bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angiotensin II Type 1 Receptor Signaling Contributes to Synaptophysin Degradation and Neuronal Dysfunction in the Diabetic Retina
Authors: Kurihara Toshihide , Ozawa Yoko , Nagai Norihiro , Shinoda Kei , Noda Kousuke , Imamura Yutaka , Tsubota Kazuo , Okano Hideyuki , Oike Yuichi , Ishida Susumu 
Published: May 2008

OBJECTIVE—Pathogenic mechanisms underlying diabetes-induced retinal dysfunction are not fully understood. The aim of the present study was to show the relationship of the renin-angiotensin system (RAS) with the synaptic vesicle protein synaptophysin and neuronal activity in the diabetic retina.
RESEARCH DESIGN AND METHODS—C57BL/6 mice with streptozotocin-induced diabetes were treated with the angiotensin II type 1 receptor (AT1R) blocker telimsartan or valsartan, and retinal function was analyzed by electroretinography. Retinal production of the RAS components and phosphorylation of ERK (extracellular-signal regulated kinase) were examined by immunoblotting. Retinal mRNA and protein levels of synaptophysin were measured by quantitative RT-PCR and immunoblot analyses, respectively. In vitro, synaptophysin levels were also evaluated using angiotensin II–stimulated PC12D neuronal cells cultured with or without the inhibition of ERK signaling or the ubiquitin-proteasome system (UPS).
RESULTS—Induction of diabetes led to a significant increase in retinal production of angiotensin II and AT1R together with ERK activation in the downstream of AT1R. AT1R blockade significantly reversed diabetes-induced electroretinography changes and reduction of synaptophysin protein, but not mRNA, levels in the diabetic retina. In agreement with the AT1R-mediated posttranscriptional downregulation of synaptophysin in vivo, in vitro application of angiotensin II to PC12D neuronal cells caused the UPS–mediated degradation of synaptophysin protein via AT1R, which proved to be induced by ERK activation.
CONCLUSIONS—These data indicate the first molecular evidence of the RAS-induced synaptophysin degradation and neuronal dysfunction in the diabetic retina, suggesting the possibility of the AT1R blockade as a novel neuroprotective treatment for diabetic retinopathy.
Consequences of Lipid Droplet Coat Protein Downregulation in Liver Cells
Authors: Bell Ming , Wang Hong , Chen Hui , McLenithan John C. , Gong Da-Wei , Yang Rong-Zee , Yu Daozhan , Fried Susan K. , Quon Michael J. , Londos Constantine , Sztalryd Carole 
Published: May 2008

OBJECTIVE—Accumulation of intracellular lipid droplets (LDs) in non-adipose tissues is recognized as a strong prognostic factor for the development of insulin resistance in obesity. LDs are coated with perilipin, adipose differentiation–related protein, tail interacting protein of 47 kd (PAT) proteins that are thought to regulate LD turnover by modulating lipolysis. Our hypothesis is that PAT proteins modulate LD metabolism and therefore insulin resistance.
RESEARCH DESIGN AND METHODS—We used a cell culture model (murine AML12 loaded with oleic acid) and small interfering RNA to directly assess the impact of PAT proteins on LD accumulation, lipid metabolism, and insulin action. PAT proteins associated with excess fat deposited in livers of diet-induced obese (DIO) mice were also measured.
RESULTS—Cells lacking PAT proteins exhibited a dramatic increase in LD size and a decrease in LD number. Further, the lipolytic rate increased by ∼2- to 2.5-fold in association with increased adipose triglyceride lipase (ATGL) at the LD surface. Downregulation of PAT proteins also produced insulin resistance, as indicated by decreased insulin stimulation of Akt phosphorylation (P &lt; 0.001). Phosphoinositide-dependent kinase-1 and phosphoinositide 3-kinase decreased, and insulin receptor substrate-1 307 phosphorylation increased. Increased lipids in DIO mice livers were accompanied by changes in PAT composition but also increased ATGL, suggesting a relative PAT deficiency.
CONCLUSIONS—These data establish an important role for PAT proteins as surfactant at the LD surface, packaging lipids in smaller units and restricting access of lipases and thus preventing insulin resistance. We suggest that a deficiency of PAT proteins relative to the quantity of ectopic fat could contribute to cellular dysfunction in obesity and type 2 diabetes.
Colonization processes on a central Alpine glacier foreland
Authors: Erschbamer Brigitta , Niederfriniger Schlag Ruth , Winkler Eckart 
Published: May 2008

