Publications by authors named "S Strauss"

846 Publications

In-Vitro Application of Magnetic Hybrid Niosomes: Targeted siRNA-Delivery for Enhanced Breast Cancer Therapy.

Pharmaceutics 2021 Mar 16;13(3). Epub 2021 Mar 16.

Institute for Particle Technology, Technische Universität Braunschweig, 38104 Braunschweig, Germany.

Even though the administration of chemotherapeutic agents such as erlotinib is clinically established for the treatment of breast cancer, its efficiency and the therapy outcome can be greatly improved using RNA interference (RNAi) mechanisms for a combinational therapy. However, the cellular uptake of bare small interfering RNA (siRNA) is insufficient and its fast degradation in the bloodstream leads to a lacking delivery and no suitable accumulation of siRNA inside the target tissues. To address these problems, non-ionic surfactant vesicles (niosomes) were used as a nanocarrier platform to encapsulate Lifeguard (LFG)-specific siRNA inside the hydrophilic core. A preceding entrapment of superparamagnetic iron-oxide nanoparticles (FeO-NPs) inside the niosomal bilayer structure was achieved in order to enhance the cellular uptake via an external magnetic manipulation. After verifying a highly effective entrapment of the siRNA, the resulting hybrid niosomes were administered to BT-474 cells in a combinational therapy with either erlotinib or trastuzumab and monitored regarding the induced apoptosis. The obtained results demonstrated that the nanocarrier successfully caused a downregulation of the LFG gene in BT-474 cells, which led to an increased efficacy of the chemotherapeutics compared to plainly added siRNA. Especially the application of an external magnetic field enhanced the internalization of siRNA, therefore increasing the activation of apoptotic signaling pathways. Considering the improved therapy outcome as well as the high encapsulation efficiency, the formulated hybrid niosomes meet the requirements for a cost-effective commercialization and can be considered as a promising candidate for future siRNA delivery agents.
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http://dx.doi.org/10.3390/pharmaceutics13030394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002368PMC
March 2021

Genetic containment in vegetatively propagated forest trees: CRISPR disruption of LEAFY function in Eucalyptus gives sterile indeterminate inflorescences and normal juvenile development.

Plant Biotechnol J 2021 Mar 27. Epub 2021 Mar 27.

Department of Forest Ecosystems and Society, Oregon State University, Corvallis, OR, 97331, USA.

Eucalyptus is among the most widely planted taxa of forest trees worldwide. However, its spread as an exotic or genetically engineered form can create ecological and social problems. To mitigate gene flow via pollen and seeds, we mutated the Eucalyptus ortholog of LEAFY (LFY) by transforming a Eucalyptus grandis x urophylla hybrid and two Flowering Locus T (FT) overexpressing (and flowering) lines with CRISPR Cas9 targeting its LFY ortholog, ELFY. We achieved high rates of elfy biallelic knock-outs, often approaching 100% of transgene insertion events. Frameshift mutations and deletions removing conserved amino acids caused strong floral alterations, including indeterminacy in floral development and an absence of male and female gametes. These mutants were otherwise visibly normal and did not differ statistically from transgenic controls in juvenile vegetative growth rate or leaf morphology in greenhouse trials. Genes upstream or near to ELFY in the floral development pathway were overexpressed, whereas floral organ identity genes downstream of ELFY were severely depressed. We conclude that disruption of ELFY function appears to be a useful tool for sexual containment, without causing statistically significant or large adverse effects on juvenile vegetative growth or leaf morphology.
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http://dx.doi.org/10.1111/pbi.13588DOI Listing
March 2021

Quantitative assessment of labeling probes for super-resolution microscopy using designer DNA nanostructures.

Chemphyschem 2021 Mar 15. Epub 2021 Mar 15.

Max Planck Institute of Biochemistry, Molecular Imaging and Bionanotechnology, Am Klopferspitz 18, 82152, Martinsried, GERMANY.

Improving labeling probes for state-of-the-art super-resolution microscopy is becoming of major importance. However, there is currently a lack of tools to quantitatively evaluate probe performance regarding efficiency, precision, and achievable resolution in an unbiased yet modular fashion. Here, we introduce designer DNA origami structures combined with DNA-PAINT to overcome this issue and evaluate labeling efficiency, precision, and quantification using antibodies and nanobodies as exemplary labeling probes. While current assessment of binders is mostly qualitative, e.g. based on an expected staining pattern, we here present a quantitative analysis platform of the antigen labeling efficiency and achievable resolution, allowing researchers to choose the best performing binder. The platform can furthermore be readily adapted for discovery and precise quantification of a large variety of additional labeling probes.
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http://dx.doi.org/10.1002/cphc.202100185DOI Listing
March 2021

Genome size evolution is associated with climate seasonality and glucosinolates, but not life history, soil nutrients or range size, across a clade of mustards.

Ann Bot 2021 Mar 1. Epub 2021 Mar 1.

Centre for Population Biology, and Department of Evolution of Ecology, University of California. One Shields Avenue, Davis, CA, USA.

Background And Aims: We investigate patterns of evolution of genome size across a morphologically and ecologically diverse clade of Brassicaceae, in relation to ecological and life history traits. While numerous hypotheses have been put forward regarding autecological and environmental factors that could favour small versus large genomes, a challenge in understanding genome size evolution in plants is that many hypothesized selective agents are intercorrelated.

Methods: We contribute genome size estimates for 47 species of Streptanthus Nutt. and close relatives, and take advantage of many data collections for this group to assemble data on climate, life history, soil affinity and composition, geographic range, and plant secondary chemistry to identify simultaneous correlates of variation in genome size in an evolutionary framework. We assess models of evolution across clades and use phylogenetically informed analyses as well as model selection and information criteria approaches to identify variables that can best explain genome size variation in this clade.

