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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.

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.

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.

Abstract Background Increased bone turnover is frequently observed in advanced cancer and predominantly related to bone metastases or therapy. Cachexia represents an important cause of morbidity and mortality in cancer patients. Key features are weight loss, muscle wasting and chronic inflammation, which induce profound metabolic changes in several organs, including the bone. However, whether cachexia contributes to abnormal bone metabolism in cancer patients is unknown. Aim of the present study was to determine the potential correlation of bone turnover markers with body composition and laboratory parameters in treatment-naïve cancer patients. Methods In this cross-sectional study we measured the levels of carboxy terminal telopeptide of collagen (CTX), an indicator of bone resorption, as well as osteocalcin (Ocn) and procollagen type I N-terminal propeptide (PINP), indicators of bone formation, in 52 cancer patients and correlated with body composition and laboratory parameters. Univariate and multivariate logistic analysis were performed to identify determinants of negative bone remodeling balance, estimated by CTX/Ocn and CTX/PINP ratio. Results Based on weight loss, body mass index and muscle mass, patients were divided into a cachectic (59.6%) and a control (40.4%) group. After correcting for the presence of bone metastases, our results showed a significant upregulation of CTX in cachectic patients compared to non-cachectic cancer patients (median 0.38 vs 0.27 ng/mL, p

Objective: Parathyroid hormone (PTH) is a key hormone in regulation of calcium homeostasis and its secretion is regulated by calcium. Secretion of PTH is attenuated during intake of nutrients, but the underlying mechanism(s) are unknown. We hypothesized that insulin acts as an acute regulator of PTH secretion. Methods: Intact PTH was measured in plasma from patients with T1D and matched healthy individuals during 4-h oral glucose tolerance tests (OGTT) and isoglycemic i.v. glucose infusions on 2 separate days. In addition, expression of insulin receptors on surgical specimens of parathyroid glands was assessed by immunochemistry (IHC) and quantitative PCR (qPCR). Results: The inhibition of PTH secretion was more pronounced in healthy individuals compared to patients with T1D during an OGTT (decrementalAUC0–240min: −5256 ± 3954 min × ng/L and −2408 ± 1435 min × ng/L, P = 0.030). Insulin levels correlated significantly and inversely with PTH levels, also after adjusting for levels of several gut hormones and BMI (P = 0.002). Expression of insulin receptors in human parathyroid glands was detected by both IHC and qPCR. Conclusion: Our study suggests that insulin may act as an acute regulator of PTH secretion in humans.

Rock glaciers are creep phenomena of mountain permafrost. Speed-up has been observed on several rock glaciers in recent years and attributed to climate change. Although rare, related long-term studies are nevertheless essential to bring a climate perspective to creep velocity changes. In the present study, we focused on changes both in the surface creep velocity and volume of the Leibnitzkopf rock glacier (Hohe Tauern Range, Austria) in the period 1954–2020. We applied 3D change detection using aerial images of both conventional (12 epochs between 1954 and 2018) and unmanned aerial vehicle (UAV)-based aerial surveys (2 epochs, 2019 and 2020), and combined this with ground and air temperature data. Photogrammetric processing (structure-from-motion, multi-view stereo) of the multi-temporal dataset resulted in high-resolution digital orthophotos/DOPs (5–50 cm spatial resolution) and digital elevation models/DEMs (10–50 cm grid spacing). Georeferencing was supported by five externally triangulated images from 2018, bi-temporal aerial triangulation of the image data relying on stable ground around the rock glacier, measured ground control points (2019 and 2020), and measured camera locations (PPK-GNSS) of the UAV flight in 2020. 2D displacement vectors based on the multi-temporal DOPs and/or DEMs were computed. Accuracy analyses were conducted based on geodetic measurements (2010–2020) and airborne laser scanning data (2009). Our analyses show high multi-annual and inter-annual creep velocity variabilities with maxima between 12 (1974–1981) and 576 cm/year (2019–2020), always detected in the same area of the rock glacier where surface disintegration was first observed in 2018. Our volume change analyses of the entire landform for the period 1954–2018 do not indicate any significant changes. This suggests little permafrost ice melt and/or general low ice content of the rock glacier. Analyses of the temperature data reveal a close relationship between higher temperatures and rock glacier acceleration despite the high probability of low ice content. This suggests that hydrogeological changes play an important role in the rock glacier system. The paper concludes with a summary of technical improvements and recommendations useful for rock glacier monitoring and a general view on the kinematic state of the Leibnitzkopf rock glacier.

