Taxonomic study of the Japanese Dacrymycetes

The class Dacrymycetes is a rather small group of brown-rot wood-decaying jelly fungi characterised by forked basidia and an orange to yellow gelatinous to cartilaginous fruit body. In Japan, dacrymycetous fungi had not been investigated for a long time, justifying a taxonomic re-examination. In the present study we attempted an investigation of the dacrymycetous fungal flora of Japan, and recognised 28 taxonomic entities, including five new taxa, i.e. Dacrymyces ancyleus, D. aureosporus, D. pinacearum, D. subarcticus and Dacryopinax sphenocarpa, and nine new records. Due to the present survey, the total number of dacrymycetous species recorded from Japan increased from 28 to 42. Of the newly described species, Dacrymyces ancyleus is characterised by recurved, cylindrical basidiocarps and hyphae with clamp connections. Dacrymyces aureosporus resembles D. chrysospermus, but differs in wall thickness of its marginal hyphae. Dacrymyces pinacearum and D. subarcticus represent new coelomycetous anamorphic species. Dacryopinax sphenocarpa has sharp, spathulate basidiocarps, and hyphae with clamp connections. Descriptions, illustrations and photographs of fruit bodies are presented with some taxonomic notes. Molecular phylogenetic analyses were conducted to verify the species identification, and the remaining problems in Dacrymycetes taxonomy are discussed based on these data

Legumes as food ingredient: characterization, processing, and applications

Editores: Jiménez-López, José Carlos (CSIC); Clemente, Alfonso (CSIC

Cold Induces Micro- and Nano-Scale Reorganization of Lipid Raft Markers at Mounds of T-Cell Membrane Fluctuations

Whether and how cold causes changes in cell-membrane or lipid rafts remain poorly characterized. Using the NSOM/QD and confocal imaging systems, we found that cold caused microscale redistribution of lipid raft markers, GM1 for lipid and CD59 for protein, from the peripheral part of microdomains to the central part on Jurkat T cells, and that cold also induced the nanoscale size-enlargement (1/3- to 2/3-fold) of the nanoclusters of lipid raft markers and even the colocalization of GM1 and CD59 nanoclusters. These findings indicate cold-induced lateral rearrangement/coalescence of raft-related membrane heterogeneity. The cold-induced re-distribution of lipid raft markers under a nearly-natural condition provide clues for their alternations, and help to propose a model in which raft lipids associate themselves or interact with protein components to generate functional membrane heterogeneity in response to stimulus. The data also underscore the possible cold-induced artifacts in early-described cold-related experiments and the detergent-resistance-based analyses of lipid rafts at 4°C, and provide a biophysical explanation for recently-reported cold-induced activation of signaling pathways in T cells. Importantly, our fluorescence-topographic NSOM imaging demonstrated that GM1/CD59 raft markers distributed and re-distributed at mounds but not depressions of T-cell membrane fluctuations. Such mound-top distribution of lipid raft markers or lipid rafts provides spatial advantage for lipid rafts or contact molecules interacting readily with neighboring cells or free molecules

Evaluating Clinical Genome Sequence Analysis by Watson for Genomics

Background: Oncologists increasingly rely on clinical genome sequencing to pursue effective, molecularly targeted therapies. This study assesses the validity and utility of the artificial intelligence Watson for Genomics (WfG) for analyzing clinical sequencing results.Methods: This study identified patients with solid tumors who participated in in-house genome sequencing projects at a single cancer specialty hospital between April 2013 and October 2016. Targeted genome sequencing results of these patients' tumors, previously analyzed by multidisciplinary specialists at the hospital, were reanalyzed by WfG. This study measures the concordance between the two evaluations.Results: In 198 patients, in-house genome sequencing detected 785 gene mutations, 40 amplifications, and 22 fusions after eliminating single nucleotide polymorphisms. Breast cancer (n = 40) was the most frequent diagnosis in this analysis, followed by gastric cancer (n = 31), and lung cancer (n = 30). Frequently detected single nucleotide variants were found in TP53 (n = 107), BRCA2 (n = 24), and NOTCH2 (n = 23). MYC (n = 10) was the most frequently detected gene amplification, followed by ERBB2 (n = 9) and CCND1 (n = 6). Concordant pathogenic classifications (i.e., pathogenic, benign, or variant of unknown significance) between in-house specialists and WfG included 705 mutations (89.8%; 95% CI, 87.5%−91.8%), 39 amplifications (97.5%; 95% CI, 86.8–99.9%), and 17 fusions (77.3%; 95% CI, 54.6–92.2%). After about 12 months, reanalysis using a more recent version of WfG demonstrated a better concordance rate of 94.5% (95% CI, 92.7–96.0%) for gene mutations. Across the 249 gene alterations determined to be pathogenic by both methods, including mutations, amplifications, and fusions, WfG covered 84.6% (88 of 104) of all targeted therapies that experts proposed and offered an additional 225 therapeutic options.Conclusions: WfG was able to scour large volumes of data from scientific studies and databases to analyze in-house clinical genome sequencing results and demonstrated the potential for application to clinical practice; however, we must train WfG in clinical trial settings

