Microsatellite instable tumors often respond to immune checkpoint blockade (ICB), however, tumor tissue is unavailable/insufficient in some patients. Two groups are reporting a blood-based assessment of the microsatellite status validated in tumor tissue and by clinical benefit in patient receiving ICB. Both approaches are highly appealing with a few caveats.
Mon Sep 16, 2019 17:09
Purpose: Bromodomain and extraterminal (BET) proteins are key epigenetic transcriptional regulators, inhibition of which may suppress oncogene expression. We report results from 2 independent first-in-human phase 1/2 dose-escalation and expansion, safety and tolerability studies of BET inhibitors INCB054329 (study INCB 54329-101; NCT02431260) and INCB057643 (study INCB 57643-101; NCT02711137). Methods: Patients (≥18 years) with advanced malignancies, ≥1 prior therapy, and adequate organ functions...
Mon Sep 16, 2019 17:09
Background: Preclinical data identified the CDK4/6 inhibitor palbociclib as synergistic with anti-estrogens in inhibiting growth of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) human breast cancer models. This observation was validated clinically in the randomized, placebo-controlled, phase 3 PALOMA-2 study. Methods: To determine markers of sensitivity and resistance to palbociclib plus letrozole, we performed comprehensive biomarker analyses, investigating...
Mon Sep 16, 2019 17:09
Purpose: Predicting surgical outcome, could improve individualizing treatment strategies for patients with advanced ovarian cancer. It has been suggested earlier, that gene expression signatures (GES) might harbor the potential to predict surgical outcome. Experimental Design: Data derived from high-grade serous tumor tissue of FIGO-stage IIIC/IV patients of AGO-OVAR11-trial were used to generate a transcriptome profiling. Previously identified molecular signatures were tested. A theoretical model...
Mon Sep 16, 2019 17:09
In recent years several clinical studies have investigated de-intensified treatments in HPV-associated head and neck squamous cell carcinoma. Two large Phase III trials, RTOG-1016 and De-ESCALaTE, which attempted to reduce toxicity by replacing radiotherapy (RT) in combination with cisplatin with the use of cetuximab in combination with RT, recently suggested that RT+cetuximab leads to inferior survival compared to standard therapy (observed hazard ratios of 1.45 and 5 in RTOG-1016 and De-ESCALaTE)....
Mon Sep 16, 2019 17:09
Purpose: The burden of esophageal cancer (EC) continues to rise, and non-invasive screening tools are needed. Methylated DNA markers (MDMs) assayed from plasma show promise in detection of other cancers. For EC detection, we aimed to discover and validate MDMs in tissue, and determine their feasibility when assayed from plasma. Experimental Design: Whole-methylome sequencing was performed on DNA extracted from 37 tissues (28 EC; 9 normal esophagus) and 8 buffy coat samples. Top MDMs were validated...
Mon Sep 16, 2019 17:09
Purpose: Napabucasin (2-acetylfuro-1,4-naphthoquinone or BBI-608) is a small molecule currently being clinically evaluated in various cancer types. It has mostly been recognized for its ability to inhibit STAT3 signaling. However, based on its chemical structure, we hypothesized that napabucasin is a substrate for intracellular oxidoreductases and therefore may exert its anti-cancer effect through redox cycling, resulting in reactive oxygen species (ROS) production and cell death. Experimental Design:...
Mon Sep 16, 2019 17:09
Once dismissed as 'junk DNA' that served no purpose, a family of 'jumping genes' found in tomatoes has the potential to accelerate crop breeding for traits such as improved drought resistance.
Mon Sep 16, 2019 21:39
Corn, soybean, and cotton farmers shudder at the thought of Palmer amaranth invading their fields. The aggressive cousin of waterhemp - itself a formidable adversary - grows extremely rapidly, produces hundreds of thousands of seeds per plant, and is resistant to multiple classes of herbicides. New research explains Palmer's evil genius.
Mon Sep 16, 2019 21:39
Early rice growers unwittingly gave barnyard grass a big hand, helping to give root to a rice imitator that is now considered one of the world's worst agricultural weeds.
00:01
Major physical changes occurred in the human heart as people shifted from hunting and foraging to farming and modern life. As a result, human hearts are now less 'ape-like' and better suited to endurance types of activity.
