Introduction
Snail, a transcription factor linked to epithelial to mesenchymal transition (EMT) during embryonic development and tumor progression, is associated with migration of cells. During ...inflammation and tissue injury, cell movement is also observed to provide the first line of defense against bacteria and to promote wound healing. Therefore, we studied the function of Snail in activated macrophages in a variety of inflammatory processes.
Materials and Methods
In this study, we examined the expression and localization of Snail during inflammation and tissue injury in rats and human tissue specimens, by immunohistochemistry, Western blot, and real-time PCR. We investigated Snail expression after stimulation of macrophages with TGF-β1, LPS, Interleukin-8, and MMP-3 in vitro. To further understand the role of Snail in activated macrophages, we used Stealth siRNA against Snail, transfected the human macrophage cell line THP-1, and measured migration of cells in an in vitro invasion assay.
Results and Discussion
We found a strong, transient, and time-dependent activation of Snail in migrating macrophages at the sites of injury in vivo and in vitro, as well as in patients with inflammatory bowel disease. Furthermore, we showed that induction of Snail in macrophages is dependent on TGF-β1 signaling pathway. Downregulation of Snail by Stealth siRNA led to impaired migration of THP-1 cells in an invasion assay after stimulation with TGF-β1.
Conclusion
We conclude that TGF-β1 induced migration of activated macrophages during inflammation and wound healing is mediated by snail. These results give insights in a novel EMT-like mechanism present in immune cell movement during tissue injury.
(
) is a common swine pathogen but also poses a threat to human health in causing meningitis and severe cases of streptococcal toxic shock-like syndrome (STSLS). Therefore, it is crucial to ...understand how
interacts with the host immune system during bacteremia. As
has the ability to introduce d-alanine into its lipoteichoic acids (LTAs), we investigated the working hypothesis that cell wall modification by LTA d-alanylation influences the interaction of
with porcine blood immune cells. We created an isogenic mutant of
strain 10 by in-frame deletion of the d-alanine d-alanyl carrier ligase (DltA). d-alanylation of LTAs was associated with reduced phagocytosis of
by porcine granulocytes, reduced deposition of complement factor C3 on the bacterial surface, increased hydrophobicity of streptococci, and increased resistance to cationic antimicrobial peptides (CAMPs). At the same time, survival of
was not significantly increased by LTA d-alanylation in whole blood of conventional piglets with specific IgG. However, we found a distinct cytokine pattern as IL-1β but not tumor necrosis factor (TNF)-α levels were significantly reduced in blood infected with the Δ
mutant. In contrast to TNF-α, activation and secretion of IL-1β are inflammasome-dependent, suggesting a possible influence of LTA d-alanylation on inflammasome regulation. Especially in the absence of specific antibodies, the association of
with porcine monocytes was reduced by d-alanylation of its LTAs. This
-dependent phenotype was also observed with a non-encapsulated
double mutant indicating that it is independent of capsular polysaccharides. High antibody levels caused high levels of
-monocyte-association followed by inflammatory cell death and strong production of both IL-1β and TNF-α, while the influence of LTA d-alanylation of the streptococci became less visible. In summary, the results of this study expand previous findings on d-alanylation of LTAs in
and suggest that this pathogen specifically modulates association with blood leukocytes through this modification of its surface.
Pancreatic resections are among the most complex procedures in visceral surgery. While mortality has decreased substantially over the past decades, morbidity remains high. The volume-outcome ...correlation in pancreatic surgery is among the strongest in the field of surgery. The German Society for General and Visceral Surgery (DGAV) established a national registry for quality control, risk assessment and outcomes research in pancreatic surgery in Germany (DGAV SuDoQ|Pancreas).
Here, we present the aims and scope of the DGAV StuDoQ|Pancreas Registry. A systematic assessment of registry quality is performed based on the recommendations of the German network for outcomes research (DNVF).
The registry quality was assessed by consensus criteria of the DNVF in regard to the domains Systematics and Appropriateness, Standardization, Validity of the sampling procedure, Validity of data collection, Validity of statistical analysis and reports, and General demands for registry quality. In summary, DGAV StuDoQ|Pancreas meets most of the criteria of a high-quality clinical registry.
The DGAV StuDoQ|Pancreas provides a valuable platform for quality assessment, outcomes research as well as randomized registry trials in pancreatic surgery.
