Abstract Cancer arises in the context of an in vivo tumor microenvironment. This microenvironment is both a cause and consequence of tumorigenesis. Tumor and host cells co-evolve dynamically through ...indirect and direct cellular interactions, eliciting multiscale effects on many biological programs, including cellular proliferation, growth, and metabolism, as well as angiogenesis and hypoxia and innate and adaptive immunity. Here we highlight specific biological processes that could be exploited as targets for the prevention and therapy of cancer. Specifically, we describe how inhibition of targets such as cholesterol synthesis and metabolites, reactive oxygen species and hypoxia, macrophage activation and conversion, indoleamine 2,3-dioxygenase regulation of dendritic cells, vascular endothelial growth factor regulation of angiogenesis, fibrosis inhibition, endoglin, and Janus kinase signaling emerge as examples of important potential nexuses in the regulation of tumorigenesis and the tumor microenvironment that can be targeted. We have also identified therapeutic agents as approaches, in particular natural products such as berberine, resveratrol, onionin A, epigallocatechin gallate, genistein, curcumin, naringenin, desoxyrhapontigenin, piperine, and zerumbone, that may warrant further investigation to target the tumor microenvironment for the treatment and/or prevention of cancer.
Examine the prevalence, patterns, and persistence of parent-reported sleep problems during the first 3 years of life.
Three hundred fifty-nine mother/child pairs participated in a prospective birth ...cohort study. Sleep questionnaires were administered to mothers when children were 6, 12, 24, and 36 months old. Sleep variables included parent response to a nonspecific query about the presence/absence of a sleep problem and 8 specific sleep outcome domains: sleep onset latency, sleep maintenance, 24-hour sleep duration, daytime sleep/naps, sleep location, restlessness/vocalization, nightmares/night terrors, and snoring.
Prevalence of a parent-reported sleep problem was 10% at all assessment intervals. Night wakings and shorter sleep duration were associated with a parent-reported sleep problem during infancy and early toddlerhood (6-24 months), whereas nightmares and restless sleep emerged as associations with report of a sleep problem in later developmental periods (24-36 months). Prolonged sleep latency was associated with parent report of a sleep problem throughout the study period. In contrast, napping, sleep location, and snoring were not associated with parent-reported sleep problems. Twenty-one percent of children with sleep problems in infancy (compared with 6% of those without) had sleep problems in the third year of life.
Ten percent of children are reported to have a sleep problem at any given point during early childhood, and these problems persist in a significant minority of children throughout early development. Parent response to a single-item nonspecific sleep query may overlook relevant sleep behaviors and symptoms associated with clinical morbidity.
MYC: Master Regulator of Immune Privilege Casey, Stephanie C; Baylot, Virginie; Felsher, Dean W
Trends in immunology,
04/2017, Letnik:
38, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Cancers are often initiated by genetic events that activate proto-oncogenes or inactivate tumor-suppressor genes. These events are also crucial for sustained tumor cell proliferation and survival, a ...phenomenon described as oncogene addiction. In addition to this cell-intrinsic role, recent evidence indicates that oncogenes also directly regulate immune responses, leading to immunosuppression. Expression of many oncogenes or loss of tumor suppressors induces the expression of immune checkpoints that regulate the immune response, such as PD-L1. We discuss here how oncogenes, and in particular MYC , suppress immune surveillance, and how oncogene-targeted therapies may restore the immune response against tumors.
'Candidatus Liberibacter asiaticus' is transmitted by psyllids and causes huanglongbing (HLB), a lethal disease of citrus. Most pathogenic 'Ca. L. asiaticus' strains carry two nearly identical ...prophages similar to SC1 and SC2 in strain UF506. SC2 was observed to replicate as a moderately high-copy excision plasmid encoding a reactive oxygen species-scavenging peroxidase (SC2_gp095), a predicted lysogenic conversion factor. SC2_gp095 was expressed at significantly higher levels in periwinkle than in citrus and was suppressed in psyllids. SC2_gp095 was cloned in a shuttle vector and transformed into Escherichia coli and Liberibacter crescens, a culturable proxy for 'Ca. L. asiaticus'. Transformed L. crescens cells showed 20 to 25% enhanced resistance to H₂O₂on agar plates, 47% greater enzymatic activity, and enhanced growth in liquid cultures. A nonclassical secretion potential was predicted for SC2_gp095 and secretion from L. crescens was confirmed by enzymatic and Western blot analyses. Transient expression of SC2_gp095 in planta resulted in strong transcriptional downregulation of RbohB, the key gatekeeper of the H₂O₂-mediated defense signaling in plants, helping explain the surprisingly long incubation period (years) before HLB symptoms appear in 'Ca. L. asiaticus'-infected citrus. 'Ca. L. asiaticus' peroxidase is likely a secreted, horizontally acquired effector that suppresses host symptom development, a tactic used by most biotrophic plant pathogens.
