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ABSTRACT Considering the spectral differences between broadleaf weeds and narrow-leaf crops and the influence of terrain and soil variables on weed infestations, integrating such information into a machine-learning algorithm can lead to accurate weed maps. Therefore, we aim to evaluate the effectiveness of these variables in classifying the occurrence of broadleaf weeds in narrow-leaf crops. Weed data was collected at georeferenced points across two areas covering 200 ha (pasture) and 106 ha (sorghum), creating classes 0 (absence) and 1 (presence). For each sample point, we obtained 11 variables: soil clay content, cation exchange capacity, soil organic matter, terrain elevation, slope, NDVI, EVI, CIgreen, BGND (derived from PlanetScope images), and spatial information (X and Y coordinates). These variables were used as predictors of broadleaf weed presence and absence in the Random Forest classification algorithm. The presence and absence of broadleaf weeds were correctly classified in 84% and 74% of all predictions in the test sample sets for pasture and sorghum areas, respectively. This strategy represents an efficient way to map and manage the occurrence of broadleaf weeds in narrow-leaf crops.

ABSTRACTPseudomonas aeruginosa, a bacterium causing infections in immunocompromised individuals, regulates several of its virulence functions using three interlinked quorum sensing (QS) systems (las, rhl, and pqs). Despite its presumed importance in regulating virulence, dysfunction of the las system regulator LasR occurs frequently in strains isolated from various environments, including clinical infections. This newfound abundance of LasR-defective strains calls into question existing hypotheses regarding their selection. Indeed, current assumptions concerning factors driving the emergence of LasR-deficient isolates and the role of LasR in the QS hierarchy must be reconsidered. Here, we propose that LasR is not the primary master regulator of QS in all P. aeruginosa genetic backgrounds, even though it remains ecologically significant. We also revisit and complement current knowledge on the ecology of LasR-dependent QS in P. aeruginosa, discuss the hypotheses explaining the putative adaptive benefits of selecting against LasR function, and consider the implications of this renewed understanding.

Abstract A hallmark of cancer is a tumor cell’s ability to evade immune destruction. Somatic mutations in tumor cells that prevent immune destruction have been extensively studied. However, somatic mutations in tumor infiltrating immune (TII) cells, to our knowledge, have not been previously studied. Understandably so since normal hematopoiesis prevents the accumulation of somatic mutations in immune cells. However, clonal hematopoiesis does result in the accumulation of somatic mutations in immune cells. These mutations cannot “drive” tumor growth, however, they may “facilitate” it by inhibiting an effective anti-tumor immune response. To identify potential immunosuppressive clonal hematopoietic (CH) mutations in TII cells, we analyzed exome and RNA sequencing data from matched tumor and normal blood samples, and single-cell RNA sequencing data, from breast cancer patients. We selected mutations that were somatic, present in TII cells, clonally expanded, potentially pathogenic, expressed in TII cells, unlikely to be a passenger mutation, and in immune response associated genes. We identified eight potential immunosuppressive CH mutations in TII cells. This work is a first step towards determining if immunosuppressive CH mutations in TII cells can affect the progression of solid tumors. Subsequent experimental confirmation could represent a new paradigm in the etiology of cancer.

This paper presents a method for designing low carbon bio-based building materials, also named bio-concretes, produced with wood wastes in shavings form (WS) and cementitious pastes. As the aggregates phase of bio-concretes is composed of plant-based particles, known as porous and high water-absorbing materials, the bio-concretes cannot be designed by using the traditional design rules used for conventional mortar or concrete. Then, the method used in the current paper is an adaptation of a previous one that has been developed in a recent paper where bio-concretes were produced with a cement matrix, three types of bio-aggregates, and a proposal of a design abacus. However, when that abacus is used for designing WBC with low cement content in the matrix, the target compressive strength is not reached. In the present paper, the method is extended to low cement content matrix (up to 70% of cement substitution) and also considering the greenhouse gas (GHG) emission of the WBC. To obtain data for proposing a new design abacus, an experimental program was carried out by producing nine workable WBCs, varying wood volumetric fractions (40–45–50%), and water-to-binder ratios. The bio-concretes produced presented adequate consistency, lightness (density between 715 and 1207 kg/m3), and compressive strength ranging from 0.64 to 12.27 MPa. In addition, the GHG emissions of the WBC were analysed through the Life Cycle Assessment methodology. From the relationships obtained between density, compressive strength, water-to-binder ratio, cement consumption, and GHG emissions of the WBC, calibration constants were proposed for developing the updated and more complete abacus regarding an integrated mix design methodology.

