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ABSTRACT Objective Tumour necrosis factor (TNF)‐α is a proinflammatory marker and has been shown to affect mitochondrial function in different tissues. We investigated the effect on adipose tissue (AT) inflammation and mitochondrial respiration in patients with hidradenitis suppurativa (HS) after 12 weeks of treatment with adalimumab, a TNF‐α inhibitor. Methods We sampled blood and an AT biopsy from 13 patients with HS and 10 control subjects after an overnight fast. The patients were retested after at least 12 weeks of treatment with adalimumab (40 mg/week). We measured macrophage content and mitochondrial respiration in the AT and interleukin (IL)‐1β, IL‐6, IL‐10, high‐sensitivity C‐reactive protein (hsCRP), interferon‐γ, TNF‐α, adiponectin and leptin in plasma. Clinical scores and Dermatology Quality of Life Index (DLQI) were assessed. Results We found a higher anti‐inflammatory macrophage content (CD206+) in the patient group compared with the control group, but no differences between before and after the intervention. No difference in mitochondrial respiration was observed. We observed higher plasma IL‐6 and hsCRP concentrations in patients with HS compared to controls, with no differences before and after the intervention. The difference between controls and HS patients was abolished after the intervention. HS patients improved their DLQI after the intervention with no change in clinical scores. Conclusion Treatment with adalimumab in patients with HS does not alter AT inflammation or mitochondrial respiratory capacity; however, we did see a higher content of anti‐inflammatory macrophages in the patient group compared with the control group.

Abstract Background Ten percent of the female population suffers from congenital abnormalities of the vagina, uterus, or oviducts, with severe consequences for reproductive and psychological health. Yet, the underlying causes of most of these malformations remain largely unknown. ADGRA3 (GPR125) is involved in WNT signaling and planar cell polarity, mechanisms vital to female reproductive tract development. Although ADGRA3 is a well-established spermatogonial stem cell marker, its role within the female urogenital system remains unclear. Results In this study, we found Adgra3 to be expressed throughout the murine female urogenital system, with higher expression pre-puberty than after sexual maturation. We generated a global Adgra3 −/− mouse line and observed imperforate vagina in 44% of Adgra3 −/− females, resulting in distension of the reproductive tract and infertility. Ovarian morphology, plasma estradiol, ovarian Cyp19a1, and vaginal estrogen receptor α (Esr1) expression were unaffected. However, compared to controls, a significantly lower bone mineral density was found in Adgra3 −/− mice. Whereas vaginal opening in mice is an estrogen-dependent process, 17β-estradiol treatment failed to induce vaginal canalization in Adgra3 −/− mice. Furthermore, a marked reduction in vaginal and ovarian progesterone receptor expression was observed concomitant with an upregulation of apoptotic regulators Bcl2, Bid, and Bmf in adult Adgra3 −/− females with a closed vagina. Conclusions Our collective results shed new insights into the complex mechanisms by which the adhesion receptor ADGRA3 regulates distal vaginal tissue remodeling during vaginal canalization via altered sex hormone responsiveness and balance in apoptotic regulators. This highlights the potential of ADGRA3 as a target in diagnostic screening and/or therapy for obstructive vaginal malformations in humans.

Cryptostegia grandiflora and C. madagascariensis (Apocynaceae) are the only two species of this Madagascan plant genus. Both have been transported around the world as ornamentals due to their attractive flowers and based on a perceived potential as sources of rubber – hence, the common name rubber vine – because of their copious latex, which also contains toxic cardiac glycosides. As a result of their vigorous growth and ability to climb over and smother vegetation, both species have become invasive, posing an actual or potential threat to native ecosystems in many tropical and sub-tropical countries, as well as to human and animal health. Classical biological control (CBC), or the introduction of co-evolved natural enemies to control an invasive alien species in its exotic range, has successfully been used to tackle C. grandiflora in northern Queensland, Australia. This strategy is currently being evaluated for its suitability to manage C. madagascariensis in north-eastern Brazil using the same Madagascan rust fungus, Maravalia cryptostegiae, released as a CBC agent in Australia. For CBC to be successful, it is critical to understand the taxonomy of the invader as well as the origin(s) of its weedy biotype(s) in order to select the best-matched co-evolved natural enemies. Based on an exhaustive search in published and unpublished sources, we summarise the taxonomy and uses of these rubber vines, follow their historical movements and track their earliest records and current weed status in more than 80 countries and territories around the world.

