Background:
Despite the growing awareness of the clinical significance of meniscus root tears, there are relatively limited biomechanical and microstructural data available on native meniscus roots ...that could improve our understanding of why they are injured and how to best treat them.
Purpose/Hypothesis:
The purpose of the study was to measure the material and microstructural properties of meniscus roots using mechanical testing and quantitative polarized light imaging. The hypothesis was that these properties vary by location (medial vs lateral, anterior vs posterior) and by specific root (anteromedial vs anterolateral, posteromedial vs posterolateral).
Study Design:
Descriptive laboratory study.
Methods:
Anterior and posterior meniscus roots of the medial and lateral meniscus were isolated from 22 cadavers (10 female, 12 male; mean ± SD age, 47.1 ± 5.1 years) and loaded in uniaxial tension. Quantitative polarized light imaging was used to measure collagen fiber organization and realignment under load. Samples were subjected to preconditioning, stress-relaxation, and a ramp to failure. Time-dependent relaxation behavior was quantified. Modulus values were computed in the toe and linear regions of the stress-strain curves. The degree of linear polarization (DoLP) and angle of polarization—measures of the strength and direction of collagen alignment, respectively—were calculated during the stress-relaxation test and at specific strain values throughout the ramp to failure (zero, transition, and linear strain).
Results:
Anterior roots had larger moduli than posterior roots in the toe (P = .007) and linear (P < .0001) regions and larger average DoLP values at all points of the ramp to failure (zero, P = .016; transition, P = .004; linear, P = .002). Posterior roots had larger values across all regions in terms of standard deviation angle of polarization (P < .001). Lateral roots had greater modulus values versus medial roots in the toe (P = .027) and linear (P = .014) regions. Across all strain points, posterolateral roots had smaller mean DoLP values than posteromedial roots.
Conclusion:
Posterior meniscus roots have smaller modulus values and more disorganized collagen alignment at all strain levels when compared with anterior roots. Posterolateral roots have lower strength of collagen alignment versus posteromedial roots.
Clinical Relevance:
These data findings may explain at least in part the relative paucity of anterior meniscus root tears and the predominance of traumatic posterolateral roots tears as compared with degenerative posteromedial root tears.
Palmer amaranth (Amaranthus palmeri) is an annual plant native to the desert Southwest of the United States and Mexico and has become invasive and caused large economic losses across much of the ...United States. In order to examine the temporal and spatial dynamics of past invasion, and to predict future invasion, we developed a broad array of species distribution models (SDMs). In particular, we constructed sequential SDMs throughout the invasion history and asked how well those predicted future invasion (1970 to present). We showed that invasion occurred from a restricted set of environments in the native range to a diverse set in the invaded range. Spatial autocorrelation analyses indicated that rapid range expansion was facilitated by stochastic, long-distance dispersal events. Regardless of SDM approach, all SDMs built using datasets from early in the invasion (1970-2010) performed poorly and failed to predict most of the current invaded range. Together, these results suggest that climate is unlikely to have influenced early stages of range expansion. SDMs that incorporated data from the most recent sampling (2011-2017) performed considerably better, predicted high suitability in regions that have recently become invaded, and identified mean annual temperature as a key factor limiting northward range expansion. Under future climates, models predicted both further northward range expansion and significantly increased suitability across large portions of the U.S. Overall, our results indicate significant challenges for SDMs of invasive species far from climate equilibrium. However, our models based on recent data make more robust predictions for northward range expansion of A. palmeri with climate change.
