bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial Flagella: Flagellar Motor
Authors: Delalez Nicolas J
Published: August 2014

The bacterial flagellar motor is a complex biological rotary molecular motor, which is situated in the cell envelopes of bacteria. Whereas most biological motors use
adenosine triphosphate
as their energy source, the rotation of the flagellar motor is driven by a flow of charged ions across the bacterial plasma membrane. The motor powers the rotation of helical flagellar filaments at speeds of up to several hundred hertz. These rotating filaments act like propellers, pushing the cells through their environment. The motors are regulated by one of the best‐characterised biological signalling pathways, the chemotaxis pathway. This pathway changes the swimming pattern of the bacteria in response to changes in the concentration of external chemicals so that they move into environments, which are optimal for their growth. Other pathways can regulate the flagellar motor and the motor itself can respond to changing conditions by adapting parts of its structure.

Key Concepts:

Many bacteria swim using a small biological rotary motor which is powered by the movement of ions (H
+
or Na
+
) across the plasma membrane.

The bacterial flagellar motor consists of a rotor which rotates against stator units that are anchored to the peptidoglycan cell wall.

Torque is generated by the interaction of the stator units, MotA and MotB (or PomA and PomB for Na
+
‐driven motors), with FliG in the rotor.

Despite the fact that the driving ions always flow in one direction through the stator units, many flagellar motors can switch between clockwise and counterclockwise rotation.

The structure of the flagellar motor is highly dynamic, some of its components undergo rapid turnover while the motor is functioning in response to changing conditions.

A complex signalling pathway regulates the motor output in response to environmental signals ensuring that bacteria swim towards nutrient rich environments.
Plant Resistance to Infection by Viruses
Authors: Revers Frédéric , Nicaise Valérie
Published: August 2014

Among the most devastating pathogens, plant viruses are responsible for considerable losses of most agronomically important crops in the fields. The development and use of cultivars that are genetically resistant to viruses is an efficient strategy to tackle the problems associated with virus diseases. Recently, important advances have been made in our understanding of the molecular nature and mechanisms associated with natural recessive and dominant resistance genes, as well as in the antiviral defence system based on ribonucleic acids, referred to as RNA silencing. In this review, the authors summarise current knowledge about the defence mechanisms that prevent or limit viral infection in plants and discuss the likely collaboration of these different antiviral strategies insuring the resistance of the whole plant.

Key Concepts:

A vast number of natural recessive resistances to plant viruses encode translational factors that are fully required for infection success.

Most of plant antiviral
R
genes encode NBS‐LRR proteins that mediate resistance through the specific (direct or indirect) recognition of a virus avirulence factor.

Plant hormone balance participates actively to plant virus resistance and can be modulated by viruses.

The mechanisms of RNA silencing (or RNA interference) target virus multiplication at the nucleic acid level.

Plant immunity against viruses results from a highly efficient build‐up of all resistance mechanisms.
Ecology of Water Relations in Plants
Authors: Araya Yoseph Negusse , Garcia‐Baquero Gonzalo
Published: August 2014

Water is an important and often limiting resource for plant growth. Water can influence plant growth and functioning as a direct resource, or indirectly by influencing availability of other resources such as nutrients and oxygen. Availability of water in soil can be quantified in a number of ways, namely as amount of water stored in soil; as depth of water level from soil surface; duration of specific water level through time; or frequency of occurrence of specified water levels in a set duration of time. Plants are sensitive to water availability and have developed sensing and adaptation strategies to ensure competitive and survival success. Variation in water availabilities can determine the distribution and interaction of plants by influencing their response, thereby establishing a basis for niche differentiation.

Key Concepts:

Water is fundamental to plant growth and function.

Water can exert its influence in plant growth and distribution directly, as a resource or indirectly by influence on availability of other resources such as nutrients and oxygen.

Availability of water for plant use is determined by soil texture, structure and meteorological drivers such as evaporation.

Appropriate quantification of water availability is important to study its influence on plant growth and distribution.

Water can determine coexistence of species in a community through niche differentiation along existing hydrological gradients.
Conservation of Plants
Authors: Hermy Martin , Honnay Olivier , Jacquemyn Hans , Brys Rein
Published: August 2014

Approximately 3.4% of the predicted total number of species on Earth is plants. Plants and their communities are an indispensable part of the Earth's biosphere as plants not only affect ecosystem functioning, but also provide essential ecosystem services for the benefit of humans. However, plants face many threats and current extinction rates have been estimated to be 100–1000 times higher than those of the prehuman era. The five most important drivers of plant extinction are: (1) habitat loss and fragmentation, (2) introduction of exotic species, (3) climate change, (4) overexploitation and (5) pollution. For conservation plans to be effective, four essential steps are needed to maintain viable plant populations in the long term. These include assessment of the biological status of a species, diagnosis of the causes of decline, prescription of management strategies that will counterbalance the decline, and implementation of management practices and further monitoring.

Key Concepts:

Approximately 17% of all known species on Earth are plant species, that is, approximately 215 600 species have been recorded.

The tropical Andes, Mesoamerica and the Caribbean contain the highest plant diversity and therefore can be considered as the world's most important plant biodiversity hotspots.