Key Results: We find differences in genome size and heterogeneity in its rate of evolution across subclades of Streptanthus and close relatives. We show that clade-wide genome size is positively associated with climate seasonality and glucosinolate compounds. Model selection and information criteria approaches identify a best model that includes temperature seasonality and fraction of aliphatic glucosinolates, suggesting a possible role of genome size in climatic adaptation or a role for biotic interactions in shaping the evolution of genome size. We find no evidence supporting hypotheses of life history, range size, or soil nutrients as forces shaping genome size in this system.

Conclusions: Our findings suggest climate seasonality and biotic interactions as potential forces shaping the evolution of genome size and highlight the importance of evaluating multiple factors in the context of phylogeny to understand possible selective agents on genome size.
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http://dx.doi.org/10.1093/aob/mcab028DOI Listing
March 2021

Vegetative phase change in Populus tremula × alba.

New Phytol 2021 Mar 3. Epub 2021 Mar 3.

Department of Biology, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Plants transition through juvenile and adult phases of vegetative development in a process known as vegetative phase change (VPC). In poplars (genus Populus) the differences between these stages are subtle, making it difficult to determine when this transition occurs. Previous studies of VPC in poplars have relied on plants propagated in vitro, leaving the natural progression of this process unknown. We examined developmental morphology of seed-grown and in vitro derived Populus tremula × alba (clone 717-1B4), and compared the phenotype of these to transgenics with manipulated miR156 expression, the master regulator of VPC. In seed-grown plants, most traits changed from node-to-node during the first 3 months of development but remained constant after node 25. Many traits remained unchanged in clones over-expressing miR156, or were enhanced when miR156 was lowered, demonstrating their natural progression is regulated by the miR156/SPL pathway. The characteristic leaf fluttering of Populus is one of these miR156-regulated traits. Vegetative development in plants grown from culture mirrored that of seed-grown plants, allowing direct comparison between plants often used in research and those found in nature. These results provide a foundation for further research on the role of VPC in the ecology and evolution of this economically important genus.
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http://dx.doi.org/10.1111/nph.17316DOI Listing
March 2021

Tactile acuity of fingertips and hand representation size in human Area 3b and Area 1 of the primary somatosensory cortex.

Neuroimage 2021 Feb 27;232:117912. Epub 2021 Feb 27.

Functional Imaging Unit, Center for Diagnostic Radiology, University Medicine of Greifswald, Walther-Rathenau-Str.46, D-17475 Greifswald, Germany. Electronic address:

Intracortical mapping in monkeys revealed a full body map in all four cytoarchitectonic subdivisions of the contralateral primary somatosensory cortex (S1), as well as positive associations between spatio-tactile acuity performance of the fingers and their representation field size especially within cytoarchitectonic Area 3b and Area 1. Previous non-invasive investigations on these associations in humans assumed a monotonous decrease of representation field size from index finger to little finger although the field sizes are known to change in response to training or in disease. Recent developments improved noninvasive functional mapping of S1 by a) adding a cognitive task during repetitive stimulation to decrease habituation to the stimuli, b) smaller voxel size of fMRI-sequences, c) surface-based analysis accounting for cortical curvature, and d) increase of spatial specificity for fMRI data analysis by avoidance of smoothing, partial volume effects, and pial vein signals. We here applied repetitive pneumatic stimulation of digit 1 (D1; thumb) and digit 5 (D5; little finger) on both hands to investigate finger/hand representation maps in the complete S1, but also in cytoarchitectonic Areas 1, 2, 3a, and 3b separately, in 21 healthy volunteers using 3T fMRI. The distances between activation maxima of D1 and D5 were evaluated by two independent raters, blinded for performance parameters. The fingertip representations showed a somatotopy and were localized in the transition region between the crown and the anterior wall of the post central gyrus agreeing with Area 1 and 3b. Participants were comprehensively tested for tactile performance using von Freyhair filaments to determine cutaneous sensory thresholds (CST) as well as grating orientation thresholds (GOT) and two-point resolution (TPD) for spatio-tactile acuity testing. Motor performance was evaluated with pinch grip performance (Roeder test). We found bilateral associations of D1-D5 distance for GOT thresholds and partially also for TPD in Area 3b and in Area 1, but not if using the complete S1 mask. In conclusion, we here demonstrate that 3T fMRI is capable to map associations between spatio-tactile acuity and the fingertip representation in Area 3b and Area 1 in healthy participants.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117912DOI Listing
February 2021

Direct supercritical angle localization microscopy for nanometer 3D superresolution.

Nat Commun 2021 02 19;12(1):1180. Epub 2021 Feb 19.

Cell Biology and Biophysics, European Molecular Biology Laboratory, Heidelberg, Germany.

3D single molecule localization microscopy (SMLM) is an emerging superresolution method for structural cell biology, as it allows probing precise positions of proteins in cellular structures. In supercritical angle localization microscopy (SALM), z-positions of single fluorophores are extracted from the intensity of supercritical angle fluorescence, which strongly depends on their distance to the coverslip. Here, we realize the full potential of SALM and improve its z-resolution by more than four-fold compared to the state-of-the-art by directly splitting supercritical and undercritical emission, using an ultra-high NA objective, and applying fitting routines to extract precise intensities of single emitters. We demonstrate nanometer isotropic localization precision on DNA origami structures, and on clathrin coated vesicles and microtubules in cells, illustrating the potential of SALM for cell biology.
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http://dx.doi.org/10.1038/s41467-021-21333-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896076PMC
February 2021

EARLY BUD-BREAK 1 and EARLY BUD-BREAK 3 control resumption of poplar growth after winter dormancy.