In this paper we present a reconstruction of the kinematics of the Tschadinhorn rock glacier using multi-temporal conventional (metric) aerial photographs (1954–2015) and additional non-metric aerial photographs (2016, 2017) taken with in-house unmanned aerial vehicles (UAVs). A rotary-wing aircraft (hexacopter twinHEX v.3.0) was used in 2016 and a fixed-wing aircraft (QuestUAV) in 2017. The historical image data was acquired from the Austrian Federal Office of Metrology and Surveying (BEV). Both a digital orthophoto (DOP) and a digital terrain model (DTM) were computed for each given epoch. Precise georeferencing of the image data was carried out in the Austrian Gauss-Krüger M31 coordinate system using available aerotriangulations (ATs) of BEV and additional ground control points (GCPs) measured geodetically during both UAV campaigns. Change detection analysis provided multi-temporal 2D flow velocity fields. Subsequently, these data were collated to produce a simpler velocity graph showing clearly the temporal evolution of the flow velocity of Tschadinhorn rock glacier: A maximum mean annual flow velocity of 3.28 m/year was obtained for 2014–2015, while the lowest annual flow velocity of 0.16 m/year was observed for 1969–1974. The velocity graph also revealed that 1954–2009 was characterized by generally moderate activity (0.16 – 0.79 m/year) and that much higher flow velocities have prevailed since 2009. The present value for 2016–2017 is 1.92 m/year.

Background Amplification of the MYCN oncogene is a molecular hallmark of aggressive neuroblastoma (NB), a childhood cancer of the sympathetic nervous system. There is evidence that MYCN promotes a non-inflamed and T-cell infiltration-poor (‘cold’) tumor microenvironment (TME) by suppressing interferon signaling. This may explain, at least in part, why patients with NB seem to have little benefit from single-agent immune checkpoint blockade (ICB) therapy. Targeting MYCN or its effectors could be a strategy to convert a cold TME into a ‘hot’ (inflamed) TME and improve the efficacy of ICB therapy.Methods NB transcriptome analyses were used to identify epigenetic drivers of a T-cell infiltration-poor TME. Biological and molecular responses of NB cells to epigenetic drugs and interferon (IFN)-γ exposure were assessed by proliferation assays, immunoblotting, ELISA, qRT-PCR, RNA-seq and ChIP-qPCR as well as co-culture assays with T cells.Results We identified H3K9 euchromatic histone-lysine methyltransferases EHMT2 and EHMT1, also known as G9a and GLP, as epigenetic effectors of the MYCN-driven malignant phenotype and repressors of IFN-γ transcriptional responses in NB cells. EHMT inhibitors enhanced IFN-γ-induced expression of the Th1-type chemokines CXCL9 and CXCL10, key factors of T-cell recruitment into the TME. In MYCN-amplified NB cells, co-inhibition of EZH2 (enhancer of zeste homologue 2), a H3K27 histone methyltransferase cooperating with EHMTs, was needed for strong transcriptional responses to IFN-γ, in line with histone mark changes at CXCL9 and CXCL10 chemokine gene loci. EHMT and EZH2 inhibitor response gene signatures from NB cells were established as surrogate measures and revealed high EHMT and EZH2 activity in MYCN-amplified high-risk NBs with a cold immune phenotype.Conclusion Our results delineate a strategy for targeted epigenetic immunomodulation of high-risk NBs, whereby EHMT inhibitors alone or in combination with EZH2 inhibitors (in particular, MYCN-amplified NBs) could promote a T-cell-infiltrated TME via enhanced Th1-type chemokine expression.