Increasing evidence that plant species diversity positively correlates with the efficiency of many ecosystem functions and services provides conservationists with strong scientific arguments for biodiversity conservation.

Rare species are an important part of recent evidence‐based approaches to biodiversity analysis, prioritisation and conservation.

Current rates of plant species extinction are estimated to be 100–1000 times higher than those of the prehuman era. One in five plant species is currently threatened with extinction.

There are five major anthropogenic drivers of plant species loss: (1) habitat loss and fragmentation, (2) introduction of exotic species, (3) climate change, (4) overexploitation and (5) pollution.

Each attempt to protect endangered plant species from going extinct should consist of four different steps: assessment, diagnosis, prescription and prognosis.

Minimal Viable Population (MVP) size has been estimated at
c
. 5000 individuals. Although still an important concept, MVP sizes should not be considered as a magic number.

A biodiversity audit consists of a methodology that aims at adopting the most efficient and feasible management interventions within a particular area, using quantitative data on all species present and considering the benefits and drawbacks for all stakeholders involved.

An efficient plant conservation strategy should create: space for plants; improve environmental quality for plants, both in the designated areas for conservation and in the surrounding landscape matrix; develop a specific plant species conservation policy (including an
in situ
and possibly an
ex situ
component) and enlarge the social basis for plant conservation through education, information and participation.
Global Carbon Cycle
Authors: Sabine Christopher L
Published: August 2014

Despite the low concentrations in the atmosphere relative to nitrogen or oxygen, carbon dioxide (CO
2
) plays a significant role in the Earth's life cycle and in controlling the global climate. The positive and negative feedback mechanisms associated with the exchange of atmospheric carbon with the ocean and organic material found on the land surface (called the terrestrial biosphere) appear to have been relatively well balanced for most of humankind's existence. Since the beginning of the industrial era, however, humans have been extracting fossil carbon from the Earth's interior and combusting it for energy production. Much of this fossil carbon is converted to CO
2
gas and released into the environment where it is altering the carbon balance between the atmosphere, ocean and terrestrial biosphere. Recent changes observed in the global climate are consistent with the predicted response to increasing CO
2
and other greenhouse gases in the atmosphere.

Key Concepts:

Carbon is an essential component of life on Earth.

Atmospheric CO
2
concentrations varied considerably in the distant past depending on the balance of several geochemical processes.

Geochemical evidence suggests that atmospheric CO
2
levels dropped below 300 ppm approximately 20 million years ago and have remained below that level until the beginning of the twentieth century.

The atmosphere, terrestrial biosphere and the ocean are the only systems that have natural exchanges of carbon on time‐scales relevant to human society.

Humans are in the process of altering the global carbon cycle at a rate that is unprecedented in Earth's history through land‐use practices and the burning of fossil fuels.

As we change the balance of the carbon cycle it is clear that the global climate is changing, but it is not clear how global ecosystems might respond.
Small Nuclear Ribonucleoproteins (sn
RNP
s)
Authors: Stone Lauren B , Riley Kasandra J
Published: August 2014

Small nuclear ribonucleoproteins (snRNPs)
are protein–
ribonucleic acid (RNA)
complexes defined by a core noncoding RNA of approximately 100–600 nucleotides and tightly bound proteins that together accumulate in the nucleus. The snRNPs are best known for their role in RNA splicing complexes, including U1, U2, U4, U5 and U6 snRNPs found in the spliceosome. Additional snRNPs are functionally diverse, but in many cases the RNA component of snRNPs can base‐pair with a substrate for precise alignment and possible catalysis. The U7 snRNP directs 3′‐end mRNA formation for histone transcripts, and the 7SK snRNP regulates transcription. Two special groups of snRNPs,
small nucleolar RNPs (snoRNPs)
and
small Cajal‐body RNPs (scaRNPs)
, are restricted to their named subnuclear compartments in order to direct post‐transcriptional modification of ribosomal and splicing RNAs, respectively. Certain herpesviruses express high levels of novel snRNPs involved in the regulation of gene expression. Due to their important biological roles, there are many diseases associated with snRNPs.

Key Concepts:

The snRNPs are small nuclear ribonucleoprotein particles, a class of dynamic RNA–protein complexes that accumulate in the nucleus.

Major and minor splicing snRNPs form super‐complexes (spliceosomes) that direct the precise splicing of messenger RNAs.

In the special process of
trans
‐splicing, splice leader (SL) snRNPs donate RNA to the ends of transcripts.

The U7 snRNP coordinates 3′ end processing of metazoan histone messenger RNAs.

The 7SK snRNP regulates transcription by selectively sequestering and rendering inactive the P‐TEFb protein, a key modulator of RNA polymerase II.

Two groups of snRNPs are singled out for specific subnuclear localisation: small nucleolar and small Cajal‐body associated (sno/scaRNPs) direct methylation and pseudouridylation of splicing and ribosomal RNAs.

Some mammalian herpesviruses express viral snRNPs, which have enigmatic and complex functions in gene regulation.

Several diseases including lupus present autoantibody production of antibodies directed at snRNP‐affiliated proteins such as Sm, Lsm and La.

