Cardiac Fibroblasts Contribute to Myocardial Dysfunction in Mice with Sepsis: The Role of NLRP3 Inflammasome Activation

Myocardial contractile dysfunction in sepsis is associated with the increased morbidity and mortality. Although the underlying mechanisms of the cardiac depression have not been fully elucidated, an exaggerated inflammatory response is believed to be responsible. Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome is an intracellular platform that is involved in the maturation and release of interleukin (IL)-1β. The aim of the present study is to evaluate whether sepsis activates NLRP3 inflammasome/caspase-1/IL-1β pathway in cardiac fibroblasts (CFs) and whether this cytokine can subsequently impact the function of cardiomyocytes (cardiac fibroblast-myocyte cross-talk). We show that treatment of CFs with lipopolysaccharide (LPS) induces upregulation of NLRP3, activation of caspase-1, as well as the maturation (activation) and release of IL-1β. In addition, the genetic (small interfering ribonucleic acid [siRNA]) and pharmacological (glyburide) inhibition of the NLRP3 inflammasome in CFs can block this signaling pathway. Furthermore, the inhibition of the NLRP3 inflammasome in cardiac fibroblasts ameliorated the ability of LPS-chalenged CFs to impact cardiomyocyte function as assessed by intracellular cyclic adenosine monophosphate (cAMP) responses in cardiomyocytes. Salient features of this the NLP3 inflammasome/ caspase-1 pathway were confirmed in in vivo models of endotoxemia/sepsis. We found that inhibition of the NLRP3 inflammasome attenuated myocardial dysfunction in mice with LPS and increased the survival rate in mice with feces-induced peritonitis. Our results indicate that the activation of the NLRP3 inflammasome in cardiac fibroblasts is pivotal in the induction of myocardial dysfunction in sepsis.     

The action of luteinizing hormone on the testis

Luteinizing hormone (LH) and human chorionic gonadotrophin (hCG) receptors are coupled to intracellular effector systems, most notably adenylate cyclase, through guanyl nucleotide-binding proteins or G-proteins. The molecular mechanism involved in the dynamic coupling of the LH/hCG receptor however, are not known. It has been postulated that receptor aggregation at the molecular level plays a critical role in this process. There have been attempts to understand the receptor association and dissociation phenomena at the molecular level. One of them involves the participation of the major histocompatibility complex (MHC) class I antigen in the mechanism of receptor activation and/or expression. One molecular basis for these mechanisms consists of a physical interaction between MHC proteins and receptors to form "compound receptors" able to transfer a hormonal signal to the cell. Using a photo-reactive probe we demonstrated that the LH/hCG receptors and the class I antigens are closely associated in the membrane. Thus, it is possible to form covalent complexes of hCG and class I antigens through the binding of the hormone to specific receptors. These findings imply that LH/hCG receptors and the MHC class I antigens may interact at the level of the plasma membrane in the mechanism of LH action. We also performed experiments using a single cell and limiting stimulation to a patch of membrane. The results stimulating the cell in a localized area suggested that even if all components are entirely free to float there is a constraint in the localization of the receptor, G-protein, and/or the effector, supporting the constraint dissociation model. Within a limited area subunits could dissociate, but they would not be free to diffuse throughout the membrane. Moreover the concept of compartmentalization that has been utilized to explain some inconsistencies in second-messenger action now can be proved by experimental design.     

Plasmonic Properties of Gold Nanostructures on Gold Film

This paper reports on a systematic study of the plasmonic properties of periodic arrays of gold cylindrical nanoparticles in contact with a gold thin film. Depending on the gold film thickness, it observes several plasmon bands. Using a simple analytical model, it is able to assign all these modes and determine that they are due to the coupling of the grating diffraction orders with the propagating surface plasmons travelling along the film. With finite difference time domain (FDTD) simulations, it demonstrates that large field enhancement occurs at the surface of the nanocylinders due to the resonant excitation of these modes. By tilting the sample, it also observes the evolution of the spectral position of these modes and their tuning through nearly the whole visible range is possible. Such plasmonic substrates combining both advantages of the propagative and localised surface plasmons could have large applications in enhanced spectroscopies.

     

Light controls stamen elongation via cryptochromes,phytochromes and COP1 through HY5 and HYH

In Arabidopsis, stamen elongation, which ensures male fertility, is controlled by the auxin response factor ARF8, which regulates the expression of the auxin repressor IAA19. Here, we uncover a role for light in controlling stamen elongation. By an extensive genetic and molecular analysis we show that the repressor of light signaling COP1, through its targets HY5 and HYH, controls stamen elongation, and that HY5 – oppositely to ARF8 – directly represses the expression of IAA19 in stamens. In addition, we show that in closed flower buds, when light is shielded by sepals and petals, the blue light receptors CRY1/CRY2 repress stamen elongation. Coherently, at flower disclosure and in subsequent stages, stamen elongation is repressed by the red and far‐red light receptors PHYA/PHYB. In conclusion, different light qualities – sequentially perceived by specific photoreceptors – and the downstream COP1–HY5/HYH module finely tune auxin‐induced stamen elongation and thus male fertility.     