Nat Commun 2021 02 18;12(1):1123. Epub 2021 Feb 18.

College of Forest Resources and Environmental Science, Michigan Technological University, Houghton, MI, USA.

Bud-break is an economically and environmentally important process in trees and shrubs from boreal and temperate latitudes, but its molecular mechanisms are poorly understood. Here, we show that two previously reported transcription factors, EARLY BUD BREAK 1 (EBB1) and SHORT VEGETATIVE PHASE-Like (SVL) directly interact to control bud-break. EBB1 is a positive regulator of bud-break, whereas SVL is a negative regulator of bud-break. EBB1 directly and negatively regulates SVL expression. We further report the identification and characterization of the EBB3 gene. EBB3 is a temperature-responsive, epigenetically-regulated, positive regulator of bud-break that provides a direct link to activation of the cell cycle during bud-break. EBB3 is an AP2/ERF transcription factor that positively and directly regulates CYCLIND3.1 gene. Our results reveal the architecture of a putative regulatory module that links temperature-mediated control of bud-break with activation of cell cycle.
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http://dx.doi.org/10.1038/s41467-021-21449-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893051PMC
February 2021

Comparative Analysis of Mesenchymal Stem Cell Cultivation in Fetal Calf Serum, Human Serum, and Platelet Lysate in 2D and 3D Systems.

Front Bioeng Biotechnol 2020 15;8:598389. Epub 2021 Jan 15.

Institute of Technical Chemistry, Leibniz University Hannover, Hanover, Germany.

two-dimensional (2D) and three-dimensional (3D) cultivation of mammalian cells requires supplementation with serum. Mesenchymal stem cells (MSCs) are widely used in clinical trials for bioregenerative medicine and in most cases, expansion and differentiation of these cells are required before application. Optimized expansion and differentiation protocols play a key role in the treatment outcome. 3D cell cultivation systems are more comparable to conditions and can provide both, more physiological MSC expansion and a better understanding of intercellular and cell-matrix interactions. Xeno-free cultivation conditions minimize risks of immune response after implantation. Human platelet lysate (hPL) appears to be a valuable alternative to widely used fetal calf serum (FCS) since no ethical issues are associated with its harvest, it contains a high concentration of growth factors and cytokines and it can be produced from expired platelet concentrate. In this study, we analyzed and compared proliferation, as well as osteogenic and chondrogenic differentiation of human adipose tissue-derived MSCs (hAD-MSC) using three different supplements: FCS, human serum (HS), and hPL in 2D. Furthermore, online monitoring of osteogenic differentiation under the influence of different supplements was performed in 2D. hPL-cultivated MSCs exhibited a higher proliferation and differentiation rate compared to HS- or FCS-cultivated cells. We demonstrated a fast and successful chondrogenic differentiation in the 2D system with the addition of hPL. Additionally, FCS, HS, and hPL were used to formulate Gelatin-methacryloyl (GelMA) hydrogels in order to evaluate the influence of the different supplements on the cell spreading and proliferation of cells growing in 3D culture. In addition, the hydrogel constructs were cultivated in media supplemented with three different supplements. In comparison to FCS and HS, the addition of hPL to GelMA hydrogels during the encapsulation of hAD-MSCs resulted in enhanced cell spreading and proliferation. This effect was promoted even further by cultivating the hydrogel constructs in hPL-supplemented media.
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http://dx.doi.org/10.3389/fbioe.2020.598389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844400PMC
January 2021

Mannose-binding lectin (MBL) and the lectin complement pathway play a role in cutaneous ischemia and reperfusion injury.

Innov Surg Sci 2020 Mar 14;5(1-2):43-51. Epub 2020 Sep 14.

Hannover Medical School, Department of Plastic, Aesthetic, Hand, and Reconstructive Surgery, Hannover, Germany.

Objectives: Cutaneous ischemia/reperfusion (CI/R) injury has shown to play a significant role in chronic wounds such as decubitus ulcers, diabetic foot ulcers, atherosclerotic lesions, and venous stasis wounds. CI/R also plays a role in free tissue transfer in reconstructive microsurgery and has been linked to clinical burn-depth progression after thermal injury. While the role of the complement system has been elucidated in multiple organ systems, evidence is lacking with respect to its role in the skin. Therefore, we evaluated the role of the complement system in CI/R injury.

Methods: Using a single pedicle skin flap mouse model of acute CI/R, we performed CI/R in wild-type (WT) mice and complement knock out (KO) mice, deficient in either C1q (C1q KO; classical pathway inhibition), mannose-binding lectin (MBL null; lectin pathway inhibition) or factor B (H2Bf KO; alternative pathway inhibition). Following 10 h ischemia and 7 days reperfusion, mice were sacrificed, flaps harvested and flap viability assessed via Image J software. The flap necrotic area was expressed as % total flap area. In another group, mice were sacrificed following CI/R with 10 h ischemia and 48 h reperfusion. Two cranial skin flap samples were taken for gene expression analysis of IL1b, IL6, TNFα, ICAM1, VCAM1, IL10, IL13 using real-time polymerase chain reaction (RT-PCR).

Results: Following CI/R, MBL null mice had a statistically significant smaller %necrotic flap area compared to WT mice (10.6 vs. 43.1%; p<0.05) suggesting protection from CI/R. A significantly reduced mean %necrotic flap area was not seen in either C1q KO or H2Bf KO mice relative to WT (22.9 and 31.3 vs. 43.1%; p=0.08 and p=0.244, respectively). There were no statistically significant differences between groups for markers of inflammation (TNFα, ICAM1, VCAM1, IL1b, IL6). In contrast, mRNA levels of IL10, a regulator of inflammation, were significantly increased in the MBL null group (p=0.047).

