The Litsea genome and the evolution of the laurel family

The laurel family within the Magnoliids has attracted attentions owing to its scents, variable inflorescences, and controversial phylogenetic position. Here, we present a chromosome-level assembly of the Litsea cubeba genome, together with low-coverage genomic and transcriptomic data for many other Lauraceae. Phylogenomic analyses show phylogenetic discordance at the position of Magnoliids, suggesting incomplete lineage sorting during the divergence of monocots, eudicots, and Magnoliids. An ancient whole-genome duplication (WGD) event occurred just before the divergence of Laurales and Magnoliales; subsequently, independent WGDs occurred almost simultaneously in the three Lauralean lineages. The phylogenetic relationships within Lauraceae correspond to the divergence of inflorescences, as evidenced by the phylogeny of FUWA, a conserved gene involved in determining panicle architecture in Lauraceae. Monoterpene synthases responsible for production of specific volatile compounds in Lauraceae are functionally verified. Our work sheds light on the evolution of the Lauraceae, the genetic basis for floral evolution and specific scents

Plasma cell subtypes analyzed using artificial intelligence algorithm for predicting biochemical recurrence, immune escape potential, and immunotherapy response of prostate cancer

BackgroundPlasma cells as an important component of immune microenvironment plays a crucial role in immune escape and are closely related to immune therapy response. However, its role for prostate cancer is rarely understood. In this study, we intend to investigate the value of a new plasma cell molecular subtype for predicting the biochemical recurrence, immune escape and immunotherapy response in prostate cancer.MethodsGene expression and clinicopathological data were collected from 481 prostate cancer patients in the Cancer Genome Atlas. Then, the immune characteristics of the patients were analyzed based on plasma cell infiltration fractions. The unsupervised clustering based machine learning algorithm was used to identify the molecular subtypes of the plasma cell. And the characteristic genes of plasma cell subtypes were screened out by three types of machine learning models to establish an artificial neural network for predicting plasma cell subtypes. Finally, the prediction artificial neural network of plasma cell infiltration subtypes was validated in an independent cohort of 449 prostate cancer patients from the Gene Expression Omnibus.ResultsThe plasma cell fraction in prostate cancer was significantly decreased in tumors with high T stage, high Gleason score and lymph node metastasis. In addition, low plasma cell fraction patients had a higher risk of biochemical recurrence. Based on the differential genes of plasma cells, plasma cell infiltration status of PCa patients were divided into two independent molecular subtypes(subtype 1 and subtype 2). Subtype 1 tends to be immunosuppressive plasma cells infiltrating to the PCa region, with a higher likelihood of biochemical recurrence, more active immune microenvironment, and stronger immune escape potential, leading to a poor response to immunotherapy. Subsequently, 10 characteristic genes of plasma cell subtype were screened out by three machine learning algorithms. Finally, an artificial neural network was constructed by those 10 genes to predict the plasma cell subtype of new patients. This artificial neural network was validated in an independent validation set, and the similar results were gained.ConclusionsPlasma cell infiltration subtypes could provide a potent prognostic predictor for prostate cancer and be an option for potential responders to prostate cancer immunotherapy

Вихретоковый анизотропный термоэлектрический первичный преобразователь лучистого потока

Представлена оригинальная конструкция первичного преобразователя лучистого потока, который может служить основой для создания приемника неселективного излучения с повышенной чувствительностью

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Relationship between light adaptation, dopamine release and coupling of horizontal cells in the mudpuppy (Necturus maculosus) retina.

The relationship between light adaptation, dopamine release and coupling of horizontal cells was studied in the retina of an amphibian, the mudpuppy, Necturus maculosus. Intracellular recordings were made from horizontal cells in the mudpuppy eyecup preparation. Changes in coupling between horizontal cells under different testing conditions were measured by comparing the changes in horizontal cell responses to stimulation of the center and surround portions of the receptive field. Dopamine caused a decrease in horizontal cell coupling and was more effective in relatively dark-adapted retinas. Both the selective D1 receptor antagonist SCH23390 and 2-amino-4-phosphonobutyrate (APB), a glutamate analog which blocks responses of On-center but not Off-center bipolar cells, caused an increase in coupling and were more effective in relatively light-adapted retinas. On the other hand, cis-2,3-piperidine dicarboxylate (PDA), a glutamate receptor antagonist which blocks responses of Off-center but not On-center bipolar cells, had little effect on coupling. In dark-adapted retinas, exposure to an adapting light caused a decrease in coupling; this effect of light was blocked in the presence of SCH23390 or APB. These results suggest that (1) dopamine regulates horizontal cell coupling via an action at D1 receptors in the mudpuppy retina; (2) the release of dopamine is decreased in dark-adapted retinas and is stimulated by light; (3) the effect of light on dopamine release is mainly via On-center bipolar cells.Ph.D.PhysiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/105159/1/9116168.pdfDescription of 9116168.pdf : Restricted to UM users only

Alpha2 Modulation of Intracellular CA++ Signal in the Inner Plexiform Layer (IPL) of the Rat Retina

There is compelling evidence from animal models of glaucoma and acute retinal ischemia that ?2 agonists protect retinal ganglion cells (RGCs) from injury. However, the mechanism of action is not well understood. We explored the role of the ?2 adrenergic system in modulation of intracellular Ca++ signaling at the IPL where communication between RGCs and their presynaptic cells takes place