Multi-Step Regulation of the TLR4 Pathway by the miR-125a~99b~let-7e Cluster

An appropriate immune response requires a tight balance between pro- and anti-inflammatory mechanisms. IL-10 is induced at late time-points during acute inflammatory conditions triggered by TLR-dependent recognition of infectious agents and is involved in setting this balance, operating as a negative regulator of the TLR-dependent signaling pathway. We identified miR-125a~99b~let-7e as an evolutionary conserved microRNA cluster late-induced in human monocytes exposed to the TLR4 agonist LPS as an effect of this IL-10-dependent regulatory loop. We demonstrated that microRNAs generated by this cluster perform a pervasive regulation of the TLR signaling pathway by direct targeting receptors (TLR4, CD14), signaling molecules (IRAK1), and effector cytokines (TNFα, IL-6, CCL3, CCL7, CXCL8). Modulation of miR-125a~99b~let-7e cluster influenced the production of proinflammatory cytokines in response to LPS and the IL-10-mediated tolerance to LPS, thus identifying this gene as a previously unrecognized major regulatory element of the inflammatory response and endotoxin tolerance

Program Comprehension: Identifying Learning Trajectories for Novice Programmers

This working group asserts that Program Comprehension (PC) plays a critical part in the writing process. For example, this abstract is written from a basic draft that we have edited and revised until it clearly presents our idea. Similarly, a program is written in an incremental manner, with each step being tested, debugged and extended until the program achieves its goal. Novice programmers should develop their program comprehen- sion as they learn to code, so that they are able to read and reason about code while they are writing it. To foster such competencies our group has identified two main goals: (1) to collect and define learning activities that explicitly cover key components of program comprehension and (2) to define possible learning trajectories that will guide teachers using those learning activities in their CS0/CS1 or K-12 courses. [...

Multi-Step Regulation of the TLR4 Pathway by the miR-125a~99b~let-7e Cluster

An appropriate immune response requires a tight balance between pro- and anti-inflammatory mechanisms. IL-10 is induced at late time-points during acute inflammatory conditions triggered by TLR-dependent recognition of infectious agents and is involved in setting this balance, operating as a negative regulator of the TLR-dependent signaling pathway. We identified miR-125a~99b~let-7e as an evolutionary conserved microRNA cluster late-induced in human monocytes exposed to the TLR4 agonist LPS as an effect of this IL-10-dependent regulatory loop. We demonstrated that microRNAs generated by this cluster perform a pervasive regulation of the TLR signaling pathway by direct targeting receptors (TLR4, CD14), signaling molecules (IRAK1), and effector cytokines (TNFα, IL-6, CCL3, CCL7, CXCL8). Modulation of miR-125a~99b~let-7e cluster influenced the production of proinflammatory cytokines in response to LPS and the IL-10-mediated tolerance to LPS, thus identifying this gene as a previously unrecognized major regulatory element of the inflammatory response and endotoxin tolerance

Negative regulation of Toll-like receptor 4 signaling by IL-10-dependent microRNA-146b

Toll-like receptors (TLRs) play key roles in detecting pathogens and initiating inflammatory responses that, subsequently, prime specific adaptive responses. Several mechanisms control TLR activity to avoid excessive inflammation and consequent immunopathology, including the anti-inflammatory cytokine IL-10. Recently, several TLR-responsive microRNAs (miRs) have also been proposed as potential regulators of this signaling pathway, but their functional role during the inflammatory response still is incompletely understood. In this study, we report that, after LPS engagement, monocytes up-regulate miR- 146b via an IL-10-mediated STAT3-dependent loop. We show evidence thatmiR-146b modulates the TLR4 signaling pathway by direct targeting of multiple elements, including the LPS receptor TLR4 and the key adaptor/signaling proteinsmyeloid differentiation primary response (MyD88), interleukin-1 receptor-associated kinase 1 (IRAK-1), and TNF receptor-associated factor 6 (TRAF6). Furthermore, we demonstrate that the enforced expression of miR-146b in human monocytes led to a significant reduction in the LPS-dependent production of several proinflammatory cytokines and chemokines, including IL-6, TNF-\u3b1, IL-8, CCL3, CCL2, CCL7, and CXCL10. Our results thus identify miR-146b as an IL-10-responsive miR with an anti-inflammatory activity based on multiple targeting of components of the TLR4 pathway in monocytes and candidate miR-146b as a molecular effector of the IL-10 anti-inflammatory activity

A randomized controlled crossover study of manual lymphatic drainage therapy in women with breast cancer-related lymphoedema.