Conclusions: We demonstrated for the first time a significant role of MBL and the lectin complement pathway in ischemia/reperfusion injury of the skin and a potential role for IL10 in attenuating CI/R injury, as IL10 levels were significantly increased in the tissue from the CI/R-protected MBL null group.
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http://dx.doi.org/10.1515/iss-2020-0017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798300PMC
March 2020

An experimental test of stabilizing forces in the field niche.

Ecology 2021 Apr 1;102(4):e03290. Epub 2021 Mar 1.

Department of Evolution and Ecology, University of California, Davis, California, 95616, USA.

Modern coexistence theory holds that stabilizing mechanisms, whereby species limit the growth of conspecifics more than that of other species, are necessary for species to coexist. Here, we used experimental and observational approaches to assess stabilizing forces in eight locally co-occurring, annual, legume species in the genus Trifolium. We experimentally measured self-limitation in the field by transplanting Trifolium species into each other's field niches while varying competition and related these patterns to the field coexistence dynamics of natural Trifolium populations. We found that Trifolium species differed in their responses to local environmental gradients and performed best in their home environments, consistent with habitat specialization and presenting a possible barrier to coexistence at fine scales. We found significant self-limitation for 5 of 42 pairwise species combinations measured experimentally with competitors absent, indicating stabilization through plant-soil feedbacks and other indirect interactions, whereas self-limitation was largely absent when neighbors were present, indicating destabilizing effects of direct plant-plant interactions. The degree of self-limitation measured in our field experiment explained year-to-year dynamics of coexistence by Trifolium species in natural communities. By assessing stabilizing forces and environmental responses in the full n-dimensional field niche, this study sheds light on the roles of habitat specialization, plant-soil feedbacks, and plant interactions in determining species coexistence at local scales.
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http://dx.doi.org/10.1002/ecy.3290DOI Listing
April 2021

Modifications in fMRI Representation of Mental Rotation Following a 6 Week Graded Motor Imagery Training in Chronic CRPS Patients.

J Pain 2021 Jan 6. Epub 2021 Jan 6.

Functional Imaging Unit, Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Germany. Electronic address:

Complex regional pain syndrome (CRPS) is a neuropathic pain condition that is difficult to treat. For behavioral interventions, graded motor imagery (GMI) showed relevant effects, but underlying neural substrates in patient groups have not been investigated yet. A previous study investigating differences in the representation of a left/right hand judgment task demonstrated less recruitment of subcortical structures, such as the putamen, in CRPS patients than in healthy controls. In healthy volunteers, the putamen activity increased after a hand judgment task training. In order to test for longitudinal effects of GMI training, we investigated 20 CRPS patients in a wait-list crossover design with 3 evaluation time points. Patients underwent a 6 week GMI treatment and a 6 week waiting period in a randomized group assignment and treatment groups were evaluated by a blinded rater. When compared to healthy matched controls at baseline, CRPS patients showed less functional activation in areas processing visual input, left sensorimotor cortex, and right putamen. Only GMI treatment, but not the waiting period showed an effect on movement pain and hand judgment task performance. Regression analyses revealed positive associations of movement pain with left anterior insula activation at baseline. Right intraparietal sulcus activation change during GMI was associated with a gain in performance of the hand judgment task. The design used here is reliable for investigating the functional representation of the hand judgment task in an intervention study. PERSPECTIVE: Twenty chronic CRPS patients underwent a 6 week GMI intervention in a randomized wait-list crossover design. functional MRI was tested pre and post for the hand lateralization task which improved over GMI but not over WAITING. Performance gain was positively related to right parietal functional MRI activation.
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http://dx.doi.org/10.1016/j.jpain.2020.12.003DOI Listing
January 2021

A digital 3D reference atlas reveals cellular growth patterns shaping the ovule.

Elife 2021 Jan 6;10. Epub 2021 Jan 6.

Plant Developmental Biology, School of Life Sciences, Technical University of Munich, Freising, Germany.

A fundamental question in biology is how morphogenesis integrates the multitude of processes that act at different scales, ranging from the molecular control of gene expression to cellular coordination in a tissue. Using machine-learning-based digital image analysis, we generated a three-dimensional atlas of ovule development in , enabling the quantitative spatio-temporal analysis of cellular and gene expression patterns with cell and tissue resolution. We discovered novel morphological manifestations of ovule polarity, a new mode of cell layer formation, and previously unrecognized subepidermal cell populations that initiate ovule curvature. The data suggest an irregular cellular build-up of expression in the primordium and new functions for in restricting nucellar cell proliferation and the organization of the interior chalaza. Our work demonstrates the analytical power of a three-dimensional digital representation when studying the morphogenesis of an organ of complex architecture that eventually consists of 1900 cells.
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http://dx.doi.org/10.7554/eLife.63262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787667PMC
January 2021

Selective Elimination of Osteosarcoma Cell Lines with Short Telomeres by Ataxia Telangiectasia and Rad3-Related Inhibitors.

ACS Pharmacol Transl Sci 2020 Dec 7;3(6):1253-1264. Epub 2020 Oct 7.

Centre for Genome Engineering and Maintenance, College of Health, Medicine and Life Sciences, Brunel University London, London UB8 3PH, United Kingdom.

