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Πέμπτη 21 Ιουνίου 2018
Scholar : Addiction Research & Theory, Volume 26, Issue 4, August 2018 is now available online on Taylor & Francis Online
Hematopoietic Hierarchy – An Updated Roadmap
Publication date: Available online 20 June 2018
Source:Trends in Cell Biology
Author(s): Yifan Zhang, Shuai Gao, Jun Xia, Feng Liu
The classical roadmap of hematopoietic hierarchy has been proposed for nearly 20 years and has become a dogma of stem cell research for most types of adult stem cells, including hematopoietic stem cells (HSCs). However, with the development of new technologies such as omics approaches at single-cell resolution, recent studies in vitro and in vivo have suggested that heterogeneity is a common feature of HSCs and their progenies. While these findings broaden our understanding of hematopoiesis, they also challenge the well-accepted hematopoietic hierarchy roadmap. Here, we review recent advances in the hematopoiesis field and provide an updated view to incorporate these new findings as well as to reflect on the complexity of HSCs and their derivatives in development and adulthood.
https://ift.tt/2ttWHFU
Apoptotic Cell-Derived Extracellular Vesicles Promote Malignancy of Glioblastoma Via Intercellular Transfer of Splicing Factors
Publication date: Available online 21 June 2018
Source:Cancer Cell
Author(s): Marat S. Pavlyukov, Hai Yu, Soniya Bastola, Mutsuko Minata, Victoria O. Shender, Yeri Lee, Suojun Zhang, Jia Wang, Svetlana Komarova, Jun Wang, Shinobu Yamaguchi, Heba Allah Alsheikh, Junfeng Shi, Dongquan Chen, Ahmed Mohyeldin, Sung-Hak Kim, Yong Jae Shin, Ksenia Anufrieva, Evgeniy G. Evtushenko, Nadezhda V. Antipova, Georgij P. Arapidi, Vadim Govorun, Nikolay B. Pestov, Mikhail I. Shakhparonov, L. James Lee, Do-Hyun Nam, Ichiro Nakano
Aggressive cancers such as glioblastoma (GBM) contain intermingled apoptotic cells adjacent to proliferating tumor cells. Nonetheless, intercellular signaling between apoptotic and surviving cancer cells remain elusive. In this study, we demonstrate that apoptotic GBM cells paradoxically promote proliferation and therapy resistance of surviving tumor cells by secreting apoptotic extracellular vesicles (apoEVs) enriched with various components of spliceosomes. apoEVs alter RNA splicing in recipient cells, thereby promoting their therapy resistance and aggressive migratory phenotype. Mechanistically, we identified RBM11 as a representative splicing factor that is upregulated in tumors after therapy and shed in extracellular vesicles upon induction of apoptosis. Once internalized in recipient cells, exogenous RBM11 switches splicing of MDM4 and Cyclin D1 toward the expression of more oncogenic isoforms.
Graphical abstract
Teaser
Pavlyukov et al. show that apoptotic GBM cells secrete vesicles enriched with components of spliceosomes to alter RNA splicing in surviving tumor cells and promote their aggressiveness. They identify RBM11 as one such factor that switches MDM4 and cyclinD1 toward the more oncogenic isoforms in recipient cells.https://ift.tt/2JZElI4
Historical accumulation and ecological risk assessment of heavy metals in sediments of a drinking water lake
Abstract
Heavy metal contamination in sediments is progressively being recognized as a challenging problem in large parts of the developing world, particularly in Asian countries. A drinking water lake in Yunnan-Guizhou plateau, China named Hongfeng Lake was selected as the research target. Forty surface sediment samples and 4 sediment cores were collected to reveal the accumulation of heavy metals in the sediments of the lake. The mean concentrations of Cr, Cu, Pb, Cd, As, and Hg in surface sediments were 81.67, 45.61, 29.78, 0.53, 22.71, and 0.25 mg/kg, respectively, which exceeded the background levels of sediment 1.1~3.3 times. The calculation of geoaccumulation (Igeo) and potential ecological risk (PER) index analysis were preformed, and the results showed a considerable risk for Cd and Hg on the whole. Spatially, the northern part showed a higher risk than the southern part and tributaries of the lake, and a moderate risk in the overall sediment of the lake. The historical level of heavy metals in Hongfeng Lake was traced by vertical sediments study and it was dated back approximately 35 years. The EF trends of a feature sampling site HF8 showed strong temporal variations, and peaked in the year 1995. After that, the EFs exhibited a declining trend, which reflects productive environmental protection and management by the local government. For the Hongfeng Lake, a typical lake with heavy metal-contaminated sediments, the in-situ remediation technique could be a suitable method for its remediation.
