bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycolytic Enzymes
Authors: Michels Paul AM , Verlinde Christophe LMJ , Fothergill‐Gilmore Linda A
Published: March 2010

All cells must burn fuels to drive the myriad of cellular processes necessary for life. The most important organic fuel is glucose, a stable and soluble sugar that is particularly well suited for its role in biology. Cellular combustion of glucose occurs in 10 well‐controlled steps in which six‐carbon glucose molecules are broken apart (literally ‘glycolysis’) into three‐carbon compounds. In the same process chemical energy is captured through the production of ATP (adenosine triphosphate), the hydrolysis of which powers many cellular processes. The 10 enzymes which catalyse the steps of glycolysis are exceptionally well characterised. They provide a fascinating array of enzymes that have been perfected over long evolution to carry out their tasks swiftly, efficiently and with finely tuned control.

Key concepts:

Glycolysis is an ancient pathway that is present at least in part in all organisms.

Ten enzymes catalyse the reactions of the glycolytic pathway.

Many enzymes occur as isoenzymes in different tissues or in response to different metabolic conditions.

Hexokinase activity is regulated by product inhibition.

A hinge‐bending motion of the two‐lobed structures of hexokinase and phosphoglycerate kinase is induced by substrate binding, and is required to position the substrates correctly for catalysis.

Several reactions of the glycolytic pathway can be catalysed by pairs of nonhomologous enzymes (i.e. glucose‐phosphate isomerase, aldolase, glyceraldehyde‐3‐phosphate dehydrogenase and phosphoglycerate mutase).

Phosphofructokinase occurs as two distantly related types that use different phospho donors: ATP or inorganic pyrophosphate.

Activities of phosphofructokinase and pyruvate kinase are allosterically regulated.

A conserved protein fold of eight parallel β‐strands and eight parallel α helices, first identified in triosephosphate isomerase and therefore known as the ‘TIM barrel’ is found in several glycolytic enzymes and occurs in approximately 10% of all enzymes.

The Rossmann fold that occurs in many nucleotide‐binding proteins was first identified in glyceraldehyde‐3‐phosphate dehydrogenase.

Pyruvate kinase activity is sometimes regulated by posttranslational phosphorylation.
Eukaryotic Replication Fork
Authors: Walther André P
Published: March 2010

In eukaryotic cells, DNA (
deoxyribonucleic acid
) synthesis occurs at specific sites that move through the genome called replication forks. Multiprotein complexes at these forks catalyse the synthesis of two new strands of DNA using parental strands as templates to produce two complete copies of the parental DNA. The eukaryotic replication fork machinery must deal with the chromatin and chromosome structure of eukaryotic genomes, be able to replicate DNA in the context of a complex cell cycle, and be able to deal with the constant threat of mutations that could arise due to replication of damaged DNA, all while trying to efficiently replicate the DNA with high fidelity. The resulting eukaryotic replication fork is a tightly controlled, yet incredibly efficient biological machine capable of synthesizing billions of base pairs of DNA in the span of hours.

Key Concepts:

Eukaryotic DNA replication requires the concerted action of multiple DNA polymerases and accessory factors that replicate the DNA with high efficiency and accuracy.

Eukaryotic chromosomes are replicated in a semidiscontinuous manner by replication forks that coordinate the simultaneous replication of the leading and lagging strands.

The eukaryotic replication machinery is equipped to displace histones that coat chromatin DNA and reconstitute fully functional nucleoprotein chromosomes after DNA replication.
Plant Alkaloids
Authors: Fester Karin
Published: March 2010

Alkaloids are traditionally defined as basic (alkali‐like), nitrogen‐containing organic constituents that occur mainly in plants. The nitrogen in the alkaloid molecule is derived from amino acid metabolism. Since the amino acid skeleton is often largely retained in the alkaloid structure, alkaloids originating from the same amino acid show similar structural features and can be classified according to their biosynthetic origin. The biosynthesis of alkaloids often follows complex pathways and includes stereospecific steps. Alkaloids often have pronounced bioactivities and are therefore thought to play an important role in the interaction of plants with their environment. Alkaloids and extracts of alkaloid‐containing plants have been used throughout human history as remedies, poisons and psychoactive drugs.

Key Concepts

Alkaloids are a heterogeneous class of secondary metabolites.

Alkaloids are defined as basic compounds derived from amino acids, often with heterocyclically bound nitrogen. Pseudoalkaloids are nitrogen‐containing natural products that do not arise from an amino acid core and acquire their nitrogen by transamination of a precursor derived from other biosynthetic pathways.

Alkaloids are biosynthesized via complex pathways that may comprise 20 or more enzymatic steps.

Many alkaloids possess pronounced biological activities, which are often associated with their amine function.

Several alkaloids are used medicinally or provide lead structures for novel synthetic drugs.

Owing to their bioactivities, alkaloids are often toxic to herbivoures. Nevertheless, they may be exploited by specialized species of herbivoures as defence compounds.

Alkaloid‐producing tissue cultures provide an alternative for exploiting slow growing or protected plants. Moreover, they can be utilized for biosynthetic studies and for the commercial production of valuable alkaloids.
Vernalization
Authors: Jean Finnegan E , Helliwell Chris , Sheldon Candice , James Peacock W , Dennis Elizabeth S
Published: March 2010

Vernalization, the promotion of flowering in response to a prolonged period of growth at low temperatures, is an important adaptation of plants growing in regions where harsh winters are followed by relatively short growing seasons. In these plants, flowering is triggered by long days but only after the vernalization requirement has been met. Thus, the requirement for vernalization prevents flowering in the long days of autumn and ensures that flowering occurs in the warmer days of spring and summer, allowing sufficient time for seed development before the onset of the next winter. Various crop plants, including the winter cereals and canola, must be vernalized if they are to initiate flowering and set seed. The key genes controlling the response to vernalization differ between monocots and dicots suggesting that this response arose independently after the divergence of the monocot and dicot lineages.