Single, double, and triple photoionization of Ne+ ions by single photons have been investigated at the synchrotron radiation source PETRA III in Hamburg, Germany. Absolute cross-sections were ...measured by employing the photon-ion merged-beams technique. Photon energies were between about 840 and 930 eV, covering the range from the lowest-energy resonances associated with the excitation of one single K-shell electron up to double excitations involving one K- and one L-shell electron, well beyond the K-shell ionization threshold. Also, photoionization of neutral Ne was investigated just below the K edge. The chosen photon energy bandwidths were between 32 and 500 meV, facilitating the determination of natural line widths. The uncertainty of the energy scale is estimated to be 0.2 eV. For comparison with existing theoretical calculations, astrophysically relevant photoabsorption cross-sections were inferred by summing the measured partial ionization channels. Discussion of the observed resonances in the different final ionization channels reveals the presence of complex Auger-decay mechanisms. The ejection of three electrons from the lowest K-shell-excited Ne+( ) level, for example, requires cooperative interaction of at least four electrons.
COVID-19 prompted rapid development of scarce resource allocation (SRA) policies to be implemented if demand eclipsed health systems' ability to provide critical care. While SRA policies follow ...general ethical frameworks, understanding priorities of those affected by policies and/or tasked with implementing them is critical.
To evaluate whether community members and health care profesionals (HCP) agree with SRA protocols at the University of California (UC).
This survey study used social media and community-partnered engagement to recruit participants to a web-based survey open to all participants aged older than 18 years who wished to enroll. This study was fielded between May and September 2020 and queried participants' values and preferences on draft SRA policy tenets. Participants were also encouraged to forward the survey to their networks for snowball sampling. Data were analyzed from July 2020 to January 2024.
Survey items assessed values and preferences, graded on Likert scales. Agreement was tabulated as difference in Likert points between expressed opinion and policy tenets. Descriptive statistics were tested for significance by HCP status. Free text responses were analyzed using applied rapid qualitative analysis.
A total of 1545 participants aged older than 18 years (mean SD age 49 16 years; 1149 female participants 74%, 478 health care practitioners 30%) provided data on SRA values and preferences. Agreement with UC SRA policy as drafted was moderately high among respondents, ranging from 67% to 83% across domains. Higher agreement with the interim policy was observed for laypersons across all domains except health-related factors. HCPs agreed more strongly on average that resources should not be allocated to those less likely to survive (HCP mean, 3.70; 95% CI, 3.16-3.59; vs layperson mean, 3.38; 95% CI, 3.17-3.59; P = .002), and were more in favor of reallocating life support from patients less likely to those more likely to survive (HCP mean, 6.41; 95% CI, 6.15-6.67; vs layperson mean, 5.40; 95% CI, 5.23-5.58; P < .001). Transparency and trust building themes were common in free text responses and highly rated on scaled items.
This survey of SRA policy values found moderate agreement with fundamental principles of such policies. Engagement with communities affected by SRA policy should continue in iterative refinement in preparation for future crises.
Sarcomas especially of histiocytic origin often possess a poor prognosis and response to conventional therapies. Interestingly, tumours undergoing mesenchymal to epithelial transition (MET) are often ...associated with a favourable clinical outcome. This process is characterized by an increased expression of epithelial markers leading to a decreased invasion and metastatic rate. Based on the failure of conventional therapies, viral oncolysis might represent a promising alternative with canine distemper virus (CDV) as a possible candidate. This study hypothesizes that a CDV infection of canine histiocytic sarcoma cells (DH82 cells) triggers the MET process leading to a decreased cellular motility. Immunofluorescence and immunoblotting were used to investigate the expression of epithelial and mesenchymal markers followed by scratch assay and an invasion assay as functional confirmation. Furthermore, microarray data were analysed for genes associated with the MET process, invasion and angiogenesis. CDV‐infected cells exhibited an increased expression of epithelial markers such as E‐cadherin and cytokeratin 8 compared to controls, indicating a MET process. This was accompanied by a reduced cell motility and invasiveness. Summarized, these results suggest that CDV infection of DH82 cells triggers the MET process by an increased expression of epithelial markers resulting in a decreased cell motility in vitro.
Clinical anastomotic leakage remains a major problem after anterior or low anterior resection for rectal cancer. The aim of this study was to assess the association between risk factors and ...anastomotic leakage and postoperative mortality.