Most snRNPs have been affiliated with diseases and are therefore promising biomarkers for diagnosis and prognosis.
Far‐field Light Microscopy
Authors: Cremer Christoph
Published: August 2014

Novel developments in optical technology and photophysics made it possible to radically overcome the diffraction limit (ca. 200 nm laterally, 600 nm along the optical axis) of conventional far‐field fluorescence microscopy. Presently, three principal ‘nanoscopy’ families have been established: Nanoscopy based on highly focused laser beams; nanoscopy based on structured illumination excitation; and nanoscopy based on localisation microscopy approaches. With such ‘superresolution’ or ‘nanoscopy’ techniques, it has become possible to analyse biostructures with a substantially enhanced light optical resolution down to a few tens of nanometre in 3D, and a few nanometre in the object plane, corresponding to 1/100 of the exciting wavelength. These methods allow to study individual membrane complexes, cellular protein distributions, nuclear nanostructures, bacteria or individual viruses down to the molecular level; they open new perspectives to combine molecular and structural biology to unravel the basic mechanisms of life and their emergence from fundamental laws.

Key Concepts

Light microscopy of biostructures has reemerged as an essential tool of the life sciences.

Conventional light microscopy methods suffer from the limited resolution and thus prevent the direct study of nanostructural details.

Novel developments in optics and photophysics have made it possible to overcome the conventional resolution limits.

Present ‘superresolution’/‘nanoscopy’ techniques are based either on focused laser beam excitation; or on patterned/structured illumination schemes; or on homogeneous wide‐field illumination.

In addition to advanced optical techniques, nanoscopy requires appropriate photostable/photoswitchable fluorochromes with specific spectral characteristics.

Far‐field light microscopy based ‘nanoscopy’ techniques presently allow to discriminate (resolve) in a cellular environment individual fluorescent molecules down to a minimum distance of few nanometre.

The combination of the novel nanoscopy approaches with molecular biology methods is expected to open an avenue towards a substantially improved understanding of the basic mechanisms of life and its emergence from the basic laws of nature.
Kinetochore: Structure, Function and Evolution
Authors: Liu Song‐Tao
Published: August 2014

Duplicated eukaryotic chromosomes are segregated into daughter cells through cell division. Faithful chromosome segregation depends on kinetochores, which are specialized macromolecular structures built upon centromeric chromatin. The dynamic kinetochore structures connect chromosomes with spindle microtubules, power chromosome movement, and signal the activation and silencing of the spindle assembly checkpoint (SAC). Molecular analyses of the components and architecture of kinetochores have advanced rapidly in recent years. A human kinetochore contains approximately 200 proteins, many of which are evolutionarily conserved in other organisms. A histone H3 variant, CENP‐A and associated constitutive centromere proteins lay the foundation for kinetochore build‐up. Multiple kinetochore‐localised microtubule‐binding proteins including the Ndc80 complex help regulate chromosome movement. The SAC signalling originates from kinetochores and contributes to the fidelity of chromosome segregation. Many fascinating properties remain to be elucidated about the kinetochore as a fundamental machinery to maintain genomic stability.

Key Concepts:

Chromosome segregation in eukaryotic cells depends upon connecting spindle microtubules with special macromolecular structures on chromosomes called kinetochores.

The centromere is the chromosomal locus where a kinetochore is built.

Laying the foundation for kinetochore assembly at centromeres are CENP‐A (a histone H3 variant) containing nucleosomes and a group of CENP‐A associated proteins (termed constitutive centromere proteins).

There are multiple microtubule motors and nonmotor microtubule‐binding proteins localised at kinetochores to coordinate chromosome movement.

A 10 protein complex called KMN network is currently thought to provide the primary end‐on microtubule‐binding activity.

The spindle assembly checkpoint (SAC) monitors the kinetochore–microtubule attachment and signals the delay of the metaphase‐to‐anaphase transition when defects are detected.

Conformational change of MAD2 and assembly of the mitotic checkpoint complex (MCC) are the key events to activate the SAC.

Comparative studies of similar and distinct kinetochore composition, structure and function in different species and during mitosis or meiosis have provided evolutionary perspectives on mechanisms regulating chromosome segregation.
Bacteriophage: Therapeutic Uses
Authors: Harper David R , Burrowes Benjamin H , Kutter Elizabeth M
Published: August 2014

Bacteriophages are viruses that grow within bacteria. Almost all bacteriophages can destroy (lyse) their bacterial host, although many are ‘temperate’ and can insert their genome into that of their bacterial host, a state referred to as lysogeny. Those that can only kill their host bacteria are termed ‘virulent’ and are preferred for therapeutic use. Lysis kills the bacterial host and releases the next generation of bacteriophages. This unique property allows localised amplification of a bacteriophage therapeutic, but only where its specific bacterial host is present. Bacteriophages are also able to target bacteria living within biofilms that can make them highly refractory to conventional antibiotics. Since their discovery in 1915, bacteriophages have been identified as having potential for the control of bacterial disease. Following the widespread appearance of resistance to conventional antibiotics, interest in this area has revived and the results of clinical trials of bacteriophage therapeutics are now being reported.

Key Concepts:

Bacteriophages are viruses that infect bacteria.

Lytic bacteriophages kill their bacterial host rapidly, taking over host metabolism and producing a new generation of bacteriophages soon after infection.