Key concepts:

Vernalization is the promotion of flowering in response to prolonged periods of low temperatures, such as those experienced in winter.

The physiological properties of vernalization are similar in dicots and monocots but the genes controlling this response differ.

The vernalized state is inherited through mitotic cell divisions; this memory of winter is provided by epigenetic changes to the chromatin of key genes in the vernalization response, although the nature of these changes differs between monocots and dicots.

Epigenetic regulation results in a heritable but potentially reversible change in gene expression that is modulated by changing the accessibility of a gene for transcription.

FLOWERING LOCUS C (FLC)
is a key regulator of vernalization responsiveness in the Brassicaceae but the role of
FLC
homologues in other dicots remains to be elucidated.

The regulation of
FLC
expression is complex and involves both genetic and epigenetic mechanisms and
FLC
has become an important model for studying epigenetic control of plant gene expression.

VERNALIZATION INSENSITIVE 3
(
VIN3
) is induced by cold and the VIN3 protein is incorporated into the Polycomb Repression Complex (PRC2) that regulates
FLC.

Polycomb proteins are conserved across kingdoms and play a role in gene repression in Drosophila,
Caenorhabditis elegans
and mammals.

The vernalized state is reset each generation; resetting occurs at different times depending on the gamete transmitting
FLC
.

An
FLC
orthologue conditions the perennial behaviour of
Arabis alpina
, a relative of
Arabidopsis thaliana
.
Fluorescence Microscopy
Authors: Jacobson Ken
Published: March 2010

Fluorescence microscopy in biomedical research is a light microscope technique designed to view fluorescence emission from a biological specimen. It has become an extremely useful tool to localize genes, messenger
ribonucleic acid
(mRNA) and proteins within live and fixed cells and tissues. Cell biology has been revolutionized by the discovery and applications of
green fluorescent protein
, and its many mutant forms, that can be fused to a cellular protein of interest, making it possible to localize and study the dynamics of that protein in living cells. In addition, the development of other fluorescent reporters, based on small molecule dyes, has made it possible to visualize spatiotemporal variations in intracellular calcium as well as other ions and metabolites and the activity of components in signal transduction networks using specialized biosensors.

Key Concepts

Fluorescence microscopy enables visualization of the emission from fluorescent compounds in various specimens to submicron spatial resolution.

Fluorophores are molecules that emit longer wavelength that emit light after absorption of shorter wavelength light.

Biosensors are fluorophores that report on the location and activity of molecules or ions that, typically, are involved in signalling networks.
Metabolic Pathway Databases
Authors: Ellis Lynda BM
Published: March 2010

Metabolic pathway databases may draw on enzyme, compound and gene databases, but usually go beyond them to show how enzyme reactions link to one another and ultimately form pathways for catabolism, anabolism or other necessary cellular functions. Public metabolic databases may contain information on pathways shared by many organisms; these may omit specialized metabolism. Others may limit themselves to share or unique pathways found in specific organisms, or specialized metabolism. Metabolic pathway databases are a resource for metabolic engineering. Genetic material from microbes, plants and animals is being modified at the present time; these modifications are often based on information mined from a pathway database. Mining of metabolic data is still in its infancy. Based on information stored in today's metabolic databases, it may be possible in the future to predict metabolic pathways for the biodegradation of novel environmental toxins or biosynthesis of needed specialty chemicals.

Key concepts:

Metabolic databases contain information on enzymes, compounds and genes organized in metabolic pathways.

Metabolic databases may contain information on pathways shared by many organisms, or may limit themselves to pathways in specific organisms or to specific types of pathways.

Metabolic databases are a resource for metabolic engineering, which needs information on the genes, enzymes and pathways found in target organisms.
Molecular Dynamics
Authors: Petrenko Roman , Meller Jarosław
Published: March 2010

Molecular dynamics (MD) is a widely used technique for computer simulation of complex systems, modelled at the atomic or some coarse‐grained level. In this article, basic concepts pertaining to MD simulations are systematically introduced and related to the underlying models of physical systems. The principles of the atomic force fields, representation of the environment, the time evolution of the system, as well as the derivation of kinetic and thermodynamic properties of interest from MD trajectories are discussed. Applications of MD to biological systems are illustrated by examples of large scale studies on protein structure and dynamics, protein–protein interactions, and drug design. Limitations and several recent extensions of classical MD, including Replica Exchange and Steered MD, are discussed in the context of applications to biological systems as well. Related simulation protocols, including Monte Carlo and free energy methods, are summarized, highlighting complementarity and common principles of these molecular simulation approaches.

Key Concepts

Computer simulations can be used to facilitate and complement experimental studies of biomolecular systems.

Empirical force fields describe interatomic interactions in the system and enable efficient computation of forces in MD simulations.

MD is routinely used to study biological macromolecules and their environment.

A physical quantity can be measured using MD simulations by taking an arithmetic average over instantaneous values of that quantity obtained from MD trajectories.

Other simulation methods, such as Monte Carlo, enhanced sampling and free energy methods, are often being used in conjunction with MD and its extensions.

Slow processes can be studied computing the relative free energies of different states.

