Neurophysiological study to assess the severity of each site through the motor neuron fiber in entrapment neuropathy

The purpose of this study is to evaluate prospectively the sensitivities of conventional and new electrophysiological techniques and to investigate their relationship with the body mass index (BMI) in a population of patients suspected of having carpal tunnel syndrome (CTS). In this study, 165 hands of 92 consecutive patients (81 female, 11 male) with clinical diagnosis of CTS were compared to reference population of 60 hands of 30 healthy subjects (26 female and 4 male). Extensive sensory and motor nerve conduction studies (NCSs) were performed in the diagnosis of subtle CTS patients. Also, the patients were divided into subgroups and sensitivities were determined according to BMI. The mean BMI was found to be significantly higher in the CTS than in the control group (p < 0.001). The sensitivity of the median sensory nerve latency (mSDL) and median motor distal latency (mMDL) were 75.8% and 68.5%, respectively. The most sensitive parameters of sensory and motor NCSs were the difference between median and ulnar sensory distal latencies to the fourth digit [(D4M-D4U), (77%)] and the median motor terminal latency index [(mTLI), (70.3%)], while the median-to-ulnar sensory action potential amplitude ratio (27%) and the median-thenar to ulnar-hypothenar motor action potential amplitude ratio (15%) were least sensitive tests. Sensory tests were more sensitive than motor NCSs. Combining mSDL with D4M-D4U, and mMDL with mTLI allowed for the detection of abnormalities in 150 (91%) and 132 (80%) hands, respectively. Measurements of all NCSs parameters were abnormal in obese than in non-obese patients when compared to the BMI. The newer nerve conduction techniques and combining different NCSs tests are more sensitive than single conventional NCS test for the diagnosis of suspected CTS. Meanwhile, CTS is associated with increasing BMI.     

Design, synthesis, and evaluation of novel kazusamycin A derivatives as potent antitumor agents

Novel kazusamycin A derivatives were designed in the viewpoint of decrease of reactivity at the alpha,beta-unsaturated delta-lactone moiety against Michael-type addition. Although 25-30 steps were required for the synthesis of each compound, their syntheses were achieved. Cytotoxicity against HPAC cell line was evaluated, and two of them exhibited comparable potency to kazusamycin A. Hepatic toxicity of these designed compounds was much lower than that of kazusamycin A.     

Deficiency of PTP1B in POMC neurons leads to alterations in energy balance and homeostatic response to cold exposure

The adipose tissue-derived hormone leptin regulates energy balance through catabolic effects on central circuits, including proopiomelanocortin (POMC) neurons. Leptin activation of POMC neurons increases thermogenesis and locomotor activity. Protein tyrosine phosphatase 1B (PTP1B) is an important negative regulator of leptin signaling. POMC neuron-specific deletion of PTP1B in mice results in reduced high-fat diet-induced body weight and adiposity gain due to increased energy expenditure and greater leptin sensitivity. Mice lacking the leptin gene (ob/ob mice) are hypothermic and cold intolerant, whereas leptin delivery to ob/ob mice induces thermogenesis via increased sympathetic activity to brown adipose tissue (BAT). Here, we examined whether POMC PTP1B mediates the thermoregulatory response of CNS leptin signaling by evaluating food intake, body weight, core temperature (T(C)), and spontaneous physical activity (SPA) in response to either exogenous leptin or 4-day cold exposure (4°C) in male POMC-Ptp1b-deficient mice compared with wild-type controls. POMC-Ptp1b(-/-) mice were hypersensitive to leptin-induced food intake and body weight suppression compared with wild types, yet they displayed similar leptin-induced increases in T(C). Interestingly, POMC-Ptp1b(-/-) mice had increased BAT weight and elevated plasma triiodothyronine (T(3)) levels in response to a 4-day cold challenge, as well as reduced SPA 24 h after cold exposure, relative to controls. These data show that PTP1B in POMC neurons plays a role in short-term cold-induced reduction of SPA and may influence cold-induced thermogenesis via enhanced activation of the thyroid axis.     

17β-estradiol represses myogenic differentiation by increasing ubiquitin-specific peptidase 19 through estrogen receptor α

Skeletal muscles express estrogen receptor (ER) α and ERβ. However, the roles of estrogens acting through the ERs in skeletal muscles remain unclear. The effects of 17β-estradiol (E2) on myogenesis were studied in C2C12 myoblasts. E2 and an ERα-selective agonist propylpyrazole-triol depressed myosin heavy chain (MHC), tropomyosin, and myogenin levels and repressed the fusion of myoblasts into myotubes. ER antagonist ICI 182,780 cancelled E2-repressed myogenesis. E2 induced ubiquitin-specific peptidase 19 (USP19) expression during myogenesis. E2 replacement increased USP19 expression in the gastrocnemius and soleus muscles of ovariectomized mice. Knockdown of USP19 inhibited E2-repressed myogenesis. Mutant forms of USP19 lacking deubiquitinating activity increased MHC and tropomyosin levels. E2 decreased ubiquitinated proteins during myogenesis, and the E2-decreased ubiquitinated proteins were increased by knockdown of USP19. Propylpyrazole-triol increased USP19 expression, and ICI 182,780 inhibited E2-increased USP19 expression. Overexpression of ERα or knockdown of ERβ enhanced the effects of E2 on the levels of USP19, MHC, and tropomyosin, whereas knockdown of ERα, overexpression of ERβ, or an ERβ-selective agonist diarylpropionitrile abolished their effects. A mutant form of ERα that is constitutively localized in the nucleus increased USP19 expression and decreased MHC and tropomyosin expression in the presence of E2. Furthermore, in skeletal muscle satellite cells, E2 inhibited myogenesis and increased USP19 expression, and diarylpropionitrile repressed E2-increased USP19 expression. These results demonstrate that (i) E2 induces USP19 expression through nuclear ERα, (ii) increased USP19-mediated deubiquitinating activity represses myogenesis, and (iii) ERβ inhibits ERα-activated USP19 expression.     