Abstract Purpose The role of locoregional therapy compared to systemic chemotherapy (SYS) for unresectable intrahepatic cholangiocarcinoma (IHC) remains controversial. The importance of hepatic disease control, either as initial or salvage therapy, is also unclear. We compared overall survival (OS) in patients treated with resection, hepatic arterial infusion pump (HAIP) chemotherapy, or SYS as it relates to hepatic recurrence or progression. We also evaluated recurrence after resection to determine the efficacy of locoregional salvage therapy. Patients and Methods In this single‐institution retrospective analysis, patients with biopsy‐proven IHC treated with either curative‐intent resection, HAIP (with or without SYS), or SYS alone were analyzed. Propensity score matching (PSM) was used to compare patients with liver‐limited, advanced disease treated with HAIP versus SYS. The impact of locoregional salvage therapies in patients with liver‐limited recurrence was analyzed in the resection cohort. Results From 2000 to 2017, 714 patients with IHC were treated, 219 (30.7%) with resectable disease, 316 (44.3%) with locally advanced disease, and 179 (25.1%) with metastatic disease. Resected patients were less likely to recur or progress in the liver (hazard ratio [HR] 0.41, 95% CI 0.34–0.45) versus those that received HAIP or SYS (HR 0.58, 95% CI 0.50–0.65 vs. HR 0.63, 95% CI 0.57–0.69, respectively). In resected patients, 161 (64.4%) recurred, with 65 liver‐only recurrences. Thirty of these patients received subsequent locoregional therapy. On multivariable analysis, locoregional therapy was associated with improved OS after isolated liver recurrence (HR 0.46, 95% CI 0.29–0.75; p = 0.002). In patients with locally advanced unresectable or multifocal liver disease (with or without distant organ metastases), PSM demonstrated improved hepatic progression‐free survival in patients treated with HAIP versus SYS (HR 0.65; 95% CI 0.46–0.91; p = 0.01), which correlated with improved OS (HR 0.59, 95% CI 0.43–0.80; p

Since the arrival of DNA nanotechnology nearly 40 years ago, the field has progressed from its beginnings of envisioning rather simple DNA structures having a branched, multi-strand architecture into creating beautifully complex structures comprising hundreds or even thousands of unique strands, with the possibility to exactly control the positions down to the molecular level. While the earliest construction methodologies, such as simple Holliday junctions or tiles, could reasonably be designed on pen and paper in a short amount of time, the advent of complex techniques, such as DNA origami or DNA bricks, require software to reduce the time required and propensity for human error within the design process. Where available, readily accessible design software catalyzes our ability to bring techniques to researchers in diverse fields and it has helped to speed the penetration of methods, such as DNA origami, into a wide range of applications from biomedicine to photonics. Here, we review the historical and current state of CAD software to enable a variety of methods that are fundamental to using structural DNA technology. Beginning with the first tools for predicting sequence-based secondary structure of nucleotides, we trace the development and significance of different software packages to the current state-of-the-art, with a particular focus on programs that are open source.

The Complete College Tennessee Act (CCTA) established benchmarks for increasing state college completion rates to the national average by 2025. This investigation explored responses on the High School Senior Opinion Survey to identify trends between two subpopulations for strategic enrollment management (SEM)--Latino American and African American students. Findings are discussed within the framework of Astin's (1991; 2012) Input-Environment-Output theory.

GABAB receptors mediate the effects of the main inhibitory neurotransmitter in the brain. Here, authors identify the cytoskeletal protein filamin A as a key player that controls the exact location and function of GABAB receptors at the cell surface.

