Comparison of Fibroblast and Vascular Cell Adhesion to Nano-Structured Poly(lactic-co-glycolic acid) Films

The success of small diameter vascular grafts may be attributed to the ability to accurately mimic the nano-structured topography of extra-cellular matrix components of natural vascular tissue. Using this knowledge, the goal of the present study was to develop synthetic biomaterials that promote vascular cell adhesion and growth, while subsequently limiting fibrous tissue formation. For this purpose, poly(lactic-co-glycolic acid) (PLGA) with increased nanometer surface roughness was created by treating the surfaces of conventional PLGA with NaOH. Cell experiments on these surfaces indicated that nano-structured PLGA enhanced vascular smooth muscle cell adhesion and growth, while decreasing endothelial cell and fibroblast adhesion and growth, compared to their conventional counterparts. These favorable results were attributed to the selective adsorption of vitronectin. In combination, results of the present in vitro study provided evidence that nano-structured surface features have the potential to significantly improve the efficacy of small diameter vascular implants

Non‐linear plant‐plant interactions modulate impact of extreme drought and recovery on a Mediterranean ecosystem

Interaction effects of different stressors, such as extreme drought and plant invasion, can have detrimental effects on ecosystem functioning and recovery after drought. With ongoing climate change and increasing plant invasion, there is an urgent need to predict the short- and long-term interaction impacts of these stressors on ecosystems. We established a combined precipitation exclusion and shrub invasion (Cistus ladanifer) experiment in a Mediterranean cork oak (Quercus suber) ecosystem with four treatments: (1) Q. suber control; (2) Q. suber with rain exclusion; (3) Q. suber invaded by shrubs; and (4) Q. suber with rain exclusion In an average precipitation year, the interaction effects of both stressors were neutral. However, the combination of imposed drought and shrub invasion led to amplifying interaction effects during an extreme drought by strongly reducing tree transpiration. Contrarily, the imposed drought reduced the competitiveness of the shrubs in the following recovery period, which buffered the negative effects of shrub invasion on Q. suber. Our results demonstrate the highly dynamic and nonlinear effects of interacting stressors on ecosystems and urges for further investigations on biotic interactions in a context of climate change pressures

Ancient Yersinia pestis genomes from across Western Europe reveal early diversification during the First Pandemic (541–750)

The first historically documented pandemic caused by Yersinia pestis began as the Justinianic Plague in 541 within the Roman Empire and continued as the so-called First Pandemic until 750. Although paleogenomic studies have previously identified the causative agent as Y. pestis, little is known about the bacterium’s spread, diversity, and genetic history over the course of the pandemic. To elucidate the microevolution of the bacterium during this time period, we screened human remains from 21 sites in Austria, Britain, Germany, France, and Spain for Y. pestis DNA and reconstructed eight genomes. We present a methodological approach assessing single-nucleotide polymorphisms (SNPs) in ancient bacterial genomes, facilitating qualitative analyses of low coverage genomes from a metagenomic background. Phylogenetic analysis on the eight reconstructed genomes reveals the existence of previously undocumented Y. pestis diversity during the sixth to eighth centuries, and provides evidence for the presence of multiple distinct Y. pestis strains in Europe. We offer genetic evidence for the presence of the Justinianic Plague in the British Isles, previously only hypothesized from ambiguous documentary accounts, as well as the parallel occurrence of multiple derived strains in central and southern France, Spain, and southern Germany. Four of the reported strains form a polytomy similar to others seen across the Y. pestis phylogeny, associated with the Second and Third Pandemics. We identified a deletion of a 45-kb genomic region in the most recent First Pandemic strains affecting two virulence factors, intriguingly overlapping with a deletion found in 17th- to 18th-century genomes of the Second Pandemic. © 2019 National Academy of Sciences. All rights reserved

Pareto Optimization of a Laser Wakefield Accelerator

Optimization of accelerator performance parameters is limited by numerous trade-offs and finding the appropriate balance between optimization goals for an unknown system is challenging to achieve. Here we show that multi-objective Bayesian optimization can map the solution space of a laser wakefield accelerator in a very sample-efficient way. Using a Gaussian mixture model, we isolate contributions related to an electron bunch at a certain energy and we observe that there exists a wide range of Pareto-optimal solutions that trade beam energy versus charge at similar laser-to-beam efficiency. However, many applications such as light sources require particle beams at a certain target energy. Once such a constraint is introduced we observe a direct trade-off between energy spread and accelerator efficiency. We furthermore demonstrate how specific solutions can be exploited using \emph{a posteriori} scalarization of the objectives, thereby efficiently splitting the exploration and exploitation phases

