Good‐bye to tropical alpine plant giants under warmer climates? Loss of range and genetic diversity in Lobelia rhynchopetalum

The main aim of this paper is to address consequences of climate warming on loss of habitat and genetic diversity in the enigmatic tropical alpine giant rosette plants using the Ethiopian endemic Lobelia rhynchopetalum as a model. We modeled the habitat suitability of L. rhynchopetalum and assessed how its range is affected under two climate models and four emission scenarios. We used three statistical algorithms calibrated to represent two different complexity levels of the response. We analyzed genetic diversity using amplified fragment length polymorphisms and assessed the impact of the projected range loss. Under all model and scenario combinations and consistent across algorithms and complexity levels, this afro‐alpine flagship species faces massive range reduction. Only 3.4% of its habitat seems to remain suitable on average by 2,080, resulting in loss of 82% (CI 75%–87%) of its genetic diversity. The remaining suitable habitat is projected to be fragmented among and reduced to four mountain peaks, further deteriorating the probability of long‐term sustainability of viable populations. Because of the similar morphological and physiological traits developed through convergent evolution by tropical alpine giant rosette plants in response to diurnal freeze‐thaw cycles, they most likely respond to climate change in a similar way as our study species. We conclude that specialized high‐alpine giant rosette plants, such as L. rhynchopetalum, are likely to face very high risk of extinction following climate warming.     

Characteristic seasonal variation in dissolved uranium concentration induced by the change of lake water pH in Lake Biwa,Japan

Epilimnion-dominated profiles of dissolved uranium (U) have been observed during summer in an oxygenated Japanese lake, Lake Biwa, contrary to the commonly accepted view that U shows conservative behavior in oxygenated seas and lakes. Monthly observations were conducted to reveal the mechanism for such characteristic distribution and geochemical behavior of dissolved U in the lake. In the surface water, dissolved U concentration started to increase in spring, peaked in summer, and decreased from autumn to winter. In contrast, the concentration remained almost constant in the middle layer (40 m depth) and decreased slightly in the bottom layer (70 m depth) throughout the stagnation period. Mass balance calculations of U suggest that the major mechanism for seasonal variations in the surface layer is the supply of U, not via water inflow from the watershed, but by internal chemical reactions within the lake. A laboratory experiment using the lake water and sediment demonstrated that U was desorbed from and adsorbed onto sediment in response to variations in lake water pH. From these results, it is inferred that the seasonal variation in the concentration of dissolved U in the epilimnion results mainly from the desorptive/adsorptive processes of U between sediment/water interface in response to variation in water pH, which is affected by biological activity in the lake.     

Adenosine A2A receptor deficiency attenuates the somnogenic effect of prostaglandin D2

Sleep and Biological Rhythms -     

Histaminergic role in sleep-wake cycle of orexin,adenosine, and prostaglandin E2 and D2

Sleep and Biological Rhythms -     

HTLV-1 bZIP Factor Impairs Anti-viral Immunity by Inducing Co-inhibitory Molecule,T Cell Immunoglobulin and ITIM Domain (TIGIT)

Human T-cell leukemia virus type 1 (HTLV-1) infects CD4⁺ T cells and induces proliferation of infected cells in vivo, which leads to the onset of adult T-cell leukemia (ATL) in some infected individuals. The HTLV-1 bZIP factor (HBZ) gene, which is encoded in the minus strand of HTLV-1, plays critical roles in pathogenesis. In this study, RNA-seq and ChIP-seq analyses using HBZ transduced T cells revealed that HBZ upregulates the expression and promoter acetylation levels of a co-inhibitory molecule, T cell immunoglobulin and ITIM domain (TIGIT), in addition to those of regulatory T cells related genes, Foxp3 and Ccr4. TIGIT was expressed on CD4⁺ T cells from HBZ-transgenic (HBZ-Tg) mice, and on ATL cells and HTLV-1 infected CD4⁺ T cells of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in vivo. Expression of Blimp1 and IL-10 was upregulated in TIGIT⁺CD4⁺ cells of HBZ-Tg mice compared with TIGIT^-CD4⁺ T cells, suggesting the correlation between TIGIT expression and IL-10 production. When CD4⁺ T cells from HBZ-Tg mice were stimulated with TIGIT’s ligand, CD155, their production of the inhibitory cytokine IL-10 was enhanced. Furthermore, dendritic cells from HBZ-Tg mice produced high levels of IL-10 after stimulation. These data suggest that HBZ alters immune system to suppressive state via TIGIT and IL-10. Importantly, TIGIT suppressed T-cell responses to another HTLV-1 virus protein, Tax, in vitro. Blocking of TIGIT and PD-1 slightly increased anti-Tax T-cell activity in some HAM/TSP patients. These results suggest that HBZ-induced TIGIT on HTLV-1 infected cells impairs T-cell responses to viral antigens. This study shows that HBZ-induced TIGIT plays a pivotal role in attenuating host immune responses and shaping a microenvironment favorable to HTLV-1.     

