Multi-site binding of epigallocatechin gallate to human serum albumin measured by NMR and isothermal titration calorimetry

The affinity of epigallocatechin gallate (EGCG) for human serum albumin (HSA) was measured in physiological conditions using NMR and isothermal titration calorimetry (ITC). NMR estimated the Ka (self-dissociation constant) of EGCG as 50 mM. NMR showed two binding events: strong (n1=1.8 ± 0.2; Kd1 =19 ± 12 μM) and weak (n2∼20; Kd2 =40 ± 20 mM). ITC also showed two binding events: strong (n1=2.5 ± 0.03; Kd1 =21.6 ± 4.0 μM) and weak (n2=9 ± 1; Kd2 =22 ± 4 mM). The two techniques are consistent, with an unexpectedly high number of bound EGCG. The strong binding is consistent with binding in the two Sudlow pockets. These results imply that almost all EGCG is transported in the blood bound to albumin and explains the wide tissue distribution and chemical stability of EGCG in vivo

1924-25: Abilene Christian College Bible Lectures - Full Text

PREFACE The lectures in this volume were delivered in the auditorium of Abilene Christian College during the last week of February in 1924 and 1925. Not all of the lectures delivered during these two weeks are given here, some of those delivering lectures not having responded with their manuscripts. These are given to the public in the belief that the splendid sermons delivered here ought to be read by thousands of Christians who did not have the opportunity of hearing them. Many of those who heard them will desire to read them. May this contribution to the literature of Christian teaching from the minds of some of our best and most faithful laborers in the Master’s vineyard be a continued blessing to all whose lives they touch. BATSELL BAXTER. __________________ PUBLISHER’S ANNOUNCEMENT This volume of Abilene Christian College Lectures is the fourth and comprises the lectures for February 1924 and 1925. The lectures for 1919 were published in one volume, 1920 and 1921 were combined in one volume, as were also the lectures for 1922 and 1923. By putting the lectures for two years in one volume, the reader is saved the expense of an additional book in order to receive the full benefit of these lectures. That these discourses are of great value is recognized by thousands who have heard them orally or have read them on the printed page. Such carefully prepared addresses really and truly merit a permanent place in the literature of the brotherhood of the churches of Christ. They are filled with expositions and analyses of much benefit to younger brethren who are entering upon lines of public service for the church, and they contain instruction on the word of God that is of much value to those out of the church as well as those in the church. The four books comprising the Abilene Christian College Lectures will make a most valuable addition to all libraries. We are at this time, January, 1926, in position to furnish complete sets or any volume to complete any broken set that any of our readers may have. When our present supply is gone, the books will probably not be reprinted as no plates have been made, and the books will be scarce. The messages of hope and love contained in this volume will find their place into the homes of many thousands, and it is to be ardently hoped that they will be read attentively and that they may contribute much to the extension of the power and kingdom of our Lord and Savior Jesus Christ. G. II. P. SHOWALTER. Austin, Texas, January 1, 1926

Business Cycle Spillovers in the European Union: What is the Message Transmitted to the Core?

We examine business cycle spillovers in the European Union over the period 1977–2014. The results of our analysis reveal that: (i) The total spillover indices are of high magnitude and very responsive to extreme economic events. (ii) The direction and magnitude of spillovers among group members (i.e. Eurozone core, Eurozone periphery, new Euro Area countries and non-European Monetary Union countries) is changing overtime. (iii) The widening of the European debt crisis can be explained by business cycle shocks in the whole Eurozone periphery. Thus, appropriate macroprudential stabilization policies aiming to steer peripheral economies towards growth should be formulated

Vascular defects and spinal cord hypoxia in spinal muscular atrophy

Acknowledgment S.H.P. is funded by The Euan MacDonald Center for Motor Neurone Disease Research and The SMA Trust. T.H.G. is funded by Muscular Dystrophy UK and The SMA Trust. K.T. is funded by The SMA Trust and the Motor Neurone Disease Association. H.Z. is funded by National Institute for Health Research and Great Ormond Street Hospital Biomedical Research Center, and F.M. is funded by the Medical Research Council and Great Ormond Street Hospital Charity. The MRC Center for Neuromuscular Diseases BioBank London (CNMD_BBL) is gratefully acknowledged.Peer reviewedPostprintPostprin