Newly produced bacteriophages can infect new host bacteria locally and can also spread to other sites of infection.

This ability to kill bacteria led to their therapeutic use against bacterial infection in the pre‐antibiotic era.

In most of the world, bacteriophages have been superseded since the 1940s by chemical antibiotics due to a combination of factors, including the limited understanding of basic bacteriophage biology and the far broader host ranges of chemical antibiotics.

Despite many years of extensive clinical study in Eastern Europe and in earlier work in Europe and the United States, a lack of clinical trials meeting current regulatory requirements has limited the development of bacteriophage therapeutics.

Interest in bacteriophages as therapeutics has been revived by the looming antibiotic resistance crisis, in an era when much more information is available about the older work and when phage biology is far better understood.

Bacteriophage products for agricultural and food use are currently being marketed.
Amidohydrolase Superfamily
Authors: Liu Aimin , Huo Lu
Published: August 2014

The amidohydrolase superfamily is a structure‐based cluster of enzymes that contain a sturdy and versatile triosephosphate isomerase (TIM)‐like (β/α)
8
‐barrel fold embracing the catalytic active site. To date, the amidohydrolase superfamily has grown into one of the largest families of enzymes, with tens of thousand of members catalysing a wide range of hydrolytic and nonhydrolytic metabolic reactions which are important in amino acid and nucleotide metabolism as well as biodegradation of agricultural and industrial compounds. Previously, the presence of a mono‐ or dinuclear
d
‐block metal cofactor in the active site was thought to be one of the main characteristics of the members in this superfamily. However, recently new members containing a trinuclear metal cofactors or no cofactor at all were discovered. It has become apparent that activating a well‐ordered water molecule by an active site residue for nucleophilic attack on the organic substrate is a common mechanistic feature for all members of the superfamily.

Key Concepts:

Amidohydrolase superfamily is one of the largest enzyme superfamilies performing a wide array of catalytic reactions.

All members in the family employ a TIM‐barrel structural fold, although some of the amidohydrolase superfamily members present an imperfect barrel.

The vast majority, but not all, of the enzymes in this superfamily are metalloenzymes.

The hallmark of the catalytic mechanisms shared by these enzymes is to use an activated water molecule to attack the organic substrate.

The catalytic centre is diverse, with one, two, three or zero metal ion(s).
Plant Virus Silencing Suppressors and
RNA
Silencing in Plants
Authors: Zhang Xiuchun , Qu Feng
Published: August 2014

Plants use
ribonucleic acid (RNA)
of virus origins to produce
small interfering RNAs (siRNAs)
that guide sequence‐specific destruction of viral RNAs through a process termed RNA silencing. In addition to siRNAs, antiviral RNA silencing requires the participation of at least four families of plant proteins, namely the dicer‐like (DCL) nucleases that process virus‐specific double‐stranded (ds) RNA to siRNAs, Argonaute proteins (AGO) that use siRNAs as the sequence‐specific guide to cleave (slice) complementary single‐stranded viral RNA, as well as dsRNA‐binding proteins (DRBs) that assist DCL processing and/or DCL‐AGO communication, and RNA‐dependent RNA polymerases (RDRs) that produce a subset of dsRNA substrates of DCLs by converting viral ssRNAs into dsRNAs. To survive the RNA silencing‐based plant defence, plant viruses have evolved to encode strong suppressors of RNA silencing (VSR). Known targets of VSRs include all major steps/components of the RNA silencing pathway(s).

Key Concepts:

RNA silencing is an RNA‐mediated, sequence‐specific surveillance system in plants and other eukaryotes.

The sequence specificity of RNA silencing is conferred by siRNAs generated through the processing of dsRNAs originated from viruses and other molecular parasites.

RNA silencing is analogous to RNA interference (RNAi) in animals. It is a highly conserved mechanism of genome defence in almost all eukaryotic organisms.

Evolutionary successful viruses encode VSRs to engage diverse components of the RNA silencing pathway and subvert this robust defence mechanism.
Sleep and Memory
Authors: Aton Sara J , Seibt Julie , Frank Marcos G
Published: August 2014

Current behavioural evidence indicates that sleep plays a central role in memory consolidation. Neural events during post‐learning sleep share key features with both early and late stages of memory consolidation. For example, recent studies have shown neuronal changes during post‐learning sleep which reflect early synaptic changes associated with consolidation, including activation of shared intracellular pathways and modifications of synaptic strength. Sleep may also play a role in later stages of consolidation involving propagation of memory traces throughout the brain. However, to date the precise molecular and physiological aspects of sleep required for this process remain unknown. The behavioural effects of sleep may be mediated by the large‐scale, global changes in neuronal activity, synchrony and intracellular communication that accompany sleep, or by synapse‐specific ‘replay’ of activity patterns associated with prior learning.

Key Concepts:

Memory consolidation involves plastic changes at the synaptic and brain‐systems levels; these changes occur over timescales of minutes (synaptic consolidation) to days or months (systems consolidation).

Cellular changes occurring during early post‐learning sleep suggest that synaptic consolidation may occur preferentially during sleep.

Brain‐imaging and gene expression studies have provided limited evidence that sleep may facilitate the gradual redistribution of memory traces throughout the brain.