AbstractQuestions:What are the colonization trends in vegetated vs. bare‐ground plots over a 10‐year period in a central Alpine glacier foreland? What are the long‐term effects of artificial seed addition to these plots?Location:Glacier foreland of the Rotmoosferner in the Central Alps, Obergurgl, Tyrol, Austria, 2380 – 2400 m a.s.l.Methods:A total of 40 permanent plots were established on moraines ice‐free for 35 and 50 years on vegetated and bare‐ground areas. Half of them were treated with a seed mixture in 1996 and 1997. Number and cover of the species were recorded in 1996 and from 2002/2003 to 2006.Results:Species richness doubled in the control plots and tripled in seeded plots on the 35‐year‐ice‐free moraine. On the 50‐year‐ice‐free moraine the increase in species number was more modest. Significant site, seeding and time effects were found. Seed addition had no effects in the bare‐ground plots on the older moraine and low effects in those on the younger moraine. All plots showed significant changes in cover of single species. The pioneer species decreased significantly in both moraines, in the control as well as in the seeded plots. A disappearance during the next years is predicted.Conclusions:Colonization in bare‐ground plots is limited by a lack of safe sites, whereas vegetated plots facilitate recruitment and establishment. Colonization on the glacier foreland is also dispersal limited. Seed addition enhanced the presence of already established species, and late successional species were newly introduced.
Glycans: Array‐Based Techniques
Authors: Oyelaran Oyindasola , Manimala Joseph C. , Gildersleeve Jeffrey C. 
Published: May 2008

Abstract
Glycan arrays are powerful tools for high throughput analysis of carbohydrate–macromolecule interactions. A glycan array is composed of many different carbohydrate structures immobilized on a solid support in an orderly arrangement. This review describes the challenges and considerations in the development of a glycan array. Various array formats, immobilization techniques, and assay systems are discussed. In addition, several interesting applications of glycan array technology are described, such as assessing the specificities of carbohydrate‐binding lectins and antibodies, profiling antiglycan antibodies in serum as biomarkers of disease, and evaluating carbohydrate‐dependent cell binding.
Förster Resonance Energy Transfer (FRET) for Proteins
Authors: Chao Lambert K. , Clegg Robert M. 
Published: May 2008

AbstractFörster Resonance Energy Transfer (FRET) is a spectroscopic technique applied throughout physics, chemistry, and biology to measure quantitatively the distance between selected locations on macromolecules and to determine the close association between interacting molecular components. Because FRET typically occurs over distances from 0.5 to 10 nm, it is especially useful for investigating many interesting biological molecular structures. It is also particularly valuable for following the dynamics and structural fluctuations of biological molecular systems. FRET can be applied in solution or under imaging conditions (such as in fluorescence microscopy, nanoscience, and even macroscopic imaging). In this article, we discuss the fundamentals of FRET. These principles apply to every FRET measurement. We present the basic rudiments and the relevant literature of FRET to provide the reader with the necessary background essential for understanding much of the past and modern literature. At the end of the article, we give a short discussion of several applications of FRET to proteins. The literature for FRET is vast, and many new applications are constantly being developed. We could not do justice to the many practitioners of FRET in such a short space, but armed with the background that is presented, we hope this basic information will help readers follow much of the literature and apply it in their own work.
Integrin Signaling
Authors: Wu Xiaoyang , Guan Jun‐Lin 
Published: May 2008

AbstractIntegrins are a large family of heterodimeric receptors that mediate the adhesive behavior of cells. Most integrins bind to extracellular matrix (ECM) molecules, and they transmit signals that are critical in growth, development, tissue homeostasis, and host defense. A central feature of these receptors is their ability to transduce bidirectional signals into and out of the cell. In this article, we will give an overview of our current understanding of the structure and cellular signaling functions of integrins.
Lipid Bilayers: Properties
Authors: Vaz Winchil L. C. 
Published: May 2008