https://ift.tt/2loUWGw
Risk of high-grade serous ovarian cancer associated with pelvic inflammatory disease, parity and breast cancer
Source:Cancer Epidemiology, Volume 55
Author(s): Louise M. Stewart, Katrina Spilsbury, Susan Jordan, Colin Stewart, C. D'Arcy J. Holman, Aime Powell, Joanne Reekie, Paul Cohen
BackgroundOvarian carcinoma is not a single disease, but rather a collection of subtypes with differing molecular properties and risk profiles. The most common of these, and the subject of this work, is high-grade serous ovarian carcinoma (HGSC).MethodsIn this population-based study we identified a cohort of 441,382 women resident in Western Australia who had ever been admitted to hospital in the State. Of these, 454 were diagnosed with HGSC. We used Cox regression to derive hazard ratios (HRs) comparing the risk of disease in women who had each of a range of medical diagnoses and surgical procedures with women who did not.ResultsWe found an increased risk of HGSC associated with a diagnosis of pelvic inflammatory disease (PID) (HR 1.47, 95% CI 1.04–2.07) but not with a diagnosis of infertility or endometriosis with HRs of 1.12 (95% CI 0.73–1.71) and 0.82 (95% CI 0.55–1.22) respectively. A personal history of breast cancer was associated with a three-fold increase in the rate of HGSC. Increased parity was associated with a reduced risk of HGSC in women without a personal history of breast cancer (HR 0.57; 95% CI 0.44-0.73), but not in women with a personal history of breast cancer (HR 1.48; 95% CI 0.74–2.95).ConclusionsOur finding of an increased risk of HGSC associated with PID lends support to the hypothesis that inflammatory processes may be involved in the etiology of HGSC.
https://ift.tt/2JXqKBe
The scientific impact and value of large, NCI-sponsored randomized phase III cancer chemoprevention trials
Publication date: August 2018
Source:Cancer Epidemiology, Volume 55
Author(s): Joseph M. Unger, William E. Barlow, Catherine M. Tangen, Scott D. Ramsey, Ian M. Thompson, Eric A. Klein, Michael LeBlanc, Charles D. Blanke, Phyllis J. Goodman, Lori M. Minasian, Van T. Nghiem, Dawn L. Hershman
BackgroundThe cancer research groups of the National Cancer Institute's National Clinical Trials Network have a history of successful conduct of large randomized phase III trials of chemoprevention for cancer. An important question for funding agencies is whether the conduct of large chemoprevention trials provides strong scientific return on investment.MethodsWe evaluated the scientific impact of four large chemoprevention trials – two for breast cancer and two for prostate cancer – using citation analysis, a bibliometric technique. The results were compared to the scientific impact of a series of treatment trials conducted over the same 20-year time period (1991–2010, inclusive). Average annual citation counts were compared using t-tests. Scientific impact was also assessed relative to trial costs.ResultsTwenty-seven treatment trials with 17,208 patients and four chemoprevention trials with 87,550 patients were examined. The mean annual citation rate for primary articles was higher for chemoprevention trials compared to treatment trials (188.1 vs. 40.4, p = .001). For both primary and secondary article publications, mean annual citations for articles associated with chemoprevention trials were also higher (483.9 vs. 69.0, p = .0003). Large chemoprevention trials were estimated to provide 50% more total citations from primary and secondary articles on a cost-adjusted basis.ConclusionBased on these criteria, the scientific impact of large phase III cancer chemoprevention trials was very high in absolute terms, and as good as or better than that of treatment trials after accounting for expenditure. For appropriate scientific questions, large chemoprevention trials provide a good scientific return on investment for federal funding agencies.
