Structural and Biochemical Bases for the Inhibition of Autophagy and Apoptosis by Viral BCL-2 of Murine γ-Herpesvirus 68

All gammaherpesviruses express homologues of antiapoptotic B-cell lymphoma-2 (BCL-2) to counter the clearance of infected cells by host antiviral defense machineries. To gain insights into the action mechanisms of these viral BCL-2 proteins, we carried out structural and biochemical analyses on the interactions of M11, a viral BCL-2 of murine γ-herpesvirus 68, with a fragment of proautophagic Beclin1 and BCL-2 homology 3 (BH3) domain-containing peptides derived from an array of proapoptotic BCL-2 family proteins. Mainly through hydrophobic interactions, M11 bound the BH3-like domain of Beclin1 with a dissociation constant of 40 nanomole, a markedly tighter affinity compared to the 1.7 micromolar binding affinity between cellular BCL-2 and Beclin1. Consistently, M11 inhibited autophagy more efficiently than BCL-2 in NIH3T3 cells. M11 also interacted tightly with a BH3 domain peptide of BAK and those of the upstream BH3-only proteins BIM, BID, BMF, PUMA, and Noxa, but weakly with that of BAX. These results collectively suggest that M11 potently inhibits Beclin1 in addition to broadly neutralizing the proapoptotic BCL-2 family in a similar but distinctive way from cellular BCL-2, and that the Beclin1-mediated autophagy may be a main target of the virus

Analysis of Serum Levels of Anti-Müllerian Hormone, Inhibin B, Insulin-Like Growth Factor-I, Insulin-Like Growth Factor Binding Protein-3, and Follicle-Stimulating Hormone with Respect to Age and Menopausal Status

This study was undertaken to investigate age-dependent and postmenopausal changes in the serum levels of anti-Müllerian hormone (AMH), inhibin B, insulin-like growth factor (IGF)-I, IGF-binding protein-3 (IGFBP-3), and follicle-stimulating hormone (FSH), and to determine which of these markers best reflects the aging process in women. A total of 144 women aged 20-59 yr were enrolled in this cross-sectional study. Blood samples were obtained on cycle day 3 of regularly menstruating women (n=111), or at random in postmenopausal women (n=33). Data were analyzed with respect to premenopausal women age groups and compared in pre- and postmenopausal women. Area under the receiver operating characteristic curve (ROCAUC) analyses were performed to assess the ability of each marker to discriminate between the pre- and postmenopausal status. Serum levels of AMH, IGF-I, and IGFBP-3 decreased and serum levels of FSH increased significantly with age in premenopausal women. Serum luteinizing hormone (LH) was higher and inhibin B was lower in women in their 20-30's than in 40's. Serum levels of AMH and IGF-I showed a consistent decrease with all age groups. ROCAUC analysis showed that the diagnostic accuracy of AMH for menopausal status was similar to those of FSH, LH, and inhibin B, and was better than that of IGF-I. In conclusion, the serum AMH level appears to be the best marker of the aging process in premenopausal women

High-performance silicon-based multicomponent battery anodes produced via synergistic coupling of multifunctional coating layers

Nanostructured Si-based materials are key building blocks for next-generation energy storage devices. To meet the requirements of practical energy storage devices, Si-based materials should exhibit high-power, low volume change, and high tap density. So far, there have been no reliable materials reported satisfying all of these requirements. Here, we report a novel Si-based multicomponent design, in which the Si core is covered with multifunctional shell layers. The synergistic coupling of Si with the multifunctional shell provides vital clues for satisfying all Si anode requirements for practical batteries. The Si-based multicomponent anode delivers a high capacity of similar to 1000 mA h g(-1), a highly stable cycling retention (similar to 65% after 1000 cycles at 1 C), an excellent rate capability (similar to 800 mA h g(-1) at 10 C), and a remarkably suppressed volume expansion (12% after 100 cycles). Our synthetic process is simple, low-cost, and safe, facilitating new methods for developing electrode materials for practical energy storage.open0

