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Research question Does complete resection of endometriosis improve embryo quality as assessed by morphokinetic parameters using time-lapse microscopy? Design For this retrospective study we analysed 237 fertilised, cultured and transferred embryos from 128 fresh IVF and/ or ICSI transfer cycles. Endometriosis was confirmed or excluded by laparoscopy. Patients were stimulated with recombinant FSH using GnRH agonist and antagonist protocols. After fertilisation, a time-lapse incubation system was used for observation. Embryo quality was assessed using the KIDScore™ D3 and D5 implantation data algorithm. Results The analysis showed a median KIDScore™ D5 of 2.6 (on a scale of 1 to 9.9) for embryos from patients with endometriosis without complete resection. The control group without endometriosis achieved a score of 6.8 (p = 0.003). The median score for embryos from endometriosis patients with complete resection was 7.2, which was a significant increase compared to embryos from patients without complete resection (p = 0.002). We observed an effect size of r = 0.4 for complete resection versus no resection of endometriosis using the KIDScore™ D5. There were no differences in KIDScore™ D3 between the three patient groups. Pregnancy and miscarriage rates showed the same clinical trends. In three of our four case series of patients who underwent IVF/ ICSI cycles before and after complete resection, we found a marked improvement in embryo quality after complete resection. Conclusions Complete resection of endometriosis could significantly improve the otherwise poor embryo quality of patients undergoing IVF-procedures. The data, therefore, strongly support recommending surgery to patients with endometriosis prior to assisted reproduction.

In addition to the well-known threats of bird and hail strikes, small unmanned aerial vehicles (sUAV) pose a new threat to manned aviation. Determining the severity of collisions between sUAVs and aircraft structures is essential for the safe use and integration of drones in airspace. A generic analytical calculation model needs to be developed to supplement the existing test and simulation data. This paper presents an analytic model for drone collisions with perpendicular and inclined targets. The targets have a rigid or elastic material behavior. The aircraft impact model, which is used for the design of nuclear reactor structures, is transferred and adjusted for sUAV impacts to calculate the impact force. A mass- and a burst load distribution are needed as input parameters. Both distributions are determined for an sUAV design depending on the flight direction. Compared to previous calculations, the new approach is to consider a moving target structure, which produces more realistic results. We compare the calculation results with simulation data from sUAV collisions with a commercial airliner windshield from the literature. The calculations show plausible results and a good agreement with literature data. Subsequently, the influence of the input parameters on the impact force is investigated. We see that spring stiffness, target mass, burst load distribution and damping have minor influence on the overall impact force. The impact velocity, mass distribution and flight orientation on the other hand have a major influence on the impact force. Further tests are needed to validate the impact model.

Depression is a common psychiatric disorder among geriatric patients that decreases the quality of life and increases morbidity and mortality. Vitamin D as a neuro-steroid hormone might play a role in the onset and treatment of depression. In the present study, the association between depressive symptoms and vitamin D concentration in serum was evaluated. 140 patients of a psychogeriatric day-care unit were included. The geriatric depression scale (GDS) and the Hamilton depression rating scale (HDRS) were assessed at the beginning and end of treatment, GDS scores additionally 6 weeks after discharge from the day-care unit. Vitamin D levels were measured at the beginning of the treatment, routinely. Patients with levels below 30 µg/L were treated with 1000 IU vitamin D per day. There was no association between the severity of depressive symptoms and the concentration of vitamin D at the beginning of the treatment. Patients with higher vitamin D levels showed a stronger decline of depressive symptoms measured by the GDS during their stay in the day-care unit. We provide evidence that vitamin D serum levels might influence antidepressant therapy response in a geriatric population. Prospective studies are necessary to determine which patients may profit from add-on vitamin D therapy.

Background: Several classification systems based on arthroscopy have been used to describe lesions of the ligamentum teres (LT) in young active patients undergoing hip-preserving surgery. Inspection of the LT and associated lesions of the adjuvant fovea capitis and acetabular fossa is limited when done arthroscopically but is much more thorough during open surgical hip dislocation. Therefore, we propose a novel grading system based on our findings during surgical dislocation comprising the full spectrum of ligamentous-fossa-foveolar complex (LFFC) lesions. Purpose: To determine (1) intraobserver reliability and (2) interobserver reproducibility of our new grading system. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: We performed this validation study on 211 hips (633 images in total) with surgical hip dislocation (2013-2021). We randomly selected 5 images per grade for each LFFC item to achieve an equal representation of all grades (resulting in 75 images). The ligament, fossa, and fovea were subcategorized into normal, inflammation, degeneration, partial, and complete defects. All surgeries were performed in a standardized way by a single surgeon. The femur was disarticulated using a bone hook, the LT was inspected, documented and resected, then the fossa and fovea were documented with the femoral head in full dislocation using a 70° arthroscope. Six observers with different levels of expertise in hip-preserving surgery independently conducted the measurements twice, and intraclass correlation coefficients (ICC) were calculated to determine (1) intraobserver reliability and (2) interobserver reproducibility of the novel grading system. Results: For intraobserver reliability, excellent ICCs were found in both the junior and the experienced raters for grading the ligament, fossa, fovea, and total LFFC (ICCs ranged from 0.91 to 0.99 for the LFFC score). We found excellent interobserver reproducibility between raters for all items of the LFFC (all interobserver ICCs ≥ 0.76). Conclusion: Our new grading system for lesions of the LFFC is highly reliable and reproducible. It covers the full spectrum of damage more precisely than arthroscopic classifications do and offers a scientific basis for standardized intraoperative evaluation.