To avoid replicative senescence or telomere-induced apoptosis, cancers employ telomere maintenance mechanisms (TMMs) involving either the upregulation of telomerase or the acquisition of recombination-based alternative telomere lengthening (ALT). The choice of TMM may differentially influence cancer evolution and be exploitable in targeted therapies. Here, we examine TMMs in a panel of 17 osteosarcoma-derived cell lines, defining three separate groups according to TMM and the length of telomeres maintained. Eight were ALT-positive, including the previously uncharacterized lines, KPD and LM7. While ALT-positive lines all showed excessive telomere length, ALT-negative cell lines fell into two groups according to their telomere length: HOS-MNNG, OHSN, SJSA-1, HAL, 143b, and HOS displayed subnormally short telomere length, while MG-63, MHM, and HuO-3N1 displayed long telomeres. Hence, we further subcategorized ALT-negative TMM into long-telomere (LT) and short-telomere (ST) maintenance groups. Importantly, subnormally short telomeres were significantly associated with hypersensitivity to three different therapeutics targeting the protein kinase ataxia telangiectasia and Rad3-related (ATR) (AZD-6738/Ceralasertib, VE-822/Berzoserib, and BAY-1895344) compared to long telomeres maintained via ALT or telomerase. Within 24 h of ATR inhibition, cells with short but not long telomeres displayed chromosome bridges and underwent cell death, indicating a selective dependency on ATR for chromosome stability. Collectively, our work provides a resource to identify links between the mode of telomere maintenance and drug sensitivity in osteosarcoma and indicates that telomere length predicts ATR inhibitor sensitivity in cancer.
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http://dx.doi.org/10.1021/acsptsci.0c00125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737214PMC
December 2020

Correction: Circumvention of common labelling artefacts using secondary nanobodies.

Nanoscale 2020 Dec;12(48):24543

Institute of Neuro- and Sensory Physiology, University Medical Center Göttingen, 37073 Göttingen, Germany.

Correction for 'Circumvention of common labelling artefacts using secondary nanobodies' by Shama Sograte-Idrissi et al., Nanoscale, 2020, 12, 10226-10239, DOI: 10.1039/D0NR00227E.
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http://dx.doi.org/10.1039/d0nr90279aDOI Listing
December 2020

SARC025 arms 1 and 2: A phase 1 study of the poly(ADP-ribose) polymerase inhibitor niraparib with temozolomide or irinotecan in patients with advanced Ewing sarcoma.

Cancer 2020 Dec 8. Epub 2020 Dec 8.

Department of Oncology, University College London Hospitals NHS Trust, London, United Kingdom.

Background: In preclinical Ewing sarcoma (ES) models, poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors were identified as a potential therapeutic strategy with synergy in combination with cytotoxic agents. This study evaluated the safety and dosing of the PARP1/2 inhibitor niraparib (NIR) with temozolomide (TMZ; arm 1) or irinotecan (IRN; arm 2) in patients with pretreated ES.

Methods: Eligible patients in arm 1 received continuous NIR daily and escalating TMZ (days 2-6 [D2-6]) in cohort A. Subsequent patients received intermittent NIR dosing (cohort B), with TMZ re-escalation in cohort C. In arm 2, patients were assigned to NIR (days 1-7 [D1-7]) and escalating doses of IRN (D2-6).

Results: From July 2014 to May 2018, 29 eligible patients (23 males and 6 females) were enrolled in arms 1 and 2, which had 7 dose levels combined. Five patients experienced at least 1 dose-limiting toxicity (DLT) in arm 1 (grade 4 [G4] neutropenia for >7 days or G4 thrombocytopenia), and 3 patients experienced at least 1 DLT in arm 2 (grade 3 [G3] colitis, G3 anorexia, or G3 alanine aminotransferase elevation). The maximum tolerated dose was NIR at 200 mg every day on D1-7 plus TMZ at 30 mg/m every day on D2-6 (arm 1) or NIR at 100 mg every day on D1-7 plus IRN at 20 mg/m every day on D2-6 (arm 2). One confirmed partial response was observed in arm 2; the median progression-free survival was 9.0 weeks (95% CI, 7.0-10.1 weeks) and 16.3 weeks (95% CI, 5.1-69.7 weeks) in arms 1 and 2, respectively. The median decrease in tumor poly(ADP-ribose) activity was 89% (range, 83%-98%).

Conclusions: The combination of NIR and TMZ or IRN was tolerable, but at lower doses in comparison with conventional cytotoxic combinations. A triple-combination study of NIR, IRN, and TMZ has commenced.
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http://dx.doi.org/10.1002/cncr.33349DOI Listing
December 2020

School Nurses Matter: Relationship Between School Nurse Employment Policies and Chronic Health Condition Policies in U.S. School Districts.

J Sch Nurs 2020 Nov 24:1059840520973413. Epub 2020 Nov 24.

Hunter-Bellevue School of Nursing, Hunter College, New York, NY, USA.

The increasing prevalence of chronic health conditions (CHCs) in school-aged children highlights the need to better understand school health services' role regarding CHCs. Using U.S. nationally representative district-level data from the 2016 School Health Policies and Practices Study, we examined whether having policies on school nurses' employment was associated with having policies on CHCs and whether having such policies varied by geographic location. Compared to districts without such employment policies, districts with such policies (52.3%) were significantly more likely to have CHC management policies. For each CHC policy examined, more than 20% of school districts did not have the CHC policy, with Northeast districts having the greatest proportion of such policies and West districts having the least. Thus, many students' CHC needs may not be met at school. It is important for school nurses to play a key role in advocating for the development of school-based policies on CHCs.
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http://dx.doi.org/10.1177/1059840520973413DOI Listing
November 2020

Imaging Glioblastoma Posttreatment: Progression, Pseudoprogression, Pseudoresponse, Radiation Necrosis.

