Backbone resonance assignments of the F-actin binding domain of mouse αN-catenin

α-Catenin is a filamentous actin (F-actin) binding protein that links the classical cadherin–catenin complex to the actin cytoskeleton at adherens junctions (AJs). Its C-terminal F-actin binding domain is required for regulating the dynamic interaction between AJs and the actin cytoskeleton during tissue development. Thus, obtaining the molecular details of this interaction is a crucial step towards understanding how α-catenin plays critical roles in biological processes, such as morphogenesis, cell polarity, wound healing and tissue maintenance. Here we report the backbone atom (¹H^N, ¹⁵N, ¹³C^α, ¹³C^β and ¹³C′) resonance assignments of the C-terminal F-actin binding domain of αN-catenin.     

A novel approach for myocardial regeneration with educated cord blood cells cocultured with cells from brown adipose tissue

Umbilical cord blood (CB) is a promising source for regeneration therapy in humans. Recently, it was shown that CB was a source of mesenchymal stem cells as well as hematopoietic stem cells, and further that the mesenchymal stem cells could differentiate into a number of cells types of mesenchymal lineage, such as cardiomyocytes (CMs), osteocytes, chondrocytes, and fat cells. Previously, we reported that brown adipose tissue derived cells (BATDCs) differentiated into CMs and these CMs could adapt functionally to repair regions of myocardial infarction. In this study, we examined whether CB mononuclear cells (CBMNCs) could effectively differentiate into CMs by coculturing them with BATDCs and determined which population among CBMNCs differentiated into CMs. The results show that BATDCs effectively induced CBMNCs that were non-hematopoietic stem cells (HSCs) (educated CB cells: e-CBCs) into CMs in vitro. E-CBCs reconstituted infarcted myocardium more effectively than non-educated CBMNCs or CD34-positive HSCs. Moreover, we found that e-CBCs after 3 days coculturing with BATDCs induced the most effective regeneration for impaired CMs. This suggests that e-CBCs have a high potential to differentiate into CMs and that adequate timing of transplantation supports a high efficiency for CM regeneration. This strategy might be a promising therapy for human cardiac disease.     

Seasonally different modes of seed dispersal in the prostrate annual, <Emphasis Type="Italic">Chamaesyce maculata</Emphasis> (L.) Small (Euphorbiaceae), with multiple overlapping generations

The modes of seed dispersal in the prostrate annual, Chamaesyce maculata, with multiple overlapping generations were investigated. We found that C. maculata has two modes of seed dispersal; autochory in the summer and myrmecochory in the autumn. Seasonally different modes of seed dispersal have not been known in other plant species. The large proportion of seeds produced in the summer was positioned further than the expanse of the parent plants by automatic mechanical seed dispersal. Therefore, autochory would be effective for avoiding competition between parent and offspring plants. No autochory occurred in the seeds produced in the autumn. The seeds of C. maculata without an elaiosome were dispersed by seed-collecting ants in the autumn. Although 18 ant species in total visited the plants of C. maculata at the 50 sites investigated, only two ant species, Tetramorium tsushimae and Pheidole noda frequently carried the seeds of C. maculata. The low frequency of seeds carried out of the nest by P. noda suggests that the workers of P. noda carry the seeds as food into their nest. So, P. noda might be a less effective seed disperser for C. maculata, corresponding to the effectiveness of seed dispersal by harvester ants. However, T. tsushimae ants frequently carried the seeds into and out of their nest, suggesting that T. tsushimae do not regard the seeds of C. maculata as a food resource. Thus, T. tsushimae may be an effective seed disperser for C. maculata.     