Background There is growing evidence for proprioceptive dysfunction in patients with Parkinson’s disease (PD). The Lee Silvermann Voice Treatment-BIG therapy (LSVT-BIG), a special training program aiming at an increase of movement amplitudes in persons with PD (PwPD), has shown to be effective on motor symptoms. LSVT-BIG is conceptionally based on improving bradykinesia, in particular the decrement of repetitive movements, by proprioceptive recalibration. Objective To assess proprioceptive impairment in PwPD as compared to matched controls and to probe potential recalibration effects of the LSVT-BIG therapy on proprioception. Methods Proprioceptive performance and fine motor skills were assessed in 30 PwPD and 15 matched controls. Measurements with significant impairment in PwPD were chosen as outcome parameters for a standardized 4 weeks amplitude-based training intervention (LSVT-BIG) in 11 PwPD. Proprioceptive performance served as primary outcome measure. Secondary outcome measures included the motor part of the MDS-UPDRS, the nine-hole-peg test, and a questionnaire on quality of life. Post-interventional assessments were conducted at weeks 4 and 8. Results Compared to the control group, PwPD showed significantly larger pointing errors. After 4 weeks of LSVT-BIG therapy and even more so after an additional 4 weeks of continued training, proprioceptive performance improved significantly. In addition, quality of life improved as indicated by a questionnaire. Conclusion LSVT-BIG training may achieve a recalibration of proprioceptive processing in PwPD. Our data indicates a probable physiological mechanism of a symptom-specific, amplitude-based behavioral intervention in PwPD.

Developmentally regulated features of innate immunity are thought to place preterm and term infants at risk of infection and inflammation-related morbidity. Underlying mechanisms are incompletely understood. Differences in monocyte function including toll-like receptor (TLR) expression and signaling have been discussed. Some studies point to generally impaired TLR signaling, others to differences in individual pathways. In the present study, we assessed mRNA and protein expression of pro- and anti-inflammatory cytokines in preterm and term cord blood (CB) monocytes compared with adult controls stimulated ex vivo with Pam3CSK4, zymosan, polyinosinic:polycytidylic acid, lipopolysaccharide, flagellin, and CpG oligonucleotide, which activate the TLR1/2, TLR2/6, TLR3, TLR4, TLR5, and TLR9 pathways, respectively. In parallel, frequencies of monocyte subsets, stimulus-driven TLR expression, and phosphorylation of TLR-associated signaling molecules were analyzed. Independent of stimulus, pro-inflammatory responses of term CB monocytes equaled adult controls. The same held true for preterm CB monocytes—except for lower IL-1β levels. In contrast, CB monocytes released lower amounts of anti-inflammatory IL-10 and IL-1ra, resulting in higher ratios of pro-inflammatory to anti-inflammatory cytokines. Phosphorylation of p65, p38, and ERK1/2 correlated with adult controls. However, stimulated CB samples stood out with higher frequencies of intermediate monocytes (CD14+CD16+). Both pro-inflammatory net effect and expansion of the intermediate subset were most pronounced upon stimulation with Pam3CSK4 (TLR1/2), zymosan (TR2/6), and lipopolysaccharide (TLR4). Our data demonstrate robust pro-inflammatory and yet attenuated anti-inflammatory responses in preterm and term CB monocytes, along with imbalanced cytokine ratios. Intermediate monocytes, a subset ascribed pro-inflammatory features, might participate in this inflammatory state.

FATWO (female adnexal tumour of probable Wolffian origin) denotes a rare tumour of the female adnexa which has been described in nearly 80 cases worldwide and which presumably originates in the remains of the Wolffian ducts. In 10 to 20 percent of patients, a metastasis or recurrence was seen subsequently and for this reason, a malignant potential is attributed to the FATWO. Because of the small number of cases, there is no clear therapeutic recommendation. The method of choice currently is surgical treatment with hysterectomy and adnexectomy. The benefit of radio- and chemotherapies is not clear and a small number of treatment attempts with imatinib have been made in cases of CD117 positivity or treatment attempts on an endocrine basis. This work provides an overview of the literature on epidemiology, imaging and histopathological diagnostic features as well as therapeutic options of this same tumour form.FATWO (female adnexal tumour of propable Wolffian origin) bezeichnet einen seltenen Tumor der weiblichen Adnexe, der weltweit in knapp 80 Fällen beschrieben wurde und dessen Ursprung vermutlich in den Residuen der Wolffʼschen Gänge liegt. Bei 10 bis 20 Prozent der Patientinnen zeigte sich im Verlauf eine Metastasierung oder ein Rezidiv, weshalb dem FATWO ein malignes Potenzial zugeschrieben wird. Aufgrund der kleinen Fallzahl existiert keine klare Therapieempfehlung. Methode der Wahl ist derzeit eine operative Sanierung mit Hysterektomie und Adnexektomie. Der Nutzen von Radio- und Chemotherapien ist nicht eindeutig, vereinzelt wurden Therapieversuche mit Imatinib bei CD117-Positivität oder Therapieversuche auf endokriner Basis unternommen. Diese Arbeit zeigt eine Literaturübersicht über Epidemiologie, bildgebende und histopathologische Diagnosemerkmale sowie Therapieoptionen dieser seltenen Tumorform.

Elderly care facilities have become a major focus of coronavirus disease (COVID-19) control. Here, we describe an outbreak of COVID-19 in a nursing home in Germany from 8 March to 4 May 2020 (58 days), and the effect of an intervention of general screening and cohort isolation. COVID-19 cases among residents and staff were recorded on a daily basis from the first positive SARS-CoV-2 test from a resident on 8 March 2020, until 4 May 2020 when the last staff member was classified COVID-19 negative. Eighty of 160 residents (50%) and 37 of 135 staff members (27%) tested positive for SARS-CoV-2. Twenty-seven of the 80 residents were asymptomatic but tested positive during the first general screening. Cohort isolation of SARS-CoV-2 positive residents by reorganising the facility proved to be a major effort. After the intervention, four further asymptomatic residents tested positive in follow-up screenings within a period of 6 days, and were possibly infected prior to the intervention. Thereafter, no further infections were recorded among residents. The described outbreak was controlled by implementing general screening and rigorous cohort isolation, providing a blueprint for similar facilities.

