Thermocycle-regulated WALL REGULATOR INTERACTING bHLH Encodes a Protein That Interacts with Secondary-Cell-Wall-Associated Transcription Factors

Lignocellulosic biomass is one of the most abundant raw materials on earth that can be utilized to created carbon-neutral biofuels as a replacement for conventional fossil fuels. In order to create ideal energy crops, the regulation and deposition of cell wall polysaccharides must first be fully understood. Improved understanding of cell wall regulation will enable selection of traits that can optimize biofuel feedstocks. Herein, I utilize the grass model system Brachypodium distachyon in order to understand the transcriptional regulation of secondary cell wall deposition. Gene expression profiling was used to elucidate transcription factors that regulate secondary cell wall biosynthesis. Through this method, WALL REGULATOR INTERACTING bHLH (WRIB) was identified and its role as a secondary cell wall regulator was tested. Yeast-one- and yeast-two-hybrid assays showed that WRIB is capable of binding to promoters of secondary cell wall biosynthesis genes, as well as interacting with known secondary cell wall transcription factor proteins and also Phytochrome B. These results suggest that WRIB plays an important role in the secondary cell wall regulatory network and could perhaps be modulated by Phytochrome B. Discovery of this novel and interesting gene furthers the overall understanding of secondary cell wall development with the goal of improving our ability to engineer biofuel feedstocks

Increased expression of programmed death ligand 1 (PD-L1) in human pituitary tumors

PURPOSE: Subsets of pituitary tumors exhibit an aggressive clinical courses and recur despite surgery, radiation, and chemotherapy. Because modulation of the immune response through inhibition of T-cell checkpoints has led to durable clinical responses in multiple malignancies, we explored whether pituitary adenomas express immune-related biomarkers that could suggest suitability for immunotherapy. Specifically, programmed death ligand 1 (PD-L1) has emerged as a potential biomarker whose expression may portend more favorable responses to immune checkpoint blockade therapies. We thus investigated the expression of PD-L1 in pituitary adenomas. METHODS: PD-L1 RNA and protein expression were evaluated in 48 pituitary tumors, including functioning and non-functioning adenomas as well as atypical and recurrent tumors. Tumor infiltrating lymphocyte populations were also assessed by immunohistochemistry. RESULTS: Pituitary tumors express variable levels of PD-L1 transcript and protein. PD-L1 RNA and protein expression were significantly increased in functioning (growth hormone and prolactin-expressing) pituitary adenomas compared to non-functioning (null cell and silent gonadotroph) adenomas. Moreover, primary pituitary adenomas harbored higher levels of PD-L1 mRNA compared to recurrent tumors. Tumor infiltrating lymphocytes were observed in all pituitary tumors and were positively correlated with increased PD-L1 expression, particularly in the functional subtypes. CONCLUSIONS: Human pituitary adenomas harbor PD-L1 across subtypes, with significantly higher expression in functioning adenomas compared to non-functioning adenomas. This expression is accompanied by the presence of tumor infiltrating lymphocytes. These findings suggest the existence of an immune response to pituitary tumors and raise the possibility of considering checkpoint blockade immunotherapy in cases refractory to conventional management

Maritime search and rescue in Nunavut, Canada : strengthening the system from the bottom up

Due to the impacts of climate change, maritime search and rescue requirements are increasing across Nunavut. The region’s vast size and cold climate combine to make time the enemy of all responders. The substantial distances involved in responding with Canadian Coast Guard (CCG) icebreakers or Royal Canadian Air Force aircraft based in the South mean that the arrival of federal resources on scene can take significant time. There are few vessels of opportunity in the region. Historically, however, there has been little sustained investment in community-based marine Search and Rescue (SAR) capabilities in the territory. This started to change in 2015 with the launch of the CCG’s Arctic SAR Project and, in 2018, with the creation of the Coast Guard’s new Arctic Region. This poster outlines the status of the community-based marine SAR system in Nunavut, assess efforts by the Coast Guard and its partners to strengthen the system, and suggest broadly applicable best practices

Addressing the challenges to search and rescue operations caused by ice conditions in Nunavut, Canada

Search and rescue (SAR) operations on the land, water, and ice of Nunavut are often complex and challenging due to austere environmental conditions, the strain they place on local resources, and the vast distances involved in responding with Canadian Coast Guard icebreakers or southern-based aerial assets. Using the results of a literature review, practitioner interviews, and three regional SAR roundtables conducted in November 2022 in cooperation with Nunavut Emergency Management, this paper will assess: a) how changing ice conditions in the region add to these challenges by increasing the risk of SAR incidents; b) the ways in which the ice affects response operations; and c) how ice conditions exacerbate other difficulties in the SAR system. This paper concludes with a discussion of how the Nunavut Search and Rescue (NSAR) Project aims to address these challenges, focusing on modelling and analysis approaches