Gudgeon fish with and without genetically determined countershading coexist in heterogeneous littoral environments of an ancient lake

Countershading, characterized by a darker dorsal surface and lighter ventral surface, is common among many animals. This dorsoventral pigment polarity is often thought to be adaptive coloration for camouflage. By contrast, noncountershaded (melanistic) morphs often occur within a species due to genetic color polymorphism in terrestrial animals. However, the polymorphism with either countershaded or melanistic morphs is poorly known in wild aquatic animals. This study explored the genetic nature of diverged color morphs of a lineage of gudgeon fish (genus Sarcocheilichthys) in the ancient Lake Biwa and propose this system as a novel model for testing hypotheses of functional aspects of countershading and its loss in aquatic environments. This system harbors two color morphs that have been treated taxonomically as separate species; Sarcocheilichthys variegatus microoculus which occurs throughout the littoral zone and Sarcocheilichthys biwaensis which occurs in and around rocky areas. First, we confirmed that the divergence of dorsoventral color patterns between the two morphs is under strict genetic control at the levels of chromatophore distribution and melanin‐related gene expression under common garden rearing. The former morph displayed sharp countershading coloration, whereas the latter morph exhibited a strong tendency toward its loss. The crossing results indicated that this divergence was likely controlled by a single locus in a two‐allele Mendelian inheritance pattern. Furthermore, our population genomic and genome‐wide association study analyses detected no genome‐wide divergence between the two morphs, except for one region near a locus that may be associated with the color divergence. Thus, these morphs are either in a state of intraspecific color polymorphism or two incipient species. Evolutionary forces underlying this polymorphism appear to be associated with heterogeneous littoral environments in this lake. Future ecological genomic research will provide insight into adaptive functions of this widespread coloration, including the eco‐evolutionary drivers of its loss, in the aquatic world.     

Current status of weighting methodologies in Japan

In Japan, requirements for the development of valuation methodology are very stringent. Several methodologies have been proposed to meet these demands in recent years. These methods, however, are quite different in many points such as selected impact categories, the numbers of substances considered, and basic concepts for the environment. The results of LCA are fully dependent on the goals of LCA practitioners and commissioners. If they misunderstand the concept of method and use it, the result may not fit for the purpose. Consequently, it is important to characterize the methods selected by the practitioner in accordance with their LCA goals. In this paper, weighting methodologies proposed in Japan have been introduced with a comparison between the results of case studies for common industrial products. Furthermore, we considered the present situations and future directions of valuation methodologies in Japan. This consideration is carried out based on the results of investigations performed by the Impact Assessment Committee of the National LCA Project of Japan     

Stabilization of quaternary structure and activity of bovine liver catalase through encapsulation in liposomes

Bovine liver catalase was encapsulated in an aqueous phase of the phospholipid vesicle (liposome) to improve the stability of its tetrameric structure and activity. The catalase-containing liposomes (CALs) prepared were 30, 50 and 100 nm in mean diameters (CAL₃₀, CAL₅₀ and CAL₁₀₀, respectively). The CAL₁₀₀ included the types I, II and III based on the amounts of catalase encapsulated. The CAL₃₀, CAL₅₀ and CAL₁₀₀-I contained one catalase molecule per liposome, and the CAL₁₀₀-II and CAL₁₀₀-III on average 5.2 and 17 molecules, respectively. The storage stability of catalase in either CAL system was significantly increased compared to that of free catalase at 4 °C in a buffer of pH 7.4. At 55 °C, free catalase was much more deactivated especially with decreasing its concentration predominantly due to enhanced dissociation of catalase into subunits while it was so done at excessively high enzyme concentration mainly due to enhanced formation of catalase intermolecular aggregates. Among the three types of CAL₁₀₀, the CAL₁₀₀-II showed the highest thermal stability, indicating that an excess amount of catalase in the CAL₁₀₀-III was also disadvantageous to maintain an active form of the catalase even in liposome. In the CAL₁₀₀-III, however, the stability of catalase was significantly improved compared to that of free catalase at the same concentration. The CAL thermal stability was little affected by the liposome size as observed in the CAL₃₀, CAL₅₀ and CAL₁₀₀-I. An intrinsic tryptophan fluorescence of the catalase recovered from the CAL₁₀₀-II thermally treated at 55 °C revealed that a partially denatured catalase molecule was stabilized through its hydrophobic interaction with liposome membrane. This interaction depressed not only dissociation of catalase into subunits but also formation of an inactive intermolecular aggregate between the catalase molecules in a liposome. Furthermore, either type of CAL₁₀₀ showed a higher stability than free catalase in the successive decompositions of 10 mM H₂O₂ at 25 °C mainly because the H₂O₂ concentration was kept low inside liposomes due to the permeation barrier of the lipid membrane to H₂O₂.