BackgroundHypertension is a major risk factor for cardiovascular disease and the leading cause of premature deaths in the United States. Hypertension is a commonly reported chronic disease in foreign-born-adult immigrants living in the United States, and psychosocial-cultural factors such as lack of health insurance and poor transportation services have been reported particularly among foreign-born immigrant women with hypertension and other chronic diseases. However, little is known about the socio-cultural factors that influence access to and utilization of hypertension health services in West-African-born immigrant women in the United States.MethodsThis study utilized a qualitative design with a phenomenological approach to interview a purposeful sample of fifteen West-African-born immigrant women that reported diagnosis of hypertension (12 with health insurance and 3 without health insurance) in the Washington District of Columbia Metropolitan area. The Patient Centered Access to Health Care Model guided the conceptual framework of the study. Thematic analysis was used to identify patterns and generate categories and themes.ResultsFive themes emerged from the analysis: Health Insurance Coverage, Frequency of Hypertension Care Visits, Interaction with HCP, Culturally Sensitive HCP, and HTN Self-Care Incentives. Eighty percent of participants had medical insurance and transportation services, but delayed seeking HTN care because their health care providers did not listen to their concerns or discuss their preferences before prescribing treatment. More than 60 percent of the women reported that clinicians did not listen to their concerns or provide culturally appropriate guidance during their visits.ConclusionsThese findings could be helpful for larger scale studies, or smaller comparative studies in other regions of the United States. Cultural competence training should be included in the continuing education curriculum of healthcare providers serving the West-African-born immigrant population.

Objective Hyperinsulinemia can be both a cause and consequence of obesity and insulin resistance. Hyperinsulinemia can result from increased insulin secretion and/or reduced insulin clearance. While many studies have focused on mechanisms triggering insulin secretion during obesity, the triggers for changes in insulin clearance during obesity are less defined. In this study, we investigated the role of the microbiota in regulating insulin clearance during diet-induced obesity. Methods Blood glucose and insulin clearance were tested in conventional male mice treated with antibiotics and germ-free mice colonized with microbes from mice that were fed a control (chow) diet or an obesogenic high-fat diet (HFD). The composition of the fecal microbiota was analyzed using 16S rRNA sequencing. Results Short-term HFD feeding and aging did not alter insulin clearance in the mice. Oral antibiotics mitigated impaired blood insulin clearance in the mice fed an HFD for 12 weeks or longer. Germ-free mice colonized with microbes from HFD-fed donor mice had impaired insulin but not C-peptide clearance. Microbe-transmissible insulin clearance impairment was only observed in germ-free mice after more than 6 weeks post-colonization upon HFD feeding. Five bacterial taxa predicted >90% of the variance in insulin clearance. Mechanistically, impaired insulin clearance was associated with lower levels of hepatic Ceacam-1 but increased liver and skeletal muscle insulin-degrading enzyme (IDE) activity. Conclusions Gut microbes regulate insulin clearance during diet-induced obesity. A small cluster of microbes or their metabolites may be targeted for mitigating defects in insulin clearance and hyperinsulinemia during the progression of obesity and type 2 diabetes.

Secao especial - The Exposition of Practice as Research as Experimental Systems Michael Schwab Editor do Journal for Artistic Research (JAR) Traducao Osmar Yang e Yara Guasque Artigo publicado originalmente em Ingles (SCHWAB, Michael. “The Exposition of Practice as Research as Experimental Systems”, 2014, pp. 31-40) como capitulo do livro CRISPIN, Darla; GILMORE, Bob. (Eds.). Artistic Experimentation in Music. An Anthology. Leuven: Leuven University Press, 2014.

Zusammenfassung Hintergrund Beratung durch Ärzte in Bezug auf Lebensstil im Allgemeinen und das Bewegungsverhalten im Speziellen steht seit dem Inkrafttreten des Präventionsgesetzes in Deutschland wieder vermehrt im Fokus. Auch für die Bewegungstherapie spielt die Anknüpfung an ärztliche Beratung eine wichtige Rolle. Die Erwartungen an ärztliche Beratung sind dabei durchaus hoch, wohingegen es eine Vielzahl an Barrieren zu geben scheint. In einem Projekt (PATEN im Rahmen vom Forschungsverbund Capital4Health) zur Bewegungsförderung im Seniorenwohnstift wurde ein Informations- bzw. Schulungsangebot erprobt. Dabei wurden Praxishilfen entwickelt, die es Ärzten erleichtern sollen, das Thema Bewegung im zeitlich begrenzten Rahmen strukturiert anzusprechen. Konzeption Die beiden Praxishilfen (Tischvorlagen) beinhalten ein potenzielles Ablaufschema für eine Kurzberatung nach den so genannten 5 A‘s sowie eine grafische Darstellung von gängigen Bewegungsempfehlungen für Ältere. Letztere beziehen sich vornehmlich auf die deutschen Nationalen Empfehlungen für Bewegung und Bewegungsförderung. Die 5A-Methode (Ask / Assess, Agree, Advise, Assist, Arrange) ist evidenzbasiert, eignet sich für die primäre Gesundheitsversorgung und wird von gängigen Leitlinien empfohlen. Diskussion Interventionen zur Bewegungsförderung in der Arztpraxis können von unterschiedlichster Dauer und inhaltlicher Ausrichtung sein. Die vorliegenden Praxishilfen können zur flexiblen Umsetzung genutzt werden. Sie sind dabei auch von Bewegungsfachleuten und evtl. anderen Berufsgruppen einsetzbar.