Expression of the chemokines MCP-1/CCL2 and RANTES/CCL5 is differentially regulated by infiltrating inflammatory cells

Expression of the chemokines MCP-1/CCL2 and RANTES/CCL5 is differentially regulated by infiltrating inflammatory cells.BackgroundChemokines are involved in the regulation of the cellular renal infiltrate in glomerulonephritis; however, it is unclear to which degree resident glomerular cells or infiltrating leukocytes contribute to the formation of chemokines in glomerular inflammatory lesions. We therefore examined whether monocytes/macrophages play a role in the expression of the C-C chemokines MCP-1/CCL2 and RANTES/CCL5 in renal tissue in a lipopolysaccharide (LPS)-induced model of inflammation, where previously we have shown increased glomerular RANTES expression and glomerular infiltration of ED-1-positive cells.MethodsInflammatory lesions were induced by an intraperitoneal injection of LPS. The infiltration of monocytes into the glomerulus was reduced by two experimental approaches. First, rats were depleted of monocytes by the use of specific monocyte-antisera or by cytotoxic drugs. Second, the infiltration of monocytes into the kidney was reduced by using intercellular adhesion molecule-1 (ICAM-1) knockout mice.ResultsBoth experimental approaches demonstrated a significant reduction in the number of infiltrating monocytes/macrophages after lipopolysaccharide injection. This reduction in the infiltration of inflammatory cells was associated with significantly reduced RANTES/CCL5 mRNA expression. However, MCP-1/CCL2 mRNA expression was not inhibited after the LPS injection by monocyte/macrophage depletion. Also, the increase in nuclear factor-κB (NF-κB) binding activity after the LPS injection was not reduced in pretreated animals. The experiments therefore demonstrate that infiltrating monocytes/macrophages contribute to increased RANTES/CCL5 mRNA expression in inflammatory renal lesions, whereas MCP-1/CCL2 mRNA expression and NF-κB activation were not reduced by monocyte/macrophage depletion.ConclusionMCP-1/CCL2 released from renal tissue upon stimulation plays a major role in the regulation of monocyte/macrophage infiltration, which contributes significantly to increased renal RANTES/CCL5 expression. This cross-talk between resident renal cells and monocytes/macrophages is therefore likely to boost the number of infiltrating inflammatory cells

Relationships between quality of life and family function in caregiver

<p>Abstract</p> <p>Background</p> <p>There are caregivers who see their quality of life (QoL) impaired due to the demands of their caregiving tasks, while others manage to adapt and overcome the crises successfully. The influence of the family function in the main caregiver's situation has not been the subject of much evaluation. The aim of this study is to analyse the relationship between the functionality of the family and the QoL of caregivers of dependent relatives.</p> <p>Methods</p> <p>We conducted a cross-sectional study including 153 caregivers. Setting: Two health centers in the city of Salamanca(Spain). Caregiver variables analysed: demographic characteristics, care recipient features; family functionality (Family APGAR-Q) and QoL (Ruiz-Baca-Q) perceived by the caregiver. Five multiple regressions are performed considering global QoL and each of the four QoL dimensions as dependent variables. The Canonical Correspondence Analysis (CCA) was used to study the influence of the family function questionnaire on QoL.</p> <p>Results</p> <p>Family function is the only one of the variables evaluated that presented an association both with global QoL and with each of the four individual dimensions (p < 0.05). Using the CCA, we found that the physical and mental well-being dimensions are the ones which present a closer relationship with family functionality, while social support is the quality dimension that is least influenced by the Family APGAR-Q.</p> <p>Conclusion</p> <p>We find an association between family functionality and the caregiver's QoL. This relation holds for both the global measure of QoL and each of its four individual dimensions.</p

Laser-accelerated electron beams at 1 GeV using optically-induced shock injection

