Phylogeographical patterns of a generalist acorn weevil: insight into the biogeographical history of broadleaved deciduous and evergreen forests

<p>Abstract</p> <p>Background</p> <p>Climatic changes during glacial periods have had a major influence on the recent evolutionary history of living organisms, even in temperate forests on islands, where the land was not covered with ice sheets. We investigated the phylogeographical patterns of the weevil <it>Curculio sikkimensis </it>(Curculionidae), a generalist seed predator of Fagaceae plants living in both deciduous oak and evergreen forests of Japan. Its genetic structure was compared to that of another host-specific seed predator, <it>C. hilgendorfi</it>, inhabiting only evergreen forests.</p> <p>Results</p> <p>We examined 921 bp of mitochondrial DNA for 115 individuals collected from 33 populations of <it>C. sikkimensis </it>from 11 plant species of three genera, <it>Quercus</it>, <it>Lithocarpus</it>, and <it>Castanopsis</it>. An analysis of molecular variance revealed that a large proportion (almost 50%, <it>P </it>< 0.001) of the total genetic variance could be explained by differences between two geographical regions, the southwestern and northeastern parts of the main islands of Japan. In contrast, no significant genetic differentiation of the weevil was observed among vegetation types of their utilized host plant species. The phylogeographical patterns of the generalist and the host-specific seed predator exhibited a congruent genetic boundary in the Chugoku-Shikoku region.</p> <p>Conclusion</p> <p>Our results suggest that geology and historical environment have contributed to shaping the present genetic structure of <it>C. sikkimensis</it>. The geographical patterns of genetic differentiation in the Chugoku-Shikoku region observed in the two types of Fagaceae-associated <it>Curculio </it>in this study have also been observed in several plant species growing in warm and cool temperate zones of Japan. The occurrence of this common pattern suggests that deciduous oak and evergreen forests of Japan survived together, or adjacent to each other, in small refugia during glacial ages, in the southwestern and northeastern parts of the main islands, although these two types of forests are presently distributed in cool and warm temperate zones of Japan, respectively.</p

Clarifying the Pathophysiological Mechanisms of Neuronal Abnormalities of NF1 by Induced-Neuronal (iN) Cells from Human Fibroblasts

Direct conversion techniques, which generate induced-neuronal (iN) cells from human fibroblasts in less than two weeks, are expected to discover unknown neuronal phenotypes of neuropsychiatric disorders. Here, we present unique gene expression and cell morphology profiles in iN cells derived from neurofibromatosis type 1 (NF1) patients. NF1 is a single-gene multifaceted disorder with relatively high co-occurrence of autism spectrum disorder (ASD). Adenylyl cyclase (AC) dysfunction is one of the candidate pathways in abnormal neuronal development in the brains of NF1 patients. In our study, microarray-based transcriptomic analysis of iN cells from healthy controls (males) and NF1 patients (males) revealed significantly different gene expression of 149 (110 were upregulated and 39 were downregulated). In iN cells derived from NF1 patients (NF1-iN cells), there was a change in the expression level of 90 genes with the addition of forskolin, an AC activator. Furthermore, treatment with forskolin dramatically changed the cell morphology, especially that of NF1-iN cells, from flat-form to spherical-form. Current pilot data indicate the potential therapeutic effect of forskolin or AC activators on neuronal growth in NF1 patients. Further translational research is needed to validate the pilot findings for future drug development of ASD

New NTP analogs: the synthesis of 4′-thioUTP and 4′-thioCTP and their utility for SELEX

The synthesis of the triphosphates of 4′-thiouridine and 4′-thiocytidine, 4′-thioUTP (7; thioUTP) and 4′-thioCTP (8; thioCTP), and their utility for SELEX (systematic evolution of ligands by exponential enrichment) is described. The new nucleoside triphosphate (NTP) analogs 7 and 8 were prepared from appropriately protected 4′-thiouridine and -cytidine derivatives using the one-pot method reported by J. Ludwig and F. Eckstein [(1989) J. Org. Chem., 54, 631–635]. Because SELEX requires both in vitro transcription and reverse transcription, we examined the ability of 7 and 8 for SELEX by focusing on the two steps. Incorporation of 7 and 8 by T7 RNA polymerase to give 4′-thioRNA (thioRNA) proceeded well and was superior to those of the two sets of frequently used modified NTP analogs for SELEX (2′-NH(2)dUTP and 2′-NH(2)dCTP; 2′-FdUTP and 2′-FdCTP), when an adequate leader sequence of DNA template was selected. We revealed that a leader sequence of about +15 of DNA template is important for the effective incorporation of modified NTP analogs by T7 RNA polymerase. In addition, reverse transcription of the resulting thioRNA into the complementary DNA in the presence of 2′-deoxynucleoside triphosphates (dNTPs) also proceeded smoothly and precisely. The stability of the thioRNA toward RNase A was 50 times greater than that of the corresponding natural RNA. With these successful results in hand, we attempted the selection of thioRNA aptamers to human α-thrombin using thioUTP and thioCTP, and found a thioRNA aptamer with high binding affinity (K(d) = 4.7 nM)

