Above the Matrix: Functional Roles for Apically Localized Integrins

Integrins are transmembrane proteins that are most typically thought of as integrating adhesion to the extracellular matrix with intracellular signaling and cell regulation. Traditionally, integrins are found at basolateral and lateral cell surfaces where they facilitate binding to the ECM and intercellular adhesion through cytosolic binding partners that regulate organization of actin microfilaments. However, evidence is accumulating that integrins also are apically localized, either endogenously or due to an exogenous stimulus. Apically localized integrins have been shown to regulate several processes by interacting with proteins such as connexins, tight junction proteins, and polarity complex proteins. Integrins can also act as receptors to mediate endocytosis. Here we review these newly appreciated roles for integrins localized to the apical cell surface.

Photoresponsive Delivery Of Nanovectors: A Review Of Concepts And Applications

: Stimuli-triggered nanovectors for drug delivery enhance the clinical efficacy and decrease the toxicity by specifically conveying the drugs to the site of target with higher specificity and efficiency. Several stimuli have been regarded, but light as an exogenous stimulus renders several benefits in clinical usage, like elevated spatial and temporal control. A number of photochemical mechanisms have been exploited in the design of photo triggered nanocarriers for biomedical applications. Light in conjugation with photosensitizers or imaging agents in nanovectors can help ensure precise diagnosis, drug delivery and improve therapeutic outcomes. Nanomedicine plays a key role in enhancing therapeutic efficacy and limiting the adverse effects. The review evaluates the multiple nanocarriers such as liposomes, polymersomes, micelles, nanogels etc., which have leveraged the advantages of phototargeting via photothermal, photochemical, photo isomerization and upconversion based activation strategies for efficient drug targeting to intracellular and other regions. An overview of the significant benefits and constraints, and the latest developments in the most popular and recent photoresponsive drug delivery methods is provided to critically judge the prospectives for success and limitations and delve upon the possible future perspectives in the field.

Pericytes secrete pro-regenerative molecules in response to platelet-derived growth factor-BB

Brain pericytes not only maintain the anatomical, biochemical and immune blood–brain barrier, but display features of mesenchymal stem cells (MSCs) in vitro. MSCs have pro-regenerative properties attributed to their secretome. However, whether also brain pericytes possess such pro-regenerative capacities is largely unknown. Here we characterize the secretome and microvesicle (MV) release of human brain pericytes mediated by platelet-derived growth factor-BB (PDGF-BB)/PDGF receptor beta (PDGFRβ) signalling. Upon PDGF-BB, pericytes release not only a plethora of growth factors and a panel of cytokines, but also MVs containing BDNF, FGFb, βNGF, VEGF and PLGF, a response that is specific for PDGFRβ signalling and activation of the ERK 1/2 pathway. In contrast, lipopolysaccharide (LPS), an activator of the innate immune system, stimulates the secretion of much higher amounts of mainly inflammatory cytokines and activates the NFκB pathway. Pericytes change their morphology and undergo opposite changes in surface marker expression, respectively. Our findings provide evidence that the secretome of human brain pericytes varies greatly depending on the exogenous stimulus. The differential secretory functions of pericytes may play an important role in either regulating neuroinflammation or contributing to neurorestoration and identify a possible new target cell for neuroregeneration.

Language switching between sentences in reading: Exogenous and endogenous effects on eye movements and comprehension

The present study explored the influence of language switching on both comprehension (utilizing a picture-sentence matching procedure) and word-level processing (utilizing eye movement registration) in reading simple German and English sentences. Language sequence was unpredictable and contained language switches (subsequent sentence in a different language) and language repetitions (subsequent sentence in the same language). The results revealed a substantial decrease of comprehension following language switches (with greater switch costs in L1 than in L2), likely indicating relatively long-lasting, endogenous inhibition processes affecting higher-level text integration. In contrast, there were comparatively minor and transient effects on eye movements (in terms of altered skipping probabilities and gaze durations) that were restricted to the initial words within a sentence, presumably representing short-lasting exogenous (stimulus-driven) activation effects after language switches (with greater switch costs in L2 than in L1). Overall, the results are in line with predictions from recent interactive-activation frameworks of bilingual language processing.

Classical swine fever virus Ernsglycoprotein antagonizes induction of interferon-β by double-stranded RNA

Classical swine fever virus (CSFV) is capable of counteracting innate cellular antiviral responses by inhibiting type I interferon (IFN)-α/β induction. A function associated with CSFV Npro, with respect to the inhibition of IFN-β production, has been clearly elucidated. In this study, we explored the role of CSFV Ernsin IFN-β induction by exogenous double-stranded (ds) RNA. Synthetic dsRNA (poly (IC)) was used as an exogenous stimulus to trigger IFN-β induction. CSFV Ernsinhibited IFN-β promoter-driven luciferase activity induced by poly (IC) in different cell lines, and the inhibitory effect was dose-dependent. Moreover, Ernsreduced IFN-β mRNA synthesis and blocked IFN-α/β production induced by poly (IC), suggesting that this inhibition occurs at the transcriptional level. Furthermore, Ernscounteracted poly (IC)-mediated IFN-β induction independent of its ribonuclease activity. In conclusion, CSFV Ernsantagonizes extracellular dsRNA-mediated IFN-β expression. These findings contribute to our understanding of the pathogenesis of CSFV.