Sleep may facilitate consolidation through large‐scale changes in neural activity, neurotransmission or gene expression associated with REM and NREM sleep.

It remains unclear whether sleep‐dependent consolidation is mediated by permissive (global) or instructive (synapse‐specific) mechanisms.
Memory (Mechanisms Other than
LTP
)
Authors: Debanne Dominique , Campanac Emilie
Published: August 2014

Synaptic plasticity is not the exclusive mode of memory storage, and persistent regulation of voltage‐gated ionic channels also participates in information storage. Long‐term changes in neuronal excitability have been reported in several brain areas following learning. Synaptic activation of glutamate receptors initiates long‐lasting modification in neuronal excitability at the pre‐ or postsynaptic side, that is, in the axon, soma and dendrites of central neurons. Intrinsic plasticity is expressed in virtually all neuronal types including principal cells and interneurons. It is mediated by changes in the expression level or biophysical properties of voltage‐gated ion channels in the membrane and can affect many different neuronal operations such as dendritic integration and action potential generation and propagation. Similarly to synaptic plasticity, long‐lasting intrinsic plasticity is bidirectional and expresses a certain level of input or cell specificity. Synaptic and intrinsic plasticities not only share common learning rules and induction pathways but also contribute in synergy with these synaptic changes to the formation of a coherent mnesic engram.

Key Concepts:

Synaptic plasticity is a major mode of memory storage.

Persistent regulation of voltage‐gated ionic channels also participates in information storage following learning.

Synaptic activation of glutamate receptors initiates long‐lasting modification in neuronal excitability at the pre‐ or postsynaptic side.

Intrinsic plasticity is mediated by changes in the expression level or biophysical properties of voltage‐gated ion channels in the membrane.

Intrinsic plasticity can affect many different neuronal operations such as dendritic integration, action potential generation, action potential shape, action potential propagation and backpropagation.

Synaptic and intrinsic plasticities share common learning rules and induction pathways.

Synaptic and intrinsic plasticities contribute in synergy to the formation of a coherent mnesic engram.
Genetic Differences Between Chimpanzee Populations
Authors: Mitchell Matthew W , Gonder Mary Katherine
Published: August 2014

The evolutionary history of chimpanzees has been widely studied by researchers for a number of years. The number, and evolutionary relationship, of chimpanzee subspecies has been disputed for a number of years. In recent years researchers have used genomic data to investigate these questions. A consensus has emerged that chimpanzees are divided into four subspecies ranging across tropical Africa. However, little is known about underlying evolutionary processes that generated these patterns. Two major mechanisms have been proposed to drive the evolutionary diversification of chimpanzees: (1) isolation and subsequent diversification of taxa in Pleistocene Refugia and (2) isolation on opposite banks of riverine barriers. Additionally, the role of intraspecific differentiation and speciation through divergent selection across habitat gradients has been the focus of several recent studies, but this mechanism is relatively understudied in primates.

Key Concepts:

There have been recent breakthroughs into understanding the genetic differences between chimpanzee populations.

Genomic science has provided a window into the evolutionary history of chimpanzees.

Understanding evolutionary processes is vital to understanding chimpanzee evolution.

Understanding chimpanzee evolutionary history is of great interest to scientists.

Common chimpanzees can be divided into four genetically distinct subspecies.
MALDI
‐Mass Spectrometric Imaging of Endogenous Metabolites in Biological Systems
Authors: Gemperline Erin , Li Lingjun
Published: August 2014

Matrix‐assisted laser desorption/ionisation (MALDI)‐mass spectrometric imaging (MSI) is a powerful, relatively new technology that allows for the detection of molecules directly from biological systems and also provides the spatial distribution for these analytes within the tissue sample. MSI has gained considerable popularity for the study of endogenous metabolites as metabolites are the end product of various biochemical processes, and represent a biological snapshot of an organism's biochemistry at a given time. Although the underlying concept is simple, factors such as choice of ionisation method, sample preparation, instrumentation and data analysis must be taken into account and tailored for successful applications of MSI, especially for the study of small molecules. MALDI‐MSI has been successfully applied to the study of endogenous metabolites in animal, plant, bacteria and fungal tissues and has provided new insights into biological functions and pathways, interspecies interactions and novel natural products.

Key Concepts:

A metabolic profile provides a snapshot of an organism's metabolism and underlying biochemistry at a given time.

MALDI‐MSI provides spatial distribution of endogenous or exogenous molecules in a sample.

Advantages of MALDI‐MSI include the ability to detect a broad mass range of compounds, the ability to detect multiple analytes in a single experiment without the need for labels or prior knowledge of the analytes and the preservation of biologically relevant spatial information.

The study of small molecules with MALDI‐MSI presents unique challenges due to matrix interference and potential analyte delocalisation.