Duchenne muscular dystrophy (DMD) is a degenerative genetic myopathy characterized by complete absence of dystrophin. Although the mdx mouse lacks dystrophin, its phenotype is milder compared to DMD patients. The incorporation of a null mutation in the Cmah gene led to a more DMD-like phenotype (i.e., more fibrosis). Although fibrosis is thought to be the major determinant of 'structural weakness', intracellular remodeling of myofibrillar geometry was shown to be a major cellular determinant thereof. To dissect the respective contribution to muscle weakness, we assessed biomechanics and extra- and intracellular architecture of whole muscle and single fibers from extensor digitorum longus (EDL) and diaphragm. Despite increased collagen contents in both muscles, passive stiffness in mdx Cmah-/- diaphragm was similar to wt mice (EDL muscles were twice as stiff). Isometric twitch and tetanic stresses were 50% reduced in mdx Cmah-/- diaphragm (15% in EDL). Myofibrillar architecture was severely compromised in mdx Cmah-/- single fibers of both muscle types, but more pronounced in diaphragm. Our results show that the mdx Cmah-/- genotype reproduces DMD-like fibrosis but is not associated with changes in passive visco-elastic muscle stiffness. Furthermore, detriments in active isometric force are compatible with the pronounced myofibrillar disarray of the dystrophic background.

In Duchenne muscular dystrophy (DMD), a lack of functional dystrophin leads to myofiber instability and progressive muscle damage that results in fibrosis. While fibrosis is primarily characterized by an accumulation of extracellular matrix (ECM) components, there are changes in ECM architecture during fibrosis that relate more closely to functional muscle stiffness. One of these architectural changes in dystrophic muscle is collagen cross-linking, which has been shown to increase the passive muscle stiffness in models of fibrosis including the mdx mouse, a model of DMD. We tested whether the intraperitoneal injections of beta-aminopropionitrile (BAPN), an inhibitor of the cross-linking enzyme lysyl oxidase, would reduce collagen cross-linking and passive stiffness in young and adult mdx mice compared to saline-injected controls. We found no significant differences between BAPN treated and saline treated mice in collagen cross-linking and stiffness parameters. However, we observed that while collagen cross-linking and passive stiffness scaled positively in dystrophic muscles, collagen fiber alignment scaled with passive stiffness distinctly between muscles. We also observed that the dystrophic diaphragm showed the most dramatic fibrosis in terms of collagen content, cross-linking, and stiffness. Overall, we show that while BAPN was not effective at reducing collagen cross-linking, the positive association between collagen cross-linking and stiffness in dystrophic muscles still show cross-linking as a viable target for reducing passive muscle stiffness in DMD or other fibrotic muscle conditions.

Background: Prostatic artery embolization (PAE) is an emerging treatment for benign prostatic hyperplasia (BPH). However, changes in public interest in PAE over time, especially relative to interest in alternative BPH treatments, are difficult to assess. The online tool for analysis of the popularity of top search queries (Google Trends; Alphabet Inc) provides a relative search volume (RSV) of specified keywords and insight about patterns of user searches.Purpose: The purpose of this study is to assess changes in public interest in PAE over time and compare them with changes in public interest in alternative BPH treatments as indicated by search queries.Material and Methods: Using Google Trends, we identified the RSV of specified keywords within search queries submitted between 2010 and 2019 in the United States. The RSVs of keywords with high search volume were identified and normalized on a scale of values from 0 to 100. Interest in PAE was assessed by comparing RSVs and trends of the keyword PAE as well as of other prostate-treatment-related keywords. Prostate embolization was a PAE-related, BPH-treatment-specific keyword with the highest average RSV. A linear regression analysis was performed to characterize annual search trends of the use of these keywords. Subsequently, the annual search trend of prostate embolization was compared with that of keywords related to transurethral resection of the prostate (TURP) and minimally invasive surgical treatments (MISTs).Results: The mean annual RSV of prostate embolization increased by 8.6 fold between 2010 and 2019. However, during this period, the mean RSV of the keywords transurethral resection of the prostate and TURP were 3.6 and 49.3 times higher, respectively (P