糖尿病網膜症の発症進展におけるポリオール代謝経路の関与

血管合併症である糖尿病網膜症は代謝異常により発症進展すると考えられている。周皮細胞は血管ネットワークにおいて、内皮細胞の安定化や成熟の他に内皮細胞の刺激および誘導に関与している。一旦、周皮細胞-内皮細胞の相互関係が破綻すると、基底膜の肥厚および血管透過性の亢進が起こり、増殖網膜症へ進展していく。我々はポリオール代謝に注目し、ストレプトゾトシン誘発糖尿病ラットを用いて、ポリオール代謝異常と周皮細胞の障害について検討した。アルドース還元酵素阻害剤によるポリオール代謝異常の是正は網膜毛細血管での周皮細胞消失、基底膜肥厚および毛細血管瘤の発現を抑制した。そこで，ポリオール代謝の意義を明らかにする為に、培養周皮細胞を用いて、ポリオール代謝の増強が細胞障害を強めるかどうかを検討した。周皮細胞の障害はポリオール代謝の増強によって強まった。続いて、我々は2型糖尿病モデルである自然発症糖尿病トリイ（SDT）ラットを用いて、ポリオール代謝異常の抑制作用が進行した網膜症に有効であるか検討した。ポリオール代謝の抑制は進行した網膜症を抑制した。以上より、ポリオール代謝異常は糖尿病網膜症の発症期から進行期の全般にわたり関係することが示唆された。The pathological changes of diabetic retinopathy, a vascular complication of diabetes, are thought to be caused by metabolic disturbances. Pericytes are involved in endothelial cell stimulation and guidance, as well as in endothelial stabilization and maturation in the vascular network. Once the pericyte-endothelial cell interaction breaks down, thickening of the basement membrane and increase in permeability occur, resulting in the onset of proliferative retinopathy. We focused on the polyol pathway, and investigated the association between the abnormality of the polyol pathway and the pericyte damage in a rat model of streptozotocin-induced diabetes. Correction of the polyol pathway disturbance by treatment with an aldose reductase inhibitor inhibited the onset of pericyte loss, thickening of the basement membrane and development of microaneurysms of the retinal capillaries. Therefore, to elucidate the significance of the polyol pathway, we examined whether activation of the pathway may potentiate the damage to the retinal pericytes. The damage to the pericytes was potentiated by activation of the polyol pathway. Furthermore, we investigated the inhibitory effects of the polyol pathway on advanced diabetic retinopathy in spontaneously diabetic Torii rats, a type Ⅱ diabetic model. Correction of the disturbed polyol pathway suppressed the progression of diabetic retinopathy. In conclusion, these results suggest that abnormality of the polyol pathway may contribute to the pathology in all stages of diabetic retinopathy

Sclerite formation in the hydrothermal-vent “scaly-foot” gastropod — possible control of iron sulfide biomineralization by the animal

A gastropod from a deep-sea hydrothermal field at the Rodriguez triple junction, Indian Ocean, has scale-shaped structures, called sclerites, mineralized with iron sulfides on its foot. No other organisms are known to produce a skeleton consisting of iron sulfides. To investigate whether iron sulfide mineralization is mediated by the gastropod for the function of the sclerites, we performed a detailed physical and chemical characterization. Nanostructural characterization of the iron sulfide sclerites reveals that the iron sulfide minerals pyrite (FeS2) and greigite (Fe3S4) form with unique crystal habits inside and outside of the organic matrix, respectively. The magnetic properties of the sclerites, which are mostly consistent with those predicted from their nanostructual features, are not optimized for magnetoreception and instead support use of the magnetic minerals as structural elements. The mechanical performance of the sclerites is superior to that of other biominerals used in the vent environment for predation as well as protection from predation. These characteristics, as well as the co-occurrence of brachyuran crabs, support the inference that the mineralization of iron sulfides might be controlled by the gastropod to harden the sclerites for protection from predators. Sulfur and iron isotopic analyses indicate that sulfur and iron in the sclerites originate from hydrothermal fluids rather than from bacterial metabolites, and that iron supply is unlikely to be regulated by the gastropod for iron sulfide mineralization. We propose that the gastropod may control iron sulfide mineralization by modulating the internal concentrations of reduced sulfur compounds

An Association Analysis between Mitochondrial DNA A10398G Polymorphism and Temperament in Japanese Young Adults

The mitochondrial (mt) DNA C5178A and A10398G polymorphisms have been reported to be associated with mental disorders such as bipolar disorder. However, the effects of these polymorphisms on temperament in healthy people are poorly understood. Evaluating healthy subjects can have the advantage of providing new strategies for maintaining psychological health and preventing mental illness. We examined the association between mtDNA polymorphisms and temperament in Japanese students. There was no significant difference in examined temperament when analysed by genotypes, 5178–10398 haplotypes, or sex. The subgroup analysis based on sex indicated that there was an interactive effect of the mtDNA A10398G polymorphism and sex on anxiety and obsession. This finding is preliminary and cannot exclude the possibility of false-positive due to small sample size (144 subjects) and multiple statistical testing. Further studies involving a larger sample size or other ethnic groups are necessary to confirm that mtDNA A10398G polymorphism can be a genetic factor for temperament