MD and related methods can be applied to systems comprising millions of atoms, providing unique insights into complex biological systems.
Nucleic Acid Backbone Structure Variations: Peptide Nucleic Acids
Authors: Nielsen Peter E
Published: March 2010

Synthetic analogues and mimics of the natural genetic material
deoxyribonucleic acid
(DNA) are potential gene therapeutic (antisense or antigene) drugs. One of these mimics, peptide nucleic acids (PNAs), are chemically closer to peptides and proteins than to DNA, but nonetheless have retained many of the structural properties of DNA. These molecules have found applications as probes in genetic diagnostics and are also being developed into antisense (RNA (
ribonucleic acid
) interference) gene therapeutic drugs, targeting selected genes through sequence‐specific recognition of (messenger or micro)RNA and in the future also antigene applications targeting the double‐stranded DNA of the genes themselves leading to gene silencing or guiding specific gene repair. Finally, the special chemical and structural properties of PNA suggest that these or similar molecules might have played a role in the prebiotic origin of life (on Earth) and also could be interesting components of possible artificial life.

Key concepts:

A range of chemical structures can mimic various functions of our genetic material, the DNA.

Chemical modifications and structural mimics of DNA are useful as genetic diagnostic probes and are being developed into gene therapeutic drugs.

RNA interference drug sequences specifically bind to cellular (messenger or micro)RNA and interfere with (inhibit) their function.

Prebiotic origin of life could have involved peptide nucleic acid molecules as predessors of RNA.
Actin Reorganization in Nerve Morphogenesis
Authors: Singh Ajeet Pratap , Rodrigues Veronica , VijayRaghavan K
Published: March 2010

Anatomists over centuries have described nerve cells which are notable for their diversity of architectures ranging from rather simple cells to highly complex and beautiful shapes. The soma of most neurons have two types of projections – dendrites which receive inputs from the environment or other nerve cells, which specialize in information transfer. The correct shape of a neuron and its connectivity which forms the basis of a functional circuit is crucial for the normal physiology of an animal. Defects in neuronal morphogenesis have been shown to be the cause of several neurological diseases. In this article we focus on a key molecule –
actin
, a component of the cytoskeleton – that forms the basis of cell shape and growth. We discuss how signals from within the cells and from its developmental milieu influence the organization of
actin
which in turn impacts on the shape and function of a nerve cell.

Key Concepts

Actin is enriched in areas of neurons which undergo rapid changes in shape.

Actin dynamics is regulated by multiple upstream signals and intracellular effectors.

Local destabilization of the actin cytoskeleton is a key downstream event during selection of an axon.

Actin dynamics in the growth cone regulates filopodial extension/retraction.

Actin cytoskeleton is highly dynamic in dendritic spines.

Neuronal activity‐dependent spine enlargement is correlated with a shift in F‐/G‐actin equilibrium towards F‐actin.

Rho GTPases are major intracellular regulators of actin dynamics.
Biomechanics of Plant Cell Growth
Authors: Jordan Benjamin M , Dumais Jacques
Published: March 2010

Plant cell growth is an irreversible yielding of the cell wall to the internal turgor pressure of the cell. Plant cells can control their expansion by modulating the structure and material properties of their wall. One major level of control is the distribution and orientation of the stiff cellulose microfibrils within the wall. When aligned, the microfibrils impart the wall with mechanical anisotropy which allows cells to expand preferentially along one direction. Moreover, growth is possible only when the stress in the wall exceeds a critical yield stress, also under cellular control. This article summarizes the key models that have been put forward to account for these aspects of cell growth. We begin with the now classic model by James Lockhart which reconciles the mechanical and hydraulic aspects of cell expansion. We then give an overview of newer modelling efforts to account for the complexity of cell wall mechanics.

Key Concepts:

Plant cell growth is an irreversible change in cell size involving stretching of the cell wall driven by the internal turgor pressure of the cell.

Growth is measured as the relative elemental growth rate (REGR).

The two main modes of cell morphogenesis are tip growth and diffuse growth.

For a cell to grow the cell surface must expand and water must enter the cell. The Lockhart equation encapsulates the balance between these two processes.

Under most circumstances, the rate of cell growth is limited by the extensibility of the cell, wall whereas the resistance to the influx of water is comparatively low (plant cell growth is said to be extensibility limited).

Cellulose microfibrils provide the cell wall with anisotropic mechanical properties which allow cells to expand along a preferred direction.
Kluyver, Albert Jan
Authors: Oren Aharon
Published: March 2010

Albert Jan Kluyver (1888–1956), a Dutch microbiologist who proposed a universal model for metabolic events in the cell based on transfer of hydrogen atoms (electrons) and formed the concept of unity in biochemistry.
van Niel, Cornelis Bernardus
Authors: Oren Aharon
Published: March 2010

Cornelis Bernardus van Niel (1897–1985), a Dutch‐born microbiologist who worked in California for most of his life; he showed that a coherent science of general microbiology could provide a foundation for unifying the life sciences and his summer courses at Pacific Grove, California, have inspired many leading biologists; he proposed a simple model to rationalize green plant and bacterial photosynthesis.
Pulsed Electron Paramagnetic Resonance Techniques for Structure Determination
Authors: Ames William M. , Larsen Russell G. , Larsen Sarah C.
Published: March 2010

Over the past several decades pulsed electron paramagnetic resonance (EPR) spectroscopy has advanced to provide a unique and useful set of tools for structural determination in systems that contain paramagnetic centers. Pulsed EPR methods use sequences of resonant microwave pulses to excite and manipulate paramagnetic centers subjected to an external magnetic field. The signals generated through these magnetic resonance methods are analyzed to provide information about the electronic and geometric structure near the paramagnetic centers.

