Epidemics on contact networks: a general stochastic approach

Dynamics on networks is considered from the perspective of Markov stochastic processes. We partially describe the state of the system through network motifs and infer any missing data using the available information. This versatile approach is especially well adapted for modelling spreading processes and/or population dynamics. In particular, the generality of our systematic framework and the fact that its assumptions are explicitly stated suggests that it could be used as a common ground for comparing existing epidemics models too complex for direct comparison, such as agent-based computer simulations. We provide many examples for the special cases of susceptible-infectious-susceptible (SIS) and susceptible-infectious-removed (SIR) dynamics (e.g., epidemics propagation) and we observe multiple situations where accurate results may be obtained at low computational cost. Our perspective reveals a subtle balance between the complex requirements of a realistic model and its basic assumptions.Comment: Main document: 16 pages, 7 figures. Electronic Supplementary Material (included): 6 pages, 1 tabl

What happens for informal caregivers during transition to increased levels of care for the person with dementia? A systematic review protocol

Abstract Background Dementia is a globally prevalent disease that requires ongoing and increasing levels of care, often provided in the first instance by informal caregivers. Supporting transitions in informal caregiving in dementia is a pertinent issue for caregivers, care providers and governments. There is no existing systematic review that seeks to identify and map the body of literature regarding the review question: ‘What happens for informal caregivers during transition to increased levels of care for the person with dementia?’ Methods/design ASSIA, CINAHL+, MEDLINE, PsycINFO, SCIE, Social Service Abstracts and Web of Science will be systematically searched. Specialist dementia research libraries will be contacted. Reviews identified as relevant during the search process, their reference lists, and reference lists of accepted papers will be hand-searched. Qualitative, quantitative and mixed methods studies that seek to represent the experiences of, or examine the impact upon, informal caregivers during transition to increased formal care for the person with dementia will be eligible for inclusion. Synthesis will be segregated into qualitative and quantitative papers. Findings will be summarised, and the review will be prepared for publication. Discussion The review will seek to identify potentially vulnerable groups in need of support and as such, inform the practice of those offering support. It will also inform future research by highlighting areas in which current literature is insubstantial. Systematic review registration PROSPERO CRD4201706724

Genome-Wide Interrogation of Mammalian Stem Cell Fate Determinants by Nested Chromosome Deletions

Understanding the function of important DNA elements in mammalian stem cell genomes would be enhanced by the availability of deletion collections in which segmental haploidies are precisely characterized. Using a modified Cre-loxP–based system, we now report the creation and characterization of a collection of ∼1,300 independent embryonic stem cell (ESC) clones enriched for nested chromosomal deletions. Mapping experiments indicate that this collection spans over 25% of the mouse genome with good representative coverage of protein-coding genes, regulatory RNAs, and other non-coding sequences. This collection of clones was screened for in vitro defects in differentiation of ESC into embryoid bodies (EB). Several putative novel haploinsufficient regions, critical for EB development, were identified. Functional characterization of one of these regions, through BAC complementation, identified the ribosomal gene Rps14 as a novel haploinsufficient determinant of embryoid body formation. This new library of chromosomal deletions in ESC (DelES: http://bioinfo.iric.ca/deles) will serve as a unique resource for elucidation of novel protein-coding and non-coding regulators of ESC activity

Dynamic thoracohumeral kinematics are dependent upon the etiology of the shoulder injury

[EN] Obtaining kinematic patterns that depend on the shoulder injury may be important when planning rehabilitation. The main goal of this study is to explore whether the kinematic patterns of continuous and repetitive shoulder elevation motions are different according to the type of shoulder injury in question, specifically tendinopathy or rotator cuff tear, and to analyze the influence of the load handled during its assessment. For this purpose, 19 individuals with tendinopathy and 9 with rotator cuff tear performed a repetitive scaption movement that was assessed with stereophotogrammetry. Furthermore, static range of motion (ROM) and isometric strength were evaluated with a goniometer and a dynamometer, respectively. Dynamic measurements of maximum elevation (Emax), variablility of the maximum angle (VMA), maximum angular velocity (Velmax), and time to maximum velocity (tmaxvel) were found to be significantly different between the tendinopathy group (TG) and the rotator cuff tear group (RTCG). No differences were found in the ROM assessed with goniometry and the isometric strength. The effect of increasing the load placed in the hand during the scaption movement led to significant differences in Emax, VMA, tmaxvel and repeatability. Therefore, only the dynamic variables showed sufficient capability of detecting differences in functional performance associated with structural shoulder injury. The differences observed in the kinematic variables between patients with tendinopathy and rotator cuff tear seem to be related to alterations in thoracohumeral rhythm and neuromuscular control. Kinematic analysis may contribute to a better understanding of the functional impact of shoulder injuries, which would help in the assessment and treatment of shoulder pain.This work was funded by the Spanish Government, Secretaria de Estado de Investigacion, Desarrollo e Innovacion, and co-financed by EU FEDER funds (Grant DPI2013-44227-R). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Lopez Pascual, J.; Page Del Pozo, AF.; Serra Añó, P. (2017). Dynamic thoracohumeral kinematics are dependent upon the etiology of the shoulder injury. PLoS ONE. 12(8). https://doi.org/10.1371/journal.pone.0183954S12

Spreading to localized targets in complex networks.