Activation of the Left Inferior Frontal Gyrus in the First 200 ms of Reading: Evidence from Magnetoencephalography (MEG)

BACKGROUND: It is well established that the left inferior frontal gyrus plays a key role in the cerebral cortical network that supports reading and visual word recognition. Less clear is when in time this contribution begins. We used magnetoencephalography (MEG), which has both good spatial and excellent temporal resolution, to address this question. METHODOLOGY/PRINCIPAL FINDINGS: MEG data were recorded during a passive viewing paradigm, chosen to emphasize the stimulus-driven component of the cortical response, in which right-handed participants were presented words, consonant strings, and unfamiliar faces to central vision. Time-frequency analyses showed a left-lateralized inferior frontal gyrus (pars opercularis) response to words between 100-250 ms in the beta frequency band that was significantly stronger than the response to consonant strings or faces. The left inferior frontal gyrus response to words peaked at approximately 130 ms. This response was significantly later in time than the left middle occipital gyrus, which peaked at approximately 115 ms, but not significantly different from the peak response in the left mid fusiform gyrus, which peaked at approximately 140 ms, at a location coincident with the fMRI-defined visual word form area (VWFA). Significant responses were also detected to words in other parts of the reading network, including the anterior middle temporal gyrus, the left posterior middle temporal gyrus, the angular and supramarginal gyri, and the left superior temporal gyrus. CONCLUSIONS/SIGNIFICANCE: These findings suggest very early interactions between the vision and language domains during visual word recognition, with speech motor areas being activated at the same time as the orthographic word-form is being resolved within the fusiform gyrus. This challenges the conventional view of a temporally serial processing sequence for visual word recognition in which letter forms are initially decoded, interact with their phonological and semantic representations, and only then gain access to a speech code

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Cell Walls and the Developmental Anatomy of the <i>Brachypodium distachyon</i> Stem Internode

<div><p>While many aspects of plant cell wall polymer structure are known, their spatial and temporal distribution within the stem are not well understood. Here, we studied vascular system and fiber development, which has implication for both biofuel feedstock conversion efficiency and crop yield. The subject of this study, <i>Brachypodium distachyon</i>, has emerged as a grass model for food and energy crop research. Here, we conducted our investigation using <i>B. distachyon</i> by applying various histological approaches and Fourier transform infrared spectroscopy to the stem internode from three key developmental stages. While vascular bundle size and number did not change over time, the size of the interfascicular region increased dramatically, as did cell wall thickness. We also describe internal stem internode anatomy and demonstrate that lignin deposition continues after crystalline cellulose and xylan accumulation ceases. The vascular bundle anatomy of <i>B. distachyon</i> appears to be highly similar to domesticated grasses. While the arrangement of bundles within the stem is highly variable across grasses, <i>B. distachyon</i> appears to be a suitable model for the rind of large C₄ grass crops. A better understanding of growth and various anatomical and cell wall features of <i>B. distachyon</i> will further our understanding of plant biomass accumulation processes.</p></div

<i>Brachypodium distachyon</i> internal stem internode anatomy with emphasis on vasculature.

<p>(<b>A</b>) Cross section of whole stem and (<b>B</b>) higher magnification of the first stem internode. Red, inner vascular bundles; pink, outer vascular bundles; cyan, interfascicular region compromised mostly of sclerenchyma fibers; gray, pith; lime green, chlorenchyma and sclerenchyma cells comprise the cortex; brown, epidermis. (<b>C</b>) Vascular bundle illustration at high magnification. Green, bundle sheath (BS); purple, phloem (P); vermilion, companion cells; tan, xylem vessels (XV); red, xylem tracheids (XT); white, lacuna (Lc); orange, xylem parenchyma cells (XP); gray, parenchyma cells (Py); blue, sclerenchyma fibers (SF). (<b>A-B</b>) Bar  =  0.1 mm, (<b>C</b>) bar  =  0.01 mm.</p

Characterization of wall composition changes associated with growth using FTIR spectroscopy.

<p>Average line spectra of stem tissue sampled from elongating (green), flowering (orange), and senesced (blue) stages of development. Wavenumbers corresponding to absorbance peaks associated with cellulose, hemicellulose, and lignin are noted. Letters indicate significant differences at <i>P</i> < 0.05.</p