This article provides a general overview of the theory and common experimental methods of pulsed EPR including electron spin echo envelope modulation (ESEEM), double electron–electron resonance (DEER), and hyperfine sublevel correlation spectroscopy (HYSCORE). Electron–nuclear and electron–electron interactions are discussed in detail, as well as how measurement of these interactions can be used to obtain structural insight for a range of important systems. Selected applications are presented to illustrate the utility of pulsed EPR methods for structure determination in real and model systems, with specific examples from materials science, astrogeology, and bioinorganic chemistry. The use of density functional theory (DFT) calculations to enhance experimental data analysis and interpretation is discussed.
1,2 and 1,3 Propanediol, Microbial Production Methods
Authors: Song Yuan‐Quan , Xu Yun‐Zhen , Liu De‐Hua
Published: March 2010

Microbial production of 1,2‐propanediol (1,2‐PD) and 1,3‐propanediol (1,3‐PD) is one of the fast developing processes of Bio‐Refinery, attracting the continuous attention all over the world. The following sections describe the details of the microbial production methods including the microorganisms used for production, biosynthesis routes, production capacity, culture conditions, application of metabolic engineering and downstream technology for the fermentation liguors. And the new development of microbial production is given in the article.
Anaerobes
Authors: Erickson Larry E. , Fung Daniel Y. C.
Published: March 2010

Many important products are produced under anaerobic conditions. These include food products, industrial chemicals, and biofuels. Methods of cultivation and identification that can be applied to industrially important strains are presented. The bioenergetics associated with growth and product formation is described and the relationship with product yields is reviewed. Important interactions associated with mixed pure cultures and mixed natural cultures are described and illustrated with examples.
Biofuel Cells, Enzyme Catalysis of Oils
Authors: Minteer Shelley D.
Published: March 2010

Biofuel cells are a type of fuel cell where biocatalysts are employed to catalyze the oxidation of fuels at the anode and/or reduction of oxygen or peroxide at the cathode. Biofuel cells are a popular research area in energy conversion, but most biofuel cells employ sugars, such as glucose, as fuels. These sugar fuels have been employed for two reasons: possible applications for implantable energy conversion devices and the prevalence of commercial enzymes for sugar oxidation due to the glucose biosensor field. However, oils are very high in energy density and could be advantageous as fuels for biofuel cells. This article explores the enzymes capable of bioelectrocatalysis of oils and describe from the literature, examples of their use in a biofuel cell.
Bryophytein vitroCultures, Secondary Products
Authors: Becker Hans
Published: March 2010

Bryophytes produce a large variety of secondary plant products that are not known from higher plants including various sesqui‐, di and triterpenes, bibenzyl‐, bisbibenzyl‐, and phenanthren derivatives. Field collection of bryophytes is difficult and often leads to only minor amounts of these tiny plants.

An alternative isin vitroculture. It has been shown in many examples that these cultures produce qualitatively and quantitatively the same secondary products. The cultures may also serve for biotransformation and biosynthetic studies.

Recently,in vitrocultures of the mossPhyscomitrella patenswere genetically transformed to produce therapeutically active proteins such as the human vascular endothelial growth factor, erythropoietin, and immunoglobulin.
Cell‐Surface Receptors: Structure, Activation, and Signaling
Authors: Thiel Kristina W. , Carpenter Graham
Published: March 2010

Cell‐surface receptors constitute the major route by which signals are conveyed from the extracellular to the intracellular environment of cells. This article focuses on the three major types of cell‐surface receptors: catalytic tyrosine kinase receptors, cytokine receptors, and seven‐transmembrane receptors.

The structure of the extracellular portions of these receptors enables them to recognize specific signals, such as growth factors, cytokines, peptides, and hormones. Binding of these signals changes the conformation of the receptors themselves, which translates to modulation of intracellular pathways. These pathways regulate diverse cellular functions such as proliferation, survival, and apoptosis. In the case of genetic diseases, mutations have been identified in many receptors, and these mutations result in aberrant signaling. By understanding the structural and molecular reasons for the pathological phenotypes, better pharmacological agents can be generated to treat these receptor‐driven diseases.
Closed Systems in Bioprocessing
Authors: Odum Jeffery
Published: March 2010

One of the fundamental foundations of bioprocess system design is the use of “closed” systems for production. As a key element of Good Manufacturing Practice (GMP) compliance, closed systems and equipment are utilized to prevent contamination of the product. But, they are also used as a means of containment to protect workers and the facility environment from exposure to potentially dangerous compounds and carrier organisms.
D‐Aminopeptidase and AlkalineD‐Peptidase
Authors: Asano Yasuhisa , Komeda Hidenobu
Published: March 2010

New d‐stereospecific enzymes, d‐aminopeptidase and alkaline d‐peptidase were isolated from Ochrobactrum anthropi andBacillus cereus, respectively. The d‐aminopeptidase acting on d‐amino acid amides and peptides containing d‐amino acids offers potential application in the d‐stereospecific hydrolysis of racemic amino acid amides, the dynamic kinetic resolution in the presence of a newly developed amino acid amide racemase, and the synthesis of d‐alanine N‐alkylamide and d‐alanine oligomers. The alkaline d‐peptidase is a d‐stereospecific dipeptidylendopeptidase acting on a synthetic peptides such as tetramer and trimer of d‐phenylalanine. The enzyme can also be applied for the synthesis of d‐phenylalanine oligomers with d‐phenylalanine methylester as a substrate. Primary structure determination of these two enzymes supports that they are new members of the penicillin‐recognizing enzymes, which include penicillin‐binding proteins and b‐lactamases.
L
‐
DOPA
, Microbial Production
Authors: Katayama Takane , Kumagai Hidehiko
Published: March 2010