Neuroimaging Clin N Am 2021 Feb;31(1):103-120

Department of Radiology, Weill Cornell Medical Center, 525 East 68th Street, Box 141, New York, NY 10065, USA. Electronic address:

Radiographic monitoring of posttreatment glioblastoma is important for clinical trials and determining next steps in management. Evaluation for tumor progression is confounded by the presence of treatment-related radiographic changes, making a definitive determination less straight-forward. The purpose of this article was to describe imaging tools available for assessing treatment response in glioblastoma, as well as to highlight the definitions, pathophysiology, and imaging features typical of true progression, pseudoprogression, pseudoresponse, and radiation necrosis.
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http://dx.doi.org/10.1016/j.nic.2020.09.010DOI Listing
February 2021

Continuous 14 Day Infusional Ifosfamide for Management of Soft-Tissue and Bone Sarcoma: A Single Centre Retrospective Cohort Analysis.

Cancers (Basel) 2020 Nov 17;12(11). Epub 2020 Nov 17.

London Sarcoma Service, University College London Hospital, Euston Road, London NW1 2PG, UK.

Ifosfamide is used to treat soft-tissue sarcoma (STS) and bone sarcoma (BS), with improved efficacy at doses above 9 g/m/cycle. To mitigate treatment-associated toxicity with higher doses, continuous infusional ifosfamide is increasingly used. However, clinical outcome data remain limited. Single-centre retrospective analysis of patients treated with four-weekly infusional ifosfamide (14 g/m/14d) between August 2012 and February 2019 was conducted. Radiological response, progression-free survival (PFS), overall survival (OS) and toxicity were evaluated. Eighty patients were treated-46 with STS and 34 with BS. Patients received a median of three cycles of infusional ifosfamide (1-24). Overall disease control rate (DCR) in STS was 50% (23 of 46 patients), with a median PFS of 3.8 months, and median OS of 13.0 months. In synovial sarcoma (SS), DCR was 80% (12/15), median PFS 8.1 months and median OS 20.9 months. Overall DCR in BS (34 patients) was 30%, with a median PFS of 2.5 months and median OS of 6.2 months. Five patients (6%) stopped treatment due to toxicity alone within the first two cycles. A further 10 patients stopped treatment due to toxicity during later treatment cycles (12%) and 18 patients (23%) required dose modification. Forty-five patients (56%) experienced grade (G) 3/4 haematological toxicity, with 12 episodes of febrile neutropenia and one treatment-related death. Twenty-seven patients (34%) experienced G3/4 non-haematological toxicity, most commonly nausea and vomiting (10, 13%). In summary, infusional ifosfamide has efficacy in STS, most notable in SS. Benefit appears limited in BS. Treatment is associated with toxicity that requires specialist supportive care.
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http://dx.doi.org/10.3390/cancers12113408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698576PMC
November 2020

Carotid Endarterectomy Versus Carotid Artery Stenting: Survey of the Quality, Readability, and Treatment Preference of Carotid Artery Disease Websites.

Interact J Med Res 2020 Nov 3;9(4):e23519. Epub 2020 Nov 3.

Division of Vascular Surgery, University of Ottawa, Ottawa, ON, Canada.

Background: The internet is becoming increasingly more important in the new era of patient self-education. Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are recognized interventions to treat patients with carotid artery stenosis. Using the Google search platform, patients encounter many websites with conflicting information, which are sometimes difficult to understand. This lack of accessibility creates uncertainty or bias toward interventions for carotid artery disease. The quality, readability, and treatment preference of carotid artery disease (CAD) websites have not yet been evaluated.

Objective: This study aimed to explore the quality, readability, and treatment preference of CAD websites.

Methods: We searched Google Canada for 10 CAD-related keywords. Returned links were assessed for publication date, medical specialty and industry affiliation, presence of randomized controlled trial data, differentiation by symptomatic status, and favored treatment. Website quality and readability were rated by the DISCERN instrument and Gunning Fog Index.

Results: We identified 54 unique sites: 18 (33.3%) by medical societies or individual physicians, 11 (20.4%) by government organizations, 9 (16.7%) by laypersons, and 1 (1.9%) that was industry-sponsored. Of these sites, 26 (48.1%) distinguished symptomatic from asymptomatic CAD. A majority of sites overall (57.4%) and vascular-affiliated (72.7%) favored CEA. In contrast, radiology- and cardiology-affiliated sites demonstrated the highest proportion of sites favoring CAS, though they were equally likely to favor CEA. A large proportion (21/54, 38.9%) of sites received poor quality ratings (total DISCERN score <48), and the majority (41/54, 75.9%) required a reading level greater than a high school senior.

Conclusions: CAD websites are often produced by government organizations, medical societies, or physicians, especially vascular surgeons. Sites ranged in quality, readability, and differentiation by symptomatic status. Google searches of CAD-related terms are more likely to yield sites favoring CEA. Future research should determine the extent of website influence on CAD patients' treatment decisions.
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http://dx.doi.org/10.2196/23519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671836PMC
November 2020

Two centuries of monarch butterfly collections reveal contrasting effects of range expansion and migration loss on wing traits.

Proc Natl Acad Sci U S A 2020 11 2;117(46):28887-28893. Epub 2020 Nov 2.

Center for Population Biology, University of California, Davis, CA 95616.

Migratory animals exhibit traits that allow them to exploit seasonally variable habitats. In environments where migration is no longer beneficial, such as oceanic islands, migration-association traits may be selected against or be under relaxed selection. Monarch butterflies are best known for their continent-scale migration in North America but have repeatedly become established as nonmigrants in the tropical Americas and on Atlantic and Pacific Islands. These replicated nonmigratory populations provide natural laboratories for understanding the rate of evolution of migration-associated traits. We measured >6,000 museum specimens of monarch butterflies collected from 1856 to the present as well as contemporary wild-caught monarchs from around the world. We determined 1) how wing morphology varies across the monarch's global range, 2) whether initial long-distance founders were particularly suited for migration, and 3) whether recently established nonmigrants show evidence for contemporary phenotypic evolution. We further reared >1,000 monarchs from six populations around the world under controlled conditions and measured migration-associated traits. Historical specimens show that 1) initial founders are well suited for long-distance movement and 2) loss of seasonal migration is associated with reductions in forewing size and elongation. Monarch butterflies raised in a common garden from four derived nonmigratory populations exhibit genetically based reductions in forewing size, consistent with a previous study. Our findings provide a compelling example of how migration-associated traits may be favored during the early stages of range expansion, and also the rate of reductions in those same traits upon loss of migration.
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http://dx.doi.org/10.1073/pnas.2001283117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682565PMC
November 2020

Reply.