Affinity Improvement of a Cancer-Targeted Antibody through Alanine-Induced Adjustment of Antigen-Antibody Interface

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Phylogeography of lethal male fighting in a social spider mite

When males fight for access to females, such conflict rarely escalates into lethal fight because the risks and costs involved, that is, severe injury or death, are too high. The social spider mite, Stigmaeopsis miscanthi, does exhibit lethal male fights, and this male–male aggressiveness varies among populations. To understand the evolution of lethal fighting, we investigated aggressiveness in 42 populations and phylogenetic relationships in 47 populations along the Japanese archipelago. By analysis of the male weapon morph, a proxy for aggressiveness, we confirmed the existence of a mildly aggressive (ML) form, besides the low aggression (LW) and high aggression (HG) forms reported earlier. To evaluate demographic history of these three forms, we employed the approximate Bayesian computation approach using mtCOI sequences and taking into consideration the postlast glacial expansion history of the host plant, Miscanthus sinensis. As results, hierarchical split models are more likely to explain the observed genetic pattern than admixture models, and the ML form in the subtropical region was considered the ancestral group. The inferred demographic history was consistent with the one reconstructed for the host plant in a previous study. The LW form was split from the ML form during the last glacial period (20,000–40,000 years BP), and subsequently, the HG form was split from the ML form at the end of or after the last glacial period (5,494–10,988 years BP). The results also suggest that the mite invaded Japan more than once, resulting in the present parapatric distribution of LW and HG forms in eastern Japan.     

Floating culture promotes the maintenance of hematopoietic stem cells

In this study we examined the effect of the specific gravity of culture medium on the frequency of hematopoietic stem cell (HSC) maintenance. We used a newly developed high-specific-gravity media. Bone marrow cells were isolated and cultured, and HSC activity was evaluated. The number of hematopoietic progenitor/stem cells was markedly higher in the medium with high specific gravity. In high-specific-gravity media, cells did not precipitate, maintenance of HSCs was increased, and there was a concomitant accumulation of beta-catenin. This novel technique for maintaining HSC populations provides an important new tool for studies in regenerative medicine.     

Fucosyl-GM1a, an endoglycoceramidase-resistant ganglioside of porcine brain

The use of bovine brain has been prohibited in many countries because of the world-wide prevalence of mad cow disease, and thus porcine brain is expected to be a new source for the preparation of gangliosides. Here, we report the presence of a ganglioside in porcine brain which is strongly resistant to hydrolysis by endoglycoceramidase, an enzyme capable of cleaving the glycosidic linkage between oligosaccharides and ceramides of various glycosphingolipids. Five major gangliosides (designated PBG-1, 2, 3, 4, 5) were extracted from porcine brain by Folch's partition, followed by mild alkaline hydrolysis and PBA column chromatography. We found that PBG-2, but not the others, was strongly resistant to hydrolysis by the enzyme. After the purification of PBG-2 with Q-Sepharose, Silica gel 60 and Prosep-PB chromatographies, the structure of PBG-2 was determined by GC, GC-MS, FAB-MS and NMR spectroscopy as Fucalpha1-2Galbeta1-3GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1-4Glcbeta1-1'Cer (fucosyl-GM1a). The ceramide was mainly composed of C18:0 and C20:0 fatty acids and d18:1 and d20:1 sphingoid bases. The apparent kcat/Km for fucosyl-GM1a was found to be 30 times lower than that for GM1a, indicating that terminal fucosylation makes GM1a resistant to hydrolysis by the enzyme. This report indicates the usefulness of endoglycoceramidase to prepare fucosyl-GM1a from porcine brain.     

Structure of the antitumour enzyme L-methionine gamma-lyase from Pseudomonas putida at 1.8 A resolution

l-Methionine gamma-lyase (EC 4.4.1.11, MGL_Pp) from Pseudomonas putida is a multifunctional enzyme, which belongs to the gamma-family of pyridoxal-5'-phosphate (PLP) dependent enzymes. In this report, we demonstrate that the three-dimensional structure of MGL_Pp has been completely solved by the molecular replacement method to an R-factor of 20.4% at 1.8 A resolution. Detailed information of the overall structure of MGL_Pp supplies a clear picture of the substrate- and PLP-binding pockets. Tyr59 and Arg61 of neighbouring subunits, which are strongly conserved in other gamma-family enzymes, contact the phosphate group of PLP. These residues are important as the main anchor within the active site. Lys240, Asp241 and Arg61 of one partner monomer and Tyr114 and Cys116 of the other partner monomer form a hydrogen-bond network in the MGL active site which is specific for MGLs. It is also suggested that electrostatic interactions at the subunit interface are involved in the stabilization of the structural conformation. The detailed structure will facilitate the development of MGL_Pp as an anticancer drug.