Fibro-adipogenic progenitors (FAPs) are essential in supporting regeneration in skeletal muscle, but in muscle pathologies FAPs the are main source of excess extracellular matrix (ECM) resulting in fibrosis. Fibrotic ECM has altered mechanical and architectural properties, but the feedback onto FAPs of stiffness or ECM properties is largely unknown. In this study, FAPs' sensitivity to their ECM substrate was assessed using collagen coated polyacrylamide to control substrate stiffness and collagen hydrogels to engineer concentration, crosslinking, fibril size, and alignment. FAPs on substrates of fibrotic stiffnesses had increased myofibroblast activation, depicted by αSMA expression, compared to substrates mimicking healthy muscle, which correlated strongly YAP nuclear localization. Surprisingly, fibrosis associated collagen crosslinking and larger fibril size inhibited myofibroblast activation, which was independent of YAP localization. Additionally, collagen crosslinking and larger fibril diameters were associated with decreased remodeling of the collagenous substrate as measured by second harmonic generation imaging. Inhibition of YAP activity through verteporfin reduced myofibroblast activation on stiff substrates but not substrates with altered architecture. This study is the first to demonstrate that fibrotic muscle stiffness can elicit FAP activation to myofibroblasts through YAP signaling. However, fibrotic collagen architecture actually inhibits myofibroblast activation through a YAP independent mechanism. These data expand knowledge of FAPs sensitivity to ECM and illuminate targets to block FAP's from driving progression of muscle fibrosis.

BackgroundHepatic arteriovenous malformations (AVMs) in hereditary hemorrhagic telangiectasia (HHT) patients are most commonly hepatic artery to hepatic venous shunts which can result in high-output heart failure. This condition can be debilitating and is a leading cause of liver transplantation in HHT patients. However, it is not known what characteristics can discriminate between asymptomatic patients and those who will develop heart failure symptoms.Results176 patients with HHT were evaluated with computed tomography angiography (CTA) between April 2004 and February 2019 at our HHT Center of Excellence. 63/176 (35.8%) patients were found to have hepatic AVMs on CTA. 18 of these patients were excluded because of the presence of another condition which could confound evaluation of heart failure symptoms. In the remaining 45 patients included in our cohort, 25/45 (55.6%) patients were classified as asymptomatic and 20/45 (44.4%) were classified as symptomatic, and these groups were compared. In symptomatic patients, mean common hepatic artery (CHA) diameter was significantly higher (11.1 versus 8.4 mm) and mean hemoglobin levels were significantly lower (10.7 vs 12.6 g/dL). A stepwise multiple logistic regression analysis demonstrated that both CHA diameter and hemoglobin level were independent predictors of heart failure symptoms with ORs of 2.554 (95% CI 1.372-4.754) and 0.489 (95% CI 0.299-0.799), respectively. The receiver operator characteristic (ROC) curve of our analysis demonstrated an AUC of 0.906 (95% CI 0.816-0.996), sensitivity 80.0% (95% CI 55.7-93.4%), and specificity 75.0% (95% CI 52.9-89.4%).ConclusionsCTA is an effective and easily reproducible method to evaluate hepatic involvement of HHT. Utilizing CTA, clinical, and laboratory data we determined CHA diameter and hemoglobin level were independent predictors of heart failure symptoms.