As an important type of dynamics on complex networks, spreading is widely used to model many real processes such as the epidemic contagion and information propagation. One of the most significant research questions in spreading is to rank the spreading ability of nodes in the network. To this end, substantial effort has been made and a variety of effective methods have been proposed. These methods usually define the spreading ability of a node as the number of finally infected nodes given that the spreading is initialized from the node. However, in many real cases such as advertising and news propagation, the spreading only aims to cover a specific group of nodes. Therefore, it is necessary to study the spreading ability of nodes towards localized targets in complex networks. In this paper, we propose a reversed local path algorithm for this problem. Simulation results show that our method outperforms the existing methods in identifying the influential nodes with respect to these localized targets. Moreover, the influential spreaders identified by our method can effectively avoid infecting the non-target nodes in the spreading process.We thank an anonymous reviewer for helpful suggestions which improve this paper. This work is supported by the National Natural Science Foundation of China (Nos 61603046 and 11547188), Natural Science Foundation of Beijing (No. 16L00077) and the Young Scholar Program of Beijing Normal University (No. 2014NT38)

Dimethyl Sulfoxide Induces Both Direct and Indirect Tau Hyperphosphorylation

Dimethyl sulfoxide (DMSO) is widely used as a solvent or vehicle for biological studies, and for treatment of specific disorders, including traumatic brain injury and several forms of amyloidosis. As Alzheimer’s disease (AD) brains are characterized by deposits of β-amyloid peptides, it has been suggested that DMSO could be used as a treatment for this devastating disease. AD brains are also characterized by aggregates of hyperphosphorylated tau protein, but the effect of DMSO on tau phosphorylation is unknown. We thus investigated the impact of DMSO on tau phosphorylation in vitro and in vivo. One hour following intraperitoneal administration of 1 or 2 ml/kg DMSO in mice, no change was observed in tau phosphorylation. However, at 4 ml/kg, tau was hyperphosphorylated at AT8 (Ser202/Thr205), PHF-1 (Ser396/Ser404) and AT180 (Thr231) epitopes. At this dose, we also noticed that the animals were hypothermic. When the mice were maintained normothermic, the effect of 4 ml/kg DMSO on tau hyperphosphorylation was prevented. On the other hand, in SH-SY5Y cells, 0.1% DMSO induced tau hyperphosphorylation at AT8 and AT180 phosphoepitopes in normothermic conditions. Globally, these findings demonstrate that DMSO can induce tau hyperphosphorylation indirectly via hypothermia in vivo, and directly in vitro. These data should caution researchers working with DMSO as it can induce artifactual results both in vivo and in vitro

Ir-LBP, an Ixodes ricinus Tick Salivary LTB4-Binding Lipocalin, Interferes with Host Neutrophil Function

BACKGROUND: During their blood meal, ticks secrete a wide variety of proteins that can interfere with their host's defense mechanisms. Among these proteins, lipocalins play a major role in the modulation of the inflammatory response. METHODOLOGY/PRINCIPAL FINDINGS: We previously identified 14 new lipocalin genes in the tick Ixodes ricinus. One of them codes for a protein that specifically binds leukotriene B4 with a very high affinity (Kd: +/-1 nM), similar to that of the neutrophil transmembrane receptor BLT1. By in silico approaches, we modeled the 3D structure of the protein and the binding of LTB4 into the ligand pocket. This protein, called Ir-LBP, inhibits neutrophil chemotaxis in vitro and delays LTB4-induced apoptosis. Ir-LBP also inhibits the host inflammatory response in vivo by decreasing the number and activation of neutrophils located at the tick bite site. Thus, Ir-LBP participates in the tick's ability to interfere with proper neutrophil function in inflammation. CONCLUSIONS/SIGNIFICANCE: These elements suggest that Ir-LBP is a "scavenger" of LTB4, which, in combination with other factors, such as histamine-binding proteins or proteins inhibiting the classical or alternative complement pathways, permits the tick to properly manage its blood meal. Moreover, with regard to its properties, Ir-LBP could possibly be used as a therapeutic tool for illnesses associated with an increased LTB4 production.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Nicotinic receptors

Regulation of normal or abnormal behaviour is critically controlled by the central serotonergic systems. Recent evidence has suggested that serotonin (5-HT) neurotransmission dysfunction contributes to a variety of pathological conditions, including depression, anxiety, schizophrenia and Parkinson’s disorders. There is also a great amount of evidence indicating that 5-HT signalling may affect the reinforcing properties of drugs of abuse by the interaction and modulation of dopamine (DA) function. This chapter is focused on one of the more addictive drugs, nicotine. It is widely recognised that the effects of nicotine are strongly associated with the stimulatory action it exhibits on mesolimbic DAergic function. We outline the role of 5-HT and its plethora of receptors, focusing on 5-HT2 subtypes with relation to their involvement in the neurobiology of nicotine addiction. We also explore the novel pharmacological approaches using 5-HT agents for the treatment of nicotine dependence. Compelling evidence shows that 5-HT2C receptor agonists may be possible therapeutic targets for smoking cessation, although further investigation is required.peer-reviewe