Large quantities of organic carbon are stored in frozen soils (permafrost) within Arctic and sub-Arctic regions. A warming climate can induce environmental changes that accelerate the microbial ...breakdown of organic carbon and the release of the greenhouse gases carbon dioxide and methane. This feedback can accelerate climate change, but the magnitude and timing of greenhouse gas emission from these regions and their impact on climate change remain uncertain. Here we find that current evidence suggests a gradual and prolonged release of greenhouse gas emissions in a warming climate and present a research strategy with which to target poorly understood aspects of permafrost carbon dynamics.
•Nrf2 is part of a complex regulatory network that responds to environmental cues.•Nrf2 allows adaptation by inducing cytoprotective genes and maintaining redox homeostasis.•Nrf2 transcription is ...positively regulated by AhR, ARNT, NF-κB, Jun, and Myc.•Nrf2 protein stability is controlled by CRLKeap1, SCFβ-TrCP, CRIF1, Siah2, and RNF4.•Nrf2 influences metabolism, including lipid, carbohydrate, amino acid, and nucleotide.
Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2, also called Nfe2l2) is a transcription factor that regulates the cellular redox status. Nrf2 is controlled through a complex transcriptional/epigenetic and post-translational network that ensures its activity increases during redox perturbation, inflammation, growth factor stimulation and nutrient/energy fluxes, thereby enabling the factor to orchestrate adaptive responses to diverse forms of stress. Besides mediating stress-stimulated induction of antioxidant and detoxification genes, Nrf2 contributes to adaptation by upregulating the repair and degradation of damaged macromolecules, and by modulating intermediary metabolism. In the latter case, Nrf2 inhibits lipogenesis, supports β-oxidation of fatty acids, facilitates flux through the pentose phosphate pathway, and increases NADPH regeneration and purine biosynthesis; these observations suggest Nrf2 directs metabolic reprogramming during stress.
The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were ...assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2 mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world.
The aim of this study was to examine the correlation between physiological parameters (namely fatness and physical fitness) with academic performance (namely mathematics and science grade point ...average GPA) in normal weight and overweight schoolchild handball players. Thirty-six young male team handball players (age: 9±1 years; body mass: 45.5±14.2 kg; height: 1.38±9.1 m; body fat: 19.7±5.6%) at the highest national league for their age group participated. Anthropometry was examined by measuring body mass, body fat percentage (%BF), and body mass index (BMI). Fitness testing included the Yo-Yo Intermittent Recovery Test (level 1), squat jumps (SJ) and counter-movement jumps (CMJ), and upper-limb throwing performance (2 kg medicine ball seated front throw), a 15 m sprint test, and a T-half test for change-of-direction (COD) ability. Academic performance was evaluated through school records of grade point average (GPA) of mathematics and science. BMI was negatively correlated with science GPA (r = -0.57, p<0.001) and mathematics GPA (r = -0.39, p<0.001). Significant correlations between Yo-Yo test performance and science GPA (r = 0.73, p<0.001) and mathematics GPA (r = 0.66, p<0.001) existed. T-half test score (less time taken meant a superior performance) was negatively correlated with science GPA (r = 0.48, p = 0.003) and mathematics GPA (r = 0.63, p<0.01). In conclusion, fatness and physical fitness (except for the upper-muscular strength) were significantly related to academic performance in in schoolchild handball players. Based on results of this study, it seems pragmatic and appropriate to engage young schoolchild in physical activity as it associates with superior academic performance.
Unsupervised class discovery is a highly useful technique in cancer research, where intrinsic groups sharing biological characteristics may exist but are unknown. The consensus clustering (CC) method ...provides quantitative and visual stability evidence for estimating the number of unsupervised classes in a dataset. ConsensusClusterPlus implements the CC method in R and extends it with new functionality and visualizations including item tracking, item-consensus and cluster-consensus plots. These new features provide users with detailed information that enable more specific decisions in unsupervised class discovery. Availability: ConsensusClusterPlus is open source software, written in R, under GPL-2, and available through the Bioconductor project (http://www.bioconductor.org/). Contact: mwilkers@med.unc.edu Supplementary Information: Supplementary data are available at Bioinformatics online.
Transcription factor nuclear factor-erythroid 2-related factor 2 (NRF2) controls cellular adaptation to oxidants and electrophiles by inducing antioxidant and detoxification genes in response to ...redox stress. NRF2 is negatively regulated by Kelch-like ECH-associated protein 1 (KEAP1). Tumours from ∼15% of patients with lung cancer harbour somatic mutations in
KEAP1 that prevent effective NRF2 repression. Recently, two
NRF2 mutation ‘hot-spots’ were identified in ∼10% of patients with lung cancer, enabling the transcription factor to evade KEAP1-mediated repression. Somatic mutations in
KEAP1 and
NRF2 provide an insight into the molecular mechanisms by which NRF2 is regulated. Moreover, constitutive NRF2 activation might cause drug resistance in tumours, and an understanding of how the transcription factor is regulated indicates ways in which this could be overcome.