O Research Catalog, RC (Catálogo de Pesquisa)e o Journal for Artistic Research, JAR (Revista de Pesquisa Artística)são projetos interligados, mas com metas e propósitos muito diferentes. O RC é um espaço de trabalho gratuito online e basicamente privativo que permite a (auto-)publicação e pesquisa artística. JAR é um periódico acadêmico, avaliado pelos pares, de livre acesso, para a publicação e disseminação de pesquisa artística. JAR atua como o primeiro de uma série de portais planejados, especializados para pesquisas selecionadas publicadas no RC que utilizam a tecnologia disponibilizada, incluindo a interface de design e o procedimento integrado de envio e publicação.

Myrcludex B acts as a hepatitis B and D virus entry inhibitor blocking the sodium taurocholate cotransporting polypeptide (SLC10A1). We investigated the effects of myrcludex B on plasma bile acid disposition, tenofovir pharmacokinetics, and perpetrator characteristics on cytochrome P450 (CYP) 3A. Twelve healthy volunteers received 300 mg tenofovir disoproxil fumarate orally and 10 mg subcutaneous myrcludex B. Myrcludex B increased total plasma bile acid exposure 19.2-fold without signs of cholestasis. The rise in conjugated bile acids was up to 124-fold (taurocholic acid). Coadministration of tenofovir with myrcludex B revealed no relevant changes in tenofovir pharmacokinetics. CYP3A activity slightly but significantly decreased by 29% during combination therapy. Myrcludex B caused an asymptomatic but distinct rise in plasma bile acid concentrations and had no relevant impact on tenofovir pharmacokinetics. Changes in CYP3A activity might be due to alterations in bile acid signaling. Long-term effects of elevated bile acids will require critical evaluation.

Introduction: Expression of fibroblast activation protein (FAP) has been detected in activated fibroblasts participating in injury response, fibrotic and inflammatory conditions, and tumorigenesis. Human endometrium is equally characterized by rapid tissue remodeling events due to the reproductive tasks comprising the activity of proteolytic enzymes. Objective: We therefore hypothesized that FAP-positive fibroblasts could also be involved in physiological processes requiring tissue remodeling, such as decidualization during early pregnancy. Methods/Results: The expression of FAP was analyzed by immunohistochemistry in frozen sections of decidual tissue from early pregnancy (gestational weeks: 6–12). All tissue samples clearly displayed a strong expression of FAP on the surface of stromal fibroblasts. Additionally, the percentage of FAP-positive fibroblasts freshly isolated from the decidua of the corresponding gestational weeks was calculated by applying FACS analysis. Decidual fibroblasts of different gestational weeks showed a significant decrease in FAP expression between the 6th and 7th weeks of gestation, which was followed by a steady slow reconstitution. By analyzing the expression of cytokines, chemokines, and growth factors of isolated FAP-positive decidual fibroblasts, we detected high levels of monocyte-attracting chemokines (growth-related oncogene alpha and monocyte chemoattractant protein-1 and -2), granulocyte-attracting chemokines (e.g., IL-8), proinflammatory factors (IL-1α and tumor necrosis factor alpha), and angiogenic substances (e.g., vascular endothelial growth factor and IL-8), which all promote an optimal microenvironment for implantation and growth of the conceptus. Conclusions: Our data demonstrate that the healthy early pregnancy decidua is characterized by a general occurrence of FAP-positive fibroblasts possibly participating in active tissue remodeling during implantation.

Src homology region 2 domain-containing phosphatase-1 (Shp1) plays an important role in modulating insulin signaling and thereby glucose homeostasis. Our laboratory has demonstrated that despite being more prone to hepatic steatosis, mice with a liver specific Shp1 knock out (Shp1H-KO) on high-fat diet (HFD) exhibit improved fasting glycaemia, reduced insulin resistance and lower inflammation than their flox/flox littermates. Microarray analysis of HFD-fed Shp1H-KO versus Shp1fl/fl livers revealed elevated levels of peroxisome proliferator-activated receptor gamma (PPARγ), an important transcription factor controlling adipogenesis. In addition, overexpression of Shp1 decreased PPARγ activity in vitro. The aim of this study was to investigate the mechanism of regulation of PPARγ by Shp1. Molecular modeling analyses suggested that Shp1 interaction with PPARγ depends on the tyrosine phosphorylation status of PPARγ. We found, by co-immunoprecipitation, that Shp1 N-terminal SH2-domains binds to PPARγ. We confirmed PPARγ tyrosine-phosphorylation and demonstrated that this phosphorylation could be reduced by Shp1 in vitro. Using mass spectrometry, we identified 5 phosphorylated tyrosine residues in PPARγ. Mutagenesis experiments showed that PPARγ significantly lost its activity when two of these sites were selectively and independently mutated to the non-phosphorylatable phenylalanine but did not interfere with the nuclear localization of PPARγ. Additionally, we generated Shp1 knockout HepG2 cells using CRISPR-Cas9 technology. We found that expression of several PPARγ regulated transcripts was upregulated in Shp1-KO cells as compared to control cells. Altogether, we show that PPARγ is a novel substrate of Shp1. Our results reveal a fine regulation of PPARγ tyrosine phosphorylation by Shp1, which might lead to novel therapeutic approaches for treating metabolic disorders related to obesity. Disclosure A. Kumar: None. M. Lavallee-Bourget: None. M. Forest: None. M. Schwab: None. K. Bellmann: None. V. Houde: None. H. Maaroufi: None. N. Beauchemin: None. A. Marette: Advisory Panel; Self; Plexus, Valbiotis. Consultant; Self; Danone Nutricia Research.