Objective: Tumour necrosis factor (TNF)‐α is a proinflammatory marker and has been shown to affect mitochondrial function in different tissues. We investigated the effect on adipose tissue (AT) inflammation and mitochondrial respiration in patients with hidradenitis suppurativa (HS) after 12 weeks of treatment with adalimumab, a TNF‐α inhibitor. Methods: We sampled blood and an AT biopsy from 13 patients with HS and 10 control subjects after an overnight fast. The patients were retested after at least 12 weeks of treatment with adalimumab (40 mg/week). We measured macrophage content and mitochondrial respiration in the AT and interleukin (IL)‐1β, IL‐6, IL‐10, high‐sensitivity C‐reactive protein (hsCRP), interferon‐γ, TNF‐α, adiponectin and leptin in plasma. Clinical scores and Dermatology Quality of Life Index (DLQI) were assessed. Results: We found a higher anti‐inflammatory macrophage content (CD206+) in the patient group compared with the control group, but no differences between before and after the intervention. No difference in mitochondrial respiration was observed. We observed higher plasma IL‐6 and hsCRP concentrations in patients with HS compared to controls, with no differences before and after the intervention. The difference between controls and HS patients was abolished after the intervention. HS patients improved their DLQI after the intervention with no change in clinical scores. Conclusion: Treatment with adalimumab in patients with HS does not alter AT inflammation or mitochondrial respiratory capacity; however, we did see a higher content of anti‐inflammatory macrophages in the patient group compared with the control group. [ABSTRACT FROM AUTHOR]

After many decades of effective control of stem rust caused by the Puccinia graminis f.sp. tritici, (hereafter Pgt) the reported emergence of race TTKSK/ Ug99 of Pgt in Uganda reignited concerns about epidemics worldwide because ∼90% of world wheat cultivars had no resistance to the new race. Since it was initially detected in Uganda in 1998, Ug99 variants have now been identified in thirteen countries in Africa and the Middle East. Stem rust has been a major problem in the past, and concern is increasing about the risk of return to Central and East Asia. Whilst control programs in North America and Europe relied on the use of resistant cultivars in combination with eradication of barberry ( Berberis spp .), the alternate host required for the stem rust pathogen to complete its full lifecycle, the focus in East Asia was principally on the use of resistant wheat cultivars. Here, we investigate potential airborne transmission pathways for stem rust outbreaks in the Middle East to reach East Asia using an integrated modelling framework combining estimates of fungal spore deposition from an atmospheric dispersion model, environmental suitability for spore germination, and crop calendar information. We consider the role of mountain ranges in restricting transmission pathways, and we incorporate a representation of a generic barberry species into the lifecycle. We find viable transmission pathways to East Asia from the Middle East to the north via Central Asia and to the south via South Asia and that an initial infection in the Middle East could persist in East Asia for up to three years due to the presence of the alternate host. Our results indicate the need for further assessment of barberry species distributions in East Asia and appropriate methods for targeted surveillance and mitigation strategies should stem rust incidence increase in the Middle East region.

Understanding the molecular and phenotypic profile of colorectal cancer (CRC) in West Africa is important for early detection and treatment. Here, the authors use a multigene next-generation sequencing panel to identify genomic differences in Nigerian CRCs compared to those from TCGA and MSKCC cohorts.

Abstract Peptides are notoriously known to display very short in vivo half-lives often measured in minutes which in many cases greatly reduces or eliminates sufficient in vivo efficacy. To obtain long half-lives allowing for up to once-weekly dosing regimen, fatty acid acylation (lipidation) have been used to non-covalently associate the peptide to serum albumin thus serving as a circulating depot. This approach is generally considered in the scientific and patent community as a standard approach to protract almost any given peptide. However, it is not trivial to prolong the half-life of peptides by lipidation and still maintain high potency and good formulation properties. Here we show that attaching a fatty acid to the obesity-drug relevant peptide PYY3-36 is not sufficient for long pharmacokinetics (PK), since the position in the backbone, but also type of fatty acid and linker strongly influences PK and potency. Furthermore, understanding the proteolytic stability of the backbone is key to obtain long half-lives by lipidation, since backbone cleavage still occurs while associated to albumin. Having identified a PYY analogue with a sufficient half-life, we show that in combination with a GLP-1 analogue, liraglutide, additional weight loss can be achieved in the obese minipig model.

Anhand von zwei Spiel- und einem Dokumentarfilm setzt sich der Beitrag mit der filmischen Inszenierung sozialer Im/Mobilität auseinander. Den Ausgangspunkt bildet die These, dass das meritokratische Versprechen eines sozialen Aufstiegs durch Leistung im Kino der Gegenwart irritiert und auf unterschiedliche Weise hinterfragt und problematisiert wird. Nicht nur die Inhalte der Filme, sondern auch die formale Gestaltung weisen ein Spannungsverhältnis zwischen linearen, narrativen Verläufen und szenischen Gefügen auf, das wir anhand der Filme Parasite (Südkorea 2019, Regie: Bong Joon-ho,), Hillbilly Elegy (USA 2020, Regie: Ron Howard) und Jetzt oder Morgen? (Österreich 2020, Regie: Lisa Weber) untersuchen. Methodisch lässt sich der Beitrag von den affekttheoretischen Thesen der Kultur- und Literaturwissenschaftlerin Lauren Berlants anleiten, die sie in ihrem 2011 erschienenen Buch Cruel Optimism entwickelt hat.

