred to as scavenging. A leukocyte’s migratory and chemokine-scavenging potential is determined by which cCKRs and ACKRs it expresses, and by the ligand specificity, signaling properties, and chemokine internalization capacity of these receptors. Most chemokines can bind at least one cCKR and one ACKR. CCL2 can bind to CCR2 (a cCKR) and two ACKRs (ACKR1 and ACKR2). In this study, by using fluorescent CCL2 uptake to label cells bearing functional CCL2 receptors, we have defined the expression profile, scavenging activity, and ligand specificity of CCL2 receptors on mouse leukocytes. We show that qualitative and quantitative differences in the expression of CCR2 and ACKR2 endow individual leukocyte subsets with distinctive CCL2 receptor profiles and CCL2- scavenging capacities. We reveal that some cells, including plasmacytoid dendritic cells, can express both CCR2 and ACKR2; that Ly6Chigh monocytes have particularly strong CCL2-scavenging potential in vitro and in vivo; and that CCR2 is a much more effective CCL2 scavenger than ACKR2. We confirm the unique, overlapping, ligand specificities of CCR2 and ACKR2 and, unexpectedly, find that cell context influences the interaction of CCL7 and CCL12 with CCR2. Fluorescent chemokine uptake assays were instrumental in providing these novel insights into CCL2 receptor biology, and the sensitivity, specificity, and versatility of these assays are discussed

An integrated analysis of human myeloid cells identifies gaps in in vitro models of in vivo biology

The Stemformatics myeloid atlas is an integrated transcriptome atlas of human macrophages and dendritic cells that systematically compares freshly isolated tissue-resident, cultured, and pluripotent stem cell-derived myeloid cells. Three classes of tissue-resident macrophage were identified: Kupffer cells and microglia; monocyte-associated; and tumor-associated macrophages. Culture had a major impact on all primary cell phenotypes. Pluripotent stem cell-derived macrophages were characterized by atypical expression of collagen and a highly efferocytotic phenotype. Myeloid subsets, and phenotypes associated with derivation, were reproducible across experimental series including data projected from single-cell studies, demonstrating that the atlas provides a robust reference for myeloid phenotypes. Implementation in Stemformatics.org allows users to visualize patterns of sample grouping or gene expression for user-selected conditions and supports temporary upload of your own microarray or RNA sequencing samples, including single-cell data, to benchmark against the atlas