Quorum quenching lactonases are enzymes capable of hydrolyzing lactones, including N-acyl homoserine lactones (AHLs). AHLs are molecules known as signals in bacterial communication dubbed quorum sensing. Bacterial signal disruption by lactonases was previously reported to inhibit behavior regulated by quorum sensing, such as the expression of virulence factors and the formation of biofilms. Herein, we report the enzymatic and structural characterization of a novel lactonase representative from the metallo-β-lactamase superfamily, dubbed GcL. GcL is a broad spectrum and highly proficient lactonase, with kcat /KM values in the range of 104 to 106 m-1 s-1 . Analysis of free GcL structures and in complex with AHL substrates of different acyl chain length, namely, C4-AHL and 3-oxo-C12-AHL, allowed their respective binding modes to be elucidated. Structures reveal three subsites in the binding crevice: 1) the small subsite where chemistry is performed on the lactone ring; 2) a hydrophobic ring that accommodates the amide group of AHLs and small acyl chains; and 3) the outer, hydrophilic subsite that extends to the protein surface. Unexpectedly, the absence of structural accommodation for long substrate acyl chains seems to relate to the broad substrate specificity of the enzyme.

The disruption of bacterial signaling (quorum quenching) has been proven to be an innovative approach to influence the behavior of bacteria. In particular, lactonase enzymes that are capable of hydrolyzing the N-acyl homoserine lactone (AHL) molecules used by numerous bacteria, were reported to inhibit biofilm formation, including those of freshwater microbial communities. However, insights and tools are currently lacking to characterize, understand and explain the effects of signal disruption on complex microbial communities. Here, we produced silica capsules containing an engineered lactonase that exhibits quorum quenching activity. Capsules were used to design a filtration cartridge to selectively degrade AHLs from a recirculating bioreactor. The growth of a complex microbial community in the bioreactor, in the presence or absence of lactonase, was monitored over a 3-week period. Dynamic population analysis revealed that signal disruption using a quorum quenching lactonase can effectively reduce biofilm formation in the recirculating bioreactor system and that biofilm inhibition is concomitant to drastic changes in the composition, diversity and abundance of soil bacterial communities within these biofilms. Effects of the quorum quenching lactonase on the suspension community also affected the microbial composition, suggesting that effects of signal disruption are not limited to biofilm populations. This unexpected finding is evidence for the importance of signaling in the competition between bacteria within communities. This study provides foundational tools and data for the investigation of the importance of AHL-based signaling in the context of complex microbial communities.

[This corrects the article DOI: 10.1371/journal.pone.0217059.].

It is known that interfering with glycolysis leads to profound modification of cancer cell proliferation. However, energy production is not the major reason for this correlation. Here, using HeLa cells as a model for cancer, we demonstrate that phosphofructokinase-P (PFK-P), which is overexpressed in diverse types of cancer including HeLa cells, modulates expression of P44/42 mitogen-activated protein kinase (MAPK). Silencing of PFK-P did not alter HeLa cell viability or energy production, including the glycolytic rate. On the other hand, silencing of PFK-P induced the downregulation of p44/42 MAPK, augmenting the sensitivity of HeLa cells to different drugs. Conversely, overexpression of PFK-P promotes the upregulation of p44/42 MAPK, making the cells more resistant to the drugs. These results indicate that overexpression of PFK-P by cancer cells is related to activation of survival pathways via upregulation of MAPK and suggest PFK-P as a promising target for cancer therapy. J. Cell. Biochem. 118: 1216-1226, 2017. © 2016 Wiley Periodicals, Inc.

Diel (also called diurnal) discharge patterns with minima in the afternoon are generally explained by the daily cycle of evapotranspiration, while maxima in the afternoon are often linked to freeze-thaw cycles. In a schistose and forested headwater catchment in Luxembourg, we observed daily discharge maxima in the afternoon, although temperatures remained persistently above zero and vegetation was still in a dormant state. We show that diel water temperature fluctuations - and therefore viscosity fluctuations - in the upper layer of the riparian zone can be an explanation for the observed daily discharge maxima in the afternoon during the dormant season. In the transition period between the dormant and the growing season, the counteracting viscosity and evapotranspiration processes cancel each other out. Subsequently, during the growing season, evapotranspiration is the dominant process guiding the diel discharge pattern; nevertheless, the viscosity effect might still be present, but invisible. We believe this finding also to be of relevance when analyzing daily fluctuations of biogeochemicals in stream water. This article is protected by copyright. All rights reserved.

Seção especial - The Exposition of Practice as Research as Experimental Systems Michael Schwab Editor do Journal for Artistic Research (JAR) Tradução Osmar Yang e Yara Guasque Artigo publicado originalmente em Inglês (SCHWAB, Michael. “The Exposition of Practice as Research as Experimental Systems”, 2014, pp. 31-40) como capítulo do livro CRISPIN, Darla; GILMORE, Bob. (Eds.). Artistic Experimentation in Music. An Anthology. Leuven: Leuven University Press, 2014.

