bluuebunny/crossref_metadata_2025_split huggingface dataset:
Programmed Cell Death as a Therapeutic Approach
Authors: Deshayes Kurt 
Published: February 2008

AbstractAlthough turnover rate varies greatly with cell type, the survival of multicellular organisms requires the constant renewal of healthy cells and the removal of pathogen‐infected or damaged cells. A critical component of homeostasis is the proper regulation of programmed cell death or apoptosis. Both oversensitivity of crucial cells and resistance of malfunctioning cells to apoptotic stimuli threaten survival. A lack of death response permits mutant cells to survive normal death stimuli and potentially proliferate. Conversely, excess apoptosis removes cells required for organism survival. Restoring homeostasis by controlling apoptosis is a potentially powerful technique for alleviating disease.
Chemical Molecules that Regulate Transcription and Facilitate Cell‐to‐Cell Communication
Authors: Wuster Arthur , Babu M. Madan 
Published: February 2008

Abstract

In this article we review cell‐to‐cell communication in three groups of organisms: bacteria, fungi, and the amoeba
Dictyostelium
. In particular, we concentrate on cell‐density‐dependent quorum sensing, which seems to have evolved independently on several occasions. The biologic and chemical properties of select systems are outlined, and the way they affect transcription, often via cross‐genome interactions, is described for each of the three groups. Furthermore, we give a short overview of the methods that can be used to study quorum sensing. We also outline the general properties of quorum sensing systems, such as positive feedback and its link to starvation‐dependent pathways.
Ras Oncoproteins
Authors: Chenette Emily J. , Der Channing J. 
Published: February 2008

AbstractThe Ras small GTPase is well known for its role in regulating normal cellular proliferation, as well as in promoting human oncogenesis when activated mutationally. In signal transduction, Ras functions as a guanine nucleotide‐regulatedON–OFFswitch. Positioned at cellular membranes, Ras relays signals initiated by diverse extracellular stimuli to a complex network of cytoplasmic signaling cascades to affect changes in gene transcription, cell‐cycle progression, survival, and differentiation. The intense research into the biologic and chemical nature of Ras has prompted the development of a variety of biologic, pharmacologic, and genetic tools to study Ras signaling. Also, Ras is the founding member of a superfamily of Ras‐related and Ras‐like proteins. The technical approaches and chemical concepts that have been generated from the study of Ras have aided greatly the studies of Ras superfamily proteins, which revealed the versatile and divergent biologic roles of small GTPases in cell physiology.
Nucleobase Self‐Assembly Codes: Constitutional Transcription
Authors: Barboiu Mihail 
Published: February 2008

AbstractThe functional self‐organization can be transcribed readily into hybrid nanostructures by using the sol‐gel process. Accordingly, we have reported synthetic routes for preparing self‐organized systems that have been “frozen” in a siloxane matrix, as a straightforward approach to design a novel class of solid hybrid nanomaterials. Nucleobases oligomerization can be an advantageous choice to reinforce the controlled communication between interconnected “dynamic supramolecular” and “fixing siloxane” systems. Moreover, the different interconverting outputs that nucleobases may form by oligomerization define a dynamic polyfunctional diversity that may be “extracted selectively” by sol‐gel polymerization in solid state under the intrinsic stability of the different nucleobase‐pairing and G‐quadruplex‐based systems. The nucleobase‐type hybrid materials presented in this review unlock the door to the new self‐organized materials world paralleling that of biology.
Steroid Hormones
Authors: Simons S. Stoney 
Published: February 2008