The transcription factor nuclear factor-erythroid 2 p45-related factor 2 (Nrf2, with gene called NFE2L2) is a master regulator of the antioxidant response. In the last decade, interest has ...intensified in this research area as its importance in several physiological and pathological processes has become widely recognized; these include redox signalling and redox homoeostasis, drug metabolism and disposition, intermediary metabolism, cellular adaptation to stress, chemoprevention and chemoresistance, toxicity, inflammation, neurodegeneration, lipogenesis and aging. Regulation of Nrf2 is complex and although much attention has focussed on its repression by Kelch-like ECH-associated protein-1 (Keap1), recently it has become increasingly apparent that it is also controlled by cross-talk with other signalling pathways including the glycogen synthase kinase-3 (GSK-3)-β-transducin repeat-containing protein (β-TrCP) axis, ERAD (endoplasmic reticulum-associated degradation)-associated E3 ubiquitin-protein ligase (Hrd1, also called synoviolin), nuclear factor-kappa B (NF-κB), Notch and AMP kinase. Due to its beneficial role in several diseases, Nrf2 has become a major therapeutic target, with novel natural, synthetic and targeted small molecules currently under investigation to modulate the pathway and in clinical trials.
The trapped-ion quantum charge-coupled device (QCCD) proposal
lays out a blueprint for a universal quantum computer that uses mobile ions as qubits. Analogous to a charge-coupled device (CCD) camera, ...which stores and processes imaging information as movable electrical charges in coupled pixels, a QCCD computer stores quantum information in the internal state of electrically charged ions that are transported between different processing zones using dynamic electric fields. The promise of the QCCD architecture is to maintain the low error rates demonstrated in small trapped-ion experiments
by limiting the quantum interactions to multiple small ion crystals, then physically splitting and rearranging the constituent ions of these crystals into new crystals, where further interactions occur. This approach leverages transport timescales that are fast relative to the coherence times of the qubits, the insensitivity of the qubit states of the ion to the electric fields used for transport, and the low crosstalk afforded by spatially separated crystals. However, engineering a machine capable of executing these operations across multiple interaction zones with low error introduces many difficulties, which have slowed progress in scaling this architecture to larger qubit numbers. Here we use a cryogenic surface trap to integrate all necessary elements of the QCCD architecture-a scalable trap design, parallel interaction zones and fast ion transport-into a programmable trapped-ion quantum computer that has a system performance consistent with the low error rates achieved in the individual ion crystals. We apply this approach to realize a teleported CNOT gate using mid-circuit measurement
, negligible crosstalk error and a quantum volume
of 2
= 64. These results demonstrate that the QCCD architecture provides a viable path towards high-performance quantum computers.
The number of sequenced plant genomes and associated genomic resources is growing rapidly with the advent of both an increased focus on plant genomics from funding agencies, and the application of ...inexpensive next generation sequencing. To interact with this increasing body of data, we have developed Phytozome (http://www.phytozome.net), a comparative hub for plant genome and gene family data and analysis. Phytozome provides a view of the evolutionary history of every plant gene at the level of sequence, gene structure, gene family and genome organization, while at the same time providing access to the sequences and functional annotations of a growing number (currently 25) of complete plant genomes, including all the land plants and selected algae sequenced at the Joint Genome Institute, as well as selected species sequenced elsewhere. Through a comprehensive plant genome database and web portal, these data and analyses are available to the broader plant science research community, providing powerful comparative genomics tools that help to link model systems with other plants of economic and ecological importance.
Head and neck cancer is the fifth most common cancer worldwide. It is often amenable to curative intent therapy when localized to the head and neck region, but it carries a poor prognosis when it is ...recurrent or metastatic. Therefore, initial treatment decisions are critical to improve patient survival. However, multimodality therapy used with curative intent is toxic. The balance between offering intensive versus tolerable and function-preserving therapy has been thrown into sharp relief with the recently described epidemic of human papillomavirus-associated head and neck squamous cell carcinomas characterized by improved clinical outcomes compared with smoking-associated head and neck tumors. Model systems and clinical trials have been slow to address the clinical questions that face the field to date. With this as a background, a host of translational studies have recently reported the somatic alterations in head and neck cancer and have highlighted the distinct genetic and biologic differences between viral and tobacco-associated tumors. This review seeks to summarize the main findings of studies, including The Cancer Genome Atlas, for the clinician scientist, with a goal of leveraging this new knowledge toward the betterment of patients with head and neck cancer.
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