Objective Dietary administration of ω-3 polyunsaturated fatty acids (PUFA) is often associated with altered adipose tissue (AT) morphology and/or function in obese mice. Yet, it is unclear whether this is an indirect consequence of reduced weight gain or results from direct actions of ω-3 PUFA. Here we studied the AT of high fat (HF)-fed fat-1 transgenic mice that convert endogenous ω-6 to ω-3 PUFA while maintaining equivalent fat accretion as their wild-type (WT) counterparts. Materials and methods Adipocyte size profiling, Affymetrix microarray pathway analysis, qPCR and protectin identification and analysis were performed in epididymal AT from hemizygous fat-1 (+/−) mice and their wild type littermates that had been fed a HF diet for 8weeks from 6weeks of age. Results Despite equivalent fat pad mass, we found that epididymal AT from HF-fed transgenic animals possesses fewer large and very large but more mid-size adipocytes compared to WT mice. In order to better understand the underlying mechanisms contributing to the observed alteration in adipocyte size we performed an Affymetrix microarray. Pathway analysis of these data highlighted adipogenesis, cholesterol biosynthesis, insulin signaling, prostaglandin synthesis/regulation and small ligand GPCRs as points where differentially expressed genes were significantly overrepresented. Observed changes were confirmed for four candidate genes: Cnr1, Cnr2 , Faah and Pparg by qPCR. Finally we demonstrated that protectin DX is present in AT and that protectin DX and protectin D1 promote comparable PPARγ transcriptional activity. Conclusions These data provide unprecedented evidence that ω-3 PUFA coordinately regulate AT gene expression programs in a manner that is independent of restriction of weight gain or fat accrual and highlight an important influence of ω-3 PUFA on adipogenesis. Furthermore we provide primary evidence suggesting that protectins likely contribute to these effects via their influence on PPARγ.

On the basis of a notion of experimentation derived from Hans-Jorg Rheinberger’s concept of ‘experimental system’, which he developed in the context of twentieth-century experimental science, this paper sketches a possible route into a genuine artistic epistemology. While experimental systems are highly conceptual in nature, they are actually meant to produce material, epistemic excess – epistemic things – that enter the world first as unknowns. Given this initial lack of knowledge, the article argues that it is less helpful to decide whether any concrete epistemic thing is fact or fiction; rather, an artistic epistemology is suggested that focuses on the radical individuality of such a thing and the way in which artistic research practice may need to protect its individuality as a site for particular knowledges. This implies a critique of Rheinberger’s emphasis on historicity in experimental systems, a critique which is explained with reference to two works by Marcel Duchamp: Fountain and Three Standard ...

Background The therapeutic potential of allogeneic hematopoietic stem cell transplantation (HSCT) mainly relies on graft-versus-leukemia effects mediated by donor-derived T cells targeting both minor histocompatibility antigens and tumor-associated antigens (TAAs). The efficacy of TAA-mediated immune responses particularly depends on the level of antigen expression in the target tissue and the presence of a proinflammatory immune environment allowing donor-derived T cells to overcome peripheral tolerance and to attack the malignant cells in a selective manner. As several TAAs with clinical relevance in tumor and/or transplant immunotherapy such as Mucin 1 (MUC-1), Preferentially expressed antigen of melanoma (PRAME), Wilms tumor protein 1 (WT1) and Human epidermal growth factor receptor 2 (HER2/neu) are highly expressed in the placental tissue we investigated the effects of pregnancy on the frequency of immune responses against these TAAs in a prospective study. A cross-sectional analysis in a previously reported group of 114 healthy volunteer blood donors revealed no significant effects of prior pregnancies. Here, we present the results of the longitudinal analysis in women during and after their first pregnancy. Materials and Methods After local ethical approval and written informed consent a total of 44 HLA-A*02:01-positive women during their first pregnancy were enrolled in this prospective study. Immune responses against TAAs were assessed at four different time points: First or second trimester (Time point A, n=43), 1 to 3 days after delivery (Time point B, n=31), 6 to 8 weeks after delivery (Time point C, n=34) and after completed nursing (Time point D, n=14). At each time point peripheral blood was drawn and peripheral blood mononuclear cells (PBMCs) were collected by density gradient centrifugation. Isolated CD8+ T cells were stimulated with irradiated T2 cells which were loaded with immunodominant peptides (0.1 and 10 µM) of HER2/neu, MUC-1, PRAME, and WT1. Interferon-gamma (IFN-γ) mRNA expression was measured by quantitative polymerase chain reaction (qPCR) after extraction of total RNA. IFN-γ mRNA expression was calculated as relative fold change compared to the irrelevant melanoma antigen Glycoprotein 100 (gp100). A two-fold change was considered as cut-off for positive results. A HLA-A*02:01 restricted CMV peptide was used as positive control. Results All results are presented in [Figure 1][1]. Positive immune responses are presented above the cut-off line. A significant number of positive immune responses against MUC-1, PRAME and WT1 were found during pregnancy (Group A) and early after delivery (Group B). The frequency of positive immune responses against these TAAs decreased during and/or after the period of nursing leaving only one borderline significant finding behind (Group C and D). Against HER2/neu there were none or only single events of immune responses detectable in any group. ![Figure][2] Conclusions The results from this longitudinal analysis show that immune responses against the transplant-relevant TAAs MUC-1, PRAME and WT1 are detectable in pregnant women but are lost after delivery. These findings are in line with our observations from the inter-individual cross-sectional study where women with prior pregnancy did not have a significantly increased frequency of immune responses against TAAs compared to women without prior pregnancies. The abrogation of the immune response as shown in a longitudinal manner is likely to be a result of an immunosuppressive environment induced by increasing levels of steroid hormones during pregnancy. As immune responses against TAAs can be found also in non-pregnant women we assume that the overexpression of TAAs in the placenta induces a boost in autoimmune responses that is consequently compromised by the immunosuppressive environment. Therefore pregnancy may be a useful model for the boost and the regulation of immune responses against TAAs with implications for immunotherapy. Disclosures: No relevant conflicts of interest to declare. [1]: #F1 [2]: pending:yes

We monitored dissolved organic carbon (DOC) and nitrate concentrations and fluxes in situ with a UV-Vis spectrometer for two years at a high temporal resolution of 15 minutes in the forested Weierbach headwater catchment. The catchment exhibits a characteristic double peak runoff response to incident rainfall during periods with wet initial conditions. When initial conditions are dry, only the first discharge peak occurs. During our observations, both DOC and nitrate concentrations increased during the first discharge peak, while only nitrate concentrations were elevated during the second discharge peak. Relying on additional biweekly end-member data of precipitation, throughfall, soil water and groundwater, we linked the first peak to near surface flowpaths and the second peak to shallow groundwater reactions and subsurface flowpaths. The mass export of DOC and nitrate is largely controlled by the discharge yield. Nevertheless, this relationship is altered by changing flowpaths during different wetness conditions in the catchment. Due to the absence of second discharge peaks during dry conditions, the DOC export is more relevant and the nitrate export is less relevant during dry catchment states. The study highlights the benefits of in-situ, long-term, and high-frequency monitoring for comparing DOC and nitrate export with runoff components that are changing rapidly during events as well as gradually between seasons.