Abstract Various bioactive food compounds may confer health and longevity benefits, possibly through altering or preserving the epigenome. While bioactive food compounds are widely being marketed for human consumption as ‘improving health and longevity’ by counteracting harmful effects of poor nutrition and lifestyle, claimed effects are often not adequately documented. Using the honey bee (Apis mellifera) as a model species, we here employed a multi-step screening approach to investigate seven compounds for effects on lifespan and DNA methylation using ELISA and whole genome bisulfite sequencing (WGBS). A positive longevity effect was detected for valproic acid, isovaleric acid, and cyanocobalamin. For curcumin, we found that lifespan shortening caused by ethanol intake, was restored when curcumin and ethanol were co-administered. Furthermore, we identified region specific DNA methylation changes as a result of ethanol intake. Ethanol specific changes in DNA methylation were fully or partially blocked in honey bees receiving ethanol and curcumin together. Ethanol-affected and curcumin-blocked differentially methylated regions covered genes involved in fertility, temperature regulation and tubulin transport. Our results demonstrate fundamental negative effects of low dose ethanol consumption on lifespan and associated DNA methylation changes and present a proof-of-principle on how longevity and DNA methylation changes can be negated by the bioactive food component curcumin. Our findings provide a fundament for further studies of curcumin in invertebrates.

In April 2001 a rock fall at the Lärchberg-Galgenwald with boulders of several cubic meters in size did occur, which reached until the 50 to 70 m wide apron of the Federal Highway B96. This event triggered the installation of a fivemeter-high protective dam and the start of a geodetic monitoring program based on rope extensometer measurements and a geodetic survey. This study area is used to test further methods of image processing-based monitoring and to show the advantages and disadvantages with the focus on the main area of the landslide. The two technologies used are structure-from-motion (SfM) and terrestrial laser scanning technology. Both systems work through contactless data acquisition by active and passive recording processes. A data set in the form of a point cloud and a digital surface model with a grid size of 10 cm, which are checked for accuracy on the basis of measured control points, was created across all methods. As a further approach, the fusion of the point clouds from the flight using an unmanned aerial vehicle (UAV) and the laser scan point clouds was carried out.

Abstract Background The aim of this study was to examine feasibility of trial processes and group-based, structured exercise training in patients with first-episode psychosis. Methods Twenty-five patients with first-episode psychosis took part in a two-arm randomised feasibility trial. They were individually randomised (1:1) via a computer-generated randomisation sequence and allocated to either an exercise intervention group (INT) or a control group (CON). Patients allocated to INT completed a physical exercise training programme at moderate-to-vigorous intensity, 1 h three times weekly for 8 weeks. CON patients were encouraged to continue their usual level of activity and were offered the training programme after 8 weeks. Primary outcomes included screening rate, recruitment rate, retention rate, attendance and adverse events. Secondary outcomes included heart rate response during training, cardiovascular health (VO2max, resting heart rate, blood pressure), body composition (muscle mass, fat percentage), muscle strength (sit-to-stand, grip strength, jump height) and balance. Results Recruitment lasted 6 weeks and 86 out of 324 patients (27%) were screened, 71 of whom (83%) were deemed eligible. Twenty-five (35%) accepted inclusion (mean age 25.5; mean body mass index 25.1) and were subsequently randomised (INT = 13, CON = 12). Retention of patients was 76% and 52% at the 8-week and 16-week follow-up, respectively. Attendance was 43% (min. 9%, max. 96%). No significant changes were observed between groups in secondary physiological outcome measures. Conclusions Feasibility was challenged by limited recruitment and retention rates, suggesting that modifications are required if a large-scale randomised controlled trial is to be conducted. Recommendations for modifications are presented and discussed. Trial registration Clinicaltrials.gov, NCT03409393 . Retrospectively registered.