MALDI‐MSI has been extensively used to study metabolites and other compounds in animal tissue and has recently been applied to the study of small molecules in plant, bacteria and fungi.
Cancer Systems Biology: Current Achievements in – Omics Data Analysis, Network Reconstruction and Mathematical Modelling
Authors: Vera Julio , Wolkenhauer Olaf , Schmitz Ulf
Published: August 2014

Systems biology is a multidisciplinary methodology in which quantitative biological experimental data are dissected using mathematical modelling and other computational and network biology tools, aiming at understanding the structure, function and dynamical regulation of biochemical networks. Systems biology will play a major role in the future molecular and clinical oncology because (a) it can be used for the analysis of cancer‐relevant high‐throughput data, (b) it provides tools for the reconstruction of the large multilevel regulatory networks that govern critical cancer phenotypes and (c) it is necessary when investigating cancer‐relevant networks holding multiple overlapping nonlinear regulatory motifs like feedback and feedforward loops. Here, the value of the systems biology approach in handling cancer genomics and transcriptomics data, the reconstruction of cancer networks and the use of mathematical modelling in the elucidation of cancer networks as well as in the design of anticancer therapies are discusses. Some recent case studies as proof of principle are highlighted.

Key Concepts:

Systems biology is a multidisciplinary approach that involves the analysis of quantitative experimental data via mathematical modelling and computational and network biology.

Modelling of cancer‐related networks is necessary because these networks display multiple nonlinear regulatory motifs like feedback loops.

Mathematical models have been used to elucidate the structure, dynamics, dysregulation and crosstalk of cancer pathways like the JAK/STAT, p53, MAPK, NFkB and intrinsinc/extrinsic apoptosis signalling pathways, as well as in microRNA cancer regulation.

Multi‐scale mathematical models can accurately describe the spatial configuration of tumours, their crosstalk with the surrounding microenvironment and their role in physiological mechanisms like angiogenesis and immune system response.

Mathematical modelling has been used to assess and personalise conventional anticancer therapies, but it is also used in the detection of new anticancer drug targets and the development of combined or immune therapies.

Cancer bioinformatics facilitates efficient analyses and integration of diverse types of biomedical high‐throughput data for the elucidation of causes of tumour initiation, progression and metastasis but also for the management, storage and exchange of experimental and clinical data.

Cancer systems biology integrates algorithms, methodologies, software tools and web resources into customised analysis workflows to explore and understand the molecular mechanisms underlying this complex disease.

Data integration and analysis is used to identify novel robust and precise biomarkers, to identify network biomarkers and to design individual patient‐tailored therapeutic interventions.
Structure–Function Relationships in the Aromatic Amino Acid Hydroxylases Enzyme Family: Evolutionary Insights
Authors: Skjærven Lars , Teigen Knut , Martinez Aurora
Published: August 2014

The nonheme iron and tetrahydrobiopterin dependent aromatic amino acid hydroxylases (AAAHs) comprise a family of enzymes that catalyse the hydroxylation of
l
‐Phe,
l
‐Tyr and
l
‐Trp. These reactions are of central physiological importance. Consequently, dysfunction of the AAAHs is associated with serious disorders, that is, the genetic metabolic disease phenylketonuria for phenylalanine hydroxylase (PAH), and neurological and neuropsychiatric disorders for tyrosine hydroxylase (TH) and tryptophan hydroxylase 1 and 2 (TPH1, TPH2). Mammalian AAAHs are tetrameric proteins that present a three‐domain structure with a remarkable high similarity, in particularly for the catalytic domains. Structural analyses have provided valuable insights on the effect of disease‐associated mutations, mechanism of catalysis, the determinants for substrate specificity and regulation of enzymatic activity. The best characterised AAAH is PAH, which also seems to be the precursor of the family. The AAAHs have developed sophisticated regulatory mechanisms during evolution to control substrate
l
‐Phe (PAH), catecholamine (TH), serotonin and melatonin (TPHs) levels.

Key Concepts:

The aromatic amino acid hydroxylases (AAAHs) are tetrahydrobiopterin (BH
4
) dependent enzymes that use dioxygen as additional substrate.

The AAAHs are involved in serious inborn errors of metabolism with neuronal impact.

The AAAHs are highly homologous, contain a catalytic mononuclear nonheme iron coordinated by a 2‐His‐1‐carboxylate facial triad and show similar reaction mechanism.

Metazoans have at least three AAAH genes: phenylalanine hydroxylase (
PAH
), tyrosine hydroxylase (
TH
) and tryptophan hydroxylase(s) (
TPH
(s)), where
PAH
appears as the precursor of the family.

Mammalian PAH, TH, TPH1 and TPH2 are tetrameric, with a three‐domain subunit structure; substrate specificity is provided by the catalytic domain.

The AAAHs are highly regulated by mechanisms at the transcriptional, translational, posttranslational and allosteric levels.