3,4‐Dihydroxyphenyl‐
L
‐alanine (
L
‐DOPA) is a therapeutic agent for Parkinson's disease. In the last few decades, enzymatic production of
L
‐DOPA using tyrosine phenol‐lyase (TPL) from
Erwinia herbicola
has been industrialized. This method is quite simple and efficient, but has an intrinsic problem of tyrosine contamination because TPL is synthesized under tyrosine‐induced conditions. We have elucidated the mechanism underlying tyrosine‐mediated induction of TPL, and identified TyrR as a tyrosine‐responsive positive regulator of
tpl
. We then introduced random mutations into the
tyrR
gene, and screened for an enhanced ability to activate the
tpl
promoter. Consequently, TyrR
V67A Y72C E201G
was isolated, and when the mutant tyrR gene was introduced into
E. herbicola
, the resulting strain became able to produce TPL under non‐induced conditions.
L
‐DOPA productivity of the recombinant strain was about 10‐fold higher than that of the tyrosine‐induced wild‐type cells.
Enzymes, Enolate Reductases “Old Yellow Enzyme”
Authors: Hall Mélanie , Yanto Yanto , Bommarius Andreas S.
Published: March 2010

Reported enoate reductase activity is mostly displayed by enzymes belonging to the “Old Yellow Enzyme” family of flavoproteins. They have received increased interest over the last couple of years due to their huge potential in biocatalysis. These FMN‐containing enzymes catalyze the asymmetric reduction of activated C═C bonds at the expense of a nicotinamide cofactor, producing up to two chiral centers. They are also involved in other reductive processes, such as cleavage of nitrate esters, reduction of aromatic nitro groups, and even reduction of alkynes.

Increasing knowledge about this family of biocatalysts together with recent advances in biotechnology render the enoate reductases a tool of choice for industrial applications, as catalyzed reactions are usually chemo‐, regio‐ and stereo‐selective, and the enzymes most importantly display a wide substrate spectrum. With enzymatic reactions and mechanisms being generally clearly understood, the efficient production of a number of enantiopure compounds via recycling of the cofactor is now feasible.
Foam Formation and Control in Bioreactors
Authors: Delvigne Frank , Lecomte Jean‐paul
Published: March 2010

The generation of foam during the course of a bioprocess remains a major technological challenge to be resolved and needs further investigation. The foaming tendency of the cultivation media used in bioreactors induces various direct,that is microbial cells stripping and contamination, as well as indirect adverse effects, that is modification of the properties of the medium subsequent to the addition of chemical antifoam leading to toxic effects at the level of the microbial metabolism and fouling of the downstream processing equipment. In this work, the mechanisms leading to foam formation are described at the molecular level (adsorption ofsurface‐activemolecule at the gas–liquid interface), and also at the process level. In view of the potential foam‐associated problems, special attention is given to the level of the compatibility of the intensification of the gas–liquid operation in bioreactors. Due to these considerations, both the chemical and mechanical antifoam techniques have been evolved. Numerous new antifoam formulations and original combinations of chemical antifoams have been especially designed in order to meet the specific requirements of bioprocesses. Original mechanical techniques to prevent foam formation in bioreactors have been elaborated from combined knowledge involving the fluid dynamics of gas–liquid dispersion and interfacial processes (e.g. the “stirring as foam disruption” concept).
Gas Holdup in Bioreactors
Authors: Sieblist Christian , Lübbert Andreas
Published: March 2010

Most industrial cultivation processes are operated as aerobic submerged cultures, where the oxygen is supplied by sparging air into the liquid medium. The volume fraction of the dispersed gas phase is referred to as the gas hold‐up. It is of considerable practical importance as it determines the maximal volume of culture broth that can be operated in a given bioreactor. Moreover, it influences the mass transfer of oxygen and carbon dioxide as it determines the cross sectional area for their transport. Additionally, the mixing performance of the usually employed stirred tank reactor is affected since the power introduced into the culture at a fixed stirrer speed usually drops with the gas holdup. Here, the relationships between the various influence variables that can be used to estimate the gas hold‐up are described.
Herbicide Tolerant Plants, Production
Authors: Songstad David D.
Published: March 2010

This book chapter reviews the current status of herbicides tolerance in plants. Much of the focus is placed on use of genetic engineering to produce crop plants tolerant to several herbicides. Also detailed are the benefits that farmers have realized from use of these plants, in particular the incorporation of no‐till framing, deceased overhead costs and improved soil conservation.
Insect Cells and Larvae, Gene Expression Systems
Authors: Narang Someet , Whiteley Erik M. , Hussain Sunyia , Betenbaugh Michael J.
Published: March 2010