Complement Receptor 1 Is a Sialic Acid-Independent Erythrocyte Receptor of Plasmodium falciparum

Plasmodium falciparum is a highly lethal malaria parasite of humans. A major portion of its life cycle is dedicated to invading and multiplying inside erythrocytes. The molecular mechanisms of erythrocyte invasion are incompletely understood. P. falciparum depends heavily on sialic acid present on glycophorins to invade erythrocytes. However, a significant proportion of laboratory and field isolates are also able to invade erythrocytes in a sialic acid-independent manner. The identity of the erythrocyte sialic acid-independent receptor has been a mystery for decades. We report here that the complement receptor 1 (CR1) is a sialic acid-independent receptor for the invasion of erythrocytes by P. falciparum. We show that soluble CR1 (sCR1) as well as polyclonal and monoclonal antibodies against CR1 inhibit sialic acid-independent invasion in a variety of laboratory strains and wild isolates, and that merozoites interact directly with CR1 on the erythrocyte surface and with sCR1-coated microspheres. Also, the invasion of neuraminidase-treated erythrocytes correlates with the level of CR1 expression. Finally, both sialic acid-independent and dependent strains invade CR1 transgenic mouse erythrocytes preferentially over wild-type erythrocytes but invasion by the latter is more sensitive to neuraminidase. These results suggest that both sialic acid-dependent and independent strains interact with CR1 in the normal red cell during the invasion process. However, only sialic acid-independent strains can do so without the presence of glycophorin sialic acid. Our results close a longstanding and important gap in the understanding of the mechanism of erythrocyte invasion by P. falciparum that will eventually make possible the development of an effective blood stage vaccine

Inherited Glutathione Reductase Deficiency and Plasmodium falciparum Malaria—A Case Study

In Plasmodium falciparum-infected red blood cells (RBCs), the flavoenzyme glutathione reductase (GR) regenerates reduced glutathione, which is essential for antioxidant defense. GR utilizes NADPH produced in the pentose phosphate shunt by glucose-6-phosphate dehydrogenase (G6PD). Thus, conditions affecting host G6PD or GR induce increased sensitivity to oxidants. Hereditary G6PD deficiency is frequent in malaria endemic areas and provides protection against severe malaria. Furthermore, GR deficiency resulting from insufficient saturation of the enzyme with its prosthetic group FAD is common. Based on these naturally occurring phenomena, GR of malaria parasites and their host cells represent attractive antimalarial drug targets. Recently we were given the opportunity to examine invasion, growth, and drug sensitivity of three P. falciparum strains (3D7, K1, and Palo Alto) in the RBCs from three homozygous individuals with total GR deficiency resulting from mutations in the apoprotein. Invasion or growth in the GR-deficient RBCs was not impaired for any of the parasite strains tested. Drug sensitivity to chloroquine, artemisinin, and methylene blue was comparable to parasites grown in GR-sufficient RBCs and sensitivity towards paraquat and sodium nitroprusside was only slightly enhanced. In contrast, membrane deposition of hemichromes as well as the opsonizing complement C3b fragments and phagocytosis were strongly increased in ring-infected RBCs of the GR-deficient individuals compared to ring-infected normal RBCs. Also, in one of the individuals, membrane-bound autologous IgGs were significantly enhanced. Thus, based on our in vitro data, GR deficiency and drug-induced GR inhibition may protect from malaria by inducing enhanced ring stage phagocytosis rather than by impairing parasite growth directly

Nanoparticles for Applications in Cellular Imaging

In the following review we discuss several types of nanoparticles (such as TiO2, quantum dots, and gold nanoparticles) and their impact on the ability to image biological components in fixed cells. The review also discusses factors influencing nanoparticle imaging and uptake in live cells in vitro. Due to their unique size-dependent properties nanoparticles offer numerous advantages over traditional dyes and proteins. For example, the photostability, narrow emission peak, and ability to rationally modify both the size and surface chemistry of Quantum Dots allow for simultaneous analyses of multiple targets within the same cell. On the other hand, the surface characteristics of nanometer sized TiO2allow efficient conjugation to nucleic acids which enables their retention in specific subcellular compartments. We discuss cellular uptake mechanisms for the internalization of nanoparticles and studies showing the influence of nanoparticle size and charge and the cell type targeted on nanoparticle uptake. The predominant nanoparticle uptake mechanisms include clathrin-dependent mechanisms, macropinocytosis, and phagocytosis

Optimal timing of R&D for effective utilization of potential resources in innovation

Contrary to its highest R&D intensity, Japan has dramatically decreased its productivity in the 1990s. This can be attributed to a low marginal productivity of technology. Such a productivity decrease compels a delay in R&D, which results in reduced R&D productivity leading to a vicious cycle between R&D and its return. In this context optimal timing of R&D is crucial, particularly during economic stagnation and consequent difficulties in financing R&D. This paper analyzes the rationale for optimal timing of R&D and its interacting relationship with marginal productivity of technology. Empirical analyses are attempted focusing on Japan’s leading high‐technology firms and their innovative products