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Using DNA from museum specimens collected in the early 20th century, researchers identified two new species of giant salamander -- one of which they suspect is the world's biggest amphibian.
04:25
For ornamental annual bedding plants, flowering performance is critical. Flowering performance includes the length of the flowering period, the longevity of individual flowers, and the number of flowers produced during the flowering period, or flowering capacity. Flowering capacity is a function of several component traits, including the number of branches producing flowers, the number of inflorescences per flowering branch, and the number of flower buds per inflorescence. We employed an F7Petunia...
Mon Sep 16, 2019 20:13
Repellent odors are widely used to prevent insect-borne diseases, making it imperative to identify the conserved molecular underpinnings of their olfactory systems. Currently, little is known about the molecules supporting odor signaling beyond the odor receptors themselves. Most known molecules function in one of two classes of olfactory sensilla, single-walled or double-walled, which have differing morphology and odor response profiles. Here, we took two approaches to discover novel genes that...
Mon Sep 16, 2019 20:13
A new paradigm has emerged that coding regions can regulate mRNA stability in model organisms. Here, due to differences in cognate tRNA abundance, synonymous codons are translated at different speeds, and slow codons then stimulate mRNA decay. To ask if this phenomenon also occurs in humans, we isolated RNA stability effects due to coding regions using the human ORFeome collection. We find that many ORF characteristics, such as length and secondary structure, fail to provide explanations for how...
Mon Sep 16, 2019 18:07
Thyroid cancers are the most common malignancy of the endocrine system; however, there is no reliable blood biomarkers for thyroid cancer diagnosis and even for aggressive and nonaggressive thyroid cancers as well as benign nodule discrimination. The present study is aimed at evaluating whether circulating microRNA (miRNA) can differentiate aggressive and nonaggressive thyroid cancer from benign thyroid nodules. In this study, we performed a multiphase, case-control study to screen serum miRNA expression...
Mon Sep 16, 2019 14:05
The CellSearch® system which is still considered the gold standard for the enumeration of circulating tumor cells (CTC) utilizes antibodies against the epithelial cell adhesion molecule (EpCAM) for CTC enrichment. Recently, CTC discarded by the CellSearch® system due to their low EpCAM expression have been isolated and analyzed. We here sought to discuss technical and biological issues concerning the isolation and characterization of EpCAMlow CTC, highlighting the enormous potential of this subpopulation...
03:05
Background and Objective. A reliable noninvasive prediction tool for the screening, diagnosis, and/or staging of colorectal cancer (CRC) before surgery is critical for the choice of treatment and prognosis. Methods. Patients admitted for initial treatment of CRC between January 1, 2015, and December 31, 2018, were retrieved and reviewed. Records of CD16+CD56+ natural killer (NK) cells were analyzed according to the stages of CRC. Results. The number of qualified participants in the healthy, stage...
05:05
Analyst, 2019, Accepted ManuscriptDOI: 10.1039/C9AN01671F, PaperNa Liu, zhen zou, Jin Liu, Cong Zhu, Jing Zheng, Rong-Hua YangAs an endothelial cell-specific mitogen and a key regulator of angiogenesis in varieties of physiological and pathological processes, the high expression of VEGF message RNA (mRNA) contributes to the VEGF-driven...The content of this RSS Feed (c) The Royal Society of Chemistry
Mon Sep 16, 2019 02:00
Analyst, 2019, Accepted ManuscriptDOI: 10.1039/C9AN01109A, Paper Open Access This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.Immaculada Martínez-Rovira, Olivier Seksek, Ibraheem YousefThe inclusion of nanoparticles (NP) in radiotherapy has shown to increase the damaging effect on tumor cells. However, the mechanisms of action of NP combined with radiotherapy, and the influence...The content of this RSS Feed (c) The Royal Society of Chemistry
Mon Sep 16, 2019 02:00