AbstractFive categories of steroid hormones exist in humans, including androgens, estrogens, glucocorticoids, mineralocorticoids, and progestins. These hormones affect virtually every tissue and organ in the human body and play major roles in the development, differentiation, and homeostasis of normal individuals. Antisteroids usually possess nonsteroidal structures but still block the actions of the steroid hormones and are important tools in endocrine therapies of pathologic conditions. Therefore, how the body regulates where, when, and how much a response to steroids occurs is of major importance. Here we survey what is known about the genomic responses to steroid hormones, each of which is mediated by a unique intracellular receptor protein that interacts with the cellular DNA to modify the rates of gene transcription. These receptors are members of a much larger superfamily of steroid/nuclear receptors, most of which bind either nonsteroidal ligands or no known ligand. Nongenomic (i.e., pathways without initial involvement of genomic DNA) and secondary responses (i.e., changes that require protein synthesis to alter gene transcription) are additional important effects of steroid hormones but are not discussed here. The emphasis is on the biochemistry of the five classes of steroid hormones, the techniques used to study steroid hormone action, and the basic mechanistic steps by which steroids alter gene expression.
Synthetic Sphingolipids as Bioactive Molecules
Authors: Bittman Robert 
Published: February 2008

Abstract
Sphingolipids are a highly diverse class of lipids, which encompasses thousands of different structural combinations of the polar head group, amino group or amide chain, and sphingoid long‐chain base. Initially regarded as inert structural components of eukaryotic cell membranes and plasma lipoproteins, sphingolipids now are recognized as key participants in the life of virtually all cell types. They influence a myriad of biological processes, including cell growth, cell death, and susceptibility to inflammation and infections. The number of known sphingolipid‐dependent cell signaling systems is increasing rapidly as research efforts in this field progress. Sphingolipids stabilize transient microdomains in membranes known as “rafts.” Signaling proteins and receptors partition into membrane rafts, and some toxins, pathogens, and viruses bind to sphingolipids that are concentrated in rafts and subsequently undergo endocytosis (see also Lipid Signals: Extracellular). Synthetic, non‐natural analogs of sphingolipids hold promise as drug candidates for treatment of various disease states via their ability to perturb cell signaling, membrane trafficking, and binding of infectious agents. The repertoire of synthetic sphingolipids includes analogs that target enzymes in the sphingolipid biosynthetic pathway and those that act as antiproliferative agents, immunomodulators, and regulators of lipid raft formation (and resultant receptor function). This review is intended to bring attention to selected synthetic analogs of sphingosine, ceramide, and glycosphingolipids that may lead to therapeutic intervention in certain patho‐physiologic conditions.
Synthetic Peptides and Proteins to Elucidate Biological Function
Authors: Becker Christian F. W. , Goody Roger S. 
Published: February 2008

AbstractThe enormous progress made in the use of gene technological techniques over the past several decades has been the main driving force in the accumulation of our knowledge of biology at the molecular level. This progress has at times tended to push more classic approaches, such as those stemming from synthetic chemistry, into the background, and there has even been a tendency to regard contributions from this area as being superfluous. This attitude has begun to change recently, with the emergence of the field now referred to as chemical biology, and it is now appreciated that synthetic chemistry can make a unique contribution to the outstanding problems in fundamental biological and medically oriented research. The full potential of these methods is beginning to be realized in the area of peptide and protein synthesis, and this will be the topic of this article.
Systems Approach to Metabolism
Authors: Aoki‐Kinoshita Kiyoko F. , Kanehisa Minoru 
Published: February 2008

Abstract
The network structure of pathways can be studied from two complementary viewpoints; as networks of enzymes or as networks of chemical compounds. This structure enables more in‐depth analysis into metabolic pathways. From these networks, new features regarding pathways on both the local and the global levels can be detected. On the one hand, global features such as the scale‐free property of pathways have attracted much attention from the bioinformatics community. On the other hand, local features of networks such as pathway modules can retrieve and characterize subnetworks of related genes that are potentially involved in a particular function of the metabolic pathway. Systems analysis of metabolic pathways must focus not only on existing pathways, but also on reconstructing pathways for new genomes or filling in information regarding missing enzymes. By using the vast amounts of genomic data available, it is possible to reconstruct the metabolic maps of new genomes. Such genomic information has proved useful to refine prediction methods, and they can be complemented with chemical‐based information that is inherent in the same network. Overall, a systems approach to metabolism covers the realm of both the genomic and the chemical worlds in an integrated manner. We will show that the concepts of local network features in terms of both these worlds produce modules that can be integrated such that the global view of metabolism can be grasped. The current findings will be described systematically while also involving manual curation such that biologically accurate systems can be produced for analysis.
Transcription Factors
Authors: Hauschild KE , Carlson CD , Donato LJ , Moretti R , Ansari AZ 
Published: February 2008