AJNR Am J Neuroradiol 2021 03 29;42(3):E12. Epub 2020 Oct 29.

Department of RadiologyWeill Cornell MedicineNew York, New York.

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http://dx.doi.org/10.3174/ajnr.A6932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959433PMC
March 2021

Molecular Analysis of Fetal and Adult Primary Human Liver Sinusoidal Endothelial Cells: A Comparison to Other Endothelial Cells.

Int J Mol Sci 2020 Oct 21;21(20). Epub 2020 Oct 21.

Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.

In humans, Factor VIII (F8) deficiency leads to hemophilia A and F8 is largely synthesized and secreted by the liver sinusoidal endothelial cells (LSECs). However, the specificity and characteristics of these cells in comparison to other endothelial cells is not well known. In this study, we performed genome wide expression and CpG methylation profiling of fetal and adult human primary LSECs together with other fetal primary endothelial cells from lung (micro-vascular and arterial), and heart (micro-vascular). Our results reveal expression and methylation markers distinguishing LSECs at both fetal and adult stages. Differential gene expression of fetal LSECs in comparison to other fetal endothelial cells pointed to several differentially regulated pathways and biofunctions in fetal LSECs. We used targeted bisulfite resequencing to confirm selected top differentially methylated regions. We further designed an assay where we used the selected methylation markers to test the degree of similarity of in-house iPS generated vascular endothelial cells to primary LSECs; a higher similarity was found to fetal than to adult LSECs. In this study, we provide a detailed molecular profile of LSECs and a guide to testing the effectiveness of production of in vitro differentiated LSECs.
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http://dx.doi.org/10.3390/ijms21207776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589710PMC
October 2020

The Bacterium Pantoea ananatis Modifies Behavioral Responses to Sugar Solutions in Honeybees.

Insects 2020 Oct 12;11(10). Epub 2020 Oct 12.

Department of Biosciences, University of Salzburg, Hellbrunnerstraße 34, 5020 Salzburg, Austria.

1. Honeybees, which are among the most important pollinators globally, do not only collect pollen and nectar during foraging but may also disperse diverse microbes. Some of these can be deleterious to agricultural crops and forest trees, such as the bacterium , an emerging pathogen in some systems. infections can lead to leaf blotches, die-back, bulb rot, and fruit rot. 2. We isolated bacteria from flowers with the aim of determining whether honeybees can sense these bacteria and if the bacteria affect behavioral responses of the bees to sugar solutions. 3. Honeybees decreased their responsiveness to different sugar solutions when these contained high concentrations of but were not deterred by solutions from which bacteria had been removed. This suggests that their reduced responsiveness was due to the taste of bacteria and not to the depletion of sugar in the solution or bacteria metabolites. Intriguingly, the bees appeared not to taste ecologically relevant low concentrations of bacteria. 4. Our data suggest that honeybees may introduce bacteria into nectar in field-realistic densities during foraging trips and may thus affect nectar quality and plant fitness.
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http://dx.doi.org/10.3390/insects11100692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601739PMC
October 2020

A WOX/Auxin Biosynthesis Module Controls Growth to Shape Leaf Form.

Curr Biol 2020 Dec 8;30(24):4857-4868.e6. Epub 2020 Oct 8.

Department of Comparative Development and Genetics, Max Planck Institute for Plant Breeding Research, Carl-von-Linné-Weg 10, 50829 Cologne, Germany. Electronic address:

A key challenge in biology is to understand how the regional control of cell growth gives rise to final organ forms. Plant leaves must coordinate growth along both the proximodistal and mediolateral axes to produce their final shape. However, the cell-level mechanisms controlling this coordination remain largely unclear. Here, we show that, in A. thaliana, WOX5, one of the WUSCHEL-RELATED HOMEOBOX (WOX) family of homeobox genes, acts redundantly with WOX1 and WOX3 (PRESSED FLOWER [PRS]) to control leaf shape. Through genetics and hormone measurements, we find that these WOXs act in part through the regional control of YUCCA (YUC) auxin biosynthetic gene expression along the leaf margin. The requirement for WOX-mediated YUC expression in patterning of leaf shape cannot be bypassed by the epidermal expression of YUC, indicating that the precise domain of auxin biosynthesis is important for leaf form. Using time-lapse growth analysis, we demonstrate that WOX-mediated auxin biosynthesis organizes a proximodistal growth gradient that promotes lateral growth and consequently the characteristic ellipsoid A. thaliana leaf shape. We also provide evidence that WOX proteins shape the proximodistal gradient of differentiation by inhibiting differentiation proximally in the leaf blade and promoting it distally. This regulation allows sustained growth of the blade and enables a leaf to attain its final form. In conclusion, we show that the WOX/auxin regulatory module shapes leaf form by coordinating growth along the proximodistal and mediolateral leaf axes.
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http://dx.doi.org/10.1016/j.cub.2020.09.037DOI Listing
December 2020

Association of Cancer History and Health Care Utilization Among Female Immigrants Using NHANES 2007-2016 Data.