Analyst, 2019, Accepted ManuscriptDOI: 10.1039/C9AN01113G, PaperMeizhe Wang, Jingjing Gao, Bo Zhao, Sankaran Thayumanavan, Richard VachetMass spectrometry (MS)-based analysis of glycoproteins and glycopeptides requires selective separation strategies to eliminate interferences from more abundant non-glycosylated biomolecules. In this work, we describe a two-phase liquid-liquid extraction method...The content of this RSS Feed (c) The Royal Society of Chemistry
Mon Sep 16, 2019 02:00
Analyst, 2019, Accepted ManuscriptDOI: 10.1039/C9AN01501A, PaperEmily Brooks, Sue Mutengwa, Aya Abdalla, Mark Yeoman, Bhavik Anil PatelSerotonin and kynurenine are formed following metabolism of the essential amino acid tryptophan. Both molecules play important biological roles and the balance of how tryptophan metabolism varies to either the...The content of this RSS Feed (c) The Royal Society of Chemistry
Mon Sep 16, 2019 02:00
Analyst, 2019, Accepted ManuscriptDOI: 10.1039/C9AN01445D, PaperLiping Zhu, Jing Ye, Mengxia Yan, Qiuju Zhu, Xiurong YangIn this study, a wavelength-resolved electrochemiluminescence resonance energy transfer (ECL-RET) ratiometric immunosensor from Au nanoparticles functionalized graphite-like carbon nitride nanosheet (Au-g-C3N4) to Au nanoclusters (Au NCs) was constructed for the...The content of this RSS Feed (c) The Royal Society of Chemistry
02:00
Analyst, 2019, Accepted ManuscriptDOI: 10.1039/C9AN01065C, PaperLina Chen, Chenghong Sun, Linli Pan, Zhang Lei , Jiaojiao Huang, Dandan Yao, Chong-Zhi Wang, Yu Zhang, Nan Jiang, Chun-Su YuanA biomimetic fluorescent nanosensor based on molecularly imprinted polymers modified with carbon dots (CDs@MIPs) has been created for rapid, selective and sensitive detection of alpha-fetoprotein (AFP) in clinical samples. The...The content of this RSS Feed (c) The Royal Society of Chemistry
02:00
Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
06:37
Chronic Respiratory Disease, Volume 16, Issue , January-December 2019. Combined exercise rehabilitation for chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) is potentially attractive. Uncertainty remains as to the baseline profiling assessments and outcome measures that should be collected within a programme. Current evidence surrounding outcome measures in cardiac and pulmonary rehabilitation were presented by experts at a stakeholder consensus event and all stakeholders...
04:49
Chronic Respiratory Disease, Volume 16, Issue , January-December 2019. There is no accepted standard for measuring mobility in hospitalized patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The objective of this study was to assess convergent, discriminant, and known-group validity and floor/ceiling effects of the de Morton Mobility Index (DEMMI) in hospitalized patients with AECOPD. Individuals with AECOPD (n = 22) admitted to an acute care hospital medical ward...
04:50
Genetic studies of both the human host and Mycobacterium tuberculosis (MTB) demonstrate independent association with tuberculosis (TB) risk. However, neither explains a large portion of disease risk or severity. Based on studies in other infectious diseases and animal models of TB, we hypothesized that the genomes of the two interact to modulate risk of developing active TB or increasing the severity of disease, when present. We examined this hypothesis in our TB household contact study in Kampala,...
Mon Sep 16, 2019 03:00
O_LIMorphometrics has become an indispensable component of the statistical analysis of size and shape variation in biological structures. Morphometric data has traditionally been gathered through low-throughput manual landmark annotation, which represents a significant bottleneck for morphometric-based phenomics. Here we propose a machine-learning-based high-throughput pipeline to collect high-dimensional morphometric data in images of semi rigid biological structures. C_LIO_LIThe proposed framework...
Mon Sep 16, 2019 03:00
Synonymous codon use is non-random. Codons most used in highly transcribed genes, often called optimal codons, typically have high gene counts of matching tRNA genes (tRNA abundance) and promote accurate and/or efficient translation. Non-optimal codons, those least used in highly expressed genes, may also affect translation. In multicellular organisms, codon optimality may vary among tissues. At present however, codon use remains poorly understood in multicellular organisms. Here, we studied codon...