Artificial neural networks for prostate carcinoma risk assessment

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34357/1/1178_ftp.pd

Thyroid-Related Protein Expression in the Human Thymus

Radioiodine whole body scan (WBS), related to sodium iodide symporter (NIS) function, is widely used to detect recurrence/metastasis in postoperative patients with thyroid cancer. However, the normal thymic uptake of radioiodine has occasionally been observed in young patients. We evaluated the expression of thyroid-related genes and proteins in the human thymus. Thymic tissues were obtained from 22 patients with thyroid cancer patients of all ages. The expression of NIS, thyroid-stimulating hormone receptor (TSHR), thyroperoxidase (TPO), and thyroglobulin (Tg) was investigated using immunohistochemistry and quantitative RT-PCR. NIS and TSHR were expressed in 18 (81.8%) and 19 samples (86.4%), respectively, whereas TPO was expressed in five samples (22.7%). Three thyroid-related proteins were localized to Hassall’s corpuscles and thymocytes. In contrast, Tg was detected in a single patient (4.5%) localized to vascular endothelial cells. The expression of thyroid-related proteins was not increased in young thymic tissues compared to that in old thymic tissues. In conclusion, the expression of NIS and TSHR was detected in the majority of normal thymus samples, whereas that of TPO was detected less frequently, and that of Tg was detected rarely. The increased thymic uptake of radioiodine in young patients is not due to the increased expression of NIS

Delithiation/lithiation behavior of LiNi<inf>0.5</inf>Mn<inf>1.5</inf>O<inf>4</inf> studied by in situ and ex situ ^6,7Li NMR spectroscopy

Delithiation and lithiation behaviors of ordered spinel LiNi0.5Mn1.5O4 and disordered spinel LiNi0.4Mn1.6O4 were investigated by using in situ (in operando) 7Li NMR and ex situ 6Li MAS NMR spectroscopy. The in situ 7Li monitoring of the ordered spinel revealed a clear appearance and subsequent disappearance of a new signal from the well-defined phase Li0.5Ni0.5Mn1.5O4, suggesting the two-phase reaction processes among Li1.0Ni0.5Mn1.5O4, Li0.5Ni0.5Mn1.5O4, and Li0.0Ni0.5Mn1.5O4. Also, for the disordered spinel, Li0.5Ni0.4Mn1.6O4 was identified with a broad distribution in Li environment. High-resolution 6Li MAS NMR spectra were also acquired for the delithiated and lithiated samples to understand the detailed local structure around Li ions. We suggested that the nominal Li-free phase Li0.0Ni0.5Mn1.5O4 can accommodate a small amount of Li ions in its structure. The tetragonal phases Li2.0Ni0.5Mn1.5O4 and Li2.0Ni0.4Mn1.6O4, which occurred when the cell was discharged down to 2.0 V, were very different in the Li environment from each other. It is found that 6, 7Li NMR is highly sensitive not only to the Ni/Mn ordering in LiNi0.5Mn1.5O4 but also to the valence changes of Ni and Mn on charge-discharge process

Early metabolic response using FDG PET/CT and molecular phenotypes of breast cancer treated with neoadjuvant chemotherapy

Background: This study was aimed 1) to investigate the predictive value of FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) for histopathologic response and 2) to explore the results of FDG PET/CT by molecular phenotypes of breast cancer patients who received neoadjuvant chemotherapy. Methods: Seventy-eight stage II or III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. FDG PET/CTs were acquired before chemotherapy and after the first cycle of chemotherapy for evaluating early metabolic response. Results: The mean pre- and post-chemotherapy standard uptake value (SUV) were 7.5 and 3.9, respectively. The early metabolic response provided by FDG PET/CT after one cycle of neoadjuvant chemotherapy was correlated with the histopathologic response after completion of neoadjuvant chemotherapy (P = 0.002). Sensitivity and negative predictive value were 85.7% and 95.1%, respectively. The estrogen receptor negative phenotype had a higher pre-chemotherapy SUV (8.6 vs. 6.4, P = 0.047) and percent change in SUV (48% vs. 30%, P = 0.038). In triple negative breast cancer (TNBC), the pre-chemotherapy SUV was higher than in non-TNBC (9.8 vs. 6.4, P = 0.008). Conclusions: The early metabolic response using FDG PET/CT could have a predictive value for the assessment of histopathologic non-response of stage II/III breast cancer treated with neoadjuvant chemotherapy. Our findings suggest that the initial SUV and the decline in SUV differed based on the molecular phenotype