Graphical abstract
https://ift.tt/2K93e05
Progress and Innovations in the Management of Adult Acute Lymphoblastic Leukemia
https://ift.tt/2M6jdMM
Estimating and Interpreting the Overall Survival Benefit of Checkpoint Inhibitors via Meta-analysis
https://ift.tt/2thle1W
Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women
https://ift.tt/2Ic30U0
Could Grape Seed Extract Be an Alternative Treatment in the Management of Hot Flashes?
https://ift.tt/2tcBQrB
Could Grape Seed Extract Be an Alternative Treatment in the Management of Hot Flashes?—Reply
https://ift.tt/2M9zl08
Estimating and Interpreting the Overall Survival Benefit of Checkpoint Inhibitors via Meta-analysis—Reply
https://ift.tt/2tcBukL
Adult Glioma Incidence and Survival by Race or Ethnicity
https://ift.tt/2IbqIjv
Need for a Oncologic Comprehensive Cost of Care Task Force
https://ift.tt/2JVfSnk
Effect of Adding Motolimod to Chemotherapy and Cetuximab Treatment of SCCHN
https://ift.tt/2M9KSwp
The reciprocal function and regulation of tumor vessels and immune cells offers new therapeutic opportunities in cancer
Source:Seminars in Cancer Biology
Author(s): Rindert Missiaen, Massimiliano Mazzone, Gabriele Bergers
Tumor angiogenesis and escape of immunosurveillance are two cancer hallmarks that are tightly linked and reciprocally regulated by paracrine signaling cues of cell constituents from both compartments. Formation and remodeling of new blood vessels in tumors is abnormal and facilitates immune evasion. In turn, immune cells in the tumor, specifically in context with an acidic and hypoxic environment, can promote neovascularization. Immunotherapy has emerged as a major therapeutic modality in cancer but is often hampered by the low influx of activated cytotoxic T-cells. On the other hand, anti-angiogenic therapy has been shown to transiently normalize the tumor vasculature and enhance infiltration of T lymphocytes, providing a rationale for a combination of these two therapeutic approaches to sustain and improve therapeutic efficacy in cancer. In this review, we discuss how the tumor vasculature facilitates an immunosuppressive phenotype and vice versa how innate and adaptive immune cells regulate angiogenesis during tumor progression. We further highlight recent results of antiangiogenic immunotherapies in experimental models and the clinic to evaluate the concept that targeting both the tumor vessels and immune cells increases the effectiveness in cancer patients.
https://ift.tt/2JVa5hI
Molecular pathway activation – new type of biomarkers for tumor morphology and personalized selection of target drugs
Source:Seminars in Cancer Biology
Author(s): Anton Buzdin, Maxim Sorokin, Andrew Garazha, Marina Sekacheva, Ella Kim, Nikolay Zhukov, Ye Wang, Xinmin Li, Souvik Kar, Christian Hartmann, Amir Samii, Alf Giese, Nicolas Borisov
Anticancer target drugs (ATDs) specifically bind and inhibit molecular targets that play important roles in cancer development and progression, being deeply implicated in intracellular signaling pathways. To date, hundreds of different ATDs were approved for clinical use in the different countries. Compared to previous chemotherapy treatments, ATDs often demonstrate reduced side effects and increased efficiency, but also have higher costs. However, the efficiency of ATDs for the advanced stage tumors is still insufficient. Different ATDs have different mechanisms of action and are effective in different cohorts of patients. Personalized approaches are therefore needed to select the best ATD candidates for the individual patients. In this review, we focus on a new generation of biomarkers – molecular pathway activation – and on their applications for predicting individual tumor response to ATDs. The success in high throughput gene expression profiling and emergence of novel bioinformatic tools reinforced quick development of pathway related field of molecular biomedicine. The ability to quantitatively measure degree of a pathway activation using gene expression data has revolutionized this field and made the corresponding analysis quick, robust and inexpensive. This success was further enhanced by using machine learning algorithms for selection of the best biomarkers. We review here the current progress in translating these studies to clinical oncology and patient-oriented adjustment of cancer therapy.