The use of the insect cell‐baculovirus system has grown significantly over the past three decades. The present chapter elucidates the fundamentals, scientific developments, technologies, and hurdles encountered in this field. The common types of insects and insect lines used as well as their specific features and culture conditions are described. Additionally, the types of baculoviruses used and the methods for generating them are also revealed. Particular emphasis has been given to describing the construction of recombinant baculoviruses that are used in production of heterologous proteins with insect cells. A major advantage in using insect cells is their ability to perform many post‐translational processing events on these proteins including glycosylation. The types of insect cell glycosylation and the differences in glycosylation patterns between insect and mammalian systems are detailed. The parameters that affect insect cell growth and baculovirus infection including bioreactor configuration, process monitoring and control, oxygen supply, sparging, and media formulations are described. In particular, cell culture processing methods including batch, fed‐batch, perfusion, and semi‐batch processes are illustrated. Additional factors affecting baculovirus infection including multiplicity, time of infection, and the generation of mutant viruses are also considered. A final section is devoted to the use of insect larvae in combination with baculovirus as a potentially alternative to cell culture for the low‐cost generation of baculoviruses and heterologous proteins. With all the advances in molecular biology and engineering processes for the baculovirus‐insect cell system, insect cell culture and its application to recombinant protein production, vaccines, pesticides, and other areas will continue to expand in the coming decades.
Stress Corrosion Cracking of Magnesium Alloys
Authors: Atrens Andrej , Winzer Nicholas , Dietzel Wolfgang
Published: March 2010

An overview is provided of Mg SCC. Intergranular stress corrosion cracking (IGSCC) is typically caused by a continuous second phase along grain boundaries. The second phase causes microgalvanic corrosion of the adjacent Mg matrix. IGSCC is expected for all creep resistant Mg alloys in contact with water whenever creep resistance is produced by a continuous second phase along the grain boundaries. IGSCC can be avoided by appropriate Mg alloy design. Transganular SCC (TGSCC) is caused by an interaction of hydrogen (H) with the microstructure so a detailed study of H‐trap interactions is needed in order to design alloys resistant to TGSCC. This understanding is urgently needed because Mg alloys are being increasingly used in load bearing applications; many common Mg alloys have a threshold stress for SCC of half the yield stress in common environments including high‐purity water.
Metal‐Free Alkyne Polyhydrothiolation: Synthesis of Functional Poly(vinylenesulfide)s with High Stereoregularity by Regioselective Thioclick Polymerization
Authors: Jim Cathy K. W. , Qin Anjun , Lam Jacky W. Y. , Mahtab Faisal , Yu Yong , Tang Ben Zhong
Published: March 2010

A new synthetic route to sulfur‐rich polymers has been developed. The alkyne polyhydrothiolations of 4,4′‐thiodibenzenethiol (1) and arylene dipropiolates (2–5) mediated by amines proceed at room temperature in a regioselective fashion, furnishing sole anti‐Markovnikov products of poly(vinylenesulfide)s (P1/2–P1/5) with high molecular weights (Mw up to 32 300) and high stereoregularities (Z content up to 81.4%) in high yields (up to 98.2%). Polymers P1/2–P1/4 are soluble in common organic solvents. They are optically transparent, allowing almost all visible and IR light to transmit through. Thanks to the high sulfur contents of the polymers, their films show high refractive indices (n = 1.73–1.70) in the wavelength region of 500–1700 nm as well as high Abbé numbers (νD' up to 539) and low optical dispersions (D' down to 0.002) at wavelengths important for telecommunications. Their refractivities can be further enhanced (n up to 2.06) by metal complexation and their films can be crosslinked by UV irradiation, which enables ready fabrication of fluorescent photopatterns.
Helically π‐Stacked Conjugated Polymers Bearing Photoresponsive and Chiral Moieties in Side Chains: Reversible Photoisomerization‐Enforced Switching Between Emission and Quenching of Circularly Polarized Fluorescence
Authors: Hayasaka Hiroyuki , Miyashita Tatsuaki , Tamura Kazuya , Akagi Kazuo
Published: March 2010

Novel multifunctional conjugated polymers, [poly(p‐phenylene)s and poly(bithienylene‐phenylene)s with (R)‐ and (S)‐configurations], which have fluorescence, chirality, and photoresponsive properties, have been designed and synthesized. The polymers are composed of π‐conjugated main chains, where poly(p‐phenylene) and poly(bithienylene‐phenylene) are fluorescence moieties, and the side chains of the photochromic dithienylethene moiety are linked with chiral alkyl groups. The polymer films exhibit right‐ or left‐handed circularly polarized fluorescence (CPF) and also show reversible quenching and emitting behaviors as a result of photochemical isomerization of the dithienylethene moiety upon irradiation with ultraviolet and visible light. This is the first report realizing the reversible switching of CPF using chirality and photoresponsive properties.
Biotemplated Synthesis of Gold Nanoparticle–Bacteria Cellulose Nanofiber Nanocomposites and Their Application in Biosensing
Authors: Zhang Taiji , Wang Wei , Zhang Dayong , Zhang Xinxiang , Ma Yurong , Zhou Yinglin , Qi Limin
Published: March 2010

Bacteria cellulose (BC) nanofibers are used as robust biotemplates for the facile fabrication of novel gold nanoparticle (NP)–bacteria cellulose nanofiber (Au–BC) nanocomposites via a one‐step method. The BC nanofibers are uniformly coated with Au NPs in aqueous suspension using poly(ethyleneimine) (PEI) as the reducing and linking agent. With the addition of different halides, Au–BC nanocomposites with different Au shell thicknesses are formed, and a possible formation mechanism is proposed by taking into account the special role played by PEI. A novel H2O2 biosensor is constructed using the obtained Au–BC nanocomposites as excellent support for horseradish peroxidase (HRP) immobilization, which allows the detection of H2O2 with a detection limit lower than 1 µM. The Au–BC nanocomposites could be further used for the immobilization of many other enzymes, and thus, may find potential applications in bioelectroanalysis and bioelectrocatalysis.
Oxygen‐Terminated Nanocrystalline Diamond Film as an Efficient Anode in Photovoltaics
Authors: Lim Candy Haley Yi Xuan , Zhong Yu Lin , Janssens Stoffel , Nesladek Milos , Loh Kian Ping
Published: March 2010