Essbegleitung stellt einen zentralen Therapiebaustein in der stationaren und teilstationaren Behandlung von Patienten mit Essstorung dar. Bisher gibt es jedoch kaum empirische Forschung, die als Grundlage fur eine wissenschaftlich fundierte, praxisorientierte Handlungsempfehlung herangezogen werden kann. Ziel der aktuellen Studie war es daher, zunachst einen umfassenden Uberblick uber die aktuelle Versorgungspraxis der Essbegleitung in Deutschland zu erhalten. An der landesweiten Umfrage nahmen 97 Mitarbeiter von insgesamt 66 deutschen Essstorungszentren teil. Die Umfrage zur Essbegleitung umfasste 4 grose Themenbereiche: (a) Setting, (b) allgemeine Rahmenbedingungen, (c) spezifische Interventionen, und (d) Perspektive der Mitarbeiter. Die Ergebnisse der Umfrage zeigen u. a., dass die Mahlzeiten in erster Linie durch Pflegepersonal begleitet werden. An etwa zwei Drittel der Zentren wird mindestens eine Essbegleitung pro Tag unter strukturierten Rahmenbedingungen angeboten. Die meisten Zentren bieten eine Patientenkuche und/oder eine Kochgruppe fur die Zubereitung von Mahlzeiten durch Patienten an. Von etwa drei Viertel der Behandler wird das Essverhalten und die Essensmenge der Patienten systematisch dokumentiert. Ferner nehmen die meisten Behandler eine Vorbildfunktion ein, indem sie selbst Mahlzeiten am Patiententisch einnehmen. Eine gezielte Nahrungsmittelexposition wird nur von einer Minderheit der Behandler angeboten. Sanktionen bei Nichteinhaltung therapeutischer Zielvereinbarungen werden deutlich haufiger eingesetzt als positive Verstarkung bei Erreichen dieser Ziele. Weniger als die Halfte der Behandler bietet eine Nachbetreuung nach dem Essen an. Die Ergebnisse der Umfrage geben wichtige Einblicke in die aktuelle Praxis der Essbegleitung und stellen einen Ausgangspunkt fur die Entwicklung klinischer Untersuchungen zur Uberprufung der Wirksamkeit spezifischer Interventionen dar.

This study assessed the effect of providing an enhanced medication plan (EMP) to patients during patient-physician conversation at hospital discharge and evaluated its immediate impact on patient knowledge on pharmacotherapy. We observed patient-physician conversations at hospital discharge in three internal medicine wards of the University Hospital Heidelberg before and after the EMP was integrated into the discharge process, and documented how and to what extent physicians provided the patients with drug information. After the conversation, the patients’ knowledge was evaluated by three standardized questions about their pharmacotherapy. We observed 90 conversations (50 before EMP-implementation, 40 after). In both phases, the conversation duration was 5.6–6 min (p = 0.56). However, the time spent on drug information increased significantly by 61.7 % after EMP-implementation (+63 s, p = 0.02). Before implementation, physicians gave at least one drug administration recommendation for 75.1 % of all drugs, compared to 84.6 % after implementation (p = 0.02). The EMP provided information for almost all drugs (98.9 %; p

Microbial colonization can be detrimental to the integrity of metal surfaces and lead to microbiologically influenced corrosion (MIC). Biocorrosion is a serious problem for aquatic and marine industries in the world. In Minnesota (USA), where this study was conducted, biocorrosion severely affects the maritime transportation industry. The anticorrosion activity of a variety of compounds, including chemical (magnesium peroxide) and biological (surfactin, capsaicin, and gramicidin) molecules were investigated as coating additives. We also evaluated a previously engineered, extremely stable, non-biocidal enzyme known to interfere in bacterial signaling, SsoPox (a quorum quenching lactonase). Experimental steel coupons were submerged in water from the Duluth Superior Harbor (DSH) for 8 weeks in the laboratory. Biocorrosion was evaluated by counting the number and the coverage of corrosion tubercles on coupons and also by ESEM imaging of the coupon surface. Three experimental coating additives significantly reduced the formation of corrosion tubercles: surfactin, magnesium peroxide and the quorum quenching lactonase by 31%, 36% and 50%, respectively. DNA sequence analysis of the V4 region of the bacterial 16S rRNA gene revealed that these decreases in corrosion were associated with significant changes in the composition of bacterial communities on the steel surfaces. These results demonstrate the potential of highly stable quorum quenching lactonases to provide a reliable, cost-effective method to treat steel structures and prevent biocorrosion.

Insulin resistance is a major disorder that links obesity to type 2 diabetes mellitus (T2D). It involves defects in the insulin actions owing to a reduced ability of insulin to trigger key signaling pathways in major metabolic tissues. The pathogenesis of insulin resistance involves several inhibitory molecules that interfere with the tyrosine phosphorylation of the insulin receptor and its downstream effectors. Among those, growing interest has been developed toward the protein tyrosine phosphatases (PTPs), a large family of enzymes that can inactivate crucial signaling effectors in the insulin signaling cascade by dephosphorylating their tyrosine residues. Herein we briefly review the role of several PTPs that have been shown to be implicated in the regulation of insulin action, and then focus on the Src homology 2 (SH2) domain-containing SHP1 and SHP2 enzymes, since recent reports have indicated major roles for these PTPs in the control of insulin action and glucose metabolism. Finally, the therapeutic potential of targeting PTPs for combating insulin resistance and alleviating T2D will be discussed.