AbstractLipid bilayers are the structural basis of biological membranes; they provide excellent structures for microencapsulation and are interesting objects of study as thermotropic and lyotropic smectic liquid crystals. This article introduces the fundamental principles that lead to the formation of lipid bilayers and briefly lists some amphiphiles that form lipid bilayers in biological systems. The temperature‐dependent phase behavior of bilayers formed from a single lipid species is discussed briefly followed by a discussion of bilayer dimensions and hydration. The article then introduces the reader to phase behavior of bilayers formed from mixtures of lipids and the consequences of phase coexistence for component compartmentalization and percolation in lipid bilayers. Special emphasis is placed on the phase behavior of bilayers that contain sterols. The article introduces the reader to some physical properties of lipid bilayers, which include the hydration force, elasto‐mechanical properties, and the resistance of bilayers to lateral stretching and/or compression and bending. Brief discussions of molecular dynamics in lipid bilayers fromtrans/gaucheisomerism and rotation of lipid chains in bilayers to rotational, wobbling, and translational diffusion of lipids in bilayers is followed by an introduction to the dynamics of insertion, desorption, and transverse translocation of lipids in bilayers. Lipid bilayers are then discussed in terms of their permeability to aqueous solutes and some models for bilayer permeation are mentioned briefly. Finally, the reader is introduced to the electrical properties of lipid bilayers with brief discussions of the dipolar potential, the surface electrostatic potential, and the transmembrane potential. The article ends with a brief discussion of lipid compositional asymmetry across the lipid bilayer in biological membranes and its possible causes. Key references are cited wherever relevant.
Metalloproteinases, Biophysics and Chemistry of
Authors: Solomon Ariel , Selzer Tzvia , E. Milla Marcos , Sagi Irit 
Published: May 2008

Abstract
Zinc‐dependent metalloproteases constitute a large family of enzymes, part of the proteinase superfamily. Fundamental to the structural integrity and catalytic activity of metalloproteases is the presence of both zinc and calcium ions in the structure of the protein. This article will focus on matrix metalloproteinases that are involved in extracellular matrix (ECM) catabolism and serve as important enzymes in many aspects of biology, ranging from cell proliferation, differentiation, and proliferation to cancer, tumor metastasis, inflammation, and other pathologic states. Despite their key role in many normal and pathologic processes, the molecular mechanisms by which zinc‐dependent proteases hydrolyze their physiologic substrates are only known partly. Recent theoretical analyses have suggested reaction models for which limited and controversial experimental evidence exists. Here we will discuss the importance of quantifying the biophysical properties and the structural dynamic behavior of these enzymes to reveal their underlying molecular mechanisms. Such molecular knowledge holds promise in providing the basis for the novel design of specific antagonists as drug candidates for these important enzymes. In addition, we will discuss the use of real‐time spectroscopic tools for studying the reactive metal sites in these enzymes.
PLP‐Dependent Enzymes, Chemistry of
Authors: Toney Michael D. 
Published: May 2008

AbstractPyridoxal phosphate‐dependent enzymes catalyze a wide variety of reaction types on amines and amino acids, generally by stabilizing carbanionic intermediates, which makes them very common in both primary and secondary metabolism. A fundamental mechanism by which reaction specificity is enforced is stereoelectronic effects; the bond to Cα that gets broken in the universal external aldimine intermediate is that which is aligned parallel to theporbitals of the conjugated, electron‐deficient π system. When a bond to Cα has been broken, enzymes must also carefully control the fate of the resulting carbanionic intermediate. Structurally, all known pyridoxal 5′‐phosphate (PLP)‐dependent enzymes are separated into five groups. The largest of these, Type 1, is the aminotransferase group, of which aspartate aminotransferase is the prototype. The prototypes for the other groups are as follows: Type 2, tryptophan synthetase; Type 3, alanine racemase; Type 4, D‐amino acid aminotransferase; and Type 5, glycogen phosphorylase.
Proteins: Chemistry and Chemical Reactivity
Authors: Tilley S. David , Joshi Neel S. , Francis Matthew B. 
Published: May 2008