In recent years, significant progress has been made in laser wakefield acceleration (LWFA), both regarding the increase in electron energy, charge and stability as well as the reduction of bandwidth of electron bunches. Simultaneous optimization of these parameters is, however, still the subject of an ongoing effort in the community to reach sufficient beam quality for next generation's compact accelerators. In this report, we show the design of slit-shaped gas nozzles providing centimeter-long supersonic gas jets that can be used as targets for the acceleration of electrons to the GeV regime. In LWFA experiments at the Centre for Advanced Laser Applications, we show that electron bunches are accelerated to 1GeV using these nozzles. The electron bunches were injected into the laser wakefield via a laser-machined density down-ramp using hydrodynamic optical-field-ionization and subsequent plasma expansion on a ns-timescale. This injection method provides highly controllable quasi-monoenergetic electron beams with high charge around 100pC, low divergence of 0.5mrad, and a relatively small energy spread of around 10% at 1GeV. In contrast to capillaries and gas cells, the scheme allows full plasma access for injection, probing or guiding in order to further improve the energy and quality of LWFA beams

The Interaction of LFA-1 on Mononuclear Cells and ICAM-1 on Tubular Epithelial Cells Accelerates TGF-β1-Induced Renal Epithelial-Mesenchymal Transition

The epithelial-mesenchymal transition (EMT) of renal epithelial cells (RTECs) has pivotal roles in the development of renal fibrosis. Although the interaction of lymphocyte function-associated antigen 1 (LFA-1) on leukocytes and its ligand, intracellular adhesion molecule 1 (ICAM-1), plays essential roles in most inflammatory reactions, its pathogenetic role in the EMT of RTECs remains to be clarified. In the present study, we investigated the effect of the interaction of LFA-1 on peripheral blood mononuclear cells (PBMCs) and ICAM-1 on HK-2 cells after stimulation with TGF-β1 on the EMT of RTECs. ICAM-1 was highly expressed in HK-2 cells. After TGF-β1 stimulation, the chemokines CCL3 and CXCL12 increased on HK-2 cells. After co-culture of PBMCs and HK-2 cells pre-stimulated with TGF-β1 (0.1 ng/ml) (HK-2-TGF-β1 (0.1)), the expression of the active form of LFA-1 increased on PBMCs; however, total LFA-1 expression did not change. The expression of the active form of LFA-1 on PBMCs did not increase after co-culture with not CCL3 but CXCL12 knockdown HK-2-TGF-β1 (0.1). The expression of epithelial cell junction markers (E-cadherin and occludin) further decreased and that of mesenchymal markers (vimentin and fibronectin) further increased in HK-2-TGF-β1 (0.1) after co-culture with PBMCs for 24 hrs (HK-2-TGF-β1 (0.1)-PBMCs). The phosphorylation of ERK 1/2 but not smad2 and smad3 increased in HK-2-TGF-β1 (0.1)-PBMCs. The snail and slug signaling did not increase HK-2-TGF-β1 (0.1)-PBMCs. Although the migration and invasion of HK-2 cells induced full EMT by a high dose (10.0 ng/ml) and long-term (72–96 hrs) TGF-β1 stimulation increased, that of HK-2-TGF-β1 (0.1)-PBMCs did not increase. These results suggested that HK-2 cells stimulated with TGF-β1 induced conformational activation of LFA-1 on PBMCs by increased CXCL12. Then, the direct interaction of LFA-1 on PBMCs and ICAM-1 on HK-2 cells activated ERK1/2 signaling to accelerate the part of EMT of HK-2 cells induced by TGF-β1

Tracking Virus-Specific CD4+ T Cells during and after Acute Hepatitis C Virus Infection

CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent or short-lived, using functional assays. Here we used a novel HLA-DR1 tetramer containing a highly targeted CD4+ T cell epitope from the hepatitis C virus non-structural protein 4 to track number and phenotype of hepatitis C virus specific CD4+ T cells in a cohort of seven HLA-DR1 positive patients with acute hepatitis C in comparison to patients with chronic or resolved hepatitis C. We observed peptide-specific T cells in all seven patients with acute hepatitis C regardless of outcome at frequencies up to 0.65% of CD4+ T cells. Among patients who transiently controlled virus replication we observed loss of function, and/or physical deletion of tetramer+ CD4+ T cells before viral recrudescence. In some patients with chronic hepatitis C very low numbers of tetramer+ cells were detectable in peripheral blood, compared to robust responses detected in spontaneous resolvers. Importantly we did not observe escape mutations in this key CD4+ T cell epitope in patients with evolving chronic hepatitis C. During acute hepatitis C a CD4+ T cell response against this epitope is readily induced in most, if not all, HLA-DR1+ patients. This antiviral T cell population becomes functionally impaired or is deleted early in the course of disease in those where viremia persists