Two hundred seventy-six elective anterior or low anterior resections with anastomosis were performed and documented on-line from January 1995 to December 2004. Univariate and multivariate analyses with Bonferroni adjustment were carried out to identify relevant risk factors.
The rate of anastomotic leakage was 14.9% (41 of 276 patients) with a mortality of 12.2% (5 of 41 patients). Overall mortality was 2.5% (7 of 276 patients). Multiple regression analysis showed that smokers had an increased risk of anastomotic leakage odds ratio (OR), 6.42; 95% confidence interval (CI), 2.68-15.36 as well as patients with coronary heart disease (OR, 7.79; 95% CI, 2.52-24.08). Smokers (OR, 13.20; 95% CI, 2.48-7.24) and patients with coronary heart disease (OR, 23.46; 95% CI, 4.33-27.04) also had an increased risk of postoperative mortality in the univariate analysis as well as patients with anastomotic leakage (OR, 16.25; 95% CI, 3.04-16.92).
Smoking and coronary heart disease are important risk factors for anastomotic leakage and postoperative mortality after elective resection for rectal cancer.
The mammalian Transmembrane BAX Inhibitor Motif (TMBIM) protein family consists of six evolutionarily conserved hydrophobic proteins that affect programmed cell death and the regulation of ...intracellular calcium levels. The bacterial ortholog BsYetJ is a pH-dependent calcium channel. We here identified seven TMBIM family members in
Drosophila melanogaster
and describe their expression levels in diverse tissues and developmental stages. A phylogenetic analysis revealed that CG30379 represents the ortholog of human TMBIM4 although these two proteins are much less related than TMBIM5 (CG2076 and CG1287/Mics1) and TMBIM6 (CG7188/Bi-1) to their respective orthologs. For TMBIM1-3 the assignment is more dubious because the fly and the human proteins cluster together. We conducted a functional analysis based on expression levels and the availability of RNAi lines. This revealed that the ubiquitous knockdown of CG3798/Nmda1 and CG3814/Lfg had no effect on development while knockdown of CG2076/dTmbim5 resulted in death at the pupa stage and knockdown of CG7188/dTmbim6 in death at the embryonic stage. Ubiquitous knockdown of the second TMBIM5 paralog CG1287/Mics1 ensued in male sterility. Knockdown of dTmbim5 and 6 in muscle and neural tissue also greatly reduced lifespan through different mechanisms. Knockdown of the mitochondrial family member dTmbim5 resulted in reduced ATP production and a pro-apoptotic expression profile while knockdown of the ER protein dTmbim6 increased the ER calcium levels similar to findings in mammalian cells. Our data demonstrate that dTmbim5 and 6 are essential for fly development and survival but affect cell survival through different mechanisms.
It is well known that every smooth cubic threefold is the zero locus of the Pfaffian of a
6
×
6
skew-symmetric matrix of linear forms in
P
4
. To compactify the space of such Pfaffian representations ...of a given cubic and to study the construction in families for singular or reducible cubics as well as, it is thus natural to consider the incidence correspondence of Pfaffian representations inside the product of the space of semistable skew-symmetric
6
×
6
matrices of linear forms in
P
4
and the space of cubics. Here we describe concretely the irreducible component of this incidence correspondence dominating the space of skew matrices.
Since membranes made of open porous polymer foams can eliminate the use of organic solvents during their manufacturing, a series of previous studies have explored the foaming process of various ...polymers including polyethersulfone (PESU) using physical blowing agents but failed to produce ultrafiltration membranes. In this study, blends containing different ratios of PESU and poly(
-vinylpyrrolidone) (PVP) were used for preparation of open-celled polymer foams. In batch foaming experiments involving a combination of supercritical CO
and superheated water as blowing agents, blends with low concentration of PVP delivered uniform open-celled foams that consisted of cells with average cell size less than 20 µm and cell walls containing open pores with average pore size less than 100 nm. A novel sample preparation method was developed to eliminate the non-foamed skin layer and to achieve a high porosity. Flat sheet membranes with an average cell size of 50 nm in the selective layer and average internal pore size of 200 nm were manufactured by batch foaming a PESU blend with higher concentration of PVP and post-treatment with an aqueous solution of sodium hypochlorite. These foams are associated with a water-flux up to 45 L/(h m
bar). Retention tests confirmed their applicability as ultrafiltration membranes.
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