A case of Graves' disease with anti-triiodothyronine antibodies

A case of Graves' disease with high serum thyroxine (T4) and low triiodothyronine (T3) levels which was therefore initially diagnosed as a T4-thyrotoxicosis is reported. Examination of the serum from the patient showed the presence of unusual protein which bound T3. It was later confirmed as IgG class anti-T3 antibodies. In addition to treatment with methylmercaptoimidazole (MMI), the patient was treated with prednisolone for 30 days (total amount 500 mg). Titers of anti-T3 antibodies in the sera were unchanged before and after prednisolone treatment. Our present case indicates that it is clinically important to bear the presence of autoantibodies in mind to account for a possible error in measuring T3 and T4 by radioimmunoassay (RIA). In the case that RIA determination gives an unexpectedly high or low T3 and/or T4 value, the presence of autoantibodies to them should be considered and a test for them is recommended.     

A new comprehensive method for detection of livestock-related pathogenic viruses using a target enrichment system

We tested usefulness of a target enrichment system SureSelect, a comprehensive viral nucleic acid detection method, for rapid identification of viral pathogens in feces samples of cattle, pigs and goats. This system enriches nucleic acids of target viruses in clinical/field samples by using a library of biotinylated RNAs with sequences complementary to the target viruses. The enriched nucleic acids are amplified by PCR and subjected to next generation sequencing to identify the target viruses. In many samples, SureSelect target enrichment method increased efficiencies for detection of the viruses listed in the biotinylated RNA library. Furthermore, this method enabled us to determine nearly full-length genome sequence of porcine parainfluenza virus 1 and greatly increased Breadth, a value indicating the ratio of the mapping consensus length in the reference genome, in pig samples. Our data showed usefulness of SureSelect target enrichment system for comprehensive analysis of genomic information of various viruses in field samples.     

Neural correlates of body comparison and weight estimation in weight-recovered anorexia nervosa: a functional magnetic resonance imaging study

Background

The neural mechanisms underlying body dissatisfaction and emotional problems evoked by social comparisons in patients with anorexia nervosa (AN) are currently unclear. Here, we elucidate patterns of brain activation among recovered patients with AN (recAN) during body comparison and weight estimation with functional magnetic resonance imaging (fMRI).

Methods

We used fMRI to examine 12 patients with recAN and 13 healthy controls while they performed body comparison and weight estimation tasks with images of underweight, healthy weight, and overweight female bodies. In the body comparison task, participants rated their anxiety levels while comparing their own body with the presented image. In the weight estimation task, participants estimated the weight of the body in the presented image. We used between-group region of interest (ROI) analyses of the blood oxygen level dependent (BOLD) signal to analyze differences in brain activation patterns between the groups. In addition, to investigate activation outside predetermined ROIs, we performed an exploratory whole-brain analysis to identify group differences.

Results

We found that, compared to healthy controls, patients with recAN exhibited significantly greater activation in the pregenual anterior cingulate cortex (pgACC) when comparing their own bodies with images of underweight female bodies. In addition, we found that, compared with healthy controls, patients with recAN exhibited significantly smaller activation in the middle temporal gyrus corresponding to the extrastriate body area (EBA) when comparing their own bodies, irrespective of weight, during self-other comparisons of body shape.

Conclusions

Our findings from a group of patients with recAN suggest that the pathology of AN may lie in an inability to regulate negative affect in response to body images via pgACC activation during body comparisons. The findings also suggest that altered body image processing in the brain persists even after recovery from AN.

     

Isolation and structure determination of a new lantibiotic cinnamycin B from <Emphasis Type="Italic">Actinomadura atramentaria</Emphasis> based on genome mining

New lantibiotic cinnamycin B was isolated from the extract of Actinomadura atramentaria NBRC 14695^T, based on genome mining and chemical investigation. The partial structure of cinnamycin B was established by 2D NMR experiments, which indicated that cinnamycin B had same methyl lanthionine bridging pattern with cinnamycin. The reduction with NaBH₄-NiCl₂ afforded the reduced cinnamycin B, and MS/MS experiment indicated the presence of hydroxy asparatic acid in the molecule. Cinnamycin B showed an antibacterial activity against Streptomyces antibioticus with dosage of 5 μg (0.5μL, 10 mg/mL solution) at spot-on-lawn testing method. The gene cluster of cinnamycin B on the genome of A. atramentaria was identified and discussed in comparison with that of cinnamycin.     