AbstractThe genome of an organism is deciphered by transcriptional processes to generate RNA and protein molecules that determine cellular fate and perform all cellular functions. The transcriptional machinery itself displays limited specificity and is involved in transcribing all genes in the genome. The exquisite specificity with which gene networks are expressed is mediated by regulatory proteins called transcription factors. Transcription factors bind to gene‐specific regulatory sites in the genome and help assemble the complex multi‐subunit machinery that transcribes the target gene(s). Spatio‐temporal regulation of gene expression permits selective expression of a subset of genes within the genome and thus governs the diversity of cell types and cellular function in response to physiologic signals. The central role of transcription factors in regulation of specific genes and networks is underscored by the fact that their malfunction is linked to the onset of a wide array of diseases, including developmental disorders, cancer, and diabetes. Thus, a major goal at the interface of chemistry, biology, and molecular medicine is the ability to generate synthetic molecules that function as transcription factors. The key requirement in the creation of these artificial transcription factors is the ability to define the properties of natural transcription factors fully. Here we discuss the common properties of transcription factors, summarize the alluring value of targeting gene expression with small molecules, and summarize the current advances toward regulating the expression of desired genes and gene networks with artificial transcription factors.
Xenobiotic Metabolism
Authors: Ioannides Costas 
Published: February 2008

Abstract
Humans are exposed continuously and unavoidably to a myriad of potentially toxic chemicals that are inherently lipophilic and, consequently, very difficult to excrete. To effect their elimination, the human body has developed appropriate enzyme systems that can transform metabolically these chemicals to hydrophilic, readily excretable, metabolites. This biotransformation process occurs in two distinct phases, Phase I and Phase II, and involves several enzyme systems, the most important being the cytochromes P450. The expression of these enzyme systems is regulated genetically but can be modulated also other factors, such as exposure to chemicals that can either increase or impair activity. Paradoxically, the same xenobiotic‐metabolizing enzyme systems also can convert biologically inactive chemicals to highly reactive intermediates that interact with vital cellular macromolecules and elicit various forms of toxicity. Thus, xenobiotic metabolism does not always lead to deactivation but can result also in metabolic activation with deleterious consequences.
Synthetic Chemistry: Formation of the Amide Bond
Authors: Montalbetti Christian A. G. N. , Falque Virginie M. 
Published: February 2008

AbstractAmide bonds are found ubiquitously in natural or synthetic molecules of biologic interest. Since the early days of synthetic organic chemistry, methods for the formation of amides have been described. More recently, with the development of solid‐phase chemistry and automated peptide synthesis, new strategies and reagents have been devised to overcome typical problems such as low conversion and racemization. This article provides an overview of the methodology that is available today. Depending on the nature of the synthetic target and the associated synthetic challenges, different approaches can be envisaged. Methods range from the rather straightforward use of acyl halides, anhydrides, and carbodiimides, to the more elaborate, low‐racemization inducing methods that use phosphonium/uronium‐based reagents. New amide bond‐mediated ligation methodologies now offer new convergent strategies for the synthesis of highly functionalized molecules of biologic interest.
Water in Biological Recognition Processes
Authors: Chaplin Martin F. 
Published: February 2008