AbstractProtein bioconjugation is a critically important tool for the elucidation of enzyme mechanisms, the tracking of biomolecules in living systems, the improvement of pharmacokinetic properties, and the construction of new materials. All these applications rely on a continually expanding set of chemical reactions that can modify native protein functionality in aqueous solution under mild pH and temperature conditions. To survey these techniques, this article provides an introduction to the chemical reactivity of the amino acid side chains, with an emphasis on the selectivity that can be achieved using a particular reactive strategy. Site‐selective techniques that target the unique reactive properties of N‐terminal residues are also reviewed, as are native chemical ligation methods for the modification of the C‐terminus. Whenever possible, the mechanistic aspects of the reactions are discussed, as these considerations provide the foundation for future reaction development. The article concludes with a brief description of labeling reactions that selectively target unnatural functional groups in the presence of native protein functionality.
Receptor–Ligand Interactions in Biological Systems
Authors: Li Liwei , Meroueh Samy O. 
Published: May 2008

AbstractDespite the significant research that has been invested in understanding molecular recognition in biological systems, accurate prediction of macroscopic properties based on microscopic interactions remains elusive, which makes it difficult to identify systematically tight binding inhibitors in computational drug design. In the past, most ligand design efforts have centered on descriptors derived mainly from structure, neglecting entropic effects that develop from receptor flexibility. The lack of explicit incorporation of receptor motion has meant that compensatory effects between enthalpy and entropy, which are essential for the accurate estimation of free energy, have also been neglected. In addition, cooperative effects, which develop from alteration in the motion of the receptor because of ligand binding, are not captured. These effects pose a challenge for the design of small molecules that allosterically modulate protein‐protein and protein‐small‐molecule interactions. Here, we describe macroscopic properties of receptor‐ligand interactions, which are followed by a discussion of how these properties are predicted with microscopic interactions. A discussion then ensues on some fundamental aspects of the molecular recognition process that have attracted renewed attention, such as conformational selection versus induced‐fit binding, entropy‐enthalpy compensation, and allostery.
RNA
Interference to Treat Human Diseases
Authors: Shan Ge , Jin Peng 
Published: May 2008

Abstract
Discovery of the RNA interference (RNAi) pathway has been revolutionary to biology and biologically based therapeutics. The messenger RNA (mRNA) targets once believed to be “undruggable” by conventional methods are now being enthusiastically pursued with RNAi‐based therapeutics. Fundamental research into the RNAi pathway and biotechnological research on the application of RNAi may one day make a new class of drugs a reality by targeting the mRNA of disease‐causing or disease‐promoting genes directly. The whole process begins with the design and validation of short‐interference RNA (siRNA) using bioinformatics and cell culture systems. siRNA that has high specificity and potency (knockdown efficiency) then could be applied to animal models of human diseases for more evaluation, with the ultimate hope of advancing to clinical trails. Numerous chemical modifications of siRNA are currently being investigated in an effort to enhance their stability, to extend their stay in the body, and, perhaps, to avoid immune stimulation. Different delivery methods are developed depending on the diseases, tissues, or organs being targeted. In short, this relatively new biotechnology is advancing quickly as we learn from its failures and successes. In the current article, we will explore the background and current state of research as well as discuss some hurdles and future directions in the application of RNAi to treat human diseases.
Solid‐Phase Synthesis of Biomolecules
Authors: Breinbauer Rolf 
Published: May 2008

Abstract
The synthesis of biopolymers, tool compounds, and molecular probes lies at the heart of any effort in chemical biology. Solution‐phase strategies are well established but usually require considerable efforts in time and labor during workup and purification steps. In contrast, solid‐phase synthesis, in which the substrate is covalently bound to an insoluble support, allows the simple removal of excess or consumed reagents by simple filtration. In the cases of oligonucleotides and peptides, the synthetic operations can be performed by robotic systems allowing the high‐throughput synthesis of these biopolymers at low cost within a short time. The solid‐phase synthesis of oligosaccharides and small‐molecule probes has made significant progress during the last several years.
Water, Properties of
Authors: Geiger Alfons , Paschek Dietmar 
Published: May 2008