Role of transglutaminase 2 in PAC1 receptor mediated protection against hypoxia-induced cell death and neurite outgrowth in differentiating N2a neuroblastoma cells

The PAC1 receptor and tissue transglutaminase (TG2) play important roles in neurite outgrowth and modulation of neuronal cell survival. In this study, we investigated the regulation of TG2 activity by the PAC1 receptor in retinoic acid-induced differentiating N2a neuroblastoma cells. TG2 transamidase activity was determined using an amine incorporation and a peptide cross linking assay. In situ TG2 activity was assessed by visualising the incorporation of biotin-X-cadaverine using confocal microscopy. TG2 phosphorylation was monitored via immunoprecipitation and Western blotting. The role of TG2 in PAC1 receptor-induced cytoprotection and neurite outgrowth was investigated by monitoring hypoxia-induced cell death and appearance of axonal-like processes, respectively. The amine incorporation and protein crosslinking activity of TG2 increased in a time and concentration-dependent manner following stimulation with pituitary adenylate cyclase-activating polypeptide-27 (PACAP-27). PACAP-27 mediated increases in TG2 activity were abolished by the TG2 inhibitors Z-DON and R283 and by pharmacological inhibition of protein kinase A (KT 5720 and Rp-cAMPs), protein kinase C (Ro 31-8220), MEK1/2 (PD 98059), and removal of extracellular Ca2+. Fluorescence microscopy demonstrated PACAP-27 induced in situ TG2 activity. TG2 inhibition blocked PACAP-27 induced attenuation of hypoxia-induced cell death and outgrowth of axon-like processes. TG2 activation and cytoprotection were also observed in human SH-SY5Y cells. Together, these results demonstrate that TG2 activity was stimulated downstream of the PAC1 receptor via a multi protein kinase dependent pathway. Furthermore, PAC1 receptor-induced cytoprotection and neurite outgrowth are dependent upon TG2. These results highlight the importance of TG2 in the cellular functions of the PAC1 receptor

Empathy matters: ERP evidence for inter-individual differences in social language processing

When an adult claims he cannot sleep without his teddy bear, people tend to react surprised. Language interpretation is, thus, influenced by social context, such as who the speaker is. The present study reveals inter-individual differences in brain reactivity to social aspects of language. Whereas women showed brain reactivity when stereotype-based inferences about a speaker conflicted with the content of the message, men did not. This sex difference in social information processing can be explained by a specific cognitive trait, one’s ability to empathize. Individuals who empathize to a greater degree revealed larger N400 effects (as well as a larger increase in γ-band power) to socially relevant information. These results indicate that individuals with high-empathizing skills are able to rapidly integrate information about the speaker with the content of the message, as they make use of voice-based inferences about the speaker to process language in a top-down manner. Alternatively, individuals with lower empathizing skills did not use information about social stereotypes in implicit sentence comprehension, but rather took a more bottom-up approach to the processing of these social pragmatic sentences

1956: Abilene Christian College Bible Lectures - Full Text

Golden Anniversary Edition featuring the theme THEY SHALL ALL BE TAUGHT OF GOD Price: $3.50 FIRM FOUNDATION PUBLISHING HOUSE Box 77 Austin, Texa

Automatically Harnessing Sparse Acceleration

Sparse linear algebra is central to many scientific programs, yet compilers fail to optimize it well. High-performance libraries are available, but adoption costs are significant. Moreover, libraries tie programs into vendor-specific software and hardware ecosystems, creating non-portable code. In this paper, we develop a new approach based on our specification Language for implementers of Linear Algebra Computations (LiLAC). Rather than requiring the application developer to (re)write every program for a given library, the burden is shifted to a one-off description by the library implementer. The LiLAC-enabled compiler uses this to insert appropriate library routines without source code changes. LiLAC provides automatic data marshaling, maintaining state between calls and minimizing data transfers. Appropriate places for library insertion are detected in compiler intermediate representation, independent of source languages. We evaluated on large-scale scientific applications written in FORTRAN; standard C/C++ and FORTRAN benchmarks; and C++ graph analytics kernels. Across heterogeneous platforms, applications and data sets we show speedups of 1.1$\times$ to over 10$\times$ without user intervention.Comment: Accepted to CC 202