Mon Sep 16, 2019 03:00
The stress response is a product of selection for an integrated suite of behavioural and physiological traits that facilitate coping with acute stressors. As such, genetic variation in the stress response is expected to reflect genetic variation in, and genetic covariation among, its behavioural and physiological components. Such genetic integration among stress response components has yet to be formally demonstrated using multivariate quantitative genetics, despite its profound implications for...
Mon Sep 16, 2019 03:00
Nations throughout the Indo-Pacific region use pyrethroid insecticides to control Aedes aegypti, the mosquito vector of dengue, often without knowledge of pyrethroid resistance status of the pest or origin of resistance. Two mutations in the sodium channel gene (Vssc) of Ae. aegypti modify ion channel function and cause target-site resistance to pyrethroid insecticides, with a third mutation having a potential additive effect. Of 27 possible genotypes involving these mutations, some allelic combinations...
Mon Sep 16, 2019 03:00
Heterochromatin suppresses repetitive DNA, and a loss of heterochromatin has been observed in aged cells of several species, including humans and Drosophila. Males often contain substantially more heterochromatic DNA than females, due to the presence of a large, repeat-rich Y chromosome, and male flies generally have shorter average life spans than females. Here we show that repetitive DNA becomes de-repressed more rapidly in old male flies relative to females, and repeats on the Y chromosome are...
Mon Sep 16, 2019 03:00
Accurate estimates of divergence times are essential to understand the evolutionary history of species. It allows linking evolutionary histories of the diverging lineages with past geological, climatic and other changes in environment and shed light on the processes involved in speciation. The pea aphid radiation includes multiple host races adapted to different legume host plants. It is thought that diversification in this system occurred very recently, over the past 8,000 to 16,000 years. This...
Mon Sep 16, 2019 03:00
Cancer genomes exhibit surprisingly weak signatures of negative selection. This may be because tumors evolve either under very weak selective pressures (weak selection) or under conditions that prevent the elimination of many deleterious passenger mutations (poor efficacy of selection). The weak selection model argues that the majority of genes are only important for multicellular function. The poor efficacy of selection model argues, in contrast, that genome-wide linkage in cancer prevents many...
Mon Sep 16, 2019 03:00
The insulin superfamily proteins (ISPs), in particular, insulin, IGFs and relaxins are key modulators of animal physiology. They are known to have evolved from the same ancestral gene and have diverged into proteins with varied sequences and distinct functions, but maintain a similar structural architecture stabilized by highly conserved disulphide bridges. A recent surge of sequence data and the structures of these proteins prompted a need for a comprehensive analysis which connects the evolution...
Mon Sep 16, 2019 03:00
Numerous lineages of mushroom-forming fungi have been subject to bursts of diversification throughout their evolutionary history, events that can impact our ability to infer well-resolved phylogenies. However, groups that have undergone quick genetic change may have the highest adaptive potential. As the second largest genus of mushroom-forming fungi, Russula provides an excellent model for studying hyper-diversification and processes in evolution that drives it. This study focuses on the morphologically...
Mon Sep 16, 2019 03:00
Chromosome metabolism is defined by the pathways that collectively maintain the genome, including chromosome replication, repair and segregation. Because aspects of these pathways are conserved, chromosome metabolism is considered resistant to evolutionary change. We used the budding yeast, Saccharomyces cerevisiae, to investigate the evolutionary plasticity of chromosome metabolism. We experimentally evolved cells constitutively experiencing DNA replication stress caused by the absence of Ctf4,...
Mon Sep 16, 2019 03:00
Recent genome sequencing studies with large sample sizes in humans have discovered a vast quantity of low-frequency variants, providing an important source of information to analyze how selection is acting on human genetic variation. In order to estimate the strength of natural selection acting on low-frequency variants, we have developed a likelihood-based method that uses the lengths of pairwise identity-by-state between haplotypes carrying low-frequency variants. We show that in some non-equilibrium...
Mon Sep 16, 2019 03:00
The biotic interactions hypothesis proposes that strong species interactions in the tropics drive faster divergence in the tropics. However, support for the idea that interactions are stronger in the tropics is mixed. Here we propose an explanation for why observed interaction strengths might often be similar across latitudes. We suggest populations might adapt to latitudinal differences in species interaction regimes, which can have the effect of flattening observed latitudinal gradients in interaction...
Mon Sep 16, 2019 03:00
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