BackgroundWound healing is one of the defining features of life and is seen not only in tissues but also within individual cells. Understanding wound response at the single-cell level is critical for determining fundamental cellular functions needed for cell repair and survival. This understanding could also enable the engineering of single-cell wound repair strategies in emerging synthetic cell research. One approach is to examine and adapt self-repair mechanisms from a living system that already demonstrates robust capacity to heal from large wounds. Towards this end, Stentor coeruleus, a single-celled free-living ciliate protozoan, is a unique model because of its robust wound healing capacity. This capacity allows one to perturb the wounding conditions and measure their effect on the repair process without immediately causing cell death, thereby providing a robust platform for probing the self-repair mechanism.ResultsHere we used a microfluidic guillotine and a fluorescence-based assay to probe the timescales of wound repair and of mechanical modes of wound response in Stentor. We found that Stentor requires ~ 100-1000 s to close bisection wounds, depending on the severity of the wound. This corresponds to a healing rate of ~ 8-80 μm2/s, faster than most other single cells reported in the literature. Further, we characterized three distinct mechanical modes of wound response in Stentor: contraction, cytoplasm retrieval, and twisting/pulling. Using chemical perturbations, active cilia were found to be important for only the twisting/pulling mode. Contraction of myonemes, a major contractile fiber in Stentor, was surprisingly not important for the contraction mode and was of low importance for the others.ConclusionsWhile events local to the wound site have been the focus of many single-cell wound repair studies, our results suggest that large-scale mechanical behaviors may be of greater importance to single-cell wound repair than previously thought. The work here advances our understanding of the wound response in Stentor and will lay the foundation for further investigations into the underlying components and molecular mechanisms involved.

Digital breast tomosynthesis (DBT) reconstructions introduce out-of-plane artifacts and false-tissue boundaries impacting the dense/adipose and breast outline (convex hull) segmentations. A virtual clinical trial method was proposed to segment both the breast tissues and the breast outline in DBT reconstructions. The DBT images of a representative population were simulated using three acquisition geometries: a left–right scan (conventional, I), a two-directional scan in the shape of a “T” (II), and an extra-wide range (XWR, III) left–right scan at a six-times higher dose than I. The nnU-Net was modified including two losses for segmentation: (1) tissues and (2) breast outline. The impact of loss (1) and the combination of loss (1) and (2) was evaluated using models trained with data simulating geometry I. The impact of the geometry was evaluated using the combined loss (1&2). The loss (1&2) improved the convex hull estimates, resolving 22.2% of the false classification of air voxels. Geometry II was superior to I and III, resolving 99.1% and 96.8% of the false classification of air voxels. Geometry III (Dice = (0.98, 0.94)) was superior to I (0.92, 0.78) and II (0.93, 0.74) for the tissue segmentation (adipose, dense, respectively). Thus, the loss (1&2) provided better segmentation, and geometries T and XWR improved the dense/adipose and breast outline segmentations relative to the conventional scan.

Globally, there has been an increase in stringent regulations governing the use of chemical soil fumigants for controlling diseases, pests, and weeds. Grafting has been identified as an effective alternative to soil fumigation for managing soilborne diseases and pests in intensive vegetable cropping systems. The majority of watermelon (Citrullus lanatus) grafting research confirms that selected rootstocks play a role in improving plant resistance or tolerance to common soilborne diseases. Currently, there is a lack of evidence-based literature on the effects of grafting on watermelon fruit quality attributes and yield components. Previous reviews report wide variation in the impact of grafting on watermelon production, depending on rootstock–scion combinations and environmental conditions. This review employed evidence-based synthesis methods to comprehensively and methodically summarize research results of the impact of grafting on watermelon, with a focus on fruit quality and yield. In this systematic review, 548 citations (studies published during 2011–21) were screened against strict inclusion criteria, and data were extracted from 47 studies. Meta-analysis of percent differences between the grafted watermelon treatment and the nongrafted or self-grafted watermelon control was performed using extracted data of yield components and a wide range of fruit quality attributes. Meta-analysis of research data with variance measures was also conducted based on a rather limited number of studies. Our findings showed higher levels of total yield, average fruit weight, fruit length and width, fruit lycopene and soluble solids content, rind thickness, flesh firmness, lightness, chroma, and flesh nitrogen (N) content in grafted watermelon treatments compared with the nongrafted or self-grafted control. In particular, total yield, average fruit weight, and flesh firmness exhibited significant increases of a more than 10% difference. In contrast, grafted plants demonstrated decreases in fruit pH, hue angle, and flesh calcium content, although the reduction was not greater than 10% relative to the control. Meta-analysis of research data with variance measures further confirmed significantly greater total yield and flesh N content in grafted watermelon treatments compared with the nongrafted or self-grafted control. In addition, the meta-analysis results confirmed greater benefits of watermelon grafting in the presence of known soilborne disease pressure in contrast to the production scenarios without soilborne disease problems.