Abstract
Water is central to biology, providing much more than the means to allow the movement of biologic molecules. It is an excellent solvent, a substrate and facilitator for reactions, and it provides a means for ionizations and extends the intricate three‐dimensional surface geometry and complex charge distribution of biomolecules out towards the bulk solution. Water's hydrogen bonds and dipoles are strong enough to present structural information concerning surfaces to distant diffusing molecules and to fine tune their orientation to match potential recognition sites, but they are weak enough to break to make way for direct binding processes. Water occupies potential interaction sites until they are recognized by suitable molecules, with the release of the water providing free energy to help compensate for the entropy loss on binding. Also, water molecules may determine the conformation of the biological molecule and directly assist and take part in the recognition process. Among the techniques available, X‐ray crystallography has provided the most information on these roles for water.
NMR‐Based Metabolomics Technology in Biomarker Research
Authors: Pan Zhengzheng , Gu Haiwei , Raftery Daniel 
Published: February 2008

Abstract
The methods and applications of NMR‐based metabolomics are introduced in this article. As important tools for systems biology research, metabolomics, metabonomics, and metabolite profiling have been applied successfully for biomarker exploration at the molecular level. In addition to the detection and identification of putative disease biomarkers, NMR‐based metabolomics also can be performed in many areas including nutritional science, disease monitoring, and drug toxicology studies. In the following sections, basic and advanced NMR technologies associated with metabolomics are summarized. Also, to process the complex spectral data and obtain useful information, pattern recognition techniques or multivariate statistical methods are necessary. These methods successfully simplify the multivariable data set, and their improvement may enhance the development of metabolomics. Finally, several important applications of NMR‐based metabolomics are summarized, and examples are described.
Phosphate Mimics: Cyclic Compounds
Authors: Nottbohm Amanda C. , Hergenrother Paul J. 
Published: February 2008

AbstractCompounds that contain phosphate and diphosphate moieties are not ideal biologic probes. Not only does their ionic character inhibit cell membrane permeability, but also, once inside a cell, the ester and the anhydride functionalities are likely targets for enzymatic cleavage. Thus, replacements for the phosphate motif are important as enzyme inhibitors, DNA or RNA analogs, phospholipid mimics, and phosphorylated metabolite analogs. To date, several classes of phosphate mimics have been developed that have been grouped into four categories: phosphorus‐containing, sulfur‐containing, dicarboxylates, and the novel cyclic mimics, which will be the focus of this review.
Pharmacokinetics of Drug Candidates
Authors: White Ronald E. 
Published: February 2008

AbstractPharmacokinetics is a mathematically based discipline that describes the time course of uptake, distribution, and elimination of a drug in an organism. This article explains the physiologic basis and clinical interpretation of the various pharmacokinetic parameters, such as half‐life, clearance, and oral bioavailability. Because of the central importance of pharmacokinetics to the clinical use of drugs, the determination of pharmacokinetics is required at several points in the research and development cycle of new drug candidates. The rationale and methods of determination are discussed.
Microarrays in Chemical Biology
Authors: Koehler Angela N. 
Published: February 2008

Abstract
Advances in both genomics and proteomics have provided researchers with access to large collections of biomolecules, including DNA, proteins, and metabolites. High‐throughput methods are needed to study the function and regulation of these biomolecules within complex systems. Microarrays have emerged as a common platform to study biomolecular interactions that involve nucleic acids, proteins, and small molecules. DNA microarrays have revolutionized genomic research by allowing researchers to study gene expression, sequence variation, and transcription factor binding sites on a whole‐genome scale. Protein microarrays can be used to study interactions with other proteins, DNA, RNA, and small molecules, including lipids, carbohydrates, and drugs. Protein microarrays can also be used as analytical tools to profile complex protein mixtures, such as fractionated cell lysates, in an effort to study antibody specificity, measure changes in protein abundance, or characterize disease states. Small‐molecule microarrays are useful tools for ligand discovery, comparing inhibitor specificity across enzyme classes, high‐throughput, cell‐based phenotypic screens, and as diagnostic tools for pathogen detection. The microarray approach has been extended to transfected cell microarrays, RNAi living cell microarrays, virus microarrays, and tissue microarrays. This article reviews chemical strategies for making microarrays and applications of microarrays in chemical biology.
Hemozoin: A Paradigm for Biominerals in Disease
Authors: Carter Melissa D. , Hoang Anh N. , Wright David W. 
Published: February 2008