J Immigr Minor Health 2020 Dec 25;22(6):1208-1216. Epub 2020 Sep 25.

Hunter-Bellevue School of Nursing, Hunter College, 425 East 25th Street, Rm.416W, New York, NY, 10010, USA.

Background: Despite health disparities in preventive care among adult female immigrants, the extent to which their health service utilization is influenced by a cancer history remains largely unknown.

Methods: Using Andersen's behavioral model, 2007-2016 National Health and Nutrition Examination Survey data were analyzed to examine the influence of a cancer history on health service utilization among adult immigrant women. Multivariate logistic regression models assessed factors related to past year health care utilization, operationalized as an outpatient doctor's visit and an inpatient overnight hospital stay.

Results: Once other factors were considered, a past cancer history increased the likelihood of a past year inpatient overnight hospital stay, but was not associated with a past year outpatient doctor's visit.

Discussion: An outpatient doctor's visit for adult female immigrant cancer survivors would provide an opportunity for essential preventive health services. They must be educated about the importance of ongoing outpatient care for cancer surveillance and health maintenance.
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http://dx.doi.org/10.1007/s10903-020-01090-7DOI Listing
December 2020

Best Practices for Post-Treatment Surveillance Imaging in Head and Neck Cancer: Application of the Neck Imaging Reporting and Data System (NI-RADS).

AJR Am J Roentgenol 2020 09 2. Epub 2020 Sep 2.

Department of Radiology, Weill Cornell Medical College, NewYork-Presbyterian.

Imaging surveillance is an important component of the post-treatment management of head and neck cancers. There is variability in the surveillance regimen utilized by various practitioners and institutions, with no official National Comprehensive Cancer Network guidelines for asymptomatic patients beyond 6 months post-treatment. Moreover, the post-treatment neck is a complex imaging exam with significant inter-reader heterogeneity, particularly in terms of the manner in which degree of suspicion for disease recurrence is expressed. The Neck Imaging Reporting and Data System (NI-RADS) was introduced by the ACR in 2018 as a practical guide to the interpreting radiologist. NI-RADS is a proposed interpretive framework that can be applied to any standardized or institutional surveillance imaging protocol. NI-RADS simplifies communication between radiologists and referring clinicians and provides management guidance linked to specific levels of suspicion. The ACR NI-RADS committee also provided general best practice recommendations for imaging surveillance modality and timing in the 2018 white paper. The manuscript will begin with a review of existing literature regarding choice of modality and timeline for surveillance in treated cancer of the head and neck. NI-RADS will then be presented as an approach to imaging reporting, interpretation and design of next steps in management.
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http://dx.doi.org/10.2214/AJR.20.23841DOI Listing
September 2020

Risk Factors Associated With Bullying at School and Electronic Bullying in U.S. Adolescent Females With Asthma.

J Sch Nurs 2020 Aug 28:1059840520951635. Epub 2020 Aug 28.

Hunter-Bellevue School of Nursing, 5924Hunter College, New York, NY, USA.

Although adolescent females with asthma are at increased risk for bullying, relationships between bullying at school and electronic bullying and demographics, mental health issues, and substance use have not specifically been studied in these young women. The purpose of this research was to examine such relationships among adolescent females with asthma. Complex sampling software was used to extrapolate frequencies and χ analyses to adolescent females with asthma. In this U.S. sample of adolescent females with asthma ( = 1,634), younger age, mental health issues, and substance use were significantly related to bullying at school and electronic bullying, while race/ethnicity and grade in school were significantly related only to bullying at school. In general, findings are consistent with previous research regarding relationships between bullying and risk factors among all U.S. adolescent females. Guidance by school nurses is needed to create effective supports for victimization reduction in this vulnerable group.
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http://dx.doi.org/10.1177/1059840520951635DOI Listing
August 2020

Olfactory Bulb Signal Abnormality in Patients with COVID-19 Who Present with Neurologic Symptoms.

AJNR Am J Neuroradiol 2020 10 27;41(10):1882-1887. Epub 2020 Aug 27.

From the Department of Radiology (S.B.S., J.E.L., L.A.H., C.D.P.), Weill Cornell Medical College, New York-Presbyterian, New York, New York

Background And Purpose: Unique among the acute neurologic manifestations of Severe Acute Respiratory Syndrome coronavirus 2, the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, is chemosensory dysfunction (anosmia or dysgeusia), which can be seen in patients who are otherwise oligosymptomatic or even asymptomatic. The purpose of this study was to determine if there is imaging evidence of olfactory apparatus pathology in patients with COVID-19 and neurologic symptoms.

Materials And Methods: A retrospective case-control study compared the olfactory bulb and olfactory tract signal intensity on thin-section T2WI and postcontrast 3D T2 FLAIR images in patients with COVID-19 and neurologic symptoms, and age-matched controls imaged for olfactory dysfunction.

Results: There was a significant difference in normalized olfactory bulb T2 FLAIR signal intensity between the patients with COVID-19 and the controls with anosmia ( = .003). Four of 12 patients with COVID-19 demonstrated intraneural T2 signal hyperintensity on postcontrast 3D T2 FLAIR compared with none of the 12 patients among the controls with anosmia ( = .028).

Conclusions: Olfactory bulb 3D T2 FLAIR signal intensity was greater in the patients with COVID-19 and neurologic symptoms compared with an age-matched control group with olfactory dysfunction, and this was qualitatively apparent in 4 of 12 patients with COVID-19. Analysis of these preliminary finding suggests that olfactory apparatus vulnerability to COVID-19 might be supported on conventional neuroimaging and may serve as a noninvasive biomarker of infection.
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http://dx.doi.org/10.3174/ajnr.A6751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661060PMC
October 2020