Synthesis and insecticidal activity of novel dihydropyrrole derivatives with N-sulfanyl,sulfinyl, and sulfonyl moieties

This paper reports the synthesis and insecticidal activity of a new type of dihydropyrrole derivatives with sulfur moieties such as sulfanyl, sulfinyl, and sulfonyl groups at the 1-position. These derivatives exhibited high insecticidal potency against Nilaparvata lugens and Nephotettix cincticeps. Investigation of the structure-activity relationships revealed that the alkoxycarbonyloxy groups at the 4-position tended to increase the systemic insecticidal activity.     

Storage of retinal in the eggs of the ascidian,Halocynthia roretzi

Retinoids in the eggs of the solitary ascidian, Halocynthia roretzi, were analyzed by high performance liquid chromatography. Retinal was the almost exclusive retinoid (>99%), and the concentration of retinal was 25.9-40.1 (30.6 on average) ng/mg of protein. The egg retinal consisted of four isomers: all-trans (50.9%), 9-cis (6.8%), 11-cis (20.4%) and 13-cis (21.9%). The presence of retinal in the eggs of this ascidian is a characteristic shared with the wide range of oviparous vertebrates, although the isomer composition differs between ascidian eggs and vertebrate eggs; in vertebrate eggs, almost all the retinal is in the all-trans form. The egg retinal was bound to a protein complex via a Schiff base linkage. The electrophoretic characteristics of the protein complex were similar to that of egg yolk proteins of oviparous vertebrates. The results presented in this study strongly suggest that, as is found with oviparous vertebrates, retinal in the ascidian eggs is the essential mode of retinoid storage, and is the precursor of photoreceptive pigment chromophores and retinoic acid during development.     

Conformational study of a highly specific CXCR4 inhibitor, T140, disclosing the close proximity of its intrinsic pharmacophores associated with strong anti-HIV activity

We report the solution structure of T140, a truncated polyphemusin peptide analogue that efficiently inhibits infection of target cells by T-cell line-tropic strains of HIV-1 through its specific binding to a chemokine receptor, CXCR4. Nuclear magnetic resonance analysis and molecular dynamic calculations revealed that T140 has a rigidly structured conformation constituted by an antiparallel beta-sheet and a type II' beta-turn. A protuberance is formed on one side of the beta-sheet by the side-chain functional groups of the three amino acid residues (L-3-(2-naphthyl)alanine, Tyr5 and Arg14), each of which is indispensable for strong anti-HIV activity. These findings provide a rationale to dissect the structural basis for the ability of this compound to block the interaction between CXCR4 and envelope glycoproteins from T-tropic strains of HIV-1.     

The thyroid function of Graves' disease patients is aggravated by depressive personality during antithyroid drug treatment

Background

Sleep disturbance is a major health issue in Japan. This before-after study aimed to evaluate the immediate effects of forest walking in a community-based population with sleep complaints.

Methods

Participants were 71 healthy volunteers (43 men and 28 women). Two-hour forest-walking sessions were conducted on 8 different weekend days from September through December 2005. Sleep conditions were compared between the nights before and after walking in a forest by self-administered questionnaire and actigraphy data.

Results

Two hours of forest walking improved sleep characteristics; impacting actual sleep time, immobile minutes, self-rated depth of sleep, and sleep quality. Mean actual sleep time estimated by actigraphy on the night after forest walking was 419.8 ± 128.7 (S.D.) minutes whereas that the night before was 365.9 ± 89.4 minutes (n = 42). Forest walking in the afternoon improved actual sleep time and immobile minutes compared with forest walking in the forenoon. Mean actual sleep times did not increase after forenoon walks (n = 26) (the night before and after forenoon walks, 380.0 ± 99.6 and 385.6 ± 101.7 minutes, respectively), whereas afternoon walks (n = 16) increased mean actual sleep times from 342.9 ± 66.2 to 475.4 ± 150.5 minutes. The trend of mean immobile minutes was similar to the abovementioned trend of mean actual sleep times.

Conclusions

Forest walking improved nocturnal sleep conditions for individuals with sleep complaints, possibly as a result of exercise and emotional improvement. Furthermore, extension of sleep duration was greater after an afternoon walk compared to a forenoon walk. Further study of a forest-walking program in a randomized controlled trial is warranted to clarify its effect on people with insomnia.     

Generation of germline-competent rat induced pluripotent stem cells

Background

Recent progress in rat pluripotent stem cell technology has been remarkable. Particularly salient is the demonstration that embryonic stem cells (ESCs) in the rat (rESCs) can contribute to germline transmission, permitting generation of gene-modified rats as is now done using mouse ESCs (mESCs) or mouse induced pluripotent stem cells (iPSCs; miPSCs). However, determinations of whether rat iPSCs (riPSCs) can contribute to germ cells are not published. Here we report the germline competency of riPSCs.

Methodology/Principal Findings

We generated riPSCs by transducing three mouse reprogramming factors (Oct3/4, Klf4, and Sox2) into rat somatic cells, followed by culture in the presence of exogenous rat leukemia inhibitory factor (rLIF) and small molecules that specifically inhibit GSK3, MEK, and FGF receptor tyrosine kinases. We found that, like rESCs, our riPSCs can contribute to germline transmission. Furthermore we found, by immunostaining of testis from mouse-rat interspecific chimeras with antibody against mouse vasa homolog, that riPSCs can contribute to embryonic development with chimera formation in mice (rat-mouse interspecific chimeras) and to interspecific germlines.