https://ift.tt/2MddWmN
Incidence of hydrological, chemical, and physical constraints on bacterial pathogens, Nocardia cells, and fecal indicator bacteria trapped in an urban stormwater detention basin in Chassieu, France
Abstract
The nature and fate of urban contaminants washed by stormwater events and accumulating in a detention basin (DB) were investigated. Relations between bacterial and chemical contaminants of trapped urban sediments, and field parameters were analyzed. Fecal indicators and some pathogens known to be environmentally transmitted (Nocardia, Pseudomonas aeruginosa, and Aeromonas caviae) were tracked, and their persistence investigated. Six sampling campaigns were carried out over 3 years, using five sites including a settling chamber (SC). Aerosolized bacteria at these sites were also monitored. Deposits in the basin were made of fine particles and their content in chemical pollutants was found highly variable. High polycyclic aromatic hydrocarbon (PAH) contents were measured but only three pesticides, over 22, were detected. Deposits were significantly contaminated by fecal indicator bacteria (FIB), P. aeruginosa, A. caviae, and by Nocardia. Only A. caviae showed significant numbers in aerosolized particles recovered over the detention basin. Nocardia spp. cells heavily contaminated the SC. The efficacy of the detention basin at reducing bacterial counts per rain event and over time were estimated. A slight drop in the counts was monitored for fecal indicators but not for the other bacterial groups. Hydrodynamic parameters had a strong impact on the distribution and features of the deposits. Multiple factors impacted the fate of FIB, P. aeruginosa, A. caviae, and Nocardia cells, but in a group dependent manner. Nocardia counts were found positively correlated with volatile organic matter. FIB appeared highly efficient colonizers of the DB.
https://ift.tt/2tsq8s7
Tuning functions for automatic detection of brief changes of facial expression in the human brain
Source:NeuroImage, Volume 179
Author(s): Arnaud Leleu, Milena Dzhelyova, Bruno Rossion, Renaud Brochard, Karine Durand, Benoist Schaal, Jean-Yves Baudouin
Efficient decoding of even brief and slight intensity facial expression changes is important for social interactions. However, robust evidence for the human brain ability to automatically detect brief and subtle changes of facial expression remains limited. Here we built on a recently developed paradigm in human electrophysiology with full-blown expressions (Dzhelyova et al., 2017), to isolate and quantify a neural marker for the detection of brief and subtle changes of facial expression. Scalp electroencephalogram (EEG) was recorded from 18 participants during stimulation of a neutral face changing randomly in size at a rapid rate of 6 Hz. Brief changes of expression appeared every five stimulation cycle (i.e., at 1.2 Hz) and expression intensity increased parametrically every 20 s in 20% steps during sweep sequences of 100 s. A significant 1.2 Hz response emerged in the EEG spectrum already at 40% of facial expression-change intensity for most of the 5 emotions tested (anger, disgust, fear, happiness, or sadness in different sequences), and increased with intensity steps, predominantly over right occipito-temporal regions. Given the high signal-to-noise ratio of the approach, thresholds for automatic detection of brief changes of facial expression could be determined for every single individual brain. A time-domain analysis revealed three components, the two first increasing linearly with increasing intensity as early as 100 ms after a change of expression, suggesting gradual low-level image-change detection prior to visual coding of facial movements. In contrast, the third component showed abrupt sensitivity to increasing expression intensity beyond 300 ms post expression-change, suggesting categorical emotion perception. Overall, this characterization of the detection of subtle changes of facial expression and its temporal dynamics open promising tracks for precise assessment of social perception ability during development and in clinical populations.
https://ift.tt/2M6g6EA
Finding decodable information that can be read out in behaviour
Publication date: 1 October 2018
Source:NeuroImage, Volume 179
Author(s): Tijl Grootswagers, Radoslaw M. Cichy, Thomas A. Carlson
Multivariate decoding methods applied to neuroimaging data have become the standard in cognitive neuroscience for unravelling statistical dependencies between brain activation patterns and experimental conditions. The current challenge is to demonstrate that decodable information is in fact used by the brain itself to guide behaviour. Here we demonstrate a promising approach to do so in the context of neural activation during object perception and categorisation behaviour. We first localised decodable information about visual objects in the human brain using a multivariate decoding analysis and a spatially-unbiased searchlight approach. We then related brain activation patterns to behaviour by testing whether the classifier used for decoding can be used to predict behaviour. We show that while there is decodable information about visual category throughout the visual brain, only a subset of those representations predicted categorisation behaviour, which were strongest in anterior ventral temporal cortex. Our results have important implications for the interpretation of neuroimaging studies, highlight the importance of relating decoding results to behaviour, and suggest a suitable methodology towards this aim.
https://ift.tt/2MMxaAQ
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Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
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Abstract Noise pollution is a major factor of environmental complaints in many cities, which has significant impacts on human health. As a...