Abstract Background During the course of history, various important lifestyle changes have caused profound transitions of the gut microbiome. These include the introduction of agriculture and animal husbandry, a shift from a nomadic to a more sedentary lifestyle, and recently increased levels of urbanization and a transition towards a more Western lifestyle. The latter is linked with shifts in the gut microbiome that have a reduced fermentative capability and which are commonly associated with diseases of affluence. In this study, in which 5193 subjects are included, we investigated the direction of microbiome shifts that occur in various ethnicities living in Amsterdam by comparing 1st and 2nd generation participants. We furthermore validated part of these findings with a cohort of subjects that moved from rural Thailand to the USA. Results The abundance of the Prevotella cluster, which includes P. copri and the P. stercorea trophic network, diminished in the 2nd generation Moroccans and Turks but also in younger Dutch, whilst the Western-associated Bacteroides/Blautia/Bifidobacterium (BBB) cluster, which has an inverse correlation with α-diversity, increased. At the same time, the Christensenellaceae/Methanobrevibacter/Oscillibacter trophic network, which is positively associated with α-diversity and a healthy BMI, decreased in younger Turks and Dutch. Large compositional shifts were not observed in South-Asian and African Surinamese, in whom the BBB cluster is already dominant in the 1st generation, but ASV-level shifts towards certain species, associated amongst others with obesity, were observed. Conclusion The Moroccan and Turkish populations, but also the Dutch population are transitioning towards a less complex and fermentative less capable configuration of the gut microbiota, which includes a higher abundance of the Western-associated BBB cluster. The Surinamese, whom have the highest prevalence of diabetes and other diseases of affluence, are already dominated by the BBB cluster. Given the continuous increase in diseases of affluence, this devolution towards low-diversity and fermentatively less capable gut microbiome compositions in urban environments is a worrying development. Video Abstract Graphical Abstract

Desminopathy is the most common intermediate filament disease in humans. The most frequent mutation causing desminopathy in patients is a R350P DES missense mutation. We have developed a rat model with an analogous mutation in R349P Des. To investigate the role of R349P Des in mechanical loading, we stimulated the sciatic nerve of wild-type littermates (WT) (n = 6) and animals carrying the mutation (MUT) (n = 6) causing a lengthening contraction of the dorsi flexor muscles. MUT animals showed signs of ongoing regeneration at baseline as indicated by a higher number of central nuclei (genotype: P

Purpose: Joint contractures in children with cerebral palsy contain muscle tissue that is mechanically stiffer with higher collagen content than typically developing children. Interestingly, the correlation between collagen content and stiffness is weak. To date, no data are available on collagen types or other extracellular matrix proteins in these muscles, nor any information regarding their function. Thus, our purpose was to measure specific extracellular protein composition in cerebral palsy and typically developing human muscles along with structural aspects of extracellular matrix architecture to determine the extent to which these explain mechanical properties. Materials and Methods: Biopsies were collected from children with cerebral palsy undergoing muscle lengthening procedures and typically developing children undergoing anterior cruciate ligament reconstruction. Tissue was prepared for the determination of collagen types I, III, IV, and VI, proteoglycan, biglycan, decorin, hyaluronic acid/uronic acid and collagen crosslinking. Results: All collagen types increased in cerebral palsy along with pyridinoline crosslinks, total proteoglycan, and uronic acid. In all cases, type I or total collagen and total proteoglycan were positive predictors, while biglycan was a negative predictor of stiffness. Together these parameters accounted for a greater degree of variance within groups than across groups, demonstrating an altered relationship between extracellular matrix and stiffness with cerebral palsy. Further, stereological analysis revealed a significant increase in collagen fibrils organized in cables and an increased volume fraction of fibroblasts in CP muscle. Conclusions: These data demonstrate a novel adaptation of muscle extracellular matrix in children with cerebral palsy that includes alterations in extracellular matrix protein composition and structure related to mechanical function.