Novel Systems for Dynamically Assessing Insulin Action in Live Cells Reveals Heterogeneity in the Insulin Response

Regulated GLUT4 trafficking is a key action of insulin. Quantitative stepwise analysis of this process provides a powerful tool for pinpointing regulatory nodes that contribute to insulin regulation and insulin resistance. We describe a novel GLUT4 construct and workflow for the streamlined dissection of GLUT4 trafficking; from simple high throughput screens to high resolution analyses of individual vesicles. We reveal single cell heterogeneity in insulin action highlighting the utility of this approach – each cell displayed a unique and highly reproducible insulin response, implying that each cell is hard‐wired to produce a specific output in response to a given stimulus. These data highlight that the response of a cell population to insulin is underpinned by extensive heterogeneity at the single cell level. This heterogeneity is pre‐programmed within each cell and is not the result of intracellular stochastic events.     

Rewiring and indirect effects underpin modularity reshuffling in a marine food web under environmental shifts

Species are characterized by physiological and behavioral plasticity, which is part of their response to environmental shifts. Nonetheless, the collective response of ecological communities to environmental shifts cannot be predicted from the simple sum of individual species responses, since co‐existing species are deeply entangled in interaction networks, such as food webs. For these reasons, the relation between environmental forcing and the structure of food webs is an open problem in ecology. To this respect, one of the main problems in community ecology is defining the role each species plays in shaping community structure, such as by promoting the subdivision of food webs in modules—that is, aggregates composed of species that more frequently interact—which are reported as community stabilizers. In this study, we investigated the relationship between species roles and network modularity under environmental shifts in a highly resolved food web, that is, a “weighted” ecological network reproducing carbon flows among marine planktonic species. Measuring network properties and estimating weighted modularity, we show that species have distinct roles, which differentially affect modularity and mediate structural modifications, such as modules reconfiguration, induced by environmental shifts. Specifically, short‐term environmental changes impact the abundance of planktonic primary producers; this affects their consumers’ behavior and cascades into the overall rearrangement of trophic links. Food web re‐adjustments are both direct, through the rewiring of trophic‐interaction networks, and indirect, with the reconfiguration of trophic cascades. Through such “systemic behavior,” that is, the way the food web acts as a whole, defined by the interactions among its parts, the planktonic food web undergoes a substantial rewiring while keeping almost the same global flow to upper trophic levels, and energetic hierarchy is maintained despite environmental shifts. This behavior suggests the potentially high resilience of plankton networks, such as food webs, to dramatic environmental changes, such as those provoked by global change.     

Regional Activation of Myosin II in Cancer Cells Drives Tumor Progression via a Secretory Cross-Talk with the Immune Microenvironment

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Overexpression of KNAT1 in lettuce shifts leaf determinate growth to a shoot-like indeterminate growth associated with an accumulation of isopentenyl-type cytokinins

Leaves are specialized organs characterized by defined developmental destiny and determinate growth. The overexpression of Knotted1-like homeobox genes in different species has been shown to alter leaf shape and development, but a definite role for this class of genes remains to be established. Transgenics that overexpress Knotted1-like genes present some traits that are characteristic of altered cytokinin physiology. Here we show that lettuce (Lactuca sativa) leaves that overexpress KNAT1, an Arabidopsis kn1-like gene, acquire characteristics of indeterminate growth typical of the shoot and that this cell fate change is associated with the accumulation of specific types of cytokinins. The possibility that the phenotypic effects of KNAT1 overexpression may arise primarily from the modulation of local ratios of different cytokinins is discussed.     

Cellulose derivative-hyaluronic acid-based microporous hydrogels cross-linked through divinyl sulfone (DVS) to modulate equilibrium sorption capacity and network stability

The aim of this work is to obtain a chemically cross-linked hydrogel from hyaluronic acid and cellulose derivatives that exhibits sensitivity to variation of the composition of the external absorbing medium and an equilibrium sorption capacity higher than a common hyaluronic acid-based hydrogel, in view of its potential use in prevention of postsurgical soft tissue adhesion. This has been achieved by chemical stabilization of hyaluronic acid (HA) and cellulose derivatives, hydroxyethylcellulose (HEC) and carboxymethylcellulose (CMCNa) through the difunctional cross-linker divinyl sulfone. Significant increase in sorption capacity, both in water and in water solutions at different ionic strength, has been observed for these samples in comparison with hydrogels obtained through chemical stabilization of hyaluronic acid. Moreover, different dehydration procedures adopted for the xerogel synthesis have been used, which resulted in a modulation of the equilibrium sorption capacity. Hyaluronic acid stability has been confirmed by means of NMR analysis.