Lactonases comprise a class of enzymes that hydrolyze lactones, including acyl-homoserine lactones (AHLs); the latter are used as chemical signaling molecules by numerous Gram-negative bacteria. Lactonases have therefore been demonstrated to quench AHL-based bacterial communication. In particular, lactonases are capable of inhibiting bacterial behaviors that depend on these chemicals, such as the formation of biofilms or the expression of virulence factors. A novel representative from the metallo-β-lactamase superfamily, named AaL, was isolated from the thermoacidophilic bacterium Alicyclobacter acidoterrestris. Kinetic characterization proves AaL to be a proficient lactonase, with catalytic efficiencies (k cat/K m) against AHLs in the region of 105 M −1 s−1. AaL exhibits a very broad substrate specificity. Its structure is expected to reveal the molecular determinants for its substrate binding and specificity, as well as to provide grounds for future protein-engineering projects. Here, the expression, purification, characterization, crystallization and X-ray diffraction data collection of AaL at 1.65 Å resolution are reported.

It is known that interfering with glycolysis leads to profound modification of cancer cell proliferation. However, energy production is not the major reason for this correlation. Here, using HeLa cells as a model for cancer, we demonstrate that phosphofructokinase-P (PFK-P), which is overexpressed in diverse types of cancer including HeLa cells, modulates expression of P44/42 mitogen-activated protein kinase (MAPK). Silencing of PFK-P did not alter HeLa cell viability or energy production, including the glycolytic rate. On the other hand, silencing of PFK-P induced the downregulation of p44/42 MAPK, augmenting the sensitivity of HeLa cells to different drugs. Conversely, overexpression of PFK-P promotes the upregulation of p44/42 MAPK, making the cells more resistant to the drugs. These results indicate that overexpression of PFK-P by cancer cells is related to activation of survival pathways via upregulation of MAPK and suggest PFK-P as a promising target for cancer therapy. J. Cell. Biochem. 118: 1216-1226, 2017. © 2016 Wiley Periodicals, Inc.

Lactonases are enzymes that are capable of hydrolyzing various lactones such as aliphatic lactones or acyl-homoserine lactones (AHLs), with the latter being used as chemical signaling molecules by numerous Gram-negative bacteria. Lactonases therefore have the ability to quench the chemical communication, also known as quorum sensing, of numerous bacteria, and in particular to inhibit behaviors that are regulated by this system, such as the expression of virulence factors or the production of biofilms. A novel representative from the metallo-β-lactamase superfamily, dubbed GcL, was isolated from the thermophilic bacteriumGeobacillus caldoxylosilyticus. Because of its thermophilic origin, GcL may constitute an interesting candidate for the development of biocontrol agents. Here, we show that GcL is a thermostable enzyme with a half-life at 75°C of 152.5 ± 10 min. Remarkably, it is also shown that GcL is among the most active lactonases characterized to date, with catalytic efficiencies (kcat/Km) against AHLs of greater than 106 M−1 s−1. The structure of GcL is expected to shed light on the catalytic mechanism of the enzyme and the molecular determinants for the substrate specificity in this class of lactonases. Here, the expression, purification, characterization, crystallization and X-ray diffraction data collection to 1.6 Å resolution of GcL are reported.

background: During the process of fertilization, human spermatozoa are confronted with phagocytic cells of the female reproductive tract. Part of this host mucosal barrier are immature dendritic cells (DCs), which play an important role in the defense of invading microbial pathogens. In the present study, we investigated the potential interaction of spermatozoa with DCs and raised the question of whether seminal plasma impacts the interaction of DCs with spermatozoa or pathogenic microbes. methods and results: Flow cytometry and microscopy detected a strong association between spermatozoa and human monocyte-derived DCs, which was partly mediated by the DC-specific adhesion receptor, DC-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN). Coincubation assays also showed that capture of spermatozoa by DCs was blocked in the presence of increasing concentrations of seminal plasma. This inhibitory effect of seminal plasma was accompanied by altered DC maturation, revealed by flow cytometry analysis of maturation-specific DC surface markers. Phalloidin-staining of the DC cytoskeleton further visualized an impact of seminal plasma on DC morphology. To elucidate the molecular nature of the inhibitory activity of seminal plasma on sperm –DC -association, binding assays were performed in the presence of individual seminal plasma components. This approach identified specific prostaglandins—in particular, PGEl, 19-OH-PGEl and PGE2, which are present in seminal plasma at high concentrations—as likely inhibitory factors. In contrast to glass beads, the yeast Candida albicans, a common commensal organism and frequent pathogen of the genital tract, was also found to be protected from capture by DCs in the presence of seminal plasma or the specific prostaglandins. conclusions: The immunomodulatory power of seminal plasma may help spermatozoa to circumvent the attack of DCs of the female reproductive tract, thereby supporting successful fertilization. At the same time, however, such protective effects of seminal plasma may also modulate DC action during host –pathogen interactions.

Bispyridylmethylamine–tyrosine–acrylamide ligands were prepared from protected tyrosine and dipyridylmethylamine by a twofold Mannich reaction and converted into acryl amides. Their manganese complexes were used as gel additives to increase the specific phosphate affinity in SDS–PAGE protein separations. The modified gel showed a distinct mobility shift of phosphorylated α-casein in comparison to the dephosphorylated protein.