Evolutionary adaptation of the enzymes is most evident at the regulatory mechanisms, along the complexity of the organisms, especially of the central nervous system (CNS).
Reversible Switching of Liquid Crystalline Order Permits Synthesis of Homogeneous Populations of Dipolar Patchy Microparticles
Authors: Wang Xiaoguang , Miller Daniel S. , de Pablo Juan J. , Abbott Nicholas L.
Published: August 2014

The spontaneous positioning of colloids on the surfaces of micrometer‐sized liquid crystal (LC) droplets and their subsequent polymerization offers the basis of a general and facile method for the synthesis of patchy microparticles. The existence of multiple local energetic minima, however, can generate kinetic traps for colloids on the surfaces of the LC droplets and result in heterogeneous populations of patchy microparticles. To address this issue, herein it is demonstrated that adsorbate‐driven switching of the internal configurations of LC droplets can be used to sweep colloids to a single location on the LC droplet surfaces, thus resulting in the synthesis of homogeneous populations of patchy microparticles. The surface‐driven switching of the LC can be triggered by addition of surfactant or salts, and permits the synthesis of dipolar microparticles as well as “Janus‐like” microparticles. By using magnetic colloids, the utility of the approach is illustrated by synthesizing magnetically responsive patchy microdroplets of LC with either dipolar or quadrupolar symmetry that exhibit distinct optical responses upon application of an external magnetic field.
Ionic liquids as novel solvents for the synthesis of sugar fatty acid ester
Authors: Mai Ngoc Lan , Ahn Kihun , Bae Sang Woo , Shin Dong Woo , Morya Vivek Kumar , Koo Yoon‐Mo
Published: August 2014

Sugar fatty acid esters are bio‐surfactants known for their non‐toxic, non‐ionic, and high biodegradability . With great emulsifying and conditioning effects, sugar fatty acids are widely used in the food, pharmaceutical, and cosmetic industries. Biosynthesis of sugar fatty acid esters has attracted growing attention in recent decades. In this study, the enzymatic synthesis of sugar fatty acid esters in ionic liquids was developed, optimized, and scaled up. Reaction parameters affecting the conversion yield of lipase‐catalyzed synthesis of glucose laurate from glucose and vinyl laurate (i.e. temperature, vinyl laurate/glucose molar ratio, and enzyme loads) were optimized by response surface methodology (RSM). In addition, production was scaled up to 2.5 L, and recycling of enzyme and ionic liquids was investigated. The results showed that under optimal reaction conditions (66.86 °C, vinyl laurate/glucose molar ratio of 7.63, enzyme load of 73.33 g/L), an experimental conversion yield of 96.4% was obtained which is close to the optimal value predicted by RSM (97.16%). A similar conversion yield was maintained when the reaction was carried out at 2.5 L. Moreover, the enzymes and ionic liquids could be recycled and reused effectively for up to 10 cycles. The results indicate the feasibility of ionic liquids as novel solvents for the biosynthesis of sugar fatty acid esters.
High‐Throughput Screening Technology for Automotive Applications
Authors: Sundermann Andreas , Gerlach Olga
Published: August 2014

The development of advanced emission control systems to meet the strict regulations requires efficient and flexible material screening capabilities. Here, a high throughput test unit is described. Two case studies demonstrate the rapid screening of relevant parameter spaces and material functionalities which can be used in product development. One involves steady‐state testing of hydrocarbon oxidation in Diesel aftertreatment systems, while the other shows the evaluation of oxygen storage capacity in the optimization of three‐way catalysts for gasoline engines.
Ionic‐Liquid‐Assisted Metal‐Free Oxidative Coupling of Amines To Give Imines
Authors: Monopoli Antonio , Cotugno Pietro , Iannone Francesco , Ciminale Francesco , Dell'Anna Maria Michela , Mastrorilli Piero , Nacci Angelo
Published: August 2014

An oxidative coupling of amines to give imines in ionic liquids (ILs) under metal‐free aerobic conditions has been developed. The high efficiency achievable in ILs is mechanistically explained in terms of activation of the starting materials (benzylamine and molecular oxygen) by an initial electron transfer, promoted by the ionic nature of the solvent. Reactivity data of variously p‐substituted benzylamines show a general deactivating effect, which would imply a change in the rate‐determining step in the reaction mechanism.
Palladium‐Catalyzed Regioselective 5‐exo‐O‐Cyclization/Oxidative Heck Cascades from o‐Alkynylbenzamides and Electron‐Deficient Alkenes
Authors: Madich Youssef , Álvarez Rosana , Aurrecoechea José M.
Published: August 2014

A Pd‐catalyzed 5‐exo‐selective oxycyclization/oxidative Heck coupling cascade is described, starting from readily available ortho‐alkynylbenzamides and functionalized olefins. The key to a high regioselectivity in the cyclization step is the choice of catalyst and/or additives. Thus, Pd(OAc)2 provides the desired 5‐exo products predominantly, whereas with PdCl2 or Pd(TFA)2, the corresponding 6‐endo products prevail. The subsequent oxidative Heck‐type coupling takes place stereoselectively with the very predominant formation of E isomers, leading to an effective preparation of structurally diverse carbonyl‐substituted allylideneisobenzofuranimines.
General Suzuki Coupling of Heteroaryl Bromides by Using Tri‐tert‐butylphosphine as a Supporting Ligand
Authors: Zou Yinjun , Yue Guizhou , Xu Jianwei , Zhou Jianrong (Steve)
Published: August 2014

A general procedure for the fast Suzuki coupling of major families of heteroaryl bromides was realized by using Pd(OAc)2/PtBu3 as the catalyst. Many couplings were finished within minutes at room temperature in n‐butanol. Different from previous studies, three typical heteroaryl bromides were systematically examined in couplings of various heteroaryl and aryl boronic acids.
Modified extended BDF scheme for the discontinuous Galerkin solution of unsteady compressible flows
Authors: Nigro A. , Ghidoni A. , Rebay S. , Bassi F.
Published: August 2014