Histone‐lysine N‐methyltransferase SETD2 (SETD2), the sole histone methyltransferase that catalyzes trimethylation of lysine 36 on histone H3 (H3K36me3), is often mutated in clear cell renal cell ...carcinoma (ccRCC). SETD2 mutation and/or loss of H3K36me3 is linked to metastasis and poor outcome in ccRCC patients. Epithelial‐to‐mesenchymal transition (EMT) is a major pathway that drives invasion and metastasis in various cancer types. Here, using novel kidney epithelial cell lines isogenic for SETD2, we discovered that SETD2 inactivation drives EMT and promotes migration, invasion, and stemness in a transforming growth factor‐beta‐independent manner. This newly identified EMT program is triggered in part through secreted factors, including cytokines and growth factors, and through transcriptional reprogramming. RNA‐seq and assay for transposase‐accessible chromatin sequencing uncovered key transcription factors upregulated upon SETD2 loss, including SOX2, POU2F2 (OCT2), and PRRX1, that could individually drive EMT and stemness phenotypes in SETD2 wild‐type (WT) cells. Public expression data from SETD2 WT/mutant ccRCC support the EMT transcriptional signatures derived from cell line models. In summary, our studies reveal that SETD2 is a key regulator of EMT phenotypes through cell‐intrinsic and cell‐extrinsic mechanisms that help explain the association between SETD2 loss and ccRCC metastasis.
Histone methyltransferase SETD2 catalyzes H3K36me3 at gene bodies and when mutated is associated with poor outcome in clear cell renal cell cancer. SETD2 loss results in activation of epithelial‐to‐mesenchymal transition (EMT), global H3K36me3 loss, and chromatin opening. The EMT and stemness phenotypes are driven intrinsically by increased transcription factor binding and extrinsically by paracrine effects mediated through secreted factors.
Phase Engineering of 2D Tin Sulfides Mutlu, Zafer; Wu, Ryan J.; Wickramaratne, Darshana ...
Small (Weinheim an der Bergstrasse, Germany)
12, Številka:
22
Journal Article
Recenzirano
Tin sulfides can exist in a variety of phases and polytypes due to the different oxidation states of Sn. A subset of these phases and polytypes take the form of layered 2D structures that give rise ...to a wide host of electronic and optical properties. Hence, achieving control over the phase, polytype, and thickness of tin sulfides is necessary to utilize this wide range of properties exhibited by the compound. This study reports on phase‐selective growth of both hexagonal tin (IV) sulfide SnS2 and orthorhombic tin (II) sulfide SnS crystals with diameters of over tens of microns on SiO2 substrates through atmospheric pressure vapor‐phase method in a conventional horizontal quartz tube furnace with SnO2 and S powders as the source materials. Detailed characterization of each phase of tin sulfide crystals is performed using various microscopy and spectroscopy methods, and the results are corroborated by ab initio density functional theory calculations.
Phase‐selective growth of 2D tin sulfides (SnS2 and SnS) is demonstrated. Highly crystalline hexagonal SnS2 and orthorhombic SnS crystals are synthesized on SiO2 substrates by atmospheric pressure vapor‐phase method using SnO2 and S as the source materials. The structural, vibrational, and electronic properties of each phase are studied by both experimental characterizations and ab initio density functional theory calculations.
Predicting range expansion of invasive species Lake, Thomas A.; Runquist, Ryan D. Briscoe; Moeller, David A.
Diversity & distributions,
12/2020, Letnik:
26, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Aim
Species distribution models (SDMs) are widely used to forecast potential range expansion of invasive species. However, invasive species occurrence datasets often have spatial biases that may ...violate key SDM assumptions. In this study, we examined alternative methods of spatial bias correction and multiple methods for model evaluation for seven invasive plant species.
Location
North America.
Taxon
Common Tansy (Tanacetum vulgare), Wild Parsnip (Pastinaca sativa), Leafy Spurge (Euphorbia virgata), Common Teasel (Dipsacus fullonum), Brown Knapweed (Centaurea jacea), Black Swallowwort (Vincetoxicum nigrum) and Dalmatian Toadflax (Linaria dalmatica).
Methods
We employed bias‐correction measures for both occurrence sampling and background sampling inputs in a factorial design for Maxent resulting in six potential models for each species. We evaluated our models for complexity, model fit and using commonly employed evaluation metrics: AUC, partial AUC, the continuous Boyce index and sensitivity. We then developed a structured process for model selection.
Results
Models developed without occurrence or background bias correction often were overly complex and did not transfer well to expanding range fronts. Conversely, models that employed occurrence and/or background bias‐correction measures were less complex, had better AICc scores and had greater projection into incipient areas. These simpler models were also more likely to be selected when evaluated using a process that integrated multiple evaluation metrics. We found that invasion history (e.g. established versus incipient) was associated with the effectiveness of spatial bias correction techniques.