Peptide Bond Synthesis by a Mechanism Involving an Enzymatic Reaction and a Subsequent Chemical Reaction

We recently reported that an amide bond is unexpectedly formed by an acyl-CoA synthetase (which catalyzes the formation of a carbon-sulfur bond) when a suitable acid and l-cysteine are used as substrates. DltA, which is homologous to the adenylation domain of nonribosomal peptide synthetase, belongs to the same superfamily of adenylate-forming enzymes, which includes many kinds of enzymes, including the acyl-CoA synthetases. Here, we demonstrate that DltA synthesizes not only N-(d-alanyl)-l-cysteine (a dipeptide) but also various oligopeptides. We propose that this enzyme catalyzes peptide synthesis by the following unprecedented mechanism: (i) the formation of S-acyl-l-cysteine as an intermediate via its “enzymatic activity” and (ii) subsequent “chemical” S → N acyl transfer in the intermediate, resulting in peptide formation. Step ii is identical to the corresponding reaction in native chemical ligation, a method of chemical peptide synthesis, whereas step i is not. To the best of our knowledge, our discovery of this peptide synthesis mechanism involving an enzymatic reaction and a subsequent chemical reaction is the first such one to be reported. This new process yields peptides without the use of a thioesterified fragment, which is required in native chemical ligation. Together with these findings, the same mechanism-dependent formation of N-acyl compounds by other members of the above-mentioned superfamily demonstrated that all members most likely form peptide/amide compounds by using this novel mechanism. Each member enzyme acts on a specific substrate; thus, not only the corresponding peptides but also new types of amide compounds can be formed.     

Antifungal and Herbicidal Effects of Fruit Essential Oils of Four Myrtus communis Genotypes

The chemical composition of the essential oils isolated by hydrodistillation from the fruits of four selected Myrtus communis L. genotypes from Turkey was characterized by GC‐FID and GC/MS analyses. 1,8‐Cineole (29.20–31.40%), linalool (15.67–19.13%), α‐terpineol (8.40–18.43%), α‐pinene (6.04–20.71%), and geranyl acetate (3.98–7.54%) were found to be the major constituents of the fruit essential oils of all M. communis genotypes investigated. The oils were characterized by high amounts of oxygenated monoterpenes, representing 73.02–83.83% of the total oil compositions. The results of the fungal growth inhibition assays showed that the oils inhibited the growth of 19 phytopathogenic fungi. However, their antifungal activity was generally lower than that of the commercial pesticide benomyl. The herbicidal effects of the oils on the seed germination and seedling growth of Amaranthus retroflexus L., Chenopodium album L., Cirsium arvense (L.) Scop ., Lactuca serriola L., and Rumex crispus L. were also determined. The oils completely or partly inhibited the seed germinations and seedling growths of the plants. The findings of the present study suggest that the M. communis essential oils might have potential to be used as natural herbicides as well as fungicides.     

Factors associated with caregiving burden and mental health conditions in caregivers of patients with anorexia nervosa in Japan

Background

There are no studies about the caregiving burdens in families of patients with eating disorders in Japan, and only limited studies on the role of caregivers’ stress coping, social support, and mental health. This study examines caregiving burdens, mental health conditions, and associated factors in caregivers of anorexia nervosa (AN) patients in Japan.

Methods

Seventy-nine principal caregivers (70 mothers, 5 fathers, 3 spouses and 1 grandmother; mean age 56.0?±?8.0 years) for outpatients with AN (all female; mean age 26.6?±?7.9 years; BMI 14.6?±?3.2 kg/m²) were evaluated using self-report questionnaires in a cross-sectional study. The questionnaires included caregiving burden (J-ZBI_8), mental health conditions (GHQ28), stress coping styles (CISS), social support (SNQ), severity of the patient’s symptoms from the family’s perspective (ABOS), and family functioning (GF-FAD). Clinical information about the patients was also obtained.