Abstract

Biomineralization is the formation of organic–inorganic composites by organisms. Originally evolved as a protective mechanism, this complex process has also become a recognized contributor to several disease states, which range from kidney stone disease (nephrolithiasis) to parasitic diseases like malaria. The characteristic three‐step process for the formation of biominerals is defined by the supramolecular preorganization of a nucleating template, the interfacial molecular recognition of crystal nuclei and the cellular processing of resultant aggregates. Hemozoin formed in the heme detoxification pathway used by the malarial parasite
Plasmodium falciparum
represents a paradigm for pathogenic biominerals. Current research indicates that a supramolecular lipid template organizes heme released previously during hemoglobin catabolism. Nucleation and growth of the heme aggregate serves to protect the parasite from the toxic effects of free heme. Given the mechanisms of biomineralization, it is not surprising to discover that century‐old antimalarial compounds function by disrupting key interactions between the heme substrate and template. Subsequently, the heme‐aggregate is released into the host vasculature and deposits in patients' brains, spleens, and livers where it disrupts host innate immune response. The underlying basis of this immunomodulating activity seems to result from hemozoin mediated lipid peroxidation. Understanding the relationships between hemozoin formation and its pathogenic activity with the host immune response represents a significant challenge to chemical biology.
Lipids: Organization and Aggregation
Authors: Vattulainen Ilpo 
Published: February 2008

AbstractLipids constitute one of the main classes of molecules in biological systems. They are involved in numerous cellular functions either as individual molecules or as lipid aggregates with varying sizes and morphologies. For example, lipids are a crucial component of cellular membranes that surround and protect cells. Lipids comprise membrane domains that provide membrane proteins with a well‐defined environment to carry out their functions. Lipids also interact specifically with some proteins, which render their functions possible. Lipids play the role of drugs and enzymes, and our skin and lung surfactant lining lung epithelial cells are composed largely of lipids. What is more, lipids are used in delivery vehicles to encompass drugs and other molecules. These functions and many others develop in part from lipids' specific properties relevant on molecular scales and also from the assembly of lipids as fascinating structures observed over a multitude of scales beyond molecular size. Here, we discuss the functions of lipids and lipid structures together with their structural and dynamic properties, including examples and highlights of recent studies.
Analysis of Variance
Authors: Bingham Derek 
Published: February 2008

Abstract

The analysis of variance is, perhaps, the most used of all data analysis techniques. Indeed, it is the standard approach for the analysis of most industrial experiments. The aim of the analysis of the variance is to determine if there exists a relationship between a response variable and one or more experimental factors. This is achieved by partitioning the variability in the response into variability due to random error and variability due to changes in the settings of the experiment factors. A statistically significant relationship is identified by the appropriate use of an
F
‐test. This article provides an overview of the analysis of variance and its use in industrial experiments.
Foldover Designs
Authors: Li William 
Published: February 2008

Abstract
Foldover is a commonly used follow‐up technique. A foldover design is constructed by reversing the signs of several columns of the initial design. We demonstrate how a foldover design can be used to untangle aliased effects, especially main effects and two‐factor interactions, found from the analysis of the initial design. We then discuss several methods for constructing foldover designs and introduce optimal foldover plans for both regular and nonregular factorial designs. The main advantage and disadvantage of the foldover method are also discussed.
Gauge Repeatability and Reproducibility (
R
&
R
) Studies
Authors: Vardeman Stephen B. 
Published: February 2008

Abstract
This article discusses basic design considerations for so‐called gauge repeatability and reproducibility studies. These common industrial measurement studies are used to investigate the precision of measurement systems that employ more than one operator to make measurements with a single gauge/measurement device. Data from them are typically used to estimate functions of variance components in random‐effects models that quantify both “within part‐by‐operator combination” and “between‐operator” variation in measurement.