Whole tumor RNA-sequencing and deconvolution reveal a clinically-prognostic PTEN/PI3K-regulated glioma transcriptional signature

The concept that solid tumors are maintained by a productive interplay between neoplastic and non-neoplastic elements has gained traction with the demonstration that stromal fibroblasts and immune system cells dictate cancer development and progression. While less studied, brain tumor (glioma) biology is likewise influenced by non-neoplastic immune system cells (macrophages and microglia) which interact with neoplastic glioma cells to create a unique physiological state (glioma ecosystem) distinct from that found in the normal tissue. To explore this neoplastic ground state, we leveraged several preclinical mouse models of neurofibromatosis type 1 (NF1) optic glioma, a low-grade astrocytoma whose formation and maintenance requires productive interactions between non-neoplastic and neoplastic cells, and employed whole tumor RNA-sequencing and mathematical deconvolution strategies to characterize this low-grade glioma ecosystem as an aggregate of cellular and acellular elements. Using this approach, we demonstrate that optic gliomas generated by altering the germlin

Extensive infrared spectroscopic study of CuO: signatures of strong spin-phonon interaction and structural distortion

Optical properties of single-crystal monoclinic CuO in the range 70 - 6000 \cm were studied at temperatures from 7 to 300 K. Normal reflection spectra were obtained from the (001) and (010) crystal faces thus giving for the first time separate data for the $A_{u}$ and $B_{u}$ phonon modes excited in the purely transverse way (TO modes). Mode parameters, including polarizations of the $B_{u}$ modes not determined by the crystal symmetry, were extracted by the dispersion analysis of reflectivity curves as a function of temperature. Spectra of all the components of the optical conductivity tensor were obtained using the Kramers-Kronig method recently extended to the case of the low-symmetry crystals. The number of strong phonon modes is in agreement with the factor-group analysis for the crystal structure, currently accepted for the CuO. However, several "extra" modes of minor intensity are detected. Comparison of frequencies of "extra" modes with the available phonon dispersion curves points to possible "diagonal" doubling of the unit cell \{{\bf a}, {\bf b}, {\bf c}\} $\to$ \{{\bf a}+{\bf c}, {\bf b}, {\bf a}-{\bf c}\} and formation of the superlattice. The previously reported softening of the $A^{3}_{u}$ mode ($\sim$ 400 \cm) with cooling at $T_{N}$ is found to be $\sim$ 10 % for the TO mode. The mode is very broad at high temperatures and strongly narrows in the AFM phase. We attribute this effect to strong resonance coupling of this mode to optical or acoustic bi-magnons and reconstruction of the magnetic excitations spectrum at the N\'eel point. A significant anisotropy of $\epsilon^{\infty}$ is observed: it was found to be 5.9 along the {\bf b}-axis, 6.2 along the {[}101{]} chains and 7.8 the {[}10$\bar{1}${]} chains. The "transverse" effective charge is value is about 2 electrons.Comment: 23 pages, 14 figures, REVTeX, submitted to PR

What are patient-reported outcomes and why they are important: improving studies of preschool wheeze

“This article has been accepted for publication in Archives of Disease in Childhood - Education and Practice. Published Online First: 31 August 2019, following peer review, and the Version of Record can be accessed online at http://dx.doi.org/10.1136/archdischild-2018-316476

Context dependent substitution biases vary within the human genome

Background: Models of sequence evolution typically assume that different nucleotide positions evolve independently. This assumption is widely appreciated to be an over-simplification. The best known violations involve biases due to adjacent nucleotides. There have also been suggestions that biases exist at larger scales, however this possibility has not been systematically explored. Results: To address this we have developed a method which identifies over- and under-represented substitution patterns and assesses their overall impact on the evolution of genome composition. Our method is designed to account for biases at smaller pattern sizes, removing their effects. We used this method to investigate context bias in the human lineage after the divergence from chimpanzee. We examined bias effects in substitution patterns between 2 and 5 bp long and found significant effects at all sizes. This included some individual three and four base pair patterns with relatively large biases. We also found that bias effects vary across the genome, differing between transposons and non-transposons, between different classes of transposons, and also near and far from genes. Conclusions: We found that nucleotides beyond the immediately adjacent one are responsible for substantial context effects, and that these biases vary across the genome

Amino acid transporters in plants

AbstractAmino acid transporters are essential participants in the resource allocation processes that support plant growth and development. Recent results have identified several new transporters that contribute to a wide array of physiological activities, and detailed molecular analysis has provided fundamental insights into the structure, function and regulation of these integral membrane proteins

Recovery of critically endangered Nassau grouper (Epinephelus striatus) in the Cayman Islands following targeted conservation actions.

Many large-bodied marine fishes that form spawning aggregations, such as the Nassau grouper (Epinephelus striatus), have suffered regional overfishing due to exploitation during spawning. In response, marine resource managers in many locations have established marine protected areas or seasonal closures to recover these overfished stocks. The challenge in assessing management effectiveness lies largely in the development of accurate estimates to track stock size through time. For the past 15 y, the Cayman Islands government has taken a series of management actions aimed at recovering collapsed stocks of Nassau grouper. Importantly, the government also partnered with academic and nonprofit organizations to establish a research and monitoring program (Grouper Moon) aimed at documenting the impacts of conservation action. Here, we develop an integrated population model of 2 Cayman Nassau grouper stocks based on both diver-collected mark-resight observations and video censuses. Using both data types across multiple years, we fit parameters for a state-space model for population growth. We show that over the last 15 y the Nassau grouper population on Little Cayman has more than tripled in response to conservation efforts. Census data from Cayman Brac, while more sparse, show a similar pattern. These findings demonstrate that spatial and seasonal closures aimed at rebuilding aggregation-based fisheries can foster conservation success

The use of electronic alerts in primary care computer systems to identify the over-prescription of short-acting beta(2)-agonists in people with asthma: a protocol for a systematic review

The authors wish to thank the Asthma UK Centre for Applied Research for funding this work. AB is an National Institute for Health Research (NIHR) Senior Investigator and additionally was supported by the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London. MT was supported by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) Wessex, NIHR School of Primary Care Research and NIHR Southampton Biomedical Research Centre. CG was supported by the NIHR CLAHRC North Thames at Bart’s Health NHS Trust

Graph complexity analysis identifies an ETV5 tumor-specific network in human and murine low-grade glioma

Conventional differential expression analyses have been successfully employed to identify genes whose levels change across experimental conditions. One limitation of this approach is the inability to discover central regulators that control gene expression networks. In addition, while methods for identifying central nodes in a network are widely implemented, the bioinformatics validation process and the theoretical error estimates that reflect the uncertainty in each step of the analysis are rarely considered. Using the betweenness centrality measure, we identified Etv5 as a potential tissue-level regulator in murine neurofibromatosis type 1 (Nf1) low-grade brain tumors (optic gliomas). As such, the expression of Etv5 and Etv5 target genes were increased in multiple independently-generated mouse optic glioma models relative to non-neoplastic (normal healthy) optic nerves, as well as in the cognate human tumors (pilocytic astrocytoma) relative to normal human brain. Importantly, differential Etv5 and Etv5 network expression was not directly the result of Nf1 gene dysfunction in specific cell types, but rather reflects a property of the tumor as an aggregate tissue. Moreover, this differential Etv5 expression was independently validated at the RNA and protein levels. Taken together, the combined use of network analysis, differential RNA expression findings, and experimental validation highlights the potential of the computational network approach to provide new insights into tumor biology