Biology subjects

Takeshita, Y.

Publications and source records attributed to Takeshita, Y..

4 recordsLinked to original sources

bioRxiv2021

IL-6 blockade suppresses the blood-brain barrier disorder, leading to prevention of onset of NMOSD

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy caused by antibodies against the aquaporin 4(AQP4) in end-feet of astrocytes. Breakdown of the blood-brain barrier (BBB) allowing ingress of AQP4 antibodies into the central nervous system (CNS) plays a key role in NMOSD. Although IL-6 blockade therapies such as satralizumab are effective in NMOSD, the therapeutic mechanism of IL-6 blockade, especially with respect to BBB disruption, are not fully understood because of the lack of the human models that are specialized to evaluate the BBB function. We constructed new in vitro human BBB models for evaluating continued barrier function, leukocyte transmigration and intracerebral transferability of IgGs utilizing the newly established triple co-culture system. In vitro and vivo experiments revealed that NMO-IgG increased intracerebral transferability of satralizumab, and that satralizumab suppressed the NMO-IgG-induced transmigration of T cells and barrier dysfunction. These results suggest that satralizumab, which can pass through the BBB in the presence of NMO-IgG, suppresses the barrier dysfunction and the disrupting controlled cellular infiltration at the BBB, leading to prevention of onset of NMOSD. One sentence summarySatralizumab and IL-6 blockade prevent lymphocyte migration and barrier dysfunction induced by NMO-IgG in EAE and novel triple co-culture BBB models.

immunology↗

bioRxiv2020

Evidence for a biological source of widespread, reproducible nighttime oxygen spikes in tropical reef ecosystems has implications for coral health

Primary producers release oxygen as the by-product of photosynthetic light reactions during the day. However, a prevalent, globally-occurring nighttime spike in dissolved oxygen in the absence of light challenges the traditional assumption that biological oxygen production is limited to daylight hours, particularly in tropical coral reefs. Here we show: 1) the widespread nature of this phenomenon, 2) its reproducibility across tropical marine ecosystems, 3) the influence of biotic and abiotic factors on this phenomenon across numerous datasets, and 4) the observation of nighttime oxygen spikes in vitro from incubations of coral reef benthic organisms. The data from this study demonstrate that in addition to physical forcing, biological processes are likely responsible for increasing dissolved oxygen at night. Additionally, we demonstrate an association between these nighttime oxygen spikes and measures of both net community calcification and net community production. These results suggest that nighttime oxygen spikes are likely a biological response associated with increased respiration and are most prominent in communities dominated by calcifying organisms.

ecology↗

bioRxiv2020

Complete sequences of Schizosaccharomyces pombe subtelomeres reveal multiple patterns of genome variation

Genome sequences have been determined for many model organisms; however, repetitive regions such as centromeres, telomeres, and subtelomeres have not yet been sequenced completely. Here, we report the complete sequences of subtelomeric homologous (SH) regions of the fission yeast Schizosaccharomyces pombe. We overcame technical difficulties to obtain subtelomeric repetitive sequences by constructing strains that possess single SH regions. Whole sequences of SH regions revealed that each SH region consists of two distinct parts: the telomere-proximal part with mosaics of multiple common segments showing high variation among subtelomeres and strains, and the telomere-distal part showing high sequence similarity among subtelomeres with some insertions and deletions. The newly sequenced SH regions showed differences in nucleotide sequences and common segment composition compared to those in the S. pombe genome database (PomBase), which is in striking contrast to the regions outside of SH, where mutations are rarely detected. Furthermore, we identified new subtelomeric RecQ-type helicase genes, tlh3 and tlh4, which add to the already known tlh1 and tlh2, and found that the tlh1-4 genes show high sequence variation. Our results indicate that SH sequences are highly polymorphic and hot spots for genome variation. These features of subtelomeres may have contributed to genome diversity and, conversely, various diseases.

genomics↗

bioRxiv2018

Biophysical and physiological causes of coral reef microbialization

Coral reefs are declining globally as their primary producer communities shift from stony coral to fleshy macroalgae dominance. Previously, we have shown that the rise of fleshy macroalgae produces dissolved organic carbon (DOC) that lead to microbialization and coral death. Here we test the hypothesis that the biophysical cause of bacterial biomass accumulation is a relative decrease in electron acceptors relative to electron donors due to O2 loss from macroalgae. We show that 37 % of photosynthetic O2 produced by reef fleshy macroalgae is lost in the form of gas through ebullition from algae surfaces. O2 loss increases DOC:O2 ratios, decoupling the photosynthetically fixed carbon from oxidative potential for respiration. This biogeochemical environment drives heterotrophic microbes to increase cell-specific DOC consumption and cell sizes, accumulating biomass. In contrast, corals do not lose oxygen and support the growth of smaller and fewer bacteria. In situ biomass and metagenomic analyses of 87 reefs across the Pacific and Caribbean show that on algae-dominated reefs bacteria accumulate organic carbon through a Warburg-like increase in aerobic glycolytic metabolism. Because of its biophysical basis, microbialization is predicted to occur in other marine ecosystems shifting primary producer assemblages, such as planktonic communities in warming and acidifying conditions.

ecology↗