Results

Mean caregiving burden assessed by J-ZBI_8 score was 12.4?±?7.0 (SD). The total GHQ score was 31.6?±?13.7 (Likert scoring) and 9.2?±?7.0 (GHQ scoring). Of the respondents, 48 (60.7 %) indicated a high risk for mental health problems that exceeded the cutoff point of the GHQ. Significantly higher caregiving burden and poor mental health conditions were shown in the group who had contact with patients?>?6 h a day compared to the group with daily patient contact?<?3 h (F (2, 76)?=?3.19, p?=?0.047 and F (2, 76)?=?9.39, p?<?0.001, respectively). Stepwise multiple regression analysis indicated that the factors that significantly predicted the caregiving burden were severity of the patient’s symptoms from the family’s perspective (β?=?0.47, p?<?0.001) and Emotion-Oriented Coping (β?=?0.38, p?=?0.002) (R²?=?0.401), while predictors of mental health conditions were Emotion-Oriented Coping (β?=?0.522, p?<?0.001), Affective Support (β?=??0.419, p?<?0.001), and contact time with patient (β?=?0.201, p?=?0.042) (R²?=?0.602).

Conclusion

Caregivers of AN patients experienced heavy burdens and manifested poor mental health conditions. The severity of the patient’s symptoms from the family’s perspective and the greater use of emotion-oriented coping were associated with higher burdens. Greater use of emotion-oriented coping, less affective support and longer contact with patients were related to worse mental health conditions. Interventions to promote caregivers’ adaptive coping styles may help reduce their caregiving burden and improve their mental health.

     

Glutathione S-transferase 4 is a putative DIF-binding protein that regulates the size of fruiting bodies in Dictyostelium discoideum

In the development of the cellular slime mold Dictyostelium discoideum, two chlorinated compounds, the differentiation-inducing factors DIF-1 and DIF-2, play important roles in the regulation of both cell differentiation and chemotactic cell movement. However, the receptors of DIFs and the components of DIF signaling systems have not previously been elucidated. To identify the receptors for DIF-1 and DIF-2, we here performed DIF-conjugated affinity gel chromatography and liquid chromatography–tandem mass spectrometry and identified the glutathione S-transferase GST4 as a major DIF-binding protein. Knockout and overexpression mutants of gst4 (gst4^– and gst4^OE, respectively) formed fruiting bodies, but the fruiting bodies of gst4^– cells were smaller than those of wild-type Ax2 cells, and those of gst4^OE cells were larger than those of Ax2 cells. Both chemotaxis regulation and in vitro stalk cell formation by DIFs in the gst4 mutants were similar to those of Ax2 cells. These results suggest that GST4 is a DIF-binding protein that regulates the sizes of cell aggregates and fruiting bodies in D. discoideum.     

Inhibition of Fatty Acid Synthase Decreases Expression of Stemness Markers in Glioma Stem Cells

Cellular metabolic changes, especially to lipid metabolism, have recently been recognized as a hallmark of various cancer cells. However, little is known about the significance of cellular lipid metabolism in the regulation of biological activity of glioma stem cells (GSCs). In this study, we examined the expression and role of fatty acid synthase (FASN), a key lipogenic enzyme, in GSCs. In the de novo lipid synthesis assay, GSCs exhibited higher lipogenesis than differentiated non-GSCs. Western blot and immunocytochemical analyses revealed that FASN is strongly expressed in multiple lines of patient-derived GSCs (G144 and Y10), but its expression was markedly reduced upon differentiation. When GSCs were treated with 20 μM cerulenin, a pharmacological inhibitor of FASN, their proliferation and migration were significantly suppressed and de novo lipogenesis decreased. Furthermore, following cerulenin treatment, expression of the GSC markers nestin, Sox2 and fatty acid binding protein (FABP7), markers of GCSs, decreased while that of glial fibrillary acidic protein (GFAP) expression increased. Taken together, our results indicate that FASN plays a pivotal role in the maintenance of GSC stemness, and FASN-mediated de novo lipid biosynthesis is closely associated with tumor growth and invasion in glioblastoma.