406 research outputs found
Cross-biome transplants of plant litter show decomposition models extend to a broader climatic range but lose predictability at the decadal time scale
We analyzed results from 10-year long field incubations of foliar and fine root litter from the Long-term Intersite Decomposition Experiment Team (LIDET) study. We tested whether a variety of climate and litter quality variables could be used to develop regression models of decomposition parameters across wide ranges in litter quality and climate and whether these models changed over short to long time periods. Six genera of foliar and three genera of root litters were studied with a 10-fold range in the ratio of acid unhydrolyzable fraction (AUF, or ‘lignin’) to N. Litter was incubated at 27 field sites across numerous terrestrial biomes including arctic and alpine tundra, temperate and tropical forests, grasslands and warm deserts. We used three separate mathematical models of first-order (exponential) decomposition, emphasizing either the first year or the entire decade. One model included the proportion of relatively stable material as an asymptote. For short-term (first-year) decomposition, nonlinear regressions of exponential or power function form were obtained with r 2 values of 0.82 and 0.64 for foliar and fine-root litter, respectively, across all biomes included. AUF and AUF : N ratio were the most explanative litter quality variables, while the combined temperature-moisture terms AET (actual evapotranspiration) and CDI (climatic decomposition index) were best for climatic effects. Regressions contained some systematic bias for grasslands and arctic and boreal sites, but not for humid tropical forests or temperate deciduous and coniferous forests. The ability of the regression approach to fit climate-driven decomposition models of the 10-year field results was dramatically reduced from the ability to capture drivers of short-term decomposition. Future work will require conceptual and methodological improvements to investigate processes controlling decadal-scale litter decomposition, including the formation of a relatively stable fraction and its subsequent decomposition.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78615/1/j.1365-2486.2009.02086.x.pd
The controversy in the management of the N0 neck for squamous cell carcinoma of the maxillary sinus
Squamous cell carcinoma (SCC) of the maxillary sinus is a relatively rare disease. As the reported incidence of regional metastasis varies widely, controversy exists as to whether or not the N0 classified neck should be treated electively. In this review, the data from published series are analyzed to decide on a recommendation of elective treatment of the neck in maxillary SCC. The published series consist of heterogeneous populations of different subsites of the paranasal sinuses, different histological types, different staging and treatment modalities used and different ways of reporting the results. These factors do not allow for recommendations based on high levels of evidence. Given this fact, the relatively high incidence rate of regional metastasis at presentation or in follow-up in the untreated N0 neck, and the relatively low toxicity of elective neck irradiation, such irradiation in SCC of the maxillary sinus should be considered
Population Health Solutions for Assessing Cognitive Impairment in Geriatric Patients.
In December 2017, the National Academy of Neuropsychology convened an interorganizational Summit on Population Health Solutions for Assessing Cognitive Impairment in Geriatric Patients in Denver, Colorado. The Summit brought together representatives of a broad range of stakeholders invested in the care of older adults to focus on the topic of cognitive health and aging. Summit participants specifically examined questions of who should be screened for cognitive impairment and how they should be screened in medical settings. This is important in the context of an acute illness given that the presence of cognitive impairment can have significant implications for care and for the management of concomitant diseases as well as pose a major risk factor for dementia. Participants arrived at general principles to guide future screening approaches in medical populations and identified knowledge gaps to direct future research. Key learning points of the summit included: recognizing the importance of educating patients and healthcare providers about the value of assessing current and baseline cognition;emphasizing that any screening tool must be appropriately normalized and validated in the population in which it is used to obtain accurate information, including considerations of language, cultural factors, and education; andrecognizing the great potential, with appropriate caveats, of electronic health records to augment cognitive screening and tracking of changes in cognitive health over time
CK1ε Is Required for Breast Cancers Dependent on β-Catenin Activity
Background: Aberrant -catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate -catenin activity for therapeutic purposes have proven elusive to date. Methodology: To uncover genetic dependencies in breast cancer cells that harbor active -catenin signaling, we performed RNAi-based loss-of-function screens in breast cancer cell lines in which we had characterized -catenin activity. Here we identify CSNK1E, the gene encoding casein kinase 1 epsilon (CK1) as required specifically for the proliferation of breast cancer cells with activated -catenin and confirm its role as a positive regulator of -catenin-driven transcription. Furthermore, we demonstrate that breast cancer cells that harbor activated -catenin activity exhibit enhanced sensitivity to pharmacological blockade of Wnt/-catenin signaling. We also find that expression of CK1 is able to promote oncogenic transformation of human cells in a -catenin-dependent manner. Conclusions/Significance: These studies identify CK1 as a critical contributor to activated -catenin signaling in cancer and suggest it may provide a potential therapeutic target for cancers that harbor active -catenin. More generally, these observations delineate an approach that can be used to identify druggable synthetic lethal interactions with signaling pathways that are frequently activated in cancer but are difficult to target with the currently available small molecule inhibitors
Synthetic Lethal Interaction between Oncogenic KRAS Dependency and STK33 Suppression in Human Cancer Cells
An alternative to therapeutic targeting of oncogenes is to perform “synthetic lethality” screens for genes that are essential only in the context of specific cancer-causing mutations. We used high-throughput RNA interference (RNAi) to identify synthetic lethal interactions in cancer cells harboring mutant KRAS, the most commonly mutated human oncogene. We find that cells that are dependent on mutant KRAS exhibit sensitivity to suppression of the serine/threonine kinase STK33 irrespective of tissue origin, whereas STK33 is not required by KRAS-independent cells. STK33 promotes cancer cell viability in a kinase activity-dependent manner by regulating the suppression of mitochondrial apoptosis mediated through S6K1-induced inactivation of the death agonist BAD selectively in mutant KRAS-dependent cells. These observations identify STK33 as a target for treatment of mutant KRAS-driven cancers and demonstrate the potential of RNAi screens for discovering functional dependencies created by oncogenic mutations that may enable therapeutic intervention for cancers with “undruggable” genetic alterations.National Institutes of Health (U.S.) (grant R33 CA128625)National Institutes of Health (U.S.) (grant NIH U54 CA112962)National Institutes of Health (U.S.) (grant P01 CA095616)National Institutes of Health (U.S.) (grant P01 CA66996)Starr Cancer ConsortiumDoris Duke Charitable FoundationMPN Research FoundationDeutsche Forschungsgemeinschaft (grant SCHO 1215/1-1)Deutsche Forschungsgemeinschaft (grant FR 2113/1-1)Brain Science FoundationLeukemia & Lymphoma Society of Americ
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