Large numbers of histopathological images have been digitized into high resolution whole slide images, opening opportunities in developing computational image analysis tools to reduce pathologists' ...workload and potentially improve inter- and intra-observer agreement. Most previous work on whole slide image analysis has focused on classification or segmentation of small pre-selected regions-of-interest, which requires fine-grained annotation and is non-trivial to extend for large-scale whole slide analysis. In this paper, we proposed a multi-resolution multiple instance learning model that leverages saliency maps to detect suspicious regions for fine-grained grade prediction. Instead of relying on expensive region- or pixel-level annotations, our model can be trained end-to-end with only slide-level labels. The model is developed on a large-scale prostate biopsy dataset containing 20,229 slides from 830 patients. The model achieved 92.7% accuracy, 81.8% Cohen's Kappa for benign, low grade (i.e. Grade group 1) and high grade (i.e. Grade group ≥ 2) prediction, an area under the receiver operating characteristic curve (AUROC) of 98.2% and an average precision (AP) of 97.4% for differentiating malignant and benign slides. The model obtained an AUROC of 99.4% and an AP of 99.8% for cancer detection on an external dataset.
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•A multi-resolution multiple instance learning model is developed for Gleason grade group classification.•The model can localize suspicious regions, and then classify cancer grade at a higher magnification with selected tiles.•The model doesn’t require fine-grained annotations and can be trained with slide-level labels from pathology reports.•The model was evaluated on a large independent test set and an external dataset, and achieved promising results.
Examine the effect of experimental sleep restriction (SR) on adolescents' subjective hunger and perceived appeal of sweet/dessert foods versus other foods. A secondary goal was to replicate previous ...findings on the effects of SR on dietary intake.
Randomized cross-over sleep restriction-extension paradigm.
Sleep was obtained and monitored at home. Outcome measures were gathered during office visits.
31 typically-developing adolescents aged 14-17 years.
The three-week protocol consisted of a baseline week, followed randomly by five consecutive nights of SR (6.5 hours in bed) versus healthy sleep duration (HS; 10 hours in bed), a 2-night wash-out period, and a 5-night cross-over.
Sleep was monitored via actigraphy. The morning after each experimental condition, teens rated their hunger, underwent a 24-hour diet recall interview, and rated the appeal of a series of pictures of sweet/dessert foods (e.g., ice cream, candy) and non-sweets (meat, eggs, fruits, vegetables).
Teens rated pictures of sweet/dessert foods to be more appealing after SR than after HS (Cohen's d = .41, t = 2.07, p = .045). The sleep manipulation did not affect self-reported hunger or the appeal of non-sweet foods (p >.10). Consistent with our prior work, intake of overall calories was 11% higher and consumption of sweet/dessert servings was 52% greater during SR than HS.
Adolescent SR appears to increase the subjective appeal of sweet/dessert foods, indicating a potential mechanism by which SR might contribute to weight gain and the risk for obesity and chronic illness.
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death. Non-alcoholic fatty liver disease (NAFLD) affects a large proportion of the US population and is considered to ...be a metabolic predisposition to liver cancer. However, the role of adaptive immune responses in NAFLD-promoted HCC is largely unknown. Here we show, in mouse models and human samples, that dysregulation of lipid metabolism in NAFLD causes a selective loss of intrahepatic CD4(+) but not CD8(+) T lymphocytes, leading to accelerated hepatocarcinogenesis. We also demonstrate that CD4(+) T lymphocytes have greater mitochondrial mass than CD8(+) T lymphocytes and generate higher levels of mitochondrially derived reactive oxygen species (ROS). Disruption of mitochondrial function by linoleic acid, a fatty acid accumulated in NAFLD, causes more oxidative damage than other free fatty acids such as palmitic acid, and mediates selective loss of intrahepatic CD4(+) T lymphocytes. In vivo blockade of ROS reversed NAFLD-induced hepatic CD4(+) T lymphocyte decrease and delayed NAFLD-promoted HCC. Our results provide an unexpected link between lipid dysregulation and impaired anti-tumour surveillance.
Payload size and weight are critical factors for small Unmanned Aerial Vehicles (UAVs). Digital color-infrared photographs were acquired from a single 12-megapixel camera that did not have an ...internal hot-mirror filter and had a red-light-blocking filter in front of the lens, resulting in near-infrared (NIR), green and blue images. We tested the UAV-camera system over two variably-fertilized fields of winter wheat and found a good correlation between leaf area index and the green normalized difference vegetation index (GNDVI). The low cost and very-high spatial resolution associated with the camera-UAV system may provide important information for site-specific agriculture.
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