This paper describes a randomized controlled crossover study examining the effects of manual lymphaticdrainage (MLD) in 31 women with breast cancer-related lymphoedema. MLD is a type of massage used incombination with skin care, support/compression therapy and exercise in the management of lymphoedema.A modified version of MLD, referred to as simple lymphatic drainage (SLD), is commonly taught as a selfhelpmeasure. There has been limited research into the efficacy of MLD and SLD. The study reported hereexplores the effects of MLD and SLD on a range of outcome measures. The findings demonstrate that MLDsignificantly reduces excess limb volume (difference, d = 71, 95% CI = 16–126, P = 0.013) and reduced dermalthickness in the upper arm (d = 0.15, 95% CI = 0.12–0.29, P = 0.03). Quality of life, in terms of emotionalfunction (d = 7.2, 95% CI = 2.3–12.1, P = 0.006), dyspnoea (d = -4.6, 95% CI = -9.1 to -0.15, P = 0.04) andsleep disturbance (d = -9.2, 95% CI = -17.4 to -1.0, P = 0.03), and a number of altered sensations, such as painand heaviness, were also significantly improved by MLD. The study provides evidence to support the use ofMLD in women with breast cancer-related lymphoedema. The limitations of the study are outlined and futureareas for study are highlighted

Synthesis and characterization of Na3PS4 and Na 2.85 P 0.85 W 0.15 S 4 as solid electrolytes

International audienceThe next generations of postlithium systems are already under development. These hold the promise of overcoming some of the remaining challenges associated with current lithium-ion battery technology related to safety, the need for scarce resources and their environmental impacts. Na₃PS₄ (NPS) is a sodium superionic conductor that crystallizes in the I-43m space group and reaches ionic conductivities in the range of the mS/cm. • X-ray diffractograms show a cubic crystalline phase of Na3PS4 and a mixture of Na3PS4 and WS2 for the Na2.85P0.85W0.15S4 sample.• SEM-EDX results confirmed that a reaction occurs between the sample holder (Macor®) and the solid electrolytes during the heat treatments.• Electrochemical results show that a heat treatment under Ar slightly improves the ionic conductivity for the NPS sample, while the HTs in presence of Macor® spacer turn the materials into ionic insulants

Silver nanoparticle engineering via oligovaline organogels

L-Valine-based oligopeptides with the chemical structure Z–(L-Val)₃–OMe and Z–(L-Val)₂–L-Cys(S-Bzl)–OMe form stable organogels in butanol. Both peptides are efficient gelators, but Z–(L-Val)₂–L-Cys(S-Bzl)–OMe crystallizes more readily than Z–(L-Val)₃–OMe. The two peptides can form mixed fibers, which also gel butanol. The resulting organogels are very similar to oligovaline organogels reported earlier (Mantion and Taubert, Macromol. Biosci., 2007, 7, 208) as they also form highly ordered peptide fibers with a predominant β-sheet structure and diameters of ca. 100 nm. The fibers can be mineralized with silver nanoparticles using DMF as a reducing agent. The fraction of the sulfur-containing peptide Z–(L-Val)₂–L-Cys(S-Bzl)–OMe controls the shape and size of the resulting nanoparticles. At high Z–(L-Val)₂–L-Cys(S-Bzl)–OMe content, small spherical particles are distributed all over the fiber. Lower contents of Z–(L-Val)₂–L-Cys(S-Bzl)–OMe lead to a size increase of the particles and to more complex shapes like plate-like and raspberry-like silver particles. The interactions between peptide and silver ions or silver particles takes place via a complexation of the silver ions to the sulfur atom of the thioether moiety, and are shown to be the key interaction in controlling particle formation

Synthesis and characterization of Na3PS4 and Na 2.85 P 0.85 W 0.15 S 4 as solid electrolytes

International audienceThe next generations of postlithium systems are already under development. These hold the promise of overcoming some of the remaining challenges associated with current lithium-ion battery technology related to safety, the need for scarce resources and their environmental impacts. Na₃PS₄ (NPS) is a sodium superionic conductor that crystallizes in the I-43m space group and reaches ionic conductivities in the range of the mS/cm. • X-ray diffractograms show a cubic crystalline phase of Na3PS4 and a mixture of Na3PS4 and WS2 for the Na2.85P0.85W0.15S4 sample.• SEM-EDX results confirmed that a reaction occurs between the sample holder (Macor®) and the solid electrolytes during the heat treatments.• Electrochemical results show that a heat treatment under Ar slightly improves the ionic conductivity for the NPS sample, while the HTs in presence of Macor® spacer turn the materials into ionic insulants