Influence of Genes Suppressing Interferon Effects in Peripheral Blood Mononuclear Cells during Triple Antiviral Therapy for Chronic Hepatitis C

The levels of expression of interferon-stimulated genes (ISGs) in liver are associated with response to treatment with pegylated interferon (PEG-IFN) plus ribavirin (RBV). However, associations between the responses of ISGs to IFN-based therapy and treatment efficacy or interleukin-28B (IL28B) genotype have not yet been determined. Therefore, we investigated the early responses of ISGs and interferon-lambdas (IFN-λs) in peripheral blood mononuclear cells (PBMCs) during PEG-IFN/RBV plus NS3/4 protease inhibitor (PI) therapy. We prospectively enrolled 50 chronic hepatitis C patients with HCV genotype 1, and collected PBMCs at baseline, 8 and 24 h after the initial administration of PEG-IFN/RBV/PI. Levels of mRNAs for selected ISGs and IFN-λs were evaluated by real-time PCR. All 31 patients with a favorable IL28B genotype and 13 of 19 with an unfavorable genotype achieved sustained virological responses (SVR). Levels of mRNA for A20, SOCS1, and SOCS3, known to suppress antiviral activity by interfering with the IFN signaling pathway, as well as IRF1 were significantly higher at 8 h in patients with an unfavorable IL28B genotype than in those with a favorable one (P = 0.007, 0.026, 0.0004, 0.0006, respectively), especially in the non-SVR group. Particularly, the fold-change of IRF1 at 8 h relative to baseline was significantly higher in non-SVR than in SVR cases with an unfavorable IL28B genotype (P = 0.035). In conclusion, levels of several mRNAs of genes suppressing antiviral activity in PBMCs during PEG-IFN/RBV/PI differed according to IL28B genotypes, paralleling treatment efficacy.     

Importance of permafrost as a source of water for plants in east Siberian taiga

Stable oxygen isotope ratios of plant water (sap water) were observed at Spasskaya Pad experimental forest near Yakutsk, Russia in 1997–1999. The ¹⁸O of sap water in larch trees (Larix gmelinii) decreased soon after leaf unfolding every year, indicating that snowmelt water was used in the beginning of summer. During mid to late summer, a clear difference in the water source used by plants was observed between wet summers and severe drought summers. The ¹⁸O values of water in larch trees were high (–17.8 to –16.1) in August 1999 (wet summer), but low (–20.4 to –19.7) in August 1998 (drought summer). These results indicated that plants used rainwater during a wet summer, but meltwater from permafrost was used by plants during a drought summer. One important role of permafrost is to provide a direct source of water for plants in a severe drought summer; another role is to keep surplus water in the soil until the next summer. If this permafrost system is disturbed by future global warming, unique monotypic stands of deciduous larch trees in east Siberia might be seriously damaged in a severe drought summer.     

Trypanosome alternative oxidase, a potential therapeutic target for sleeping sickness, is conserved among Trypanosoma brucei subspecies

Trypanosoma brucei rhodesiense and T. b. gambiense are known causes of human African trypanosomiasis (HAT), or “sleeping sickness,” which is deadly if untreated. We previously reported that a specific inhibitor of trypanosome alternative oxidase (TAO), ascofuranone, quickly kills African trypanosomes in vitro and cures mice infected with another subspecies, non-human infective T. b. brucei, in in vivo trials. As an essential factor for trypanosome survival, TAO is a promising drug target due to the absence of alternative oxidases in the mammalian host. This study found TAO expression in HAT-causing trypanosomes; its amino acid sequence was identical to that in non-human infective T. b. brucei. The biochemical understanding of the TAO including its 3 dimensional structure and inhibitory compounds against TAO could therefore be applied to all three T. brucei subspecies in search of a cure for HAT. Our in vitro study using T. b. rhodesiense confirmed the effectiveness of ascofuranone (IC₅₀ value: 1 nM) to eliminate trypanosomes in human infective strain cultures.     

Associations between Lifetime Traumatic Events and Subsequent Chronic Physical Conditions: A Cross-National,Cross-Sectional Study

Background

Associations between lifetime traumatic event (LTE) exposures and subsequent physical ill-health are well established but it has remained unclear whether these are explained by PTSD or other mental disorders. This study examined this question and investigated whether associations varied by type and number of LTEs, across physical condition outcomes, or across countries.