The potential of using p‐doped nanocrystalline diamond as the anode for organic solar cells, because of its outstanding photostability and well‐matched energetics with organic dyes, is demonstrated. The interface dipole and open‐circuit potential can be tuned by varying the surface termination on diamond. Oxygenated nanocrystalline diamond (O‐NCD) exhibits the best photocurrent conversion among all the surface‐treated electrodes studied in this work because of its large open‐circuit potential. The good energy alignment of the valence band of O‐NCD with the HOMO of poly(3‐hexylthiophene), as well as its p‐doped characteristics, suggest that O‐NCD can replace the hole transport layer, such as PEDOT:PSS, needed for efficient performance on indium tin oxide (ITO) electrodes. If the sheet resistance and optical transparency on NCD can be further optimized, chemical‐vapor‐deposited diamond electrodes may offer a viable alternative to ITO and fluorinated tin oxide (FTO).
Standardized discharge orders after stroke: Results of the quality improvement in stroke prevention (QUISP) cluster randomized trial
Authors: Johnston S. Claiborne , Sidney Stephen , Hills Nancy K. , Grosvenor David , Klingman Jeffrey G. , Bernstein Allan , Levin Eleanor
Published: March 2010

Objective

Proven strategies to reduce risk of stroke recurrence are under‐utilized. We sought to evaluate the impact of standardized stroke discharge orders on treatment practices in a cluster‐randomized trial.

Methods

The Quality Improvement in Stroke Prevention (QUISP) trial randomized 12 hospitals to continue usual care or to receive assistance in the development and implementation of standardized stroke discharge orders. All patients with ischemic stroke were identified during a 12‐month period prior to implementation and for 12 months afterward, and were followed for 6 months after discharge. The primary outcome was optimal treatment at 6 months, defined as taking a statin, having blood pressure <140/90mmHg, and receiving anticoagulation if atrial fibrillation was diagnosed. The primary analysis treated the hospital as the unit of analysis, comparing optimal treatment rates—adjusted for race, age, dementia, atrial fibrillation, and history of bleeding—between intervention and non‐intervention hospitals using a paired t test.

Results

In the primary analysis with hospital as the unit of analysis, the odds of optimal treatment was not significantly increased at intervention compared to non‐intervention hospitals (odds ratio, 1.39; 95% confidence interval, 0.71–2.76; p = 0.27). However, in analyses conducted at the level of the individual patients (N = 3,361), rates of optimal treatment increased from 37% to 45% in the intervention hospitals (p = 0.001) and did not change significantly in the non‐intervention hospitals (39% to 40%; p = 0.27).

Interpretation

Implementation of standardized discharge orders after stroke was associated with increased rates of optimal secondary prevention; this improvement was not significant in the primary analysis at the hospital level. ANN NEUROL 2010;67:579–589
Disrupted SOX10 regulation of GJC2 transcription causes Pelizaeus‐Merzbacher‐like disease
Authors: Osaka Hitoshi , Hamanoue Haruka , Yamamoto Ryoko , Nezu Atsuo , Sasaki Megumi , Saitsu Hirotomo , Kurosawa Kenji , Shimbo Hiroko , Matsumoto Naomichi , Inoue Ken
Published: March 2010

Mutations in the gap junction protein gamma‐2 gene, GJC2, cause a central hypomyelinating disorder; Pelizaeus‐Merzbacher‐like disease (PMLD; MIM311601). Using a homozygosity mapping and positional candidate gene approach, we identified a homozygous mutation (c.‐167A>G) within the GJC2 promoter at a potent SOX10 binding site in a patient with mild PMLD. Functionally, this mutation completely abolished the SOX10 binding and attenuated GJC2 promoter activity. These findings suggest not only that the SOX10‐to‐GJC2 transcriptional dysregulation is a cause of PMLD, but also that GJC2 may be in part responsible for the central hypomyelination caused by SOX10 mutations. ANN NEUROL 2010;68:250–254
Gentamicin‐induced readthrough of stop codons in duchenne muscular dystrophy
Authors: Malik Vinod , Rodino‐Klapac Louise R. , Viollet Laurence , Wall Cheryl , King Wendy , Al‐Dahhak Roula , Lewis Sarah , Shilling Christopher J. , Kota Janaiah , Serrano‐Munuera Carmen , Hayes John , Mahan John D. , Campbell Katherine J. , Banwell Brenda , Dasouki Majed , Watts Victoria , Sivakumar Kumaraswamy , Bien‐Willner Ricardo , Flanigan Kevin M. , Sahenk Zarife , Barohn Richard J. , Walker Christopher M. , Mendell Jerry R.
Published: March 2010

Objective

The objective of this study was to establish the feasibility of long‐term gentamicin dosing to achieve stop codon readthrough and produce full‐length dystrophin. Mutation suppression of stop codons, successfully achieved in the mdx mouse using gentamicin, represents an important evolving treatment strategy in Duchenne muscular dystrophy (DMD).