Cognitive decline is a common feature of aging, particularly in memory domains supported by the medial temporal lobe (MTL). The ability to identify intervention strategies to treat or prevent this decline is challenging due to substantial variability between adults in terms of age of onset, rate and severity of decline, and many factors that could influence cognitive reserve. These factors can be somewhat mitigated by use of within-subject designs. Aged outbred Long-Evans rats have proven useful for identifying translationally relevant substrates contributing to age-related decline in MTL-dependent memory. In this population, some animals show reliable impairment on MTL-dependent tasks while others perform within the range of young adult rats. However, currently there are relatively few within-subject behavior protocols for assessing MTL function over time, and most require extensive training and appetitive motivation for associative learning. In the current study, we aimed to test whether water maze learning impairments in aged Long-Evans rats would be predictive of delayed recognition memory impairments and whether these odor memory impairments would be stable within subjects over multiple rounds of testing.

BackgroundImmunotherapy of cancer is an emerging field with the potential to improve long-term survival. Thus far, adoptive transfer of tumor-specific T cells represents an effective treatment option for tumors of the hematological system such as lymphoma, leukemia or myeloma. However, in solid tumors, treatment efficacy is low owing to the immunosuppressive microenvironment, on-target/off-tumor toxicity, limited extravasation out of the blood vessel, or ineffective trafficking of T cells into the tumor region. Superparamagnetic iron oxide nanoparticles (SPIONs) can make cells magnetically controllable for the site-specific enrichment. MethodsIn this study, we investigated the influence of SPION-loading on primary human T cells for the magnetically targeted adoptive T cell therapy. For this, we analyzed cellular mechanics and the T cell response after stimulation via an exogenous T cell receptor (TCR) specific for the melanoma antigen MelanA or the endogenous TCR specific for the cytomegalovirus antigen pp65 and compared them to T cells that had not received SPIONs.ResultsSPION-loading of human T cells showed no influence on cellular mechanics, therefore retaining their ability to deform to external pressure. Additionally, SPION-loading did not impair the T cell proliferation, expression of activation markers, cytokine secretion, and tumor cell killing after antigen-specific activation mediated by the TCR. ConclusionIn summary, we demonstrated that SPION-loading of T cells did not affect cellular mechanics or the functionality of the endogenous or an exogenous TCR, which allows future approaches using SPIONs for the magnetically enrichment of T cells in solid tumors.

Key pointsThe amount of fibrotic material in dystrophic mouse muscles relates to contractile function, but not passive function. Collagen fibres in skeletal muscle are associated with increased passive muscle stiffness in fibrotic muscles. The alignment of collagen is independently associated with passive stiffness in dystrophic skeletal muscles. These outcomes demonstrate that collagen architecture rather than collagen content should be a target of anti-fibrotic therapies to treat muscle stiffness.AbstractFibrosis is prominent in many skeletal muscle pathologies including dystrophies, neurological disorders, cachexia, chronic kidney disease, sarcopenia and metabolic disorders. Fibrosis in muscle is associated with decreased contractile forces and increased passive stiffness that limits joint mobility leading to contractures. However, the assumption that more fibrotic material is directly related to decreased function has not held true. Here we utilize novel measurement of extracellular matrix (ECM) and collagen architecture to relate ECM form to muscle function. We used mdx mice, a model for Duchenne muscular dystrophy that becomes fibrotic, and wildtype mice. In this model, extensor digitorum longus (EDL) muscle was significantly stiffer, but with similar total collagen, while the soleus muscle did not change stiffness, but increased collagen. The stiffness of the EDL was associated with increased collagen crosslinking as determined by collagen solubility. Measurement of ECM alignment using polarized light microscopy showed a robust relationship between stiffness and alignment for wildtype muscle that broke down in mdx muscles. Direct visualization of large collagen fibres with second harmonic generation imaging revealed their relative abundance in stiff muscles. Collagen fibre alignment was linked to stiffness across all muscles investigated and the most significant factor in a multiple linear regression-based model of muscle stiffness from ECM parameters. This work establishes novel characteristics of skeletal muscle ECM architecture and provides evidence for a mechanical function of collagen fibres in muscle. This finding suggests that anti-fibrotic strategies to enhance muscle function and excessive stiffness should target large collagen fibres and their alignment rather than total collagen.