Methods

Cross-sectional, face-to-face household surveys of adults (18+) were conducted in 14 countries (n = 38, 051). The Composite International Diagnostic Interview assessed lifetime LTEs and DSM-IV mental disorders. Chronic physical conditions were ascertained by self-report of physician''s diagnosis and year of diagnosis or onset. Survival analyses estimated associations between the number and type of LTEs with the subsequent onset of 11 physical conditions, with and without adjustment for mental disorders.

Findings

A dose-response association was found between increasing number of LTEs and odds of any physical condition onset (OR 1.5 [95% CI: 1.4–1.5] for 1 LTE; 2.1 [2.0–2.3] for 5+ LTEs), independent of all mental disorders. Associations did not vary greatly by type of LTE (except for combat and other war experience), nor across countries. A history of 1 LTE was associated with 7/11 of the physical conditions (ORs 1.3 [1.2–1.5] to 1.7 [1.4–2.0]) and a history of 5+ LTEs was associated with 9/11 physical conditions (ORs 1.8 [1.3–2.4] to 3.6 [2.0–6.5]), the exceptions being cancer and stroke.

Conclusions

Traumatic events are associated with adverse downstream effects on physical health, independent of PTSD and other mental disorders. Although the associations are modest they have public health implications due to the high prevalence of traumatic events and the range of common physical conditions affected. The effects of traumatic stress are a concern for all medical professionals and researchers, not just mental health specialists.     

Isolation and Characterization of a Free Gibberellin and Glucosyl Esters of Gibberellins in Mature Seeds of Phaseolus vulgaris

Treatment of N⁶,N⁶,5′-O-tribenzoyl-2′,3′-O-isopropylidenetubercidin (VI) with aqueous acetic acid afforded N⁶,5′-O-dibenzoyltubercidin (V), which was mesylated to yield the dimesylate X. On treatment of X with sodium iodide and zinc dust, the 2′,3′-unsaturated derivatives of tubercidin XI and XIII were obtained.

N⁶,5′-O-Dibenzoyltubercidin 2′,3′-thionocarbonate (XIV), prepared from V by treatment with Corey-Winter reagent, was converted to the 1-methyl-2′,3′-unsaturated derivative XV in refluxing trimethyl phosphite.     

A proposal of the method of deer density estimate without fecal decomposition rate: a case study of fecal accumulation rate technique in Japan

The accuracy of estimating deer density using the fecal pellet count method is greatly limited by variability of the fecal decomposition rate. The fecal accumulation rate technique can avoid the issue of decomposition rate. However, the precision of this technique is not clear when the decomposition rate is relatively high, such as in Japanese forests. We estimated deer population densities on Yakushima Island by the fecal accumulation rate technique and compared them between seasons. The estimated densities were similar to reported estimates, and did not differ seasonally, in accord with reports that deer on Yakushima do not migrate seasonally. Thus, we conclude that the fecal accumulation rate technique is applicable in Japanese forests.     

Serologic dissection of HLA-D specificities by the use of monoclonal antibodies

To study the gene products of the HLA complex, we produced two monoclonal antibodies, termed HU-18 and HU-23. They were active in complement-dependent cytotoxicity and detected B-cell alloantigens encoded by a locus (or loci) linked to HLA. When three types of HLA-DR4 homozygous B-cell lines with different HLA-D specificities were tested for reactivity with HU-18 and HU-23, they displayed distinct reaction patterns depending on the HLA-D specificities they possessed: EBV-Wa (HLA-DYT homozygous), negative for both HU-18 and HU-23; KT2 and KOB (HLA-DKT2 homozygous), positive only for HU-18; and ER (HLA-Dw4 homozygous), positive for both. These differential reaction patterns were further confirmed by testing against a panel of 17 HLA-DR4-positive peripheral blood lymphocytes with known HLA-D specificities. Thus, these monoclonal antibodies allow us to identify HLA-DYT, HLA-DKT2, and HLA-Dw4 solely by serologic methods. This is the first clearcut serologic identification of these three HLA-DR4-associated HLA-D specificities, which have been indistinguishable by conventional serology and identified only by cellular techniques. It is hoped that immunochemical investigations using HU-18 and HU-23 will advance our understanding of the HLA-D region on a molecular level.