AbstractWater is well known for its unusual properties, which are the so‐called “anomalies” of the pure liquid, as well as for its special behavior as solvent, such as the hydrophobic hydration effects. During the past few years, a wealth of new insights into the origin of these features has been obtained by various experimental approaches and from computer simulation studies. In this review, we discuss points of special interest in the current water research. These points comprise the unusual properties of supercooled water, including the occurrence of liquid–liquid phase transitions, the related structural changes, and the onset of the unusual temperature dependence of the dynamics of the water molecules. The problem of the hydrogen‐bond network in the pure liquid, in aqueous mixtures and in solutions, can be approached by percolation theory. The properties of ionic and hydrophobic solvation are discussed in detail.
Catalytic Modes in Natural Ribozymes
Authors: Harris Michael E. 
Published: May 2008

Abstract
In nature, RNA transmits genetic information, and it catalyzes reactions that are universal in biology. The reactions of phosphorus and carbon esters that are catalyzed by natural ribozymes occur with specific geometries and are susceptible to both acid and base catalysis as well as catalysis that involves metal ions. High‐resolution structures of a few ribozymes implicate the involvement of individual nucleotides in performing these catalytic strategies. Detailed biochemical tests of the mechanisms of these ribozymes provide evidence for the involvement of nucleobase functional groups in acid/base catalysis, yet debate continues concerning their precise roles in proton transfer. Complementary structural and biochemical support has been gained for the involvement of specific RNA functional groups in positioning metal ions for catalysis. Still, only a few systems have been probed in sufficient depth to infer mechanistic detail and to achieve a complete chemical description of how ribozyme active sites enact specific catalytic strategies remains a key goal.
Base–Base Bifunctional Catalysis: A Practical Strategy for Asymmetric Michael Addition of Malonates to α,β‐Unsaturated Aldehydes
Authors: Wang Yongcan , Li Pengfei , Liang Xinmiao , Ye Jinxing 
Published: May 2008

AbstractLewis base–Brønsted base bifunctional catalysis is a novel and practical strategy for the asymmetric Michael addition. The addition of malonates to a series of α,β‐unsaturated aldehydes can take place under base–base bifunctional catalytic conditions using 0.5–5 mol% of (S)‐2‐[diphenyl(trimethylsilyloxy)methyl]pyrrolidine as catalyst and 5–30 mol% of lithium 4‐fluorobenzoate as additive base with up to 99% ee.
Organocatalytic Enantioselective Hydrophosphonylation of Sulfonylimines having a Heteroarenesulfonyl Group as a Novel Stereocontroller
Authors: Nakamura Shuichi , Nakashima Hiroki , Yamamura Akiko , Shibata Norio , Toru Takeshi 
Published: May 2008

AbstractOrganocatalytic enantioselective hydrophosphonylation of imines having the a heteroarenesulfonyl group afforded the respective products with high enantioselectivity. Both enantiomers of α‐amino phosphonates were obtained by using different Cinchona alkaloids with up to 98% ee.
Fast and Scalable Route to Aryl Polyallyl Dendrons and Dendrimers
Authors: Nlate Sylvain , Plault Lauriane , Felpin François‐Xavier , Astruc Didier 
Published: May 2008

AbstractIn the quest for general and efficient synthetic procedures for dendrons and dendrimers, allylphenol, allylnaphthol and 6‐bromonaphthalene AB3 dendrons have been successfully prepared on a large‐scale by a rapid and clean route starting from commercially available esters and allyl bromide. In contrast to the known organoiron strategy, the above‐mentioned methodology enables the large‐scale synthesis of AB3 dendrons in only two days.
Total Synthesis of Marine Oxylipins Solandelactones A–H
Authors: Pietruszka Jörg , Rieche Anja C. M. 
Published: May 2008

AbstractThe Solandelactones A–H have been synthesized via a short convergent approach utilizing common building blocks. Based on the diastereoselectivity of the crucial final addition step and on the comparison of prominent NMR data, a structural revision was necessary.