Main Conclusions
While challenges exist in building climate‐based correlative species distribution models for invasive species, we found that methods relying on maximizing AUC performed poorly for invasive species. We advocate for the use of multiple and diverse metrics for model evaluation. Users of species distribution models need to incorporate explicit consideration of model discrimination, model fit and model complexity into their decision‐making processes if they are to build biologically realistic models.
Elastic fibers are an essential component of the extracellular matrix of connective tissues. The focus of both clinical management and scientific investigation of elastic fiber disorders has centered ...on the cardiovascular manifestations due to their significant impact on morbidity and mortality. As such, the current understanding of the orthopedic conditions experienced by these patients is limited. The musculoskeletal implications of more subtle elastic fiber abnormalities, whether due to allelic variants or age‐related tissue degeneration, are also not well understood. Recent advances have begun to uncover the effects of elastic fiber deficiency on tendon and ligament biomechanics; future research must further elucidate mechanisms governing the role of elastic fibers in these tissues. The identification of population‐based genetic variations in elastic fibers will also be essential. Minoxidil administration, modulation of protein expression with micro‐RNA molecules, and direct injection of recombinant elastic fiber precursors have demonstrated promise for therapeutic intervention, but further work is required prior to consideration for orthopedic clinical application. This review provides an overview of the role of elastic fibers in musculoskeletal tissue, summarizes current knowledge of the orthopedic manifestations of elastic fiber abnormalities, and identifies opportunities for future investigation and clinical application.
Roach, Robert C., Peter H. Hackett, Oswald Oelz, Peter Bärtsch, Andrew M. Luks, Martin J. MacInnis, J. Kenneth Baillie, and The Lake Louise AMS Score Consensus Committee. The 2018 Lake Louise Acute ...Mountain Sickness Score. High Alt Med Biol 19:1-4, 2018.- The Lake Louise Acute Mountain Sickness (AMS) scoring system has been a useful research tool since first published in 1991. Recent studies have shown that disturbed sleep at altitude, one of the five symptoms scored for AMS, is more likely due to altitude hypoxia per se, and is not closely related to AMS. To address this issue, and also to evaluate the Lake Louise AMS score in light of decades of experience, experts in high altitude research undertook to revise the score. We here present an international consensus statement resulting from online discussions and meetings at the International Society of Mountain Medicine World Congress in Bolzano, Italy, in May 2014 and at the International Hypoxia Symposium in Lake Louise, Canada, in February 2015. The consensus group has revised the score to eliminate disturbed sleep as a questionnaire item, and has updated instructions for use of the score.
Chemical immunotherapeutic strategies including Antibody Recruiting Molecules (ARMs ‐ bivalent small molecules containing an antibody‐binding domain (ABD) and a target‐binding domain (TBD)) direct ...immune‐mediated clearance of diseased cells. Anti‐cancer ARM function relies on high tumor antigen valency, limiting function against lower antigen expressing tumors. To address this limitation, we report a tunable multivalent immune recruitment (MIR) platform to amplify/stabilize antibody recruitment to cells with lower antigen valencies. An initial set of polymeric ARMs (pARMs) were synthesized and screened to evaluate ABD/TBD copy number, ratio, and steric occlusion on specific immune induction. Most pARMs demonstrated simultaneous high avidity binding to anti‐dinitrophenyl antibodies and prostate‐specific membrane antigens on prostate cancer. Optimized pARMs mediated enhanced anti‐cancer immune function against lower antigen expressing target cells compared to an analogous ARM.
Bifunctional chemical immunotherapeutics allow endogenous immune components to identify and destroy diseased targets. Herein we introduce and optimize polymeric antibody recruiting molecules (pARMs) for simultaneous avidity enhanced binding to prostate cancer cells and anti‐dinitrophenyl antibodies. The tunability and avidity‐enhanced potency of pARMs allows for increased immune proximity induction as compared to a monomeric construct.
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