Mobility of the terminal regions of flagellin in solution.

The mobility of the disordered terminal regions of flagellin was examined in detail based on 1H NMR chemical shifts and spin-lattice relaxation times in the rotating frame. Proteolytic fragments of flagellin with terminal deletions of different sizes were used to compare the dynamical properties of various N- and C-terminal segments. We found that dynamic properties of different terminal segments were similar to each other and were close to those of the heat-denatured state of flagellin. The main chain of these terminal segments undergoes rapid motions with effective correlation times of 1.3-4.1 x 10(-9) s. The terminal regions contain no large segments with well-defined structure. However, comparison with the random-coiled state of poly-L-lysine suggests significant structural constraints in the terminal regions (as well as in the heat-denatured flagellin) which may reflect the existence of some highly fluctuating secondary structure, as suggested by earlier CD studies.     

Differences in flowering phenology,architecture, sexual expression and resource allocation between a heavily haired and a lightly haired nettle population: relationships with sika deer

Plant Ecology - Japanese stinging nettles, Urtica thunbergiana, in Nara Park (660 ha), central Japan, where several hundred sika deer Cervus nippon have been protected for...     

The Tumor Suppressor BCL7B Functions in the Wnt Signaling Pathway

Human BCL7 gene family consists of BCL7A, BCL7B, and BCL7C. A number of clinical studies have reported that BCL7 family is involved in cancer incidence, progression, and development. Among them, BCL7B, located on chromosome 7q11.23, is one of the deleted genes in patients with Williams-Beuren syndrome. Although several studies have suggested that malignant diseases occurring in patients with Williams-Beuren syndrome are associated with aberrations in BCL7B, little is known regarding the function of this gene at the cellular level. In this study, we focused on bcl-7, which is the only homolog of BCL7 gene family in Caenorhabditis elegans, and analyzed bcl-7 deletion mutants. As a result, we found that bcl-7 is required for the asymmetric differentiation of epithelial seam cells, which have self-renewal properties as stem cells and divide asymmetrically through the WNT pathway. Distal tip cell development, which is regulated by the WNT pathway in Caenorhabditis elegans, was also affected in bcl-7-knockout mutants. Interestingly, bcl-7 mutants exhibited nuclear enlargement, reminiscent of the anaplastic features of malignant cells. Furthermore, in KATOIII human gastric cancer cells, BCL7B knockdown induced nuclear enlargement, promoted the multinuclei phenotype and suppressed cell death. In addition, this study showed that BCL7B negatively regulates the Wnt-signaling pathway and positively regulates the apoptotic pathway. Taken together, our data indicate that BCL7B/BCL-7 has some roles in maintaining the structure of nuclei and is involved in the modulation of multiple pathways, including Wnt and apoptosis. This study may implicate a risk of malignancies with BCL7B-deficiency, such as Williams-Beuren syndrome.     

Computer-Aided Prediction of Long-Term Prognosis of Patients with Ulcerative Colitis after Cytoapheresis Therapy

Cytoapheresis (CAP) therapy is widely used in ulcerative colitis (UC) patients with moderate to severe activity in Japan. The aim of this study is to predict the need of operation after CAP therapy of UC patients on an individual level using an artificial neural network system (ANN). Ninety UC patients with moderate to severe activity were treated with CAP. Data on the patients’ demographics, medication, clinical activity index (CAI) and efficacy of CAP were collected. Clinical data were divided into training data group and validation data group and analyzed using ANN to predict individual outcomes. The sensitivity and specificity of predictive expression by ANN were 0.96 and 0.97, respectively. Events of admission, operation, and use of immunomodulator, and efficacy of CAP were significantly correlated to the outcome. Requirement of operation after CAP therapy was successfully predicted by using ANN. This newly established ANN strategy would be used as powerful support of physicians in the clinical practice.     

Characterization of sarcoplasmic reticulum Ca ATPase nucleotide binding domain mutants using NMR spectroscopy

Sarcoplasmic reticulum Ca²⁺ ATPase (SERCA) is essential for muscle function by transporting Ca²⁺ from the cytosol into the sarcoplasmic reticulum through ATP hydrolysis. In this report, the effects of substitution mutations on the isolated SERCA-nucleotide binding domain (SERCA-N) were studied using NMR. ¹⁵N–¹H HSQC spectra of substitution mutants at the nucleotide binding site, T441A, R560V, and C561A, showed chemical shift changes, primarily in residues adjacent to the mutation sites, indicating only local effects. Further, the patterns of chemical shift changes upon AMP–PNP binding to these mutants were similar to that of the wild type SERCA-N (WT). In contrast to these nucleotide binding site mutants, a mutant found in patients with Darier’s disease, E412G, showed small but significant chemical shift changes throughout the protein and rapid precipitation. However, the AMP–PNP dissociation constant (∼2.5 mM) was similar to that of WT (∼3.8 mM). These results indicate that the E412G mutant retains its catalytic activity but most likely reduces its stability. Our findings provide molecular insight into previous clinical, physiological, and biochemical observations.     

Toward more comprehensive environmental impact assessments: interlinked global models of LCIA and IAM applicable to this century

The International Journal of Life Cycle Assessment - Despite the long-standing demand for research on dynamic lifecycle assessment (LCA) for policymaking, only a few studies have addressed this...     

miR-34a-5p might have an important role for inducing apoptosis by down-regulation of SNAI1 in apigenin-treated lung cancer cells

Molecular Biology Reports - Apigenin is a flavonoid with antioxidant and anticancer effects. It has been reported that apigenin inhibits proliferation, migration, and invasion and induces apoptosis...     

A synergy of activity,stability, and inhibitor‐interaction of HIV‐1 protease mutants evolved under drug‐pressure

A clinically‐relevant, drug‐resistant mutant of HIV‐1 protease (PR), termed Flap+_(I54V) and containing L10I, G48V, I54V and V82A mutations, is known to produce significant changes in the entropy and enthalpy balance of drug‐PR interactions, compared to wild‐type PR. A similar mutant, Flap+_(I54A), which evolves from Flap+_(I54V) and contains the single change at residue 54 relative to Flap+_(I54V), does not. Yet, how Flap+_(I54A) behaves in solution is not known. To understand the molecular basis of V54A evolution, we compared nuclear magnetic resonance (NMR) spectroscopy, fluorescence spectroscopy, isothermal titration calorimetry, and enzymatic assay data from four PR proteins: PR (pWT), Flap+_(I54V), Flap+_(I54A), and Flap+_(I54), a control mutant that contains only L10I, G48V and V82A mutations. Our data consistently show that selection to the smaller side chain at residue 54, not only decreases inhibitor affinity, but also restores the catalytic activity.