Methods

Two DMD cohorts received 14‐day gentamicin (7.5mg/kg/day): Cohort 1 (n = 10) stop codon patients and Cohort 2 (n = 8) frameshift controls. Two additional stop codon DMD cohorts were gentamicin treated (7.5mg/kg) for 6 months: Cohort 3 (n = 12) dosed weekly and Cohort 4 (n = 4) dosed twice weekly. Pre‐ and post‐treatment biopsies were assessed for dystrophin levels, as were clinical outcomes.

Results

In the 14‐day study, serum creatine kinase (CK) dropped by 50%, which was not seen in frameshift DMD controls. After 6 months of gentamicin, dystrophin levels significantly increased (p = 0.027); the highest levels reached 13 to 15% of normal (1 in Cohort 3, and 2 in Cohort 4), accompanied by reduced serum CK favoring drug‐induced readthrough of stop codons. This was supported by stabilization of strength and a slight increase in forced vital capacity. Pretreatment stable transcripts predicted an increase of dystrophin after gentamicin. Readthrough efficiency was not affected by the stop codon or its surrounding fourth nucleotide. In 1 subject, antigen‐specific interferon‐γ enzyme‐linked immunospot assay detected an immunogenic dystrophin epitope.

Interpretation

The results support efforts to achieve drug‐induced mutation suppression of stop codons. The immunogenic epitope resulting from readthrough emphasizes the importance of monitoring T‐cell immunity during clinical studies that suppress stop codons. Similar principles apply to other molecular strategies, including exon skipping and gene therapy. ANN NEUROL 2010;67:771–780
Synthesis and Antifungal Activity of 1‐Aryl‐3‐phenethylamino‐1‐propanone Hydrochlorides and 3‐Aroyl‐4‐aryl‐1‐phenethyl‐4‐piperidinols
Authors: Mete Ebru , Ozelgul Canan , Kazaz Cavit , Yurdakul Dilsad , Sahin Fikrettin , Gul Halise Inci
Published: March 2010

Mono‐Mannich bases, 1‐aryl‐3‐phenethylamino‐1‐propanone hydrochlorides, 1a, 2a, 3a, 4a, 5a, 6a, 7a, 8a, 9a, and semi‐cyclic mono‐Mannich bases, 3‐aroyl‐4‐aryl‐1‐phenethyl‐4‐piperidinols, 1b, 2b, 3b, 4b, 5b, 6b, 7b, 8b, 9b, were synthesized by a non‐classical Mannich reaction. The aryl part was: C6H5 for 1a, 1b; 4‐CH3C6H4 for 2a, 2b; 4‐CH3OC6H4 for 3a, 3b; 4‐ClC6H4 for 4a, 4b; 4‐FC6H4 for 5a, 5b; 4‐BrC6H4 for 6a, 6b; 2,4‐(Cl)2C6H3 for 7a, 7b; 4‐NO2C6H4 for 8a, 8b; and C4H3S(2‐yl) i. e., 2‐thienyl for 9a, 9b. Piperidinol compounds 2b, 3b, 4b, 5b, 7b, 8b, and 9b are reported here for the first time. The synthesized compounds were tested against seven types of plant pathogenic fungi and three types of human pathogenic fungi using the agar dilution assay. Itraconazole was tested against Candida parapsilosis as the reference compound, while Nystatin was tested as the reference compound against the other fungi. Compounds 1a, 1b, 2a, 4a, 4b, 5a, 5b, 6a, 7a, 8a, 9a, and 9b can be selected as model compounds to develop new antifungal agents against the human pathogen Microsporum canis. Compounds 8a and 8b, which had a similar antifungal activity compared with the reference compound Nystatin against the plant pathogen Aspergillus flavus, can serve as model compounds to develop new antifungal agents to solve agricultural problems.
Design and Synthesis of Novel Pyrazino[2,1‐a]isoquinolin Derivatives with Potent Antifungal Activity
Authors: Tang Hui , Zheng Can‐hui , Zhu Ju , Fu Bing‐yue , Zhou You‐jun , Lv Jia‐guo
Published: March 2010

A series of novel pyrazino[2,1‐a]isoquinolin compounds were designed, synthesized, and their antifungal activities in vitro were evaluated. The results showed that all of the title compounds exhibited antifungal activities. Most of them exhibited stronger antifungal activities than the lead compounds; compound 7c is more potent than fluconazole against two of the three tested fungal strains. The studies presented here provide a new structural type for the development of novel antifungal agents.
Phosphatidylcholine‐specific phospholipase C activity and level increase evidently in thromboangitis obliterans
Authors: Wang Mao‐hua , Jin Xing , Wu Xue‐jun , Zhang Jing‐yong , Miao Jun‐ying
Published: March 2010

Thromboangitis obliterans (TAO) is considered to be an inflammatory disease. Previous research has demonstrated that phosphatidylcholine‐specific phospholipase C (PC‐PLC) plays critical roles in various inflammatory responses. However, the connection between PC‐PLC and TAO is undetermined. Therefore, we sought to investigate whether PC‐PLC was implicated in TAO. In our study, there were two groups: TAO group and control group. The PC‐PLC activity of serum of two groups (16 TAO patients and 11 controls) was detected by PC‐PLC activity assay. The level and distribution of PC‐PLC in posterior tibial arteries in seven TAO patients and four controls were detected by immunofluorescence staining method. PC‐PLC activity increased greatly in serum of TAO patients. Immunofluorescence analysis also revealed an upregulation of PC‐PLC in the vascular endothelium of TAO patients. Our data suggest that PC‐PLC activity and level increase obviously in TAO patients. Our study may provide new clues for seeking pathogenesis of TAO. Furthermore, it may bring new insights into clinical diagnosis and treatment of TAO.