In this paper, a high‐order DG method coupled with a modified extended backward differentiation formulae (MEBDF) time integration scheme is proposed for the solution of unsteady compressible flows. The objective is to assess the performance and the potential of the temporal scheme and to investigate its advantages with respect to the second‐order BDF. Furthermore, a strategy to adapt the time step and the order of the temporal scheme based on the local truncation error is considered. The proposed DG‐MEBDF method has been evaluated for three unsteady test cases: (i) the convection of an inviscid isentropic vortex; (ii) the laminar flow around a cylinder; and (iii) the subsonic turbulent flow through a turbine cascade. Copyright © 2014 John Wiley & Sons, Ltd.
An evaluation of interactive computer training to teach instructors to implement discrete trials with children with autism
Authors: Pollard Joy S. , Higbee Thomas S. , Akers Jessica S. , Brodhead Matthew T.
Published: August 2014

Discrete‐trial instruction (DTI) is a teaching strategy that is often incorporated into early intensive behavioral interventions for children with autism. Researchers have investigated time‐ and cost‐effective methods to train staff to implement DTI, including self‐instruction manuals, video modeling, and interactive computer training (ICT). ICT combines the best components of self‐instruction manuals and video models, and have the same benefits; however, there is limited research on this training method. Therefore, the purpose of this study was to investigate ICT to teach university students to implement DTI with children with autism. All participants' teaching fidelity increased during both role‐plays with an adult and instructional sessions with a child with autism. In addition, participants demonstrated an increase in teaching fidelity with untrained instructional programs. All participants were able to complete training in an average of 2 hr, and social validity ratings were high.
Effects of data sampling on graphical depictions of learning
Authors: Carey Mary‐Katherine , Bourret Jason C.
Published: August 2014

Continuous and discontinuous data‐collection methods were compared in the context of discrete‐trial programming. Archival data sets were analyzed using trial sampling (1st 5 trials, 1st 3 trials, and 1st trial only) and session sampling (every other session, every 3rd session, and every 5th session). Results showed that trial sampling systematically underestimated the number of sessions and days to mastery and overestimated the number of sessions and days to the 1st independent response. Session sampling systematically overestimated both sessions and days to mastery and sessions and days to the 1st independent response. A time‐savings analysis was included to evaluate empirically how much time would be saved by using each sampling method. Results suggested that data sampling would produce relatively minimal time savings.
Microwave heating and hydrolysis of rubber wood biomass in ionic liquids
Authors: Darji Dazylah , Alias Yatimah , Mohd Som Fauzi , Abd Razak Nurul Hainiza
Published: August 2014

BACKGROUND

Biomass from rubber wood has been gaining interest due to its availability and relative economic value. However it is difficult to separate the biomass using common solvents due to its complicated structure. The recent application of ionic liquids as reaction solvents has offered a new platform for its efficient utilization. The dissolution of biomass in ionic liquid via microwave has been investigated to reduce the dissolution time.

RESULTS

The pretreatment involves dissolving the biomass in various ionic liquids under domestic microwave radiation. The dissolution rate is dependent on the type of ionic liquid and biomass was found to be easily dissolved in acetate based imidazolium ionic liquid. The highest (up to 85%) substantial dissolution of rubber biomass was reached in 1‐ethyl‐3‐methylimidazolium acetate [C2mim][OAc] and 1‐butyl‐3‐methylimidazolium acetate [C4mim][OAc]. Furthermore, the amount of glucose resulting from pretreatment with [C2mim] [OAc] and [C4mim][OAc] was also higher than that from pretreatment with cloride anion. This is due to changes in physico chemical properties such as decreasing crystallinity in biomass as confirmed by XRD, TGA and FTIR analyses.

CONCLUSION

Anion acetate based imidazolium ionic liquid was discovered to be a good solvent for the dissolution of rubber biomass under microwave irradiation for converting cellulose to glucose. © 2014 Society of Chemical Industry
Evaluating radiographers' diagnostic accuracy in screen‐reading mammograms: what constitutes a quality study?
Authors: Debono Josephine C. , Poulos Ann E.
Published: August 2014

Introduction

The aim of this study was to first evaluate the quality of studies investigating the diagnostic accuracy of radiographers as mammogram screen‐readers and then to develop an adapted tool for determining the quality of screen‐reading studies.

Methods

A literature search was used to identify relevant studies and a quality evaluation tool constructed by combining the criteria for quality of Whiting, Rutjes, Dinnes et al. and Brealey and Westwood. This constructed tool was then applied to the studies and subsequently adapted specifically for use in evaluating quality in studies investigating diagnostic accuracy of screen‐readers.

Results

Eleven studies were identified and the constructed tool applied to evaluate quality. This evaluation resulted in the identification of quality issues with the studies such as potential for bias, applicability of results, study conduct, reporting of the study and observer characteristics. An assessment of the applicability and relevance of the tool for this area of research resulted in adaptations to the criteria and the development of a tool specifically for evaluating diagnostic accuracy in screen‐reading.

Conclusions

This tool, with further refinement and rigorous validation can make a significant contribution to promoting well‐designed studies in this important area of research and practice.