Recent increase of surface particulate matter concentrations in the Seoul Metropolitan Area, Korea

Recent changes of surface particulate matter (PM) concentration in the Seoul Metropolitan Area (SMA), South Korea, are puzzling. The long-term trend of surface PM concentration in the SMA declined in the 2000s, but since 2012 its concentrations have tended to incline, which is coincident with frequent severe hazes in South Korea. This increase puts the Korean government&apos;s emission reduction efforts in jeopardy. This study reports that interannual variation of surface PM concentration in South Korea is closely linked with the interannual variations of wind speed. A 12-year (2004-2015) regional air quality simulation was conducted over East Asia (27-km) and over South Korea (9-km) to assess the impact of meteorology under constant anthropogenic emissions. Simulated PM concentrations show a strong negative correlation (i.e. R = -0.86) with regional wind speed, implying that reduced regional ventilation is likely associated with more stagnant conditions that cause severe pollutant episodes in South Korea. We conclude that the current PM concentration trend in South Korea is a combination of long-term decline by emission control efforts and short-term fluctuation of regional wind speed interannual variability. When the meteorology-driven variations are removed, PM concentrations in South Korea have declined continuously even after 2012

Scientific opinion on dietary reference values for thiamin

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derived dietary reference values (DRVs) for thiamin (vitamin B1). The Panel considers that data from depletion\u2013repletion studies in adults on the amount of dietary thiamin intake associated with the erythrocyte transketolase activity coefficient (\u3b1ETK) &lt; 1.15, generally considered to reflect an adequate thiamin status, or with the restoration of normal (baseline) erythrocyte transketolase activity, without a sharp increase in urinary thiamin excretion, can be used to estimate thiamin requirement. In the absence of new scientific evidence, the Panel endorses the average requirement (AR) of 0.072 mg/MJ (0.3 mg/1,000 kcal) for all adults proposed by the Scientific Committee for Food (SCF) in 1993 on the basis of one depletion\u2013repletion study, in which both \u3b1ETK and urinary thiamin excretion were measured. Results from other depletion\u2013repletion studies are in agreement with this value. The Panel agrees on the coefficient of variation of 20% used by the SCF to cover uncertainties related to distribution of thiamin requirements in the general population, and endorses the population reference intake (PRI) of 0.1 mg/MJ (0.4 mg/1,000 kcal) set by the SCF for all adults. The same AR and PRI as for adults, expressed in mg/MJ, are proposed for infants aged 7\u201311 months, children aged 1 to &lt; 18 years, and during pregnancy and lactation, under the assumption that the relationship between thiamin requirement and energy requirement is the same in all population groups

Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: a summary of available findings

Considerable interest has been shown in the ability of caloric restriction (CR) to improve multiple parameters of health and to extend lifespan. CR is the reduction of caloric intake - typically by 20 - 40% of ad libitum consumption - while maintaining adequate nutrient intake. Several alternatives to CR exist. CR combined with exercise (CE) consists of both decreased caloric intake and increased caloric expenditure. Alternate-day fasting (ADF) consists of two interchanging days; one day, subjects may consume food ad libitum (sometimes equaling twice the normal intake); on the other day, food is reduced or withheld altogether. Dietary restriction (DR) - restriction of one or more components of intake (typically macronutrients) with minimal to no reduction in total caloric intake - is another alternative to CR. Many religions incorporate one or more forms of food restriction. The following religious fasting periods are featured in this review: 1) Islamic Ramadan; 2) the three principal fasting periods of Greek Orthodox Christianity (Nativity, Lent, and the Assumption); and 3) the Biblical-based Daniel Fast. This review provides a summary of the current state of knowledge related to CR and DR. A specific section is provided that illustrates related work pertaining to religious forms of food restriction. Where available, studies involving both humans and animals are presented. The review includes suggestions for future research pertaining to the topics of discussion