Resting-state functional connectivity-based biomarkers and functional MRI-based neurofeedback for psychiatric disorders: a challenge for developing theranostic biomarkers

Psychiatric research has been hampered by an explanatory gap between psychiatric symptoms and their neural underpinnings, which has resulted in poor treatment outcomes. This situation has prompted us to shift from symptom-based diagnosis to data-driven diagnosis, aiming to redefine psychiatric disorders as disorders of neural circuitry. Promising candidates for data-driven diagnosis include resting-state functional connectivity MRI (rs-fcMRI)-based biomarkers. Although biomarkers have been developed with the aim of diagnosing patients and predicting the efficacy of therapy, the focus has shifted to the identification of biomarkers that represent therapeutic targets, which would allow for more personalized treatment approaches. This type of biomarker (i.e., theranostic biomarker) is expected to elucidate the disease mechanism of psychiatric conditions and to offer an individualized neural circuit-based therapeutic target based on the neural cause of a condition. To this end, researchers have developed rs-fcMRI-based biomarkers and investigated a causal relationship between potential biomarkers and disease-specific behavior using functional MRI (fMRI)-based neurofeedback on functional connectivity. In this review, we introduce recent approach for creating a theranostic biomarker, which consists mainly of two parts: (i) developing an rs-fcMRI-based biomarker that can predict diagnosis and/or symptoms with high accuracy, and (ii) the introduction of a proof-of-concept study investigating the relationship between normalizing the biomarker and symptom changes using fMRI-based neurofeedback. In parallel with the introduction of recent studies, we review rs-fcMRI-based biomarker and fMRI-based neurofeedback, focusing on the technological improvements and limitations associated with clinical use.Comment: 46 pages, 5 figure

Metastases of soft tissue sarcoma to the liver: A Historical Cohort Study from a Hospital-based Cancer Registry

Background: Hepatic metastasis of soft tissue sarcoma is rare compared to lung metastasis, and the literature is scarce. We examined the risk of hepatic metastasis according to the site of occurrence and histological type. Methods: From a Hospital-based Cancer Registry, 658 patients registered between 2007 and 2017 with soft tissue sarcomas were evaluated. The exclusion criteria were gastrointestinal stromal tumors, tumors of unknown origin, and follow-up periods of less than 1 month. SPSS 25 was used for statistical analysis. Results: The risk of hepatic metastasis was significantly higher in the retroperitoneum (HR, 5.981; 95% CI, 2.793-12.808) and leiomyosarcoma (HR, 4.303; 95% CI, 1.782-10.390). Multivariate analysis showed that the risk of hepatic metastasis as first distant metastasis was high in leiomyosarcoma (HR, 4.546; 95% CI, 2.275-9.086) and retroperitoneal onset (HR, 4.588; 95% CI, 2.280-9.231). The 2-year survival rate after hepatic metastasis was 21.7%. Conclusions: The onset of hepatic metastasis indicates a poor prognosis. However, hepatic metastasis from retroperitoneal sarcoma and leiomyosarcoma may be the first distant metastasis in some cases. For retroperitoneal sarcoma and leiomyosarcoma, additional screening for hepatic metastasis such as contrast CT should be considered during staging and follow-up after treatment.ArticleCancer medicine 17(17) : 6159-6165(2020)journal articl

Maackiain Suppresses H1R and IL-4 Gene Transcriptions

Kujin contains antiallergic compounds that inhibit upregulation of histamine H1 receptor (H1R) and interleukin (IL)‐4 gene expression. However, the underlying mechanism remains unknown. We sought to identify a Kujin‐derived antiallergic compound and investigate its mechanism of action. The H1R and IL‐4 mRNA levels were determined by real‐time quantitative RT‐PCR. To investigate the effects of maackiain in vivo, toluene‐2,4‐diisocyanate (TDI)‐sensitized rats were used as a nasal hypersensitivity animal model. We identified (−)‐maackiain as the responsible component. Synthetic maackiain showed stereoselectivity for the suppression of IL‐4 gene expression but not for H1R gene expression, suggesting distinct target proteins for transcriptional signaling. (−)‐Maackiain inhibited of PKCδ translocation to the Golgi and phosphorylation of Tyr311 on PKCδ, which led to the suppression of H1R gene transcription. However, (−)‐maackiain did not show any antioxidant activity or inhibition of PKCδ enzymatic activity per se. Pretreatment with maackiain alleviated nasal symptoms and suppressed TDI‐induced upregulations of H1R and IL‐4 gene expressions in TDI‐sensitized rats. These data suggest that (−)‐maackiain is a novel antiallergic compound that alleviates nasal symptoms in TDI‐sensitized allergy model rats through the inhibition of H1R and IL‐4 gene expression. The molecular mechanism underlying its suppressive effect for H1R gene expression is mediated by the inhibition of PKCδ activation