Abstract Objective Drugs increase fall risk and decrease performance on balance and mobility tests. Conversely, whether biofeedback training to reduce fall risk also decreases scores on a published drug-based fall risk index has not been documented. Forty-eight community-dwelling older adults underwent either treadmill gait training plus visual feedback (+VFB), or walked on a treadmill without feedback. The Quantitative Drug Index (QDI) was derived from each participant’s drug list and is based upon all cause drug-associated fall risk. Analysis of covariance assessed changes in the QDI during the study, and data is presented as mean ± standard error of the mean. Results The QDI scores decreased significantly (p = 0.031) for participants receiving treadmill gait training +VFB (− 0.259 ± 0.207), compared to participants who walked on the treadmill without VFB (0.463 ± 0.246). Changes in participants QDI scores were dependent in part upon their age, which was a significant covariate (p = 0.007). These preliminary results demonstrate that rehabilitation to reduce fall risk may also decrease use of drugs associated with falls. Determination of which drugs or drug classes that contribute to the reduction in QDI scores for participants receiving treadmill gait training +VFB, compared to treadmill walking only, will require a larger participant investigation. Trial Registration ISRNCT01690611, ClinicalTrials.gov #366151-1, initial 9/24/2012, completed 4/21/2016

Rock glaciers are creep phenomena of mountain permafrost. Typically, these landforms look like lava flows from a bird’s eye view. Active rock glaciers move downslope with flow velocities in the range of few centimeters to several meters per year. Thus, large masses of rock and ice can be gradually transported down-valley. In this paper we present a comparative study analyzing surface change for Tschadinhorn rock glacier, a relatively fast moving rock glacier located in the Hohe Tauern Range of the Austrian Alps. Aerial photographs (1954–2017) of both metric (conventional) and non-metric (UAV-based) aerial surveys were compared to derive multi-annual to annual flow vector fields and surface height change. For each time interval given we computed a single representative value for flow velocity and, if applicable, also for area-wide surface height change, i.e. volume change. The velocity graph obtained represents the temporal evolution of the kinematics of the rock glacier with good discrimination. Volume change was difficult to quantify since temporal changes were rather small and close to insignificance. The precision and accuracy of the results obtained were numerically quantified. Our study showed that for the Tschadinhorn rock glacier UAV-based aerial surveys can substitute conventional aerial surveys as carried out by national mapping agencies, such as the Austrian Federal Office of Metrology and Surveying (BEV). Thus, UAV-based aerial surveys can help to bridge the data gap between regular aerial surveys. The high accuracy of the UAV-derived results would even allow intra-annual change detection of flow velocity.

Abstract Background Cyclooxygenase (COX) activity is increased in endoscopic normal colonic mucosa from patients with colorectal neoplasia (CRN). COX-2 is thought to be the predominant COX isozyme involved in neoplasia. Meanwhile, relative contributions of COX-1 and COX-2 isoforms are unknown. Knowledge about their mutual activity in colonic mucosa is important for diagnostics and targeted therapy for CRN. The aim of this study was to assess the relative function, expression and localization of COX-1 and COX-2 enzymes in colonic non-neoplastic human mucosa and thereby to potentially reveal a mucosal disease predisposition for better treatment. Methods Biopsies were pinched from normal appearing colonic mucosa in patients undergoing endoscopy. Ussing chamber technique was applied for an indirect assessment of epithelial activity, RT-qPCR for expression and immunohistochemistry for localization of COX-1 and COX-2 enzymes in patients without (ctrls) and with a history of CRN (CRN-pts). Results Combined COX-1 and COX-2 activity was higher in CRN-pts, p = 0.036. COX-2 was primarily localized in absorptive cells, while COX-1 appeared to be restricted to nonenteroendocrine tuft cells of the colonic epithelium. Conclusions In biopsies from endoscopic normal appearing colonic mucosa, combined activity of COX-1 and COX-2 enzymes is increased in CRN-pts compared with ctrls. This indicates that COX-1 and COX-2 together contribute to an increased proliferation process. Of note, in colonic epithelial cell lining, the COX-1 enzyme seems localized in tuft cells.

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.