Conclusions/Significance

Our data clearly demonstrate that using only three reprogramming factors (Oct3/4, Klf4, and Sox2) rat somatic cells can be reprogrammed into a ground state. Our generated riPSCs exhibited germline transmission in either rat-rat intraspecific or mouse-rat interspecific chimeras.     

Complete mitochondrial genomes of Diplogonoporus balaenopterae and Diplogonoporus grandis (Cestoda: Diphyllobothriidae) and clarification of their taxonomic relationships

Although the diplogonadic human tapeworm, Diplogonoporus grandis, has long been considered to be a synonym of the whale tapeworm, Diplogonoporus balaenopterae, the identity of the both species at the complete mitochondrial genomes and nuclear DNA levels has been not sufficiently undertaken to date. In the present study, to clarify the taxonomic relationships between D. balaenopterae and D. grandis at the molecular level, the complete mitochondrial genomes of both species were sequenced and compared. In addition, the genetic variation in the mitochondrial cytochrome c oxidase subunit 1 gene (cox1) and the nuclear internal transcribed spacer-1 (ITS-1) region of the ribosomal RNA gene were examined. The complete mitochondrial genomes of D. balaenopterae and D. grandis consisted of 13,724 bp and 13,725 bp, respectively. These mitochondrial genomes contained 12 protein-coding, 22 transfer RNA and 2 ribosomal RNA genes and two longer non-coding regions. Except for Hymenolepis diminuta, the genomic organization in both species was essentially identical to that in other cestode genomes examined to date. However, differences were observed between Diplogonoporus and Diphyllobothrium species in abbreviated stop codons, sequences and the number of repeat units in the 2nd non-coding regions. The genetic differences observed in the mitochondrial genomes, cox1 and ITS-1 regions of both species were considered typical of intraspecific variation. In conclusion, D. balaenopterae is a taxonomically valid species and D. grandis is a junior synonym of D. balaenopterae based on the zoological nomenclature. Further, molecular-phylogenetic analysis confirmed that D. balaenopterae is more closely related to Diphyllobothrium stemmacephalum, the type-species of the genus Diphyllobothrium, and the taxonomical validity of the genera Diplogonoporus and Diphyllobothrium was also discussed.     

Immunological and regenerative aspects of hepatic mast cells in liver allograft rejection and tolerance

The precise roles of mast cells in liver allograft rejection and tolerance are still unknown. This study aimed to explore the roles of mast cells in immune regulation and liver regeneration for tolerance induction by using rat models of orthotopic liver transplantation (OLT). Stem cell factor (SCF) and its receptor c-Kit, which are critical to the migration and development of not only stem cells but also mast cells, significantly increased in the tolerogenic livers as compared with rejected livers. The significant elevation of mast cell tryptase, high-affinity IgE receptor, and histamine suggested the activation of mast cells in liver allografts at the tolerogenic phase after OLT. Immunohistochemical analysis using confocal microscope clearly showed colocalization of mast cells, Foxp3+ Tregs, γδ T cells, and recipient-derived hepatic progenitor cells with higher expression of SCF, IL-9, IL-10, TGF-β1, and IL-17 related to immunoregulation and liver regeneration in the donor grafts of a tolerogenic OLT model. Cross-talk among mast cells and other cells was evaluated by in vitro studies demonstrating that syngeneic bone marrow-derived mast cells (BMMCs) co-cultured with na?ve splenocytes or primary hepatocytes significantly increased the population of splenic γδ T cells by mitogen stimulation or by mast cell degranulation, and also significantly induced the hepatocyte proliferation, respectively. Our results suggested that mast cells in the donor grafts may play important roles in the induction/maintenance of immune tolerance and liver regeneration resulting in the replacement of hepatic cells from donor to recipient.     

Gamma band neural synchronization deficits for auditory steady state responses in bipolar disorder patients

Periodic auditory click stimulation has been reported to elicit an auditory steady state response (ASSR). The ASSR has been suggested to reflect the efficiency of γ-amino butyric acid (GABA) inhibitory interneuronal activity. Although a potential role for GABAergic dysfunction has been previously proposed, the role of neural synchronization in the ASSR in people with bipolar disorder (BD) has received little attention. In the current study, we investigated ASSRs to 20 Hz, 30 Hz, 40 Hz and 80 Hz click trains in BD patients. A total of 14 (4 males) BD patients and 25 (10 males) healthy controls participated in this study. ASSRs were obtained using whole-head 306-channel magnetoencephalography to calculate, ASSR power values and phase locking factors (PLF). BD patients exhibited significantly reduced mean ASSR power and PLF values bilaterally at frequencies of 30, 40, and 80 Hz (p<0.05 for these frequencies). At 20 Hz, bipolar patients showed no significant reduction in mean ASSR power and PLF values. There was a significant negative correlation between 80 Hz-ASSR-power values obtained from the right hemisphere and scores on the Hamilton Depression Rating Scale (rho = −0.86, p = 0.0003). The current study showed reduced low and high gamma band ASSR power and PLF bilaterally with no significant beta band ASSR reduction in BD patients. BD patients are characterized by deficits in gamma band oscillations, which